6-Gingerol

Chemical Properties

Light yellow ceraceous solid

Uses

[6]-Gingerol has been used:

• to study its effects on transient receptor potential (TRP) channels
• to study its effects on experimental models of non-alcoholic steatohepatitis
• to determine its effects on microsomal prostaglandine E2 synthase 1 (mPGES-1), glycