research progress on chemical constituents of zingiber officinale roscoe

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Bioactive Compounds and Bioactivities of Ginger ( Zingiber officinale Roscoe)

Qian-qian mao.

1 Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China; nc.ude.usys.2liam@qqoam (Q.-Q.M.); nc.ude.usys.2liam@35yxux (X.-Y.X.); nc.ude.usys.2liam@3yhsoac (S.-Y.C.)

Ren-You Gan

2 Department of Food Science & Technology, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China; nc.ude.utjs@ekroch

Harold Corke

3 Department of Food & Human Nutritional Sciences, University of Manitoba, Winnipeg, MB R3T 2N2, Canada; [email protected]

4 Richardson Centre for Functional Foods and Nutraceuticals, University of Manitoba, Winnipeg, MB R3T 2N2, Canada

Ginger ( Zingiber officinale Roscoe) is a common and widely used spice. It is rich in various chemical constituents, including phenolic compounds, terpenes, polysaccharides, lipids, organic acids, and raw fibers. The health benefits of ginger are mainly attributed to its phenolic compounds, such as gingerols and shogaols. Accumulated investigations have demonstrated that ginger possesses multiple biological activities, including antioxidant, anti-inflammatory, antimicrobial, anticancer, neuroprotective, cardiovascular protective, respiratory protective, antiobesity, antidiabetic, antinausea, and antiemetic activities. In this review, we summarize current knowledge about the bioactive compounds and bioactivities of ginger, and the mechanisms of action are also discussed. We hope that this updated review paper will attract more attention to ginger and its further applications, including its potential to be developed into functional foods or nutraceuticals for the prevention and management of chronic diseases.

1. Introduction

Ginger ( Zingiber officinale Roscoe), which belongs to the Zingiberaceae family and the Zingiber genus, has been commonly consumed as a spice and an herbal medicine for a long time [ 1 ]. Ginger root is used to attenuate and treat several common diseases, such as headaches, colds, nausea, and emesis. Many bioactive compounds in ginger have been identified, such as phenolic and terpene compounds. The phenolic compounds are mainly gingerols, shogaols, and paradols, which account for the various bioactivities of ginger [ 2 ]. In recent years, ginger has been found to possess biological activities, such as antioxidant [ 3 ], anti-inflammatory [ 4 ], antimicrobial [ 5 ], and anticancer [ 6 ] activities. In addition, accumulating studies have demonstrated that ginger possesses the potential to prevent and manage several diseases, such as neurodegenerative diseases [ 7 ], cardiovascular diseases [ 8 ], obesity [ 9 ], diabetes mellitus [ 10 ], chemotherapy-induced nausea and emesis [ 11 ], and respiratory disorders [ 12 ]. In this review, we focus on the bioactive compounds and bioactivities of ginger, and we pay special attention to its mechanisms of action.

2. Bioactive Components and Bioactivities of Ginger

2.1. bioactive components.

Ginger is abundant in active constituents, such as phenolic and terpene compounds [ 13 ]. The phenolic compounds in ginger are mainly gingerols, shogaols, and paradols. In fresh ginger, gingerols are the major polyphenols, such as 6-gingerol, 8-gingerol, and 10-gingerol. With heat treatment or long-time storage, gingerols can be transformed into corresponding shogaols. After hydrogenation, shogaols can be transformed into paradols [ 2 ]. There are also many other phenolic compounds in ginger, such as quercetin, zingerone, gingerenone-A, and 6-dehydrogingerdione [ 14 , 15 ]. Moreover, there are several terpene components in ginger, such as β-bisabolene, α-curcumene, zingiberene, α-farnesene, and β-sesquiphellandrene, which are considered to be the main constituents of ginger essential oils [ 16 ]. Besides these, polysaccharides, lipids, organic acids, and raw fibers are also present in ginger [ 13 , 16 ].

2.2. Antioxidant Activity

It has been known that overproduction of free radicals, such as reactive oxygen species (ROS), plays an important part in the development of many chronic diseases [ 17 ]. It has been reported that a variety of natural products possess antioxidant potential, such as vegetables, fruits, edible flowers, cereal grains, medicinal plants, and herbal infusions [ 18 , 19 , 20 , 21 , 22 , 23 , 24 ]. Several studies have found that ginger also has high antioxidant activity [ 14 , 25 ].

The antioxidant activity of ginger has been evaluated in vitro via ferric-reducing antioxidant power (FRAP), 2,2-diphenyl-1-picrylhydrazyl (DPPH), and 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) methods. The results revealed that dried ginger exhibited the strongest antioxidant activity, because the number of phenolic compounds was 5.2-, 1.1-, and 2.4-fold higher than that of fresh, stir-fried, and carbonized ginger, respectively. The antioxidant activity of different gingers had a tendency to be the following: dried ginger > stir-fried ginger > carbonized ginger > fresh ginger. This was mainly associated with their polyphenolic contents. When fresh ginger was heated, dried ginger with higher antioxidant activity was obtained, because fresh ginger contains a higher moisture content. However, when dried ginger was further heated to obtain stir-fried ginger and carbonized ginger, the antioxidant activity decreased, because the processing could change gingerols into shogaols [ 26 ]. Additionally, a fraction of the dried ginger powder abundant in polyphenols showed high antioxidant activity based on data from FRAP, oxygen radical absorbance capacity, and cellular antioxidant activity assays [ 27 ]. Besides, the type of extraction solvent could have an effect on the antioxidant activity of ginger. An ethanolic extract of ginger showed high Trolox-equivalent antioxidant capacity and ferric-reducing ability, and an aqueous extract of ginger exhibited strong free radical scavenging activity and chelating ability [ 16 ]. Moreover, ethanolic, methanolic, ethyl acetate, hexane, and water extracts of ginger respectively inhibited 71%, 76%, 67%, 67%, and 43% of human low-density lipoprotein (LDL) oxidation induced by Cu 2+ [ 28 ]. Results from a xanthine/xanthine oxidase system showed that an ethyl acetate extract and an aqueous extract had higher antioxidant properties than ethanol, diethyl ether, and n -butanol extracts did [ 3 ].

Several studies have indicated that ginger was effective for protection against oxidative stress. The underlying mechanisms of antioxidant action were investigated in cell models [ 14 , 29 ]. Ginger extract showed antioxidant effects in human chondrocyte cells, with oxidative stress mediated by interleukin-1β (IL-1β). It stimulated the expression of several antioxidant enzymes and reduced the generation of ROS and lipid peroxidation [ 30 ]. Additionally, ginger extract could reduce the production of ROS in human fibrosarcoma cells with H 2 O 2 -induced oxidative stress [ 31 ]. In stressed rat heart homogenates, ginger extract decreased the content of malondialdehyde (MDA), which was related to lipid peroxidation [ 29 ]. Ginger and its bioactive compounds (such as 6-shogaol) exhibited antioxidant activity via the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway ( Figure 1 ) [ 32 ]. In human colon cancer cells, 6-shogaol increased intracellular glutathione/glutathione disulfide (GSH/GSSG) and upregulated Nrf2 target gene expression, such as with heme oxygenase-1 ( HO-1) , metallothionein 1 ( MT1 ), aldo-keto reductase family 1 member B10 ( AKR1B10 ), ferritin light chain ( FTL ), and γ-glutamyltransferase-like activity 4 ( GGTLA4 ). Besides, 6-shogaol also enhanced the expression of genes involved in glutathione synthesis, such as the glutamate-cysteine ligase catalytic subunit ( GCLC ) and the glutamate-cysteine ligase modifier subunit ( GCLM ). Further analysis revealed that 6-shogaol and its metabolite activated Nrf2 via the alkylation of cysteine residues of Kelch-like ECH-associated protein 1 (Keap1) [ 33 ]. Moreover, ginger phenylpropanoids improved Nrf2 activity and enhanced the levels of glutathione S-transferase P1 (GSTP1) as well as the downstream effector of the Nrf2 antioxidant response element in foreskin fibroblast cells [ 15 ]. In a human mesenchymal stem cell model, ginger oleoresin was investigated for its effects on injuries that were induced by ionizing radiation. The treatment of oleoresin could decrease the level of ROS by translocating Nrf2 to the cell nucleus and activating the gene expression of HO-1 and NQO1 (nicotinamide adenine dinucleotide phosphate (NADPH) quinone dehydrogenase 1) [ 14 ].

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The potential mechanism for the antioxidant action of 6-shogoal: 6-shogoal leads to the translocation of Nrf2 into the nucleus and increases the expression of Nrf2 target genes by modifying Keap1 and preventing Nrf2 from proteasomal degradation. Thus, the level of GSH increases, and the level of ROS decreases. Abbreviations: Nrf2, nuclear factor erythroid 2-related factor 2; Keap1, Kelch-like ECH-associated protein 1; NQO1 , nicotinamide adenine dinucleotide phosphate (NADPH) quinone dehydrogenase 1; HO-1 , heme oxygenase-1; GCLC , glutamate-cysteine ligase catalytic subunit; GCLM , glutamate-cysteine ligase modifier subunit; Trx1 , thioredoxin 1; TrxR1 , thioredoxin reductase 1; AKR1B10, Aldo-keto reductase family 1 member B10; FTL , ferritin light chain; GGTLA4 , γ-glutamyltransferase-like activity 4; ROS, reactive oxygen species; GSH, glutathione; ARE, antioxidant response element.

An animal model has also been used to investigate the antioxidant properties of ginger and its bioactive compounds in vivo. There, 6-shogaol exhibited antioxidant potential by inducing the expression of Nrf2 target genes such as MT1 , HO-1 , and GCLC in the colon of wild-type mice, but not Nrf2 −/− mice [ 33 ]. In addition, rats with a gastric ulcer induced by diclofenac sodium were treated with the butanol extract of ginger. It could prevent an increase in the level of MDA and a decrease in catalase activity as well as the level of glutathione [ 34 ]. Moreover, the 6-gingerol-rich fraction from ginger could reduce the levels of H 2 O 2 and MDA, enhance antioxidant enzyme activity, and increase glutathione in rats with oxidative damage induced by chlorpyrifos [ 25 ]. Furthermore, treatment with ginger extract elevated the contents of antioxidants and testosterone in serum and protected rat testes from injuries in chemotherapy with cyclophosphamide [ 35 ].

Overall, in vitro and in vivo studies have demonstrated that ginger and its bioactive compounds, such as 6-shogaol, 6-gingerol, and oleoresin, possess strong antioxidant activity ( Table 1 ). Moreover, the activation of the Nrf2 signaling pathway is crucial to the underlying mechanisms of action. It should also be pointed out that the overproduction of ROS in the human body is considered to be a cause of many diseases. Theoretically, antioxidants should be effective. However, several factors, such as health conditions, individual differences, the lifestyles of people, other dietary factors, and the dosage, solubility, and oral intake of antioxidants could affect the bioaccessibility and bioavailability of antioxidants, leading to low blood concentrations overall, which probably could explain why most antioxidants do not work in the real world.

The antioxidant activity and potential mechanisms of ginger.

Constituent	Study Type	Subjects	Dose	Potential Mechanisms	Ref.
6-shogaol	In vivo	HCT-116 human colon cancer cells	20 μM	Increasing the intracellular GSH/GSSG ratio; decreasing the level of ROS; upregulating the expression of and genes	[ ]
6-shogaol	In vitro	Wild-type and Nrf2 C57BL/6J mice	100 mg/kg	Upregulating the expression of , and	[ ]
Ginger oleoresin	In vitro	Human mesenchymal stem cells	100 μg/mL	Reducing ROS production; inducing the translocation of Nrf2 to the cell nucleus; activating and gene expression	[ ]
Ginger phenylpropanoids	In vitro	BJ foreskin fibroblasts	40 μg/mL	Increasing Nrf2 activity and the level of GSTP1	[ ]
6-gingerol-rich fraction	In vivo	Female Wistar rats	50 and 100 mg/kg	Reducing the levels of H O and MDA; increasing the activities of antioxidant enzymes and the level of GSH	[ ]
Ginger extract	In vivo	Male Wistar albino rats	100 mg/kg	Reducing the level of MDA; preventing the depletion of catalase activity and GSH content	[ ]
	In vitro	C28I2 human chondrocyte cells	5 and 25 μg/mL	Increasing the gene expression of antioxidant enzymes; reducing the content of ROS and lipid peroxidation	[ ]
	In vitro	HT1080 human fibrosarcoma cells	200 and 400 μg/mL	Reducing the generation of ROS	[ ]
	In vitro	Rat heart homogenates	78–313 μg/mL	Decreasing the level of MDA	[ ]

GSSG, glutathione disulfide; MT1, metallothionein 1; GSTP1, glutathione S-transferase P1; MDA, malondialdehyde; Ref, reference.

2.3. Anti-Inflammatory Activity

A series of studies showed that ginger and its active constituents possessed anti-inflammatory activity ( Table 2 ), which could protect against inflammation-related diseases such as colitis [ 4 , 36 ]. The anti-inflammatory effects were mainly related to phoshatidylinositol-3-kinase (PI3K), protein kinase B (Akt), and the nuclear factor kappa light chain-enhancer of activated B cells (NF-κB).

Anti-inflammatory activity and potential mechanisms of ginger.

Constituent	Study Type	Subjects	Dose	Potential Mechanisms	Ref.
6-shogaol	In vitro	HT-29/B6 and Caco-2 human intestinal epithelial cells	100 μM	Inhibiting the PI3K/Akt and NF-κB signaling pathways	[ ]
6-shogaol and 6-gingerol, 6-dehydroshogaol	In vitro	RAW 264.7 mouse macrophage cells	2.5, 5, and 10 μM	Inhibiting the production of NO and PGE	[ ]
6-gingerol-rich fraction	In vivo	Female Wistar rats	50 and 100 mg/kg	Increasing the levels of myeloperoxidase, NO, and TNF-α	[ ]
GDNPs 2	In vivo	Female C57BL/6 FVB/NJ mice	0.3 mg	Increasing the levels of IL-10 and IL-22; decreasing the levels of TNF-α, IL-6, and IL-1β	[ ]
Ginger extract and zingerone	In vivo	Female BALB/c mice	0.1, 1, 10, and 100 mg/kg	Inhibiting NF-κB activation and decreasing the level of IL-1β	[ ]
Ginger extract	In vivo	C57BL6/J mice	50 mg/mL	Inhibiting the production of TNF-α; Activating Akt and NF-κB	[ ]

NO, nitric oxide; PGE 2 , prostaglandin E 2 ; TNF-α, tumor necrosis factor α; GDNPs 2, nanoparticles derived from edible ginger.

In addition, 6-shogaol showed protective effects against tumor necrosis factor α (TNF-α)-induced intestinal barrier dysfunction in human intestinal cell models. It also prevented the upregulation of Claudin-2 and the disassembly of Claudin-1 via the suppression of signaling pathways involved with PI3K/Akt and NF-κB [ 37 ]. In addition, 6-dehydroshogaol was more potent than 6-shogaol and 6-gingerol in reducing the generation of proinflammatory mediators such as nitric oxide (NO) and prostaglandin E 2 (PGE 2 ) in mouse macrophage RAW 264.7 cells [ 36 ]. Besides, ginger extract and zingerone inhibited NF-κB activation and decreased the level of IL-1β in the colons of mice, which alleviated colitis induced by 2, 4, 6-trinitrobenzene sulfonic acid [ 38 ]. Ginger also protected against anti-CD3 antibody-induced enteritis in mice, and ginger could reduce the production of TNF-α as well as the activation of Akt and NF-κB [ 39 ]. Moreover, nanoparticles derived from edible ginger (GDNPs 2) could prevent intestinal inflammation by increasing the levels of anti-inflammatory cytokines such as interleukin-10 (IL-10) and IL-22 and decreasing the levels of proinflammatory cytokines such as TNF-α, IL-6, and IL-1β in mice with acute colitis and chronic colitis [ 4 ]. In addition, nanoparticles loaded with 6-shogaol were found to attenuate colitis symptoms and improve colitis wound repair in mice with dextran sulfate sodium-induced colitis [ 40 ]. Moreover, microRNAs of ginger exosome-like nanoparticles (GELN) ameliorated mouse colitis by inducing the production of IL-22, a barrier function improvement factor [ 41 ]. Additionally, a fraction rich in 6-gingerol prevented an increase in inflammatory markers such as myeloperoxidase, NO, and TNF-α in the brain, ovaries, and uterus of rats treated with chlorpyrifos [ 25 ]. Furthermore, 28 male endurance runners consumed capsules of 500 mg of ginger powder. The results showed that the treatment could attenuate the post-exercise elevation of several cytokines that promote inflammation, such as plasma IL-1β, IL-6, and TNF-α [ 42 ].

In general, ginger and its active compounds have been found to be effective in alleviating inflammation, especially in inflammatory bowel diseases. The anti-inflammatory mechanisms of ginger are probably associated with the inhibition of Akt and NF-κB activation, an enhancement in anti-inflammatory cytokines, and a decline in proinflammatory cytokines. Notably, the application of ginger nanoparticles has the potential to improve the prevention of and therapy for inflammatory bowel disease.

2.4. Antimicrobial Activity

The spread of bacterial, fungal, and viral infectious diseases has been a major public threat due to antimicrobial resistance. Several herbs and spices have been developed into natural effective antimicrobial agents against many pathogenic microorganisms [ 43 ]. In recent years, ginger has been reported to show antibacterial, antifungal, and antiviral activities [ 44 , 45 ].

Biofilm formation is an important part of infection and antimicrobial resistance. One result found that ginger inhibited the growth of a multidrug-resistant strain of Pseudomonas aeruginosa by affecting membrane integrity and inhibiting biofilm formation [ 46 ]. In addition, treatment with ginger extract blocked biofilm formation via a reduction in the level of bis-(3′-5′)-cyclic dimeric guanosine monophosphate (c-di-GMP) in Pseudomonas aeruginosa PA14 [ 47 ]. Moreover, a crude extract and methanolic fraction of ginger inhibited biofilm formation, glucan synthesis, and the adherence of Streptococcus mutans by downregulating virulence genes. Consistent with the in vitro study, a reduction in caries development caused by Streptococcus mutans was found in a treated group of rats [ 48 ]. Furthermore, an in vitro study revealed that gingerenone-A and 6-shogaol exhibited an inhibitory effect on Staphylococcus aureus by inhibiting the activity of 6-hydroxymethyl-7, 8-dihydropterin pyrophosphokinase in the pathogen [ 49 ].

The compounds in ginger essential oil possess lipophilic properties, making the cell wall as well as the cytoplasmic membrane more permeable and inducing a loss of membrane integrity in fungi [ 50 ]. An in vitro study revealed that ginger essential oil effectively inhibited the growth of Fusarium verticillioides by reducing ergosterol biosynthesis and affecting membrane integrity. It could also decrease the production of fumonisin B 1 and fumonisin B 2 [ 51 ]. In addition, ginger essential oil had efficacy in suppressing the growth of Aspergillus flavus as well as aflatoxin and ergosterol production [ 50 ]. Moreover, the γ-terpinene and citral in ginger essential oil showed potent antifungal properties against Aspergillus flavus and reduced the expression of some genes related to aflatoxin biosynthesis [ 44 ]. Furthermore, fresh ginger was found to inhibit plaque formation induced by human respiratory syncytial virus (HRSV) in respiratory tract cell lines. Ginger was effective in blocking viral attachment and internalization [ 52 ]. In a clinical trial, ginger extract decreased hepatitis C virus (HCV) loads, the level of α-fetoprotein (AFP), and markers relevant to liver function, such as aspartate aminotransferase (AST) and alanine aminotransferase (ALT), in Egyptian HCV patients [ 53 ].

Therefore, ginger has been demonstrated to inhibit the growth of different bacteria, fungi, and viruses. These effects could be mainly related to the suppression of bacterial biofilm formation, ergosterol biosynthesis, and viral attachment and internalization ( Table 3 ).

Antimicrobial activity and potential mechanisms of ginger.

Constituent	Study Type	Subjects	Dose	Potential Mechanisms	Ref.
Ginger essential oil	In vitro		500, 1000, 2000, 3000, 4000, and 5000 μg/mL	Reducing ergosterol biosynthesis; affecting membrane integrity; decreasing the production of fumonisin B1 and fumonisin B2	[ ]
Ginger essential oil	In vitro		5, 10, 15, 20, 25, 50, 100, and 150 μg/mL	Reducing ergosterol biosynthesis; affecting membrane integrity; inhibiting the production of aflatoxin	[ ]
Gingerenone-A and shogaol	In vitro		25, 50, and 75 μg/mL	Inhibiting the activity of 6-hydroxymethyl-7, 8-dihydropterin pyrophosphokinase	[ ]
Ginger extract	In vitro		50, 100, 150, and 200 μg/mL	Affecting membrane integrity; inhibiting biofilm formation	[ ]
	In vitro		8, 16, 32, 64, and 128 μg/mL	Inhibiting biofilm formation, glucan synthesis, and adherence	[ ]
	In vitro	HEp-2 human larynx epidermoid carcinoma cells and A549 human lung carcinoma cells with HRSV	10, 30, 100, and 300 μg/mL	Blocking viral attachment and internalization	[ ]

HRSV, human respiratory syncytial virus.

2.5. Cytotoxicity

Cancer is documented to be a dominant cause of death, and there were approximately 9.6 million cases of death in 2018 [ 54 ]. Several research works have demonstrated that natural products such as fruits and medicinal plants possess anticancer activity [ 55 , 56 ]. Recently, ginger has been widely investigated for its anticancer properties against different cancer types, such as breast, cervical, colorectal, and prostate cancer [ 4 , 57 , 58 ]. The potential mechanisms of action involve the inhibition of proliferation and the induction of apoptosis in cancer ( Figure 2 ) [ 59 , 60 ].

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Several signaling pathways are involved in the anticancer mechanisms of 6-gingerol. CDK: Cyclin-dependent kinase; PI3K: Phosphoinositide 3-kinase; Akt: Protein kinase B; mTOR: Mammalian target of rapamycin; AMPK: 5’adenosine monophosphate-activated protein kinase; Bax: Bcl-2-associated X protein; Bcl-2: B-cell lymphoma 2.

Several investigations have demonstrated that ginger and its bioactive compounds can interfere with the carcinogenic processes of colorectal cancer. It was observed in an in vitro study that a fraction rich in the polyphenols of dried ginger powder suppressed the proliferation of colorectal cancer cells and gastric adenocarcinoma cells [ 27 ]. Besides, treatment with ginger extract promoted apoptosis by decreasing the expression of genes involved with the Ras/extracellular signal-regulated kinase (ERK) and PI3K/Akt pathways, such as the v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog ( KRAS ), ERK, Akt , and B-cell lymphoma-extralarge ( Bcl-xL ). It also increased the expression of caspase 9, which promoted apoptosis in HT-29 colorectal cancer cells [ 60 ]. In rats with 1,2-dimethylhydrazine-induced colon cancer, ginger extract loading with coated alginate beads increased the activities of NADH dehydrogenase and succinate dehydrogenase [ 61 ]. In addition, GDNPs 2 treatment decreased tumor numbers and tumor loads in mice with colitis-associated cancer induced by azoxymethane and dextran sodium sulfate. The levels of proinflammatory cytokines were decreased, and intestinal epithelial cell proliferation was inhibited [ 4 ]. In a pilot, randomized, and controlled trial, ginger extract supplementation decreased proliferation and increased apoptosis in the colonic mucosa of patients with a high risk of colorectal cancer. Ginger extract supplementation induced a decrease in the expression of two markers of cell proliferation, telomerase reverse transcriptase (hTERT) and MIB-1 (epitope of Ki-67), and increased the expression of pro-apoptotic gene Bcl-2-associated X ( Bax ) [ 6 ]. In subjects with a high risk of colorectal cancer, ginger supplementation decreased cyclooxygenase-1 (COX-1) expression, a key enzyme in the production of PGE 2 , which indicated the preventive potential of ginger in colorectal cancer [ 62 ].

The cytotoxic effects and underlying mechanisms of ginger in prostate cancer were evaluated both in vivo and in vitro. It was found that 6-gingerol, 10-gingerol, 6-shogaol, and 10-shogaol showed an antiproliferative effect on human prostate cancer cells via a downregulation of the protein expression of multidrug resistance associated protein 1 (MRP1) and glutathione-S-transferase (GSTπ) [ 59 ]. In addition, binary combinations of ginger phytochemicals, such as 6-gingerol, 8-gingerol, 10-gingerol, and 6-shogaol, synergistically inhibited the proliferation of PC-3 prostate cancer cells [ 63 ]. An in vivo study investigated the effect of ginger on athymic nude mice with human prostate tumor xenografts. A natural ginger extract showed a 2.4-fold higher inhibitory effect on the growth of tumors than an artificial mixture of 6-shogaol, 6-gingerol, 8-gingerol, and 10-gingerol [ 64 ]. Additionally, 6-shogaol could be more significant than 6-gingerol and 6-paradol in reducing cell survival and inducing apoptosis in human and mouse prostate cancer cells. It worked mainly through the suppression of signal transducer and activator of transcription 3 (STAT3) and NF-κB signaling. It also decreased the expression of cyclinD1, survivin, c-Myc, and B-cell lymphoma 2 ( Bcl-2 ), and enhanced Bax expression [ 56 ].

Ginger also exhibits cytotoxic activity against other types of cancer, such as breast, cervical, liver, and pancreatic cancer. An in vitro study revealed that 6-gingerol could inhibit the growth of HeLa human cervical adenocarcinoma cells, and it induced cell cycle arrest in the G 0 /G 1 -phase by decreasing the protein levels of cyclin A and cyclin D1. Apoptosis in Hela cells was induced by increasing the expression of caspase and inhibiting mammalian target of rapamycin (mTOR) signaling [ 65 ]. Besides, ginger extract protected against breast cancer in mice through the activation of 5’adenosine monophosphate-activated protein kinase (AMPK) and the downregulation of cyclin D1. The extract promoted apoptosis via an increase in the expression of the tumor suppressor gene p53 and a decrease in the level of NF-κB in tumor tissue [ 58 ]. Additionally, 10-gingerol was found to be potent in inhibiting human and mouse breast carcinoma cell growth. It reduced cell division and induced S phase cell cycle arrest and apoptosis [ 66 ]. Moreover, fluorescent carbon nanodots (C-dots) prepared from ginger effectively controlled tumor growth in nude mice, where the tumor was caused by HepG2 human hepatocellular carcinoma cells. The in vitro experiment found that C-dots increased the content of ROS in the HepG2 cells, which upregulated the expression of p53 and promoted apoptosis [ 67 ]. Furthermore, ginger extract and 6-shogaol suppressed the growth of human pancreatic cancer cells and led to ROS-mediated and caspase-independent cell death. Ginger extract suppressed tumor growth from pancreatic cancer in both a peritoneal dissemination model and an orthotopic model of mice without serious adverse effects [ 68 ].

Experimental studies have demonstrated that ginger can prevent and treat several types of cancer, such as colorectal, prostate, breast, cervical, liver, and pancreatic cancer ( Table 4 ). The anticancer mechanisms mainly involve the induction of apoptosis and the inhibition of the proliferation of cancer cells.

Cytotoxic activity and potential mechanisms of ginger.

Constituent	Study Type	Subjects	Dose	Potential Mechanisms	Ref.
6-shogaol	In vitro	LNCaP, DU145, and PC-3 human prostate cancer cells	10, 20, and 40 μM	Inducing apoptosis; inhibiting STAT3 and NF-κB signaling; downregulating the expression of and	[ ]
6-gingerol	In vitro	HeLa human cervical adenocarcinoma cells	60, 100, and 140 μM	Inducing cell cycle arrest in the G /G -phase; decreasing the levels of cyclin A, cyclin D1, and cyclin E1; increasing the expression of caspase; inhibiting the mTOR signaling pathway	[ ]
10-gingerol	In vitro	Human and mouse breast carcinoma cells	50, 100, and 200 μM	Inhibiting cell growth; reducing cell division; inducing S phase cell cycle arrest and apoptosis	[ ]
6-gingerol, 10-gingerol, 6-shogaol, and 10-shogaol	In vitro	PC-3 human prostate cancer cells	1,10, and 100 μM	Inhibiting prostate cancer cell proliferation; downregulating the expression of MRP1and GSTπ	[ ]
GDNPs 2	In vivo	Female C57BL/6 mice	0.3 mg	Suppressing the expression of cyclin D1; inhibiting intestinal epithelial cell proliferation	[ ]
Ginger extract	In vitro	HT29 human colorectal adenocarcinoma cells	2–10 mg/mL	Promoting apoptosis; upregulating the caspase 9 gene; downregulating , and	[ ]
Ginger extract	In vivo	Female Swiss albino mice	100 mg/kg	Activating AMPK; decreasing the expression of cyclin D1 and the level of NF-κB; increasing the expression of	[ ]
Ginger extract with alginate beads	In vivo	Male Wistar rats	50 mg/kg	Increasing the activity of NADH dehydrogenase and succinate dehydrogenase	[ ]
Ginger extract-based fluorescent carbon nanodots	In vitro	HepG2 human hepatocellular carcinoma cells	1.11 mg/mL	Increasing the level of ROS; upregulating the expression of ; promoting apoptosis	[ ]

STAT3, signal transducer and activator of transcription 3; Bcl-2, B-cell lymphoma 2; mTOR, mammalian target of rapamycin; MRP1, multidrug resistance associated protein 1; GSTπ, glutathione-S-transferase; AMPK, 5’adenosine monophosphate-activated protein kinase; NF-κB, nuclear factor kappa light chain-enhancer of activated B cells.

2.6. Neuroprotection

Some individuals, especially elderly people, have a high risk for neurodegenerative diseases, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) [ 69 ]. Recently, many investigations have revealed that ginger positively affects memory function and exhibits anti-neuroinflammatory activity, which might contribute to the management and prevention of neurodegenerative diseases [ 70 , 71 ].

The results from a lipopolysaccharide (LPS)-activated BV2 microglia culture model revealed that 10-gingerol was responsible for the strong anti-neuroinflammatory capacity of fresh ginger. It inhibited the expression of proinflammatory genes by blocking NF-κB activation, which led to a decline in the levels of NO, IL-1β, IL-6, and TNF-α [ 7 ]. Additionally, in mice with scopolamine-induced memory deficits, ginger extract could ameliorate the cognitive function of mice, which was assessed by a novel object recognition test. Further experiments in mouse hippocampi and rat C6 glioma cells revealed that ginger extract promoted the formation of synapses in the brain through the activation of extracellular signal-regulated kinase (ERK) induced by nerve growth factor (NGF) and cyclic AMP response element-binding protein (CREB) [ 69 ]. Another study found that 6-shogaol exhibited neuroprotective activity by activating Nrf2, scavenging free radicals, and elevating the levels of several phase II antioxidant molecules, such as NQO1 and HO-1, in neuron-like rat pheochromocytoma PC12 cells [ 32 ]. In addition, 6-dehydrogingerdione exhibited cytoprotection against neuronal cell damage induced by oxidative stress. It could effectively scavenge various free radicals in PC12 cells [ 72 ].

In a mouse model of AD induced by amyloid β 1–42 plaque, fermented ginger ameliorated memory impairment by protecting neuronal cells in mouse hippocampi, and it increased the levels of presynaptic and postsynaptic proteins [ 71 ]. In addition, ginger extract had protective effects against AD in rats, and a high dose of ginger extract decreased latency in showing significant memory deficits, as well as the levels of NF-κB, IL-1β, and MDA [ 73 ]. Moreover, 6-shogaol could alleviate cognitive dysfunction in mice with AD by inhibiting inflammatory responses, upregulating the level of NGF, and enhancing synaptogenesis in the brain [ 74 ]. Furthermore, in rat mesencephalic cells treated with 1-methyl-4-phenylpyridinium (MPP + ), 6-shogaol improved the amount of tyrosine hydroxylase-immunoreactive (TH-IR) neurons and inhibited the levels of TNF-α and NO. Treatment with 6-shogaol ameliorated motor coordination and bradykinesia in vivo in PD [ 70 ].

The above studies found that ginger and its bioactive compounds, such as 10-gingerol, 6-shogaol, and 6-dehydrogingerdione, exhibited protective effects against AD and PD. The antioxidant and anti-inflammatory activities of ginger contributed to neuroprotection.

2.7. Cardiovascular Protection

Cardiovascular diseases have been considered to be a leading cause of premature death, and 17.9 million people die per year [ 75 ]. Dyslipidemia and hypertension are known to be risk factors for cardiovascular diseases, including stroke and coronary heart disease [ 8 , 76 ]. A series of studies has shown that ginger can decrease the levels of blood lipids and blood pressure [ 77 , 78 ], contributing to protection from cardiovascular diseases.

Ginger extract reduced the body weight of rats fed a high-fat diet and enhanced the level of serum high-density lipoprotein-cholesterol (HDL-C), a protective factor against coronary heart disease. Besides, ginger extract increased the levels of apolipoprotein A-1 and lecithin-cholesterol acyltransferase mRNA in the liver, which was related to high-density lipoprotein (HDL) formation [ 79 ]. Additionally, total cholesterol (TC) and LDL concentrations were decreased by ginger extract in rats fed a high-fat diet, and the level of HDL increased through the combined application of aerobic exercise and ginger extract [ 76 ]. Moreover, ginger extract could reduce the levels of plasma TC, triglyceride (TG), and very low-density lipoprotein (VLDL) cholesterol in high-fat diet rats. The mechanism was related to higher liver expression of peroxisome proliferator-activated receptors (PPARα and PPARγ), which were related to atherosclerosis [ 78 ].

Vascular smooth muscle cell proliferation is a process in the pathogenesis of cardiovascular diseases. In an in vitro study, 6-shogaol exerted antiproliferative effects through increasing the number of cells in the G 0 /G 1 phase and activating the Nrf2 and HO-1 pathways [ 80 ]. In addition, ginger decreased the activities of angiotensin-1 converting enzyme (ACE) and arginase and increased the level of NO, a well-known vasodilator molecule. Thus, blood pressure decreased in hypertensive rats pretreated with ginger [ 8 ]. Besides, ginger protected against hypertension-derived complications by decreasing platelet adenosine deaminase (ADA) activity and increasing the level of adenosine, which prevented platelet aggregation and promoted vasodilation in hypertensive rats [ 77 ]. Moreover, ginger extract exhibited vasoprotective effects on porcine coronary arteries by suppressing NO synthase and cyclooxygenase [ 81 ]. Furthermore, a cross-sectional study found that the probability of hypertension and coronary heart disease declined when a daily intake of ginger was increased [ 82 ].

Generally, ginger has exhibited cardiovascular protective effects by attenuating hypertension and ameliorating dyslipidemia, such as in the improvement of HDL-C, TC, LDL, TG, and VLDL.

2.8. Antiobesity Activity

Obesity is a risk factor for many chronic diseases, such as diabetes, hypertension, and cardiovascular diseases [ 83 ]. Several studies have reported that ginger is effective in the management and prevention of obesity [ 9 , 84 ].

In 3T3-L1 preadipocyte cells, gingerenone A exhibited a greater inhibitory effect on adipogenesis and lipid accumulation than gingerols and 6-shogaol. Gingerenone A could also modulate fatty acid metabolism via the activation of AMPK in vivo, attenuating diet-induced obesity [ 9 ]. In cultured skeletal muscle myotubes, 6-shogaol and 6-gingerol could increase peroxisome proliferator-activated receptor δ (PPARδ)-dependent gene expression, and this resulted in the enhancement of cellular fatty acid catabolism [ 83 ]. In addition, both ginger and orlistat reduced the body weight and lipid profile of high-fat diet rats, while ginger had a greater effect on increasing the level of HDL-C than orlistat did [ 84 ]. In a randomized, double-blind, and placebo-controlled study, obese women receiving 2 g of ginger powder daily had a decreased body mass index (BMI) [ 85 ]. Moreover, the intake of dried ginger powder could reduce respiratory exchange ratios and promote fat utilization by increasing fat oxidation in humans [ 86 ].

Ginger and its bioactive constituents, including gingerenone A, 6-shogaol, and 6-gingerol, have shown antiobesity activity, with the mechanisms mainly related to the inhibition of adipogenesis and the enhancement of fatty acid catabolism.

2.9. Antidiabetic Activity

Diabetes mellitus is known as a severe metabolic disorder caused by insulin deficiency and/or insulin resistance, resulting in an abnormal increase in blood glucose. Prolonged hyperglycemia could accelerate protein glycation and the formation of advanced glycation end products (AGEs) [ 87 ]. Many research works have evaluated the antidiabetic effect of ginger and its major active constituents [ 88 ].

An in vitro experiment resulted in both 6-shogaol and 6-gingerol preventing the progression of diabetic complications, and they inhibited the production of AGEs by trapping methylglyoxal (MGO), the precursor of AGEs [ 87 ]. Additionally, 6-gingerol reduced the levels of plasma glucose and insulin in mice with high-fat diet-induced obesity. Nε-carboxymethyl-lysine (CML), a marker of AGEs, was decreased by 6-gingerol through Nrf2 activation [ 88 ]. In 3T3-L1 adipocytes and C2C12 myotubes, 6-paradol and 6-shogaol promoted glucose utilization by increasing AMPK phosphorylation. In addition, in a mouse model fed a high-fat diet, 6-paradol significantly reduced the level of blood glucose [ 10 ]. In another study, 6-gingerol facilitated glucose-stimulated insulin secretion and ameliorated glucose tolerance in type 2 diabetic mice by increasing glucagon-like peptide 1 (GLP-1). Besides, 6-gingerol treatment activated glycogen synthase 1 and increased cell membrane presentation of glucose transporter type 4 (GLUT4), which increased glycogen storage in skeletal muscles [ 89 ]. Furthermore, the consumption of ginger could reduce the levels of fasting plasma glucose, glycated hemoglobin A (HbA1 C ), insulin, TG, and TC in patients with type 2 diabetes mellitus (DM2) [ 90 ]. Moreover, ginger extract treatment improved insulin sensitivity in rats with metabolic syndrome, which might have been relevant to the energy metabolism improvement induced by 6-gingerol [ 91 ]. In addition, ginger extract alleviated retinal microvascular changes in rats that had diabetes induced by streptozotocin. Ginger extract could reduce the levels of NF-κB, TNF-α, and vascular endothelial growth factor in the retinal tissue [ 92 ]. In a randomized, double-blind, and placebo-controlled trial, the ingestion of ginger decreased the levels of insulin, low-density lipoprotein cholesterol (LDL-C), and TG; decreased the homeostasis model assessment index; and increased the quantitative insulin sensitivity check index in patients with DM2 [ 93 ].

The studies have demonstrated that ginger and its bioactive compounds could protect against diabetes mellitus and its complications, probably by decreasing the level of insulin, but increasing the sensitivity of insulin.

2.10. Antinausea and Antiemetic Activities

Ginger has been traditionally used to treat gastrointestinal symptoms, and recent research has demonstrated that ginger could effectively alleviate nausea and emesis [ 11 , 94 , 95 ].

In a clinical trial, inhaling ginger essence could attenuate nausea intensity and decrease emesis episodes two and six hours after a nephrectomy in patients [ 96 ]. In addition, dried ginger powder treatment reduced episodes of intraoperative nausea in elective cesarean section patients [ 97 ]. Moreover, nausea and emesis are common side effects of chemotherapy [ 98 ]. The activation of vagal afferent mediated by serotonin (5-HT) is crucial in the mechanism of emesis. An in vitro experiment revealed that 6-shogaol, 6-gingerol, and zingerone inhibited emetic signal transmission in vagal afferent neurons by suppressing the 5-HT receptor, and 6-shogaol had the strongest inhibitory efficacy [ 99 ]. Furthermore, ginger extract alleviated chemotherapy-induced nausea and emesis by suppressing the activation of 5-HT receptors in enteric neurons [ 11 ]. In a double-blind, randomized, and placebo-controlled trial, supplementation with ginger could improve the nausea-related quality of life in patients after chemotherapy [ 94 ]. Moreover, ginger alleviated the nausea induced by antituberculosis drugs and antiretroviral therapy, and it reduced the frequency of mild, moderate, and severe episodes of nausea in patients [ 100 , 101 ].

Previous results have shown that ginger could attenuate pregnancy-induced nausea and emesis and motion sickness, while recent studies have focused on the preventive efficacy of ginger on postoperative and chemotherapy-induced nausea and emesis [ 102 ].

2.11. Protective Effects against Respiratory Disorders

Natural herbal medicines have a long history of application in the treatment of respiratory disorders such as asthma, and ginger is one of these remedies [ 12 , 103 ]. Ginger and its bioactive compounds have exhibited bronchodilating activity and antihyperactivity in several studies [ 104 ].

Ginger induced significant and rapid relaxation in the isolated human airway smooth muscle. In results from guinea pig and human tracheas models, 6-gingerol, 8-gingerol, and 6-shogaol could lead to the rapid relaxation of precontracted airway smooth muscle. The nebulization of 8-gingerol attenuated airway resistance via a reduction in Ca 2+ influx in mice [ 12 ]. In another study, 6-gingerol, 8-gingerol, and 6-shogaol promoted β-agonist-induced relaxation in human airway smooth muscle via the suppression of phosphodiesterase 4D [ 103 ]. In addition, ginger ameliorated allergic asthma by reducing allergic airway inflammation and suppressed Th2-mediated immune responses in mice with ovalbumin-induced allergic asthma [ 105 ]. Moreover, the water-extracted polysaccharides of ginger could decrease times of coughing, which was induced through citric acid in guinea pigs [ 106 ]. Besides, ginger oil and its bioactive compounds, including citral and eucalyptol, inhibited rat tracheal contraction induced by carbachol in rats [ 104 ]. Furthermore, in patients with acute respiratory distress syndrome (ARDS), an enteral diet with rich ginger contributed to gas exchange and reduced the duration of mechanical ventilation [ 107 ].

The above results indicate that ginger and its bioactive constituents, including 6-gingerol, 8-gingerol, 6-shogaol, citral, and eucalyptol, have protective effects against respiratory disorders, at least mediating them through the induction of relaxation in airway smooth muscle and the attenuation of airway resistance and inflammation.

2.12. Other Bioactivities of Ginger

Apart from the bioactivities mentioned above ( Figure 3 ), ginger has other beneficial effects, such as hepatoprotective and antiallergic effects [ 108 , 109 ].

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Object name is foods-08-00185-g003.jpg

An overview of the bioactivities of ginger.

In a rat nephropathy model induced by gentamicin, gingerol dose-dependently ameliorated renal function and reduced lipid peroxidation and nitrosative stress. Gingerol also increased the levels of GSH and the activity of superoxide dismutase (SOD) [ 110 ]. Additionally, ginger extract ameliorated histological and biochemical alterations in the radiation-induced kidney damage of rats through antioxidant and anti-inflammatory activities [ 111 ]. Furthermore, liver histological results showed that ginger essential oil reduced lipid accumulations in the liver of obese mice fed a high-fat diet. Ginger essential oil could protect against steatohepatitis by enhancing antioxidant capacity and reducing inflammatory responses in the liver [ 109 ]. In another study with mice fed an alcohol-containing liquid diet, ginger essential oil ameliorated alcoholic fatty liver disease by decreasing the levels of AST, ALT, TG, and TC and increasing liver antioxidant enzyme activity, such as catalase and SOD [ 112 ]. To our knowledge, there has been no literature reporting the liver toxicity of ginger up to now. Additionally, in a mouse model of allergic rhinitis induced by ovalbumin (OVA), a ginger diet attenuated the severity of sneezing and nasal rubbing and inhibited the infiltration of mast cells into nasal mucosa as well as the secretion of serum immunoglobulin E. The in vitro study indicated that 6-gingerol could alleviate allergic rhinitis by reducing cytokine production for T cell activation and inhibiting the activation of B cells and mast cells [ 108 ]. Moreover, treatment with ginger could reduce blood loss in women with heavy menstrual bleeding [ 113 ]. In a double-blinded randomized clinical trial, treatment with ginger powder alleviated a common migraine attack and had fewer clinical adverse effects than the clinical medicine sumatriptan [ 114 ].

It is interesting to note that several plants in Zingiberaceae have also attracted increasing attention, such as Curcuma longa L. (turmeric), Zingiber officinale Roscoe (ginger), and Alpinia zerumbet (shell ginger) [ 115 ]. In a previous paper, we reviewed the bioactivities of curcumin (main active component of Curcuma longa ) [ 116 ], and a comparison between ginger and shell ginger is given in Table 5 . Shell ginger has exhibited similar biological activities to ginger, including antioxidant, anti-inflammatory, antimicrobial, anticancer, cardiovascular protective, antiobesity, and antidiabetic activities [ 115 ]. Differently, ginger has also been reported to have neuroprotective, respiratory protective, antinausea, and antiemetic activities, while shell ginger might contribute to longevity. In particular, shell ginger has been found to play an important contributory role in the longevity of people in Okinawa [ 115 ].

The comparison between ginger and shell ginger.

Items	Ginger	Shell Ginger	Ref.
Scientific name	Roscoe	(Pers.) B.L. Burtt & R.M. Sm.	[ , ]
Family and genus	Zingiberaceae family and genus	Zingiberaceae family and genus	[ , ]
Edible parts	Rhizomes	Leaves and rhizomes	[ , ]
Bioactive compounds	Gingerols, shogaols, paradols, and essential oils	Dihydro-5,6-dehydrokawain, 5,6-dehydrokawain, essential oils, and flavonoids	[ , , ]
Biological activities	Antioxidant, anti-inflammatory, antimicrobial, anticancer, cardiovascular protective, antiobesity, antidiabetic, neuroprotective, respiratory protective, antinausea, and antiemetic activities	Antioxidant, anti-inflammatory, antimicrobial, anticancer, cardiovascular protective, antiobesity, antidiabetic activities, longevity	[ , , , , , , , , , , ]

3. Conclusions

In conclusion, ginger contains diverse bioactive compounds, such as gingerols, shogaols, and paradols, and possesses multiple bioactivities, such as antioxidant, anti-inflammatory, and antimicrobial properties. Additionally, ginger has the potential to be the ingredient for functional foods or nutriceuticals, and ginger could be available for the management and prevention of several diseases such as cancer, cardiovascular diseases, diabetes mellitus, obesity, neurodegenerative diseases, nausea, emesis, and respiratory disorders. In the future, more bioactive compounds in ginger could be isolated and clearly identified, and their biological activities and related mechanisms of action should be further investigated. Notably, well-designed clinical trials of ginger and its various bioactive compounds are warranted to prove its efficacy against these diseases in human beings.

Author Contributions

Conceptualization, Q.-Q.M., R.-Y.G., and H.-B.L.; writing—original draft preparation, Q.-Q.M. and X.-Y.X.; writing—review and editing, X.-Y.X., S.-Y.C., R.-Y.G., H.C., T.B., and H.-B.L.; supervision, R.-Y.G. and H.-B.L.; funding acquisition, R.-Y.G., H.C., and H.-B.L.

This study was supported by the National Key R&D Program of China (2017YFC1600100), the Shanghai Basic and Key Program (18JC1410800), the Agri-X Interdisciplinary Fund of Shanghai Jiao Tong University (Agri-X2017004), and the Key Project of the Guangdong Provincial Science and Technology Program (2014B020205002).

Conflicts of Interest

The authors declare no conflicts of interest.

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Research Progress on Chemical Constituents of Zingiber officinale Roscoe

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Zingiber officinale Roscoe is commonly used in food and pharmaceutical products but can also be used in cosmetics and daily necessities.

In recent years, many scholars have studied the chemical composition of Zingiber officinale Roscoe; therefore, it is necessary to comprehensively summarize the chemical composition of Zingiber officinale Roscoe in one article.

The purpose of this paper is to provide a comprehensive review of the chemical constituents of Zingiber officinale Roscoe.

The results show that Zingiber officinale Roscoe contains 194 types of volatile oils, 85 types of gingerol, and 28 types of diarylheptanoid compounds, which can lay a foundation for further applications of Zingiber officinale Roscoe.

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Liu, Yan& Liu, Jincheng& Zhang, Yongqing. 2019. Research Progress on Chemical Constituents of Zingiber officinale Roscoe. BioMed Research International، Vol. 2019, no. 2019, pp.1-21. https://search.emarefa.net/detail/BIM-1125985

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Research Progress on Chemical Constituents of Zingiber officinale Roscoe

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Chemical Constituents of the Fresh Rhizome of Zingiber officinale

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Acknowledgment

This research was supported by the Shanghai Municipal Committee of Science and Technology in China (Grant Nos. 14431900300 and 15431900400) and the Development Project of Shanghai Peak Disciplines-Integrative Medicine in China (Grant No. 20150407).

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Wei, WJ., Tan, SB., Guo, T. et al. Chemical Constituents of the Fresh Rhizome of Zingiber officinale . Chem Nat Compd 57 , 968–969 (2021). https://doi.org/10.1007/s10600-021-03526-4

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Research Progress on Chemical Constituents of Zingiber officinale Roscoe

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Zingiber officinale Roscoe is commonly used in food and pharmaceutical products but can also be used in cosmetics and daily necessities. In recent years, many scholars have studied the chemical composition of Zingiber officinale Roscoe; therefore, it is necessary to comprehensively summarize the chemical composition of Zingiber officinale Roscoe in one article. The purpose of this paper is to provide a comprehensive review of the chemical constituents of Zingiber officinale Roscoe. The results show that Zingiber officinale Roscoe contains 194 types of volatile oils, 85 types of gingerol, and 28 types of diarylheptanoid compounds, which can lay a foundation for further applications of Zingiber officinale Roscoe.

1. Introduction

Zingiber officinale Roscoe (ZOR, also Shengjiang in Chinese) is a perennial herb from the Zingiberaceae family, native to the Pacific Islands. It can be found in the Chinese provinces of Shandong, Henan, Hubei, Yunnan, Guangdong, Sichuan, and Jiangsu. ZOR is the fresh root of ginger, which is not only an important condiment but also one of the most commonly used Chinese medicines in clinical practice. Traditional Chinese medicine believes that ZOR has effects of releasing exterior and dissipating cold, arresting vomiting, resolving phlegm, and relieving coughs and can be used to treat fish and crab poison, stomach colds and vomiting, and cold sputum cough [1]. Modern pharmacological studies have shown that ZOR can promote digestion, improve blood circulation, lower blood lipids, lower blood sugar, relieve vestibular stimulation, and provide anti-inflammatory, antitumor, antimicrobial, and antioxidant effects [2-5]. Due to its rich active constituents, ZOR has been used in cosmetics [6], toothpaste [7], and health foods [8-10].

All development and utilization of ZOR are based on its material composition. The chemical composition of ZOR is complex, includes more than 300 types of species, and can be broadly divided into three categories: volatile oils, gingerol, and diarylheptanoids [11-13]. In this paper, the existing research literature of ZOR is systematically summarized, and each chemical composition and its chemical structure are listed in detail, with a view to providing references for quality control, cultivation production, and further development of ZOR.

2. Constituents

2.1. Volatile Oils. Volatile oils, also known as ginger essential oils, are generally composed of terpenoids [14]. Ginger essential oils give ZOR a unique aromatic smell [11]. The volatile oil composition varies based on where the ZOR is harvested. Currently, the ingredients identified in the volatile oils of ZOR and their chemical structures are shown in Table 1.

2.2. Gingerol. Gingerol is the spicy component of ZOR. It is a mixture of various substances, all of which contain the 3-methoxy-4-hydroxyphenyl functional group. Gingerols can be divided into gingerols, shogaols, paradols, zingerones, gingerdiones, and gingerdiols, according to the different fatty chains connected by this functional group [28, 29]. The structural formulas are given in Table 2.

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Yan Liu [ID], (1) Jincheng Liu, (2) and Yongqing Zhang [ID](1)

Research Progress on Chemical Constituents of Zingiber officinale Roscoe. Biomed Res Int . 2019; 2019:5370823. BR

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Diarylheptanoids
Fatty Alcohols
Oils, Volatile
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Zingiber officinale : a systematic review of botany, phytochemistry and pharmacology of gut microbiota-related gastrointestinal benefits.

Wenjing Lai ,
Shasha Yang ,
Xing Zhang ,
You Huang ,
Jingwei Zhou ,
Chaomei Fu ,
Rui Li , and

State Key Laboratory of Southwestern Chinese Medicine Resources, Pharmacy College, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, P. R. China

These authors contributed equally to this work.

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E-mail Address: [email protected]

Correspondence to: Prof. Chaomei Fu, State Key Laboratory of Southwestern Chinese Medicine Resources, Pharmacy College, Chengdu University of Traditional Chinese Medicine, 1166 Liutai Avenue, Wenjiang District, Chengdu 611137, P. R. China. Tel: (+86) 28-6180-0000, Fax: (+86) 28-6180-0000.

Correspondence to: Prof. Rui Li, State Key Laboratory of Southwestern Chinese Medicine Resources, Pharmacy College, Chengdu University of Traditional Chinese Medicine, 1166 Liutai Avenue, Wenjiang District, Chengdu 611137, P. R. China. Tel: (+86) 28-6180-0000, Fax: (+86) 28-6180-0000.

Key Laboratory of Quality Control and Efficacy Evaluation of Traditional Chinese Medicine Formula Granules, Sichuan New Green Medicine Science and Technology Development Co., Ltd., Pengzhou 610081, P. R. China

Correspondence to: Associate Prof. Zhen Zhang, State Key Laboratory of Southwestern Chinese Medicine Resources, Pharmacy College, Chengdu University of Traditional Chinese Medicine, 1166 Liutai Avenue, Wenjiang District, Chengdu 611137, P. R. China; Key Laboratory of Quality Control and Efficacy Evaluation of Traditional Chinese Medicine Formula Granules, Sichuan New Green Medicine Science and Technology Development Co., Ltd., 279 Donghe East Road, Zhihe Town, Pengzhou 610081, P. R. China. Tel: (+86) 28-6180-0000, Fax: (+86) 28-6180-0000.

Ginger ( Zingiber officinale Rosc.) is a traditional edible medicinal herb with a wide range of uses and long cultivation history. Fresh ginger (Zingiberis Recens Rhizoma; Sheng Jiang in Chinese, SJ) and dried ginger (Zingiberis Rhizoma; Gan Jiang in Chinese, GJ) are designated as two famous traditional Chinese herbal medicines, which are different in plant cultivation, appearances and functions, together with traditional applications. Previous researches mainly focused on the differences in chemical composition between them, but there was no systematical comparison on the similarity concerning research achievements of the two herbs. Meanwhile, ginger has traditionally been used for the treatment of gastrointestinal disorders, but so far, the possible interaction with human gut microbiota has hardly been considered. This review comprehensively presents similarities and differences between SJ and GJ retrospectively, particularly proposing them the significant differences in botany, phytochemistry and ethnopharmacology, which can be used as evidence for clinical application of SJ and GJ. Furthermore, the pharmacology of gut microbiota-related gastrointestinal benefits has also been discussed in order to explore better ways to prevent and treat gastrointestinal disorders, which can be used as a reference for further research.

Zingiber Officinale Rosc
Fresh Ginger
Dried Ginger
Gut Microbiota
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Composition of zingiber officinale roscoe (ginger), soil properties and soil enzyme activities grown in different concentration of mineral fertilizers.

1. Introduction

2. materials and methods, 2.1. experimental design, 2.2. measurement of plant nutrients, 2.3. analysis of soil nutrients, 2.4. analysis of soil enzymes, 2.5. statistical analyses, 3.1. measurement of plant nutrients, 3.2. analysis of soil nutrients, 3.3. analysis of soil enzymes, 4. discussion, 5. conclusions, author contributions, institutional review board statement, informed consent statement, acknowledgments, conflicts of interest.

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Click here to enlarge figure

Parameter	T-1	T-2	T-3	T-4
K	11,232 ± 4.31	13,322 ± 3.38	15,406 ± 1.85	27,474 ± 9.65
Ca	14,721 ± 2.39	24,570 ± 10	20,719 ± 4.15	35,885 ± 7.21
P	5209.6 ± 6	5544.2 ± 2.1	6592.4 ± 10.3	7542.7 ± 9.02
Mg	5534 ± 2.97	5774.3 ± 8.71	6374.3 ± 0.058	9055 ± 4.58
Na	1555.7 ± 0.972	1890 ± 0.998	1923.4 ± 2.78	3771.4 ± 3.46

Parameter	T-1	T-2	T-3	T-4
Fe	375.61 ± 0.995	574.7 ± 7.9	602.35 ± 0.568	645.42 ± 3.06
Mn	69.146 ± 1.001	113.93 ± 2.04	134.18 ± 0.989	171.41 ± 1.58
Zn	3.371 ± 0.04	4.273 ± 0.115	5.262 ± 0.106	5.493 ± 0.005
Cu	2.779 ± 0.009	6.413 ± 0.09	5.242 ± 0.018	5.905 ± 0.005
Cr	1.663 ± 0.095	1.667 ± 0.015	1.452 ± 0.011	1.624 ± 0.005
Mo	0.16 ± 0.01	0.161 ± 0.009	0.261 ± 0.001	0.21 ± 0.01
Si	0.155 ± 0.011	0.213 ± 0.015	0.212 ± 0.012	0.309 ± 0.001

Parameter	T-1	T-2	T-3	T-4
Li	0.297 ± 0.012	0.29 ± 0.01	0.367 ± 0.002	0.44 ± 0.001
Be	0.02 ± 0.01	0.012 ± 0.002	0.012 ± 0.001	0.014 ± 0.004
V	0.332 ± 0.001	0.489 ± 0.01	0.568 ± 0.002	0.625 ± 0.005
Co	0.119 ± 0.003	0.144 ± 0.001	0.135 ± 0.003	0.155 ± 0.002
Ga	0.313 ± 0.005	0.355 ± 0.005	0.367 ± 0.003	0.314 ± 0.017
Ge	0.002 ± 0.001	0.002 ± 0.001	0.002 ± 0.001	0.002 ± 0.001
Nb	0.001 ± 0.001	0.001 ± 0.001	0.001 ± 0.001	0.001 ± 0.001
Ag	0.015 ± 0.001	0.025 ± 0.002	0.03 ± 0.01	0.019 ± 0.001
Cd	0.008 ± 0.001	0.008 ± 0.001	0.008 ± 0.001	0.008 ± 0.001
In	0 ± 0	0 ± 0	0 ± 0	0 ± 0
Sn	0.033 ± 0	0.033 ± 0	0.033 ± 0	0.033 ± 0
Sb	0.013 ± 0.006	0.013 ± 0.006	0.013 ± 0.006	0.013 ± 0.006
Cs	0.003 ± 0.001	0.003 ± 0.001	0.003 ± 0.001	0.003 ± 0.001
Ta	0 ± 0	0 ± 0	0 ± 0	0 ± 0
W	0.003 ± 0.001	0.003 ± 0.001	0.003 ± 0.001	0.003 ± 0.001
Re	0 ± 0	0 ± 0	0 ± 0	0 ± 0

Parameter	T-0	T-1	T-2	T-3	T-4
Active P O mg/kg	31.33 ± 0.58	35.3 ± 1	37.6 ± 0.1	39.5 ± 1	42.6 ± 1.1
Active K O mg/kg	351.67 ± 0.76	120.57 ± 1.03	135.66 ± 1.88	140.69 ± 0.09	152.45 ± 1.05
N-NO mg/kg	89.13 ± 1.03	10.25 ± 0.05	28.483 ± 0.9	33.44 ± 0.06	35.12 ± 1.02
Total P O %	0.19 ± 0.02	0.19 ± 0.01	0.241 ± 0.001	0.21 ± 0.01	0.32 ± 0.02
Total K O%	1.87 ± 0.02	0.837 ± 0.012	0.92 ± 0.02	0.96 ± 0.02	0.98 ± 0.02
N%	0.09 ± 0	0.124 ± 0.002	0.128 ± 0.001	0.137 ± 0.012	0.195 ± 0.002
Humus, %	1.7 ± 0	1.996 ± 0.005	2.02 ± 0.01	2.013 ± 0.015	2.41 ± 0.01
C%	0.98 ± 0	1.157 ± 0.004	1.172 ± 0.002	1.166 ± 0.006	1.396 ± 0.005
C/N	10.4 ± 0.1	9.367 ± 0.116	9.1 ± 0.3	8.9 ± 0.1	7.733 ± 0.153
CO %	8.92 ± 0.07	6.45 ± 0.05	6.4 ± 0.01	6.01 ± 0.01	6.013 ± 0.006
Total HCO %	0.02 ± 0	0.014 ± 0.004	0.013 ± 0.001	0.011 ± 0.002	0.021 ± 0.001
Cl%	0.09 ± 0	0.008 ± 0.001	0.006 ± 0.001	0.004 ± 0.001	0.005 ± 0.001
SO %	0.28 ± 0.01	1.003 ± 0.006	0.98 ± 0.01	0.743 ± 0.006	1.122 ± 0.001
Ca%	0.24 ± 0	0.14 ± 0.01	0.12 ± 0.01	0.133 ± 0.058	0.213 ± 0.006
Mg%	0.06 ± 0	0.032 ± 0.002	0.03 ± 0.01	0.013 ± 0.006	0.054 ± 0.001

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Jabborova, D.; Choudhary, R.; Azimov, A.; Jabbarov, Z.; Selim, S.; Abu-Elghait, M.; Desouky, S.E.; Azab, I.H.E.; Alsuhaibani, A.M.; Khattab, A.; et al. Composition of Zingiber officinale Roscoe (Ginger), Soil Properties and Soil Enzyme Activities Grown in Different Concentration of Mineral Fertilizers. Horticulturae 2022 , 8 , 43. https://doi.org/10.3390/horticulturae8010043

Jabborova D, Choudhary R, Azimov A, Jabbarov Z, Selim S, Abu-Elghait M, Desouky SE, Azab IHE, Alsuhaibani AM, Khattab A, et al. Composition of Zingiber officinale Roscoe (Ginger), Soil Properties and Soil Enzyme Activities Grown in Different Concentration of Mineral Fertilizers. Horticulturae . 2022; 8(1):43. https://doi.org/10.3390/horticulturae8010043

Jabborova, Dilfuza, Ravish Choudhary, Abdulahat Azimov, Zafarjon Jabbarov, Samy Selim, Mohammed Abu-Elghait, Said E. Desouky, Islam H. El Azab, Amnah Mohammed Alsuhaibani, Adel Khattab, and et al. 2022. "Composition of Zingiber officinale Roscoe (Ginger), Soil Properties and Soil Enzyme Activities Grown in Different Concentration of Mineral Fertilizers" Horticulturae 8, no. 1: 43. https://doi.org/10.3390/horticulturae8010043

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Ginger (Zingiber officinale Rosc.) and its bioactive components are potential resources for health beneficial agents

Affiliations.

1 School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
2 Basic Medical School, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
PMID: 32954562
DOI: 10.1002/ptr.6858

Zingiber officinale Rosc. (Zingiberacae), commonly known as ginger, is a perennial and herbaceous plant with long cultivation history. Ginger rhizome is one of the most popular food spices with unique pungent flavor and is prescribed as a well-known traditional Chinese herbal medicine. To date, over 160 constituents, including volatile oil, gingerol analogues, diarylheptanoids, phenylalkanoids, sulfonates, steroids, and monoterpenoid glycosides compounds, have been isolated and identified from ginger. Increasing evidence has revealed that ginger possesses a broad range of biological activities, especially gastrointestinal-protective, anti-cancer, and obesity-preventive effects. In addition, gingerol analogues such as 6-gingerol and 6-shogaol can be rapidly eliminated in the serum and detected as glucuronide and sulfate conjugates. Structural variation would be useful to improve the metabolic characteristics and bioactivities of lead compounds derived from ginger. Furthermore, some clinical trials have indicated that ginger can be consumed for attenuating nausea and vomiting during early pregnancy; however, there is not sufficient data available to rule out its potential toxicity, which should be monitored especially over longer periods. This review provides an up-to-date understanding of the scientific evidence on the development of ginger and its active compounds as health beneficial agents in future clinical trials.

Keywords: Zingiber officinale; anti-cancer; antiemetic; ginger; gingerols and shogaols; pharmacokinetics.

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REVIEW article

Potential role of ginger ( zingiber officinale roscoe) in the prevention of neurodegenerative diseases.

$\nRaúl Arcusa$

Department of Pharmacy, Faculty of Health Sciences, Catholic University of San Antonio (UCAM), Murcia, Spain

Ginger is composed of multiple bioactive compounds, including 6-gingerol, 6-shogaol, 10-gingerol, gingerdiones, gingerdiols, paradols, 6-dehydrogingerols, 5-acetoxy-6-gingerol, 3,5-diacetoxy-6-gingerdiol, and 12-gingerol, that contribute to its recognized biological activities. Among them, the major active compounds are 6-shogaol and 6-gingerol. Scientific evidence supports the beneficial properties of ginger, including antioxidant and anti-inflammatory capacities and in contrast, a specific and less studied bioactivity is the possible neuroprotective effect. The increase in life expectancy has raised the incidence of neurodegenerative diseases (NDs), which present common neuropathological features as increased oxidative stress, neuroinflammation and protein misfolding. The structure-activity relationships of ginger phytochemicals show that ginger can be a candidate to treat NDs by targeting different ligand sites. Its bioactive compounds may improve neurological symptoms and pathological conditions by modulating cell death or cell survival signaling molecules. The cognitive enhancing effects of ginger might be partly explained via alteration of both the monoamine and the cholinergic systems in various brain areas. Moreover, ginger decreases the production of inflammatory related factors. The aim of the present review is to summarize the effects of ginger in the prevention of major neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and multiple sclerosis.

Introduction

The number of people over the age of 65 has progressively grown in Western countries, increasing the risk of age-related neurodegenerative diseases. The most common pathology is Alzheimer's disease, with more than 26 million people affected worldwide today. This number is expected to quadruple by 2050. No effective treatments are available for aging-related neurodegenerative diseases, which tend to progress in an irreversible manner and are associated with large personal and socioeconomic costs ( 1 ).

The prevention of these pathologies and the search for new nutraceuticals and drugs to combat them are the great challenges of scientific research. Plant-derived products are known to have protective effects including anti-inflammatory and antioxidant actions, related to improvements in cognitive impairment ( 2 ).

In recent years, several pharmacological activities of ginger and its bioactive compounds have been explored ( 3 ). Zingiber officinale is a perennial herb member of the Zingiberaceae family and its thick tuberous rhizomes is very popular for medicinal uses and as a spice and additive agent for flavoring foods and drinks ( 4 , 5 ). Its origin is little known but it is thought to be in South-East Asia or India ( 4 ). The composition in bioactive compounds of Zingiber officinale varies according to the place where it is grown and the drying techniques. In general terms, the rhizome of Zingiber officinale is mainly composed of essential oils in small quantities, oleoresins, mineral salts, sugars, mucilage, starch, gums and organic acids. Starch constitutes 40–60% of the dry weight of the rhizome of Zingiber officinale . Ginger contains a variety of bioactive compounds responsible of its biological activities (as 6-gingerol, 6-shogaol, 10-gingerol, gingerdiones, gingerdiols, paradols, 6-dehydrogingerols, 12-gingerol 3,5-diacetoxy-6-gingerdioal and 5-acetoxy-6-gingerol), among which 6-gingerol and 6-shogaol stand out ( 6 ).

In recent years, ginger has been found to possess biological activities, such as antimicrobial, anti-inflammatory, antioxidant, anticancer (by improvement in the expression level of markers for colorectal cancer risk) and anti-allergic activities ( 7 ). In this sense, numerous studies have demonstrated that ginger possesses the potential to prevent cardiovascular diseases and associated pathologies that act as risk factors (diabetes, obesity and metabolic syndrome), chemotherapy-induced emesis and nausea, arthritis, gastric dysfunction, pain, respiratory disorders and neurodegenerative diseases ( 8 , 9 ). Ginger could modulate obesity through various potential mechanisms including increasing lipolysis and thermogenesis, inhibition of lipogenesis, decrease of fat absorption and appetite control ( 10 ). Ginger has been documented to ameliorate hyperglycemia and hyperlipidemia. These beneficial effects are mediated by modulation of transcription factors, such as nuclear factor κB, peroxisome proliferator–activated receptors and adenosine monophosphate–activated protein kinase ( 11 ). In this sense, Zhu et al. ( 12 ) showed that ginger improves insulin sensitivity, decreases the levels of glycosylated hemoglobin in type 2 diabetes mellitus and ameliorates plasma lipid profile.

Neurodegenerative diseases are generally characterized by neuroinflammation, oxidative stress and protein misfolding than leads to brain damage, synaptic dysfunction and neuronal apoptosis ( 13 ). In Alzheimer's disease, oxidative stress is mainly caused by mitochondrial dysfunction, the intracellular accumulation of hyperphosphorylated tau (τ) proteins in the form of neurofibrillary tangles, the excessive accumulation of extracellular plaques of beta-amyloid (Aβ), as well as environmental and genetic factors. Gingerols have shown antioxidant, anti-amyloidogenic, anti-inflammatory and anti-cholinesterase properties ( 14 ). The major component extracted from Zingiber officinale , 6-gingerol, showed antioxidant and anti-inflammatory activity and inhibition of astrocyte overactivation. Lipopolysaccharide stimulated microglia induced pro-inflammatory cytokines, such as IL-6, IL-1β, increments of intercellular nitric oxide concentrations, as well as iNOS enzyme activity, and all of them were suppressed by the treatment with 6-gingerol ( 15 ).

Parkinson disease is the second most common neurodegenerative pathology after Alzheimer's disease ( 16 ). Its prevalence increases with age and is characterized by the accumulation of α-synuclein protein within neurons, inside Lewy neurites and Lewy bodies ( 17 ). Parkinson disease can be caused by environmental and hereditary factors, including iron accumulation in the brain and oxidative stress. Medeiros et al. ( 18 ) showed than oxidative stress levels and inflammatory markers were significantly increased in Parkinson disease patients. Mohd et al. ( 19 ) suggests that the active compound in ginger may reduce the associated cognitive dysfunction by inhibiting the inflammatory response, increasing levels of nerve growth factor and stimulating synapse formation.

Multiple sclerosis is characterized by chronic inflammatory response-induced demyelination of the neurons and degeneration of the axons within the central nervous system. Factors as inflammatory, oxidative and immunopathological parameters are related in the development and progression of multiple sclerosis. Ginger and its bioactive compounds could be considered as potential agents to treat multiple sclerosis due to their anti-inflammatory, antioxidant and immunomodulatory properties ( 20 ).

As oxidative stress and inflammation play an important role in the pathogenesis of the above mentioned diseases, the introduction of anti-inflammatory and antioxidant agents, such as ginger and derived products, could be useful for the treatment and prevention of neurodegenerative conditions. Hence, the aim of the present review is to summarize the effects of ginger in the prevention of major neurodegenerative diseases, focusing on Alzheimer's disease, Parkinson's disease and multiple sclerosis. For this purpose, literature search has been carried out consulting the scientific publications related to ginger published in Web of Science, Scopus, Science Direct and Pubmed databases. Articles published in the last 10 years have been selected, with some exceptions on publication date in those previous works of major relevance.

Bioactive Compounds Present in Ginger

Rhizome of Zingiber officinale is composed of 69 volatile compounds, which constitute 97 % of its total composition in essential oils. Those molecules present at higher concentrations are α-Zingiberene (28,62%), Camphene (9,32%), Ar-curcumene (9,09%), β-Phellandrene (7,97%), E-α-Farnesene (5,52%), β-Bisabolene (5,40%), α-Pinene (2,57%) ( 21 ). It has been documented their biological properties such as antimicrobial, antioxidant, cytotoxic, insecticidal and anti-inflammatory effects as well as their usefulness to preserve food characteristics ( 22 ).

Non-volatile compounds (oleoresins) are the main source of bioactive compounds in the rhizome of Zingiber officinale . At present, 34 oleoresins have been discovered, which constitute 88.6% of the total composition ( 21 ), among which Gingerols (1-(4-hydroxy-3-methoxyphenyl)-5-hydroxyalcan-3-one), Shogaols (1-(4-hydroxy-3-methoxy-phenyl)-4-decen-3-one) and Paradols are the most important groups. Shogaols are the more abundant components in the dried rhizome and gingerols are mainly found in the fresh rhizomes of ginger ( 23 ).

Gingerol analogs are thermally labile and undergo dehydration reactions to form the corresponding shogaols, which are more stable and have greater pharmacological effects than their precursors and are responsible of the characteristic pungent taste of dried ginger. This chemical change occurs in the process of thermal drying of the rhizomes and long-term storage ( 24 ). 6-shogaol is converted to 6-paradol by bacterial metabolism ( 13 , 25 ) ( Figure 1 ). Other phenolic compounds are also present in ginger, as quercetin, zingerone, gingerenone-A, and 6-dehydrogingerdione.

Figure 1 . Chemical structures and properties of ginger bioactive compounds.

The maturation state, cultivar, environment, and processing steps are major factors that influence the biosynthesis and concentration of bioactive compounds in ginger. Besides, different composition of normal ginger and black ginger from different countries has been reported, evidencing that gingerol-related phenolic acids were present in normal ginger, while black ginger was characterized by the presence of methoxyflavones ( 26 ).

Bioavailability and Pharmacokinetics

Ingested dietary gingerols need to be available in the circulation and tissues to produce an effect in the organism. Multiple factors influence the amount of a compound distributed to the different tissues to exert its action, including the solubility in the gastrointestinal fluid and possible degradation in gastrointestinal tract, permeability of enterocytes membrane, protein-mediated intestinal efflux or pre-systemic gut and/or hepatic metabolism ( 27 ).

Nutritional and clinical use of ginger in nutraceuticals or enriched-food products is limited due to its poor bioavailability. Gingerols and derivatives are lipid soluble compounds and therefore it would be expected a good absorption by passive diffusion across intestinal epithelium. However, prior to absorption, they must reach brush border cells, what implies be solubilized in an aqueous media; due to their chemical structure, they present a low solubility in water. This phenomenon is related to the concept Bioaccesibility, the amount of ingested nutrient available for absorption, which is different to the concept Bioavailability, that represents a step forward, that is, the portion of the ingested dose of a compound that reaches the general circulation and specific sites where it can exert its action. Bioaccesibility is the first limiting step in whether or not a compound may exert an effect in the organism ( 28 ).

Unlike other types of compounds, such as flavonoids, gingerols are not naturally present in glycosylated form, so that they are not hydrolyzed by glycosidase enzymes of intestinal brush border. However, gingerols are substrates of P-glycoprotein. This protein is highly expressed in the outer membranes of the enterocytes in the small intestine, as well as in liver, brain and kidney. It behaves as a major barrier to the intestinal absorption of many drugs, as a defense mechanism against toxics ( 29 ).

Once absorbed, gingerols are carried by the hepatic portal vein to the liver and undergo hepatic metabolism or “first-pass effect.” Half-life of these compounds is extremely low and they suffer from Phase II conjugative reactions, such as glucuronidation catalyzed by UDP-glucuronosyl-transferases (UGTs) and sulphation by sulphotransferases (SULTs), producing more polar molecules for biliary or renal excretion. Isoforms UGT1A1, 1A3 and 2B7 are responsible for gingerol conjugation ( 30 ).

Moreover, enterohepatic circulation occurs with these compounds, by biliary excretion and intestinal reabsorption. The hydrophilic metabolite 6-gingerol glucuronide diffuses out of the hepatic cells and is secreted in the bile into the small intestine. There it can be hydrolyzed by intestinal β-glucuronidases and re-enter into the blood stream through the enterocyte ( 31 ). All these phenomena are associated to extended half-life in plasma and prolonged pharmacological effect ( Figure 2 ).

Figure 2 . Scheme of bioaccessibility and bioavailability routes of gingerols in the organism.

Human Studies on Bioavailability of Gingerols

Most studies on ginger activity and bioavailability have been performed in animal studies and human trials are scarce. Zick et al. ( 32 ) investigated the pharmacokinetics of 6-, 8- and 10-gingerol and 6-shogaol and related metabolites in healthy subjects, with doses ranging from 100 mg to 2 g. The compounds showed a rapid absorption, as glucuronide metabolites appeared within 1 h and the elimination half-lives ranged between 75 and 120 min, depending on the administered dose. All detected compounds were glucuronide conjugates, and no free forms were detected.

The authors used an HPLC method with LOQ ranging from 0.1 to 0.25 μg/mL. The determination of bioactive phytochemicals and their metabolites presents the difficulty of the low concentrations at which they are found in biological fluids. The development of highly sensitive techniques such as mass spectrometry coupled to liquid chromatography has made it possible to better detect and quantify metabolites in animal and human studies after ingestion of ginger or food products made with ginger. The same authors developed and validated a more sensitive, LC-MS/MS method to characterize the pharmacokinetics of 6-, 8-, and 10-gingerols and 6-shogaol in human plasma and colon tissues ( 33 ). After an oral dose of 2 g of ginger extract (GE), concentrations of free 10-gingerol and 6-shogaol were detected (peak concentrations of 9.5 and 13.6 ng/mL, respectively). Most compounds existed as glucuronide and sulfate metabolites, mainly 6-gingerol-glucuronide (0.47 μg/mL). LOQ was established in 5 ng/mL, with similar T max between 45 and 60 min and half-lives of all compounds and their metabolites between 1 and 3 h. Peak concentrations of sulfate metabolites were lower than glucuronide, being the higher value for 6-gingerol-sulfate (0.28 μg/mL). The multiple doses treatment consisted of 250 mg GE capsules daily for 28 days and no accumulation was observed for any of the quantified compounds, due to their short half-lives and fast clearance.

These studies have estimated the concentrations of gingerol glucuronides as the difference of gingerol concentrations prior to and after β-glucuronidase hydrolyzation, and not directly quantifying each compound. In this sense, Schoenknecht et al. ( 34 ) developed a direct liquid chromatography-tandem mass spectrometry method, using stable isotope synthesized standards of glucuronide forms, to detect and quantify gingerol glucuronides in human plasma. After SPE extraction and LC-MS analysis, the authors showed that the consumption of 1 liter of ginger tea led to a fast absorption and metabolization of gingerols, with maximum concentrations reached at 30 min post-ingestion. Plasma concentrations resembled the levels of each gingerol free form in the food product, with maximum plasma concentrations for 6-gingerol glucuronide (623.3 nmol/L), followed by 8-gingerol glucuronide (103.8 nmol/L) and 10-gingerol glucuronide (25.8 nmol/L). The authors collected pharmacokinetic parameters in plasma and urine, observing that the maximum concentrations and half-life in plasma were related to the carbon chain length and therefore to the hydrophobicity of the molecules. Pharmacokinetic parameters of urinary elimination indicated that the more lipid-soluble compounds remained longer in the body. 6-gingerol was still quantified in the interval 9–12 h. Recovery rates were between 45% of the administered dose for 6-gingerol and 10 % for 8-gingerol, expressed as glucuronide derivatives.

Some authors have hypothesized that glucuronide forms (inactive) interconvert to free (active) species in tissues by the presence of β-glucuronidase enzyme, establishing an equilibrium between both forms, what has been called “reverse pharmacokinetics.” The free form would exert its effects on its multiple target receptors. This might explain the disconnect observed between the efficacy of free gingerols and their sub-therapeutic plasma concentrations ( 35 ). The authors demonstrated the accumulation of conjugated forms within various tissues, including brain, after repeated daily oral administration of ginger extract at 250 mg/kg for seven days.

New Technologies to Improve the Bioavailability of Ginger Bioactive Compounds

Low bioavailability of gingerols has been related to its poor water solubility and excessive phase II hepatic metabolism. Different strategies have been implemented to enhance the bioavailability of poorly water-soluble compounds. These technologies include nanoparticles, micelles, emulsions or solid dispersion ( 36 , 37 ), liposomes ( 38 ) or self-microemulsifying drug delivery systems ( 39 ). Studies performed in animal models on these forms of encapsulation of single and combined ginger compounds revealed better pharmacokinetic profiles in all cases.

Xu et al. ( 39 ) conducted a bioavailability study with a 6-gingerol-loaded self-microemulsifying drug delivery system (SMEDDS) for oral administration in rats. It was formulated with 250 mg/kg dose of 6-gingerol and the system consisted of a mixture of oil phase and surfactants, creating an oil-in-water microemulsion. The 6-gingerol-SMEDDS exhibited prolonged plasma circulation, and significant higher absorption than free 6-gingerol (t 1/2 = 210 min and AUC = 2,987 min μg/mL, compared to free form t 1/2 = 82 min and AUC = 454 min μg/mL).

Similar results were observed by Wei et al. ( 40 ), who developed nanostructured lipid carriers (NLC) to improve oral solubility and bioavailability of 6-gingerol. After oral administration in rats, AUC was significantly higher compared to controls. Encapsulation of the drug in a lipid core coated with surfactants might help to first, increase the diffusion to epithelial space and improve the absorption and second, to avoid the first-pass effect. The small particle size contributes to a greater surface/volume ratio and major absorption.

Liposomes are new drug carriers prepared by the formation of vesicle enveloping drug molecules in the phospholipid bilayer membrane. Wang et al. ( 38 ) demonstrated that 6-gingerol encapsulated in proliposomes was retained in the blood stream much longer than the free form. The plasma concentration was significantly higher 30 min after oral administration of a dose of 250 mg/kg in rats.

Another approach conducted by Ogino et al. ( 31 ) was the solid dispersion of ginger extract (GE). Solid dispersions consist of a dispersion of a drug in a solid matrix made of either a small molecule or a polymer. The dispersed drug can exist in different isoforms or crystallization states. In this study, the solid dispersion was made using a hydrophilic polymer, hydroxypropyl cellulose, by a freeze-drying technique. Oral absorption (dose administered 100 mg GE/kg) was higher than that of GE alone, with enhanced AUC and C max of each gingerol. 6-gingerol and 8-gingerol showed 5-fold higher bioavailability than their respective counterparts in free GE.

In an acute study with doses of 250 mg/kg of 6-gingerol administered in rats, polyethylene glycol-based polymeric micelles significantly improved (up to 3-fold) the bioavailability of 6-gingerol compared to 6-gingerol control group ( 37 ). Besides, there was a better brain distribution, what suggested that the micelle could overcome the brain-blood barrier. It has been hypothesized that the components of the micelles work as P-glycoprotein inhibitors, by suppressing its ATPase activity, hence improving the passage through biological barriers ( 41 , 42 ).

In all studies, in vitro release assays were performed and an enhanced solubility of the compound was observed, compared to the free drug, which could be partly responsible of the improved oral bioavailability in circulation. Nevertheless, further research is required to confirm the usefulness of these preparations as nanocarriers, as well as thorough toxicity studies prior to human administration.

Antioxidant and Inflammatory Activity

The production of free radicals, such as reactive oxygen species (ROS) or nitrogen reactive species (NOS) leads to the development of many oxidative-related disorders, such as the most common neurogenerative diseases ( 43 ). Hopefully, antioxidant bioactive compounds are widely spread over a large number of food matrices as fruits, vegetables, cereal grains, edible flowers or medicinal plants ( 44 – 50 ). Moreover, the latest scientific literature has found promising bioactive compounds contained in ginger that possess antioxidant and anti-inflammatory activities ( 20 , 51 , 52 ). Gingerols and shogaols have a plethora of biological activities such as antioxidant, antimicrobial, anticancer, anti-inflammatory, antiallergic and prevention of neurodegenerative diseases ( 7 ).

The antioxidant activity of ginger has been evaluated in vitro , showing better performance for dried ginger compared with fresh, stir-fried or carbonized ginger. This fact was principally related with the concentration of polyphenols, higher in dried ginger, as the temperatures applied for stir-fried or carbonized ginger could change gingerols into shogaols, leading to minor antioxidant capacity ( 53 ).

Moreover, the scientific literature has reported that ginger can be useful for the prevention of oxidative-related injury ( 51 , 54 ). An extract from ginger showed antioxidant capacity related to interleukin-1β in human chondrocyte cell model, stimulating the expression of enzymes related to oxidative protection, reducing the generation of ROS leading to decreased lipid peroxidation ( 55 ). Ginger extract was also able to reduce ROS in human fibrosarcoma cells ( 56 ). Besides, another marker of lipid peroxidation as malondialdehyde was reduced in rat heart homogenates after the treatment with a ginger extract ( 54 ).

Particularly, ginger has shown antioxidant capacity via the nuclear factor erythroid 2-related factor 2 signaling pathway (Nrf2) ( 57 , 58 ). In human colon cancer cells 6-shogaol is able to increase intracellular glutathione/glutathione disulfide ratio (GSH/GSSG), upregulating the expression of Nrf2, metallothionein 1 (MT1), heme oxygenase-1 (HO-1), ferritin light chain (FTL), aldo-keto reductase family 1 member B10 (AKR1B10), and γ-glutamyltransferase-like 4 activities (GGTLA4).

Despite the fact that doses, routes of administration and duration of treatment vary among studies, it has been reported that the effective anti-inflammatory and antioxidant doses of ginger extract in vivo studies range from 200 to 500 mg/kg/day, and the effective immunomodulatory doses range from 28 to 720 mg/kg/day. In human studies doses of 500 mg/day for 3 months, 1,000 mg/day for 2 months and 1,500 mg/day for 6 weeks were observed ( 20 ). Doses of up to 4 grams of ginger per day have been reported to be safe ( 59 ).

Both in vitro and in vivo studies have revealed that ginger and related bioactive secondary compounds, such as 6-shogaol, 6-gingerol, and oleoresin, exert potent antioxidant capacity by direct free radical scavenging. Additionally, the triggering of the Nrf2 signaling route is decisive to the underlying mechanisms of action. Importantly, the excess on the production of ROS and NOS is considered a cause of some diseases as neurodegenerative pathologies and antioxidants are crucial for their prevention ( 60 , 61 ) ( Figure 3 ).

Figure 3 . Studies on the mechanisms related to the antioxidant activity of ginger.

Results on the anti-inflammatory capacity of ginger and its bioactive compounds have shown some variability ( 62 , 63 ), which may be attributed to differences in the study design, length of interventions, individual characteristics, and doses administered. The anti-inflammatory mechanisms of ginger are probably associated with a decline in proinflammatory cytokines linked to the inhibition of Akt and NF-κB activation ( 8 ). NF- kβ pathway is widely used by eukaryotic cells as a regulator of genes that control cell proliferation and cell survival. NF-kβ is the key regulator of the inflammatory process, activating the expression of inflammatory target genes, including cytokines, chemokines, and COX2.This enzyme triggers the formation of some prostaglandins, responding to inflammation and enhancing the formation of proinflammatory cytokines. Ginger has being able to inhibit inflammatory response by suppressing NF-kβ, which lead to the reduction of cytokine gene expression ( 11 ). In 2016, a meta-analysis reported that C-reactive protein (CRP) and other acute-phase proteins were also suppressed after ginger supplementation ( 64 ). Naderi et al. ( 65 ) published that treatment for 12 weeks with ginger powder at a dose of 1 g/day was able to decrease the plasma concentration of CRP, in accordance to previous studies ( 66 ). Likewise, the anti-inflammatory capacity of ginger can be justified by its ability to inhibit COX-2 and 5-lipoxygenase enzymes, which results in the suppression of amino acid metabolism. In fact, it has demonstrated to reduce platelet aggregation, as well as the formation of pro-inflammatory thromboxanes and prostaglandins ( 67 ). Specifically, the anti-inflammatory effects of ginger are related to the inhibition of COX-2 without affecting COX-1, which seems to be an advantage over traditional NSAIDs due to the related side effects ( 68 , 69 ). Van Breemen et al. through pulsed ultrafiltration mass spectrometry, showed that several compounds related to gingerol were COX-2 ligands. COX-2 inhibition would prevent the conversion of arachidonic acid into prostaglandin (PG) H2, preventing its subsequent conversion into proinflammatory prostaglandins such as PGD2 and PGE2 ( 68 ). It has also been reported the inhibition of the formation of nitric oxide, inflammatory cytokines, and the inhibition of the enzymatic activity of prostaglandin synthase, which could lead to a decrease in the inflammatory component ( 69 – 73 ) ( Figure 4 ).

Figure 4 . Studies on the mechanisms of action related to the anti-inflammatory activity of ginger.

Health state, genetics, lifestyle habits and dietary factors of individuals, or the dosage and solubility aspects of ginger forms could affect the bioaccessibility and bioavailability and ultimately the bioactivity of ginger compounds, which may justify the contradictory or controversial results emerged from in vitro and in vivo studies.

Alzheimer's Disease and Ginger

Alzheimer's disease (AD) is a neurodegenerative condition linked to profound memory impairment and loss of cognitive function. Among others, cellular damage due to β-amyloid protein aggregation, tau protein hyperphosphorylation, neurotransmitter imbalances, oxidative stress, apoptosis and inflammatory responses is responsible for its occurrence ( 3 , 74 ).

Due to the inadequate efficacy of the conventional drugs currently used, their adverse effects and pharmacokinetic problems, together with the scientific evidence that in recent years suggests that traditional medicinal plants could be useful both in the prevention and treatment of a multitude of pathologies, a great opportunity has led for their evaluation in the treatment of memory disorders, as it is the case of Zingiber officinale ( 3 , 75 ).

The main characteristics of Zingiber officinale for its possible use in neurodegenerative diseases, specifically Alzheimer's, are its anti-inflammatory and antioxidant effects. In particular, clinical studies have shown that the use of ginger has increased the expression of nerve growth factor (NGF), playing a key role in improving memory function, simplifying long-term hippocampal enhancement and accelerating neurite outgrowth.

Preclinical trials in mice ( Table 1 ) showed that increasing NGF levels in the hippocampus initiated the activation of extracellular signal regulatory kinases (ERK) and cAMP response element binding protein (CREB), leading to increased synaptogenesis ( 76 ). Furthermore, studies have shown that ginger blocks the expression of pro-inflammatory cytokines and chemokines in THP-1 cells. Animal studies concluded that the use of ginger significantly inhibited the expression of mRNA related to the expression of pro-inflammatory cytokines and endothelial adhesion activating factors such as LPS, TNF-α, IL-1 β, COX-2, MIP-1A, MCP-1 and IP-10, among others ( 77 ).

Table 1 . Preclinical studies of ginger and Alzheimer's disease.

In vitro and animal studies conclude that various bioactive compounds of Zingiber officinale cross the blood-brain barrier, allowing us to think that the beneficial properties observed in diverse pathologies could have application against neurodegenerative diseases, specifically AD ( 82 ).

Zingiber officinale might also have therapeutic properties for other diseases affecting the nervous system, such as brain tumors, cardiovascular accidents, neurosis, depression, insomnia and psychiatric disorders. It is included on the US Food and Drug Administration's (FDA) “Generally Recognized as Safe” (GRAS) list and can be defined as a safe nutraceutical that could be used to combat neurodegenerative disorders ( 75 ).

However, clinical studies in humans are scarce and some of them refer to supplements consisting of a mixture of herbs, including ginger, used in traditional oriental medicine, as Davaie Loban or Kihito ( Table 2 ). Other authors have reported improvements in cognitive abilities using Cognitex, a nutritional supplement containing sage, blueberry and Zingiber officinale. Saenhong et al. ( 83 ) evaluated the individual effect of ginger and findings are noteworthy. The researchers conducted a placebo-controlled study with standardized ginger extracts, observing an enhance in cognitive processing capabilities, with greater effects at higher doses of 800 mg/day ( Table 2 ).

Table 2 . Human clinical studies on ginger and cognitive function.

Parkinson Disease and Ginger

Parkinson's disease (PD) is a complex neurodegenerative process that appears in adulthood and is the second most common neurodegenerative disease behind Alzheimer's dementia. Its pathological basis is characterized by the progressive loss of dopaminergic neurons of the substantia nigra pars compacta (SNpc) of the midbrain, as well as the presence of intracellular inclusions called Lewy bodies, which are formed by insoluble aggregates of abnormally folded alpha-synuclein protein. The result of this neurodegeneration is the dopaminergic denervation of the projections of the SNpc toward the striatum, which conditions an alteration in the normal physiology of the basal ganglia ( 87 , 88 ). These phenomena leads to a deficit of dopamine (DA) and the subsequent appearance of the cardinal signs of the disease, that is, the tremor resting, bradykinesia, posture rigidity and instability. In addition to the motor symptoms, there is the manifestation of non-motor symptoms, the prevalence of which increases as the disease progresses (apathy or depression, sleep disturbances, autonomic dysfunction or sensory symptoms) ( 87 , 89 ).

PD can be caused by hereditary and environmental factors, including oxidative stress and iron accumulation in the brain. It is clear that neuroinflammation plays an important role in the development and progression of PD and other neurodegenerative diseases ( 19 , 90 ). In PD, oxidative stress is a result of mitochondrial deficiency, in addition to a chronic inflammatory process, in which both produce reactive oxygen species (ROS) and reactive nitrogen species (RNS). These reactive species meet the accumulated iron in the brain and harm structures, leading to the death of dopaminergic neurons in the substantia nigra. This process creates a cycle of cell damage, neuroinflammation, and ROS/RNS production, resulting in neuronal death ( 18 , 91 ). The combination of oxidative stress and high levels of tissular iron cause harm to the brain structure, with the death of dopaminergic neurons in the substantia nigra. Consequently, the loss of these dopaminergic neurons in the substantia nigra lead to progressive motor impairment in PD ( 18 ). In fact, oxidative stress levels and inflammatory markers are significantly increased in PD patients.

Currently available treatments have a strictly symptomatic effect. The most effective drug for treating the motor manifestations of PD is levodopa. To date, there is no treatment that slows the progression of the disease, as current drugs improve the symptoms of PD but not the underlying neurodegeneration of PD. In recent years, interest has increased in the discover of the possible beneficial effect of natural products as ginger on the development and progression of PD. Park et al. ( 92 ) reported a neuroprotective effect of 6-shogaol in a PD model; 6-shogaol protected dopaminergic cells against MPP+ - and MPTP-induced neurotoxicity via the inhibition of neuroinflammatory responses of microglia. In this way, results of Moon et al. ( 76 ) suggest that 6-shogaol may play a role in inhibiting glial cell activation and reducing memory impairment in animal models of dementia ( Table 3 ).

Table 3 . Parkinson's disease and ginger.

Kongsui et al. ( 90 ) suggested that ginger crude extract might be a potential neuroprotective agent for the treatment of lipopolysaccharide-induced neurodegenerative diseases. Other study carry out by Hussein et al. ( 93 ) clearly indicates a neuroprotective effect of ginger against MSG-induced neurodegenerative disorders and these beneficial effects could be attributed to the polyphenolic compounds present ( Table 3 ).

Multiple Sclerosis and Ginger

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS) characterized by inflammation, demyelination of neurons and axonal degeneration even in the early stages of the disease. MS is one of the most common causes of neurological disability in young people ( 94 , 95 ) and usually appears in women with ages comprised between 25 and 30 years ( 95 , 96 ).

Currently MS is considered as multifocal chronic inflammatory disease that associates neurodegeneration ( 97 ). Some individuals are genetically predisposed to such an abnormal autoimmune response, and the development and progression of the disease will be affected by various environmental factors. Genetic predisposition is mediated especially by the major histocompatibility complex. Among the risk factors with the best available evidence are the association with Epstein-Barr virus infection, high BMI during adolescence, low vitamin D levels and smoking ( 95 , 96 ). The number of population affected by MS has increased in recent decades and it is estimated that 2.5 million people worldwide suffer from the disease, affecting some 700,000 population in Europe ( 96 , 98 ).

As for the pathogenesis, despite decades of research, the exact etiology is still unknown to the scientific community and it is believed that the symptoms of MS result from damage to the myelin sheath and disruption of myelinated tracts in the CNS ( 99 ). In most patients, the characteristic clinical symptoms of the disease include cognitive, sensory, motor, and autonomic disturbances. These symptoms manifest as loss of coordination and balance, impaired vision, deficits in executive functioning, chronic pain and mood disturbance ( 94 ). There is currently no definitive cure for MS. However, different pharmaceutical and rehabilitation therapies are available to treat acute attacks, improve symptoms and modify the course of the disease ( 100 ). In recent years, complementary and alternative medicine methods such as the use of herbal therapy appear to have promising therapeutic approach to treat MS ( 101 ). Such therapies among which ginger is included, could be effective in the treatment of MS by reducing demyelination, enhancing remyelination and especially by suppressing/reducing inflammatory processes. Regarding the reduction of inflammatory processes, it occurs by inhibiting the infiltration of inflammatory cells in the CNS, reducing the proinflammatory cytokine production.

Demyelination and neurodegeneration are closely related to inflammation (a key feature in MS), being much more pronounced in acute and relapsing phases ( 101 ). Within the CNS there is an infiltration of leukocytes including neutrophils, DCs, macrophages, CD4+ T cells, and CD8+ T cells), with CD4 + T cells having the greatest impact on demyelination of neurons and axonal damage ( 101 , 102 ). As for DCs they cross the damaged blood-brain barrier promoting a polarization of myelin-specific T-lymphocytes to different subsets of effector T-cells; Th1, Th2, Th9, Th17, Th22 and Treg cells. While Th1 and Th17 cells act pathogenically in the immunopathological process of MS, Treg and Th2 cells exert protective action against autoimmune diseases ( 103 – 105 ). Astrocytes and microglia cells also contribute to the pathogenesis of MS by releasing proinflammatory cytokines ( 20 ).

There are currently more than a dozen drugs on the market to treat MS. However, they are questioned both for their moderate efficacy and side effects. The possibility of using ginger to attenuate the symptoms of MS arises from the fact that there are certain components derived from plants with anti-inflammatory and immunomodulatory properties and with low side effects ( 20 ).

Among the possible therapeutic potentials of ginger and its components for the treatment of MS, its immunomodulatory, anti-inflammatory and antioxidant effects are depicted in Table 4 , and their mechanisms are extensively detailed by Jafarzadeh et al. ( 20 ).

Table 4 . The anti-inflammatory, antioxidant activities and immunomodulatory effects of ginger and its components.

According to a recent systematic review on the concomitant consumption of ginger extract and other drugs it can be concluded that ginger consumption is safe and there is no potential risk of clinically relevant interactions in the treatment of MS ( 106 ). The only contraindications were observed in the coadministration together with anticoagulants, due to the anticoagulant properties of ginger.

Experimental autoimmune encephalomyelitis (EAE) is a model of inducible human MS in vulnerable animals. It is usually induced in mice due to the fact that it is a highly reliable model to study both the pathogenesis of MS to test drugs in development to treat MS ( 107 , 108 ). In different studies performed in mice with EAE, it was observed that after the administration of ginger extract the clinical symptoms of EAE appeared later and the clinical scores of the disease were lower compared to placebo ( 109 , 110 ). The main feature of MS and EAE is primary demyelination of axons, causing blocking of signal conduction or reduced conduction at the demyelinated site ( 111 ). Administration of ginger extract prior to EAE appears to reduce the clinical symptoms, through up-regulation of inflammatory cytokines and chemokines (IL-23, IL-33, IFN-γ, CCL20 and CCL22) ( 109 , 112 ). Moreover, a recent investigation in mice with EAE showed that both 6-shogaol and 6-paradol appear to reduce clinical symptoms. In addition, they were also associated with attenuation of astrogliosis, microglial activation and TNF-α expression, suppressing neuroinflammatory responses. Therefore, it seems that 6-shogaol and 6-paradol could be the active ingredients responsible for the efficacy of ginger extract ( 111 ).

The research in mice with EAE seems to be effective to further our knowledge of all the possible mechanisms involved in the pathogenesis and treatment of MS, due to the similarities ( 113 ). Therefore, although more research is needed, we consider it a promising and necessary first step for the assessment of the efficacy prior to human studies.

Conclusions

Ginger contains diverse bioactive compounds, such as gingerols, shogaols, and paradols and possesses antioxidant and anti-inflammatory properties that might help reduce the levels of inflammation and oxidative stress in neurodegenerative diseases. In fact, several inflammatory, oxidative and immunopathological parameters are involved in their pathogenesis and drugs used for treatment are of limited efficacy and can also generate adverse side effects. It seems that ginger, given its antioxidant, immunomodulatory and anti-inflammatory capacity, has the ability to intercept all the main elements involved in the development of multiple sclerosis as well as to attenuate the symptoms of neurological diseases including Parkinson's, Alzheimer's, migraine, and epilepsy. Even though with the doses studied, no considerable adverse effects are observed, further research is needed to study whether higher doses and/or longer administration protocols are more effective without causing adverse side effects.

Inclusion of ginger or ginger extracts in nutraceutical formulations could provide valuable protection against neurodegenerative diseases. The low bioavailability and extensive phase II metabolism have limited the use of ginger in neurodegenerative pathologies and new pharmaceutical forms for delivering ginger's bioactive compounds that overcome these limitations are currently being developed. Further toxicological and pharmacokinetic studies of these new formulations will be necessary before their application in human trials, but the evidence is promising for the therapeutic potential of ginger in neurodegenerative diseases.

Author Contributions

PZ: conceptualization, supervision, and project administration. JM, BC, RA, MC, PZ, and DV: methodology, investigation, and writing—original draft preparation. JM, BC, RA, PZ, and DV: writing—review and editing. All authors have read and agreed to the published version of the manuscript.

Conflict of Interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Publisher's Note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

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Keywords: ginger, neurodegenerative diseases, Alzheimer's disease, Parkinson's disease, multiple sclerosis, gingerol, antioxidants

Citation: Arcusa R, Villaño D, Marhuenda J, Cano M, Cerdà B and Zafrilla P (2022) Potential Role of Ginger ( Zingiber officinale Roscoe) in the Prevention of Neurodegenerative Diseases. Front. Nutr. 9:809621. doi: 10.3389/fnut.2022.809621

Received: 05 November 2021; Accepted: 15 February 2022; Published: 18 March 2022.

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Copyright © 2022 Arcusa, Villaño, Marhuenda, Cano, Cerdà and Zafrilla. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Débora Villaño, dvillano@ucam.edu

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

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Research Progress on Chemical Constituents of Zingiber officinale Roscoe
Zingiber officinale Roscoe is commonly used in food and pharmaceutical products but can also be used in cosmetics and daily necessities. In recent years, many scholars have studied the chemical composition of Zingiber officinale Roscoe; therefore, it is necessary to comprehensively summarize the chemical composition of Zingiber officinale Roscoe in one article.
Research Progress on Chemical Constituents of Zingiber officinale Roscoe
ZingiberofficinaleRoscoe nu ,1 JinchengLiu,2 dYongqingg 1 ... 2.Constituents 2.1.Volatile. Volatile,alsonasgingerl, e y composed of terpenoids [14]. Ginger ... s s have di=erent s d chemical.d[30]dquantitativeanalysison eextractsofefromeeginger dJapaneseturmericddthatettof
Research Progress on Chemical Constituents of Zingiber officinale Roscoe
The purpose of this paper is to provide a comprehensive review of the chemical constituents of Zingiber officinale Roscoe. The results show that Zingiber officinale Roscoe contains 194 types of ...
Research Progress on Chemical Constituents of Zingiber officinale
Zingiber officinale Roscoe is commonly used in food and pharmaceutical products but can also be used in cosmetics and daily necessities. In recent years, many scholars have studied the chemical composition of Zingiber officinale Roscoe; therefore, it is necessary to comprehensively summarize the chemical composition of Zingiber officinale Roscoe in one article.
Research Progress on Chemical Constituents of Zingiber officinale Roscoe
The results show that Zingiber officinale Roscoe contains 194 types of volatile oils, 85 types of gingerol, and 28 types of diarylheptanoid compounds, which can lay a foundation for further applications of Zingib officinales Roscoe. Zingiber officinale Roscoe is commonly used in food and pharmaceutical products but can also be used in cosmetics and daily necessities. In recent years, many ...
Bioactive Compounds and Bioactivities of Ginger (Zingiber officinale
Ginger ( Zingiber officinale Roscoe) is a common and widely used spice. It is rich in various chemical constituents, including phenolic compounds, terpenes, polysaccharides, lipids, organic acids, and raw fibers. The health benefits of ginger are mainly attributed to its phenolic compounds, such as gingerols and shogaols.
Research Progress on Chemical Constituents of Zingiber officinale Roscoe
The purpose of this paper is to provide a comprehensive review of the chemical constituents of Zingiber officinale Roscoe. The results show that Zingiber officinale Roscoe contains 194 types of volatile oils, 85 types of gingerol, and 28 types of diarylheptanoid compounds, which can lay a foundation for further applications of Zingiber ...
Zingiber officinale Roscoe: A comprehensive review of clinical
Research Progress on Chemical Constituents of Zingiber officinale Roscoe. BioMed Res. Int., 2019 (2019), Article e5370823, 10.1155/2019/5370823. ... Ginger (Zingiber officinale Roscoe) in the Prevention of Ageing and Degenerative Diseases: Review of Current Evidence, Evid. Based Complement. Alternat.
Research Progress on Chemical Constituents of Zingiber officinale Roscoe
DOI: 10.1155/2019/5370823 Corpus ID: 210157437; Research Progress on Chemical Constituents of Zingiber officinale Roscoe @article{Liu2019ResearchPO, title={Research Progress on Chemical Constituents of Zingiber officinale Roscoe}, author={Yan Liu and Jincheng Liu and Yongqing Zhang}, journal={BioMed Research International}, year={2019}, volume={2019} }
Review on ginger (Zingiber officinale Roscoe): phytochemical
The results show that Zingiber officinale Roscoe contains 194 types of volatile oils, 85 types of gingerol, and 28 types of diarylheptanoid compounds, which can lay a foundation for further ...
Zingiber officinale Roscoe: A comprehensive review of clinical
Research Progress on Chemical Constituents of Zingiber officinale Roscoe. BioMed Res. Int. (2019) Q.Q. Mao et al. Bioactive compounds and bioactivities of ginger (zingiber officinale roscoe) Foods (2019) A.L. Braga, A.- ... Effects of Ginger (Zingiber officinale Roscoe) on Type 2 Diabetes Mellitus and Components of the Metabolic Syndrome: A ...
Chemical Constituents of the Fresh Rhizome of Zingiber officinale
Ginger is the fresh rhizome of Zingiber officinale Roscoe, belonging to the genus Zingiber of the Zingiberaceae family, which has been used as a spice and in traditional Chinese medicine for a long time. Phytochemical investigations of Z. officinale have led to the isolation of volatile oil, gingerol, diphenylheptane, monoterpenoid, flavonoid ...
Research Progress on Chemical Constituents of Zingiber officinale Roscoe
Gale OneFile includes Research Progress on Chemical Constituents of Zingiber by Yan Liu, Jincheng Liu, and Yongqing Zhang. Click to explore.
Some phytochemical, pharmacological and toxicological properties of
Introduction. Ginger (Zingiber officinale Roscoe, Zingiberacae) is widely used around the world in foods as a spice.For centuries, it has been an important ingredient in Chinese, Ayurvedic and Tibb-Unani herbal medicines for the treatment of catarrh, rheumatism, nervous diseases, gingivitis, toothache, asthma, stroke, constipation and diabetes (Awang, 1992, Wang and Wang, 2005, Tapsell et al ...
Research Progress on Chemical Constituents of Zingiber officinale Roscoe
Zingiber officinale Roscoe is commonly used in food and pharmaceutical products but can also be used in cosmetics and daily necessities. In recent years, many scholars have studied the chemical composition of Zingiber officinale Roscoe; therefore, it is necessary to comprehensively summarize the chemical composition of Zingiber officinale Roscoe in one article. The purpose of this paper is to ...
Zingiber officinale: A Systematic Review of Botany, Phytochemistry and
Research progress on chemical constituents of Zingiber officinale Roscoe. Biomed. Res. Int. 2019: 1-21, 2019. ... Ginger (Zingiber officinale roscoe) prevents morphine-induced addictive behaviors in conditioned place preference test in rats. Addict. Health 6: 65-72, 2014.
Bioactive Compounds and Bioactivities of Ginger (Zingiber officinale
Ginger (Zingiber officinale Roscoe) is a common and widely used spice. It is rich in various chemical constituents, including phenolic compounds, terpenes, polysaccharides, lipids, organic acids, and raw fibers. The health benefits of ginger are mainly attributed to its phenolic compounds, such as gingerols and shogaols. Accumulated investigations have demonstrated that ginger possesses ...
Composition of Zingiber officinale Roscoe (Ginger), Soil Properties and
Ginger is rich in different chemical compounds such as phenolic compounds, terpenes, polysaccharides, lipids, organic acids, minerals, and vitamins. The present study investigated the effect of mineral fertilizers on the content of mineral elements in the rhizomes of Zingiber officinale Roscoe, soil enzymes activity, and soil properties in Surkhandarya Region, Uzbekistan. To the best of our ...
PDF Review on ginger (Zingiber officinale Roscoe): phytochemical
Chemical Society, Science Direct, Springer, Francis and Taylor, Wiley, and BioMed Central. The keywords used are Ginger or (Zingiber officinale Roscoe) or (Zingiber officinale Roscoe var. officinale) or (Zingiber officinale Roscoe var. rubrum) + phytochemicals or chemical composition + biological activities or pharmacological
Preparation, characterization, and bioactivity of Zingiber officinale
INTRODUCTION. Zingiber officinale Rosc. (Zingiberaceae) is used extensively worldwide to flavor dishes and beverages. It is also used as functional food and nutraceutical product with an annual sales increase of 6.5%. 1 Several works confirmed the healthy properties of ginger with particular reference to its antioxidant, anti-diabetic, and anti-obesity effects. 2, 3 At the same time ...
Ginger (Zingiber officinale Rosc.) and its bioactive components are
Zingiber officinale Rosc. (Zingiberacae), commonly known as ginger, is a perennial and herbaceous plant with long cultivation history. Ginger rhizome is one of the most popular food spices with unique pungent flavor and is prescribed as a well-known traditional Chinese herbal medicine. To date, over …
Potential Role of Ginger ( Zingiber officinale Roscoe) in the
The composition in bioactive compounds of Zingiber officinale varies according to the place where it is grown and the drying techniques. In general terms, the rhizome of Zingiber officinale is mainly composed of essential oils in small quantities, oleoresins, mineral salts, sugars, mucilage, starch, gums and organic acids.
Sci-Hub
Liu, Y., Liu, J., & Zhang, Y. (2019). Research Progress on Chemical Constituents of Zingiber officinale Roscoe. BioMed Research International, 2019, 1-21. doi:10. ...

Bioactive Compounds and Bioactivities of Ginger ( Zingiber officinale Roscoe)

Ren-You Gan

Harold Corke

1. Introduction

2. Bioactive Components and Bioactivities of Ginger

2.2. Antioxidant Activity

2.3. Anti-Inflammatory Activity

2.4. Antimicrobial Activity

2.5. Cytotoxicity

2.6. Neuroprotection

2.7. Cardiovascular Protection

2.8. Antiobesity Activity

2.9. Antidiabetic Activity

2.10. Antinausea and Antiemetic Activities

2.11. Protective Effects against Respiratory Disorders

2.12. Other Bioactivities of Ginger

3. Conclusions

Author Contributions

Conflicts of Interest

Research Progress on Chemical Constituents of Zingiber officinale Roscoe

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Research Progress on Chemical Constituents of Zingiber officinale Roscoe

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Chemical Constituents of the Fresh Rhizome of Zingiber officinale

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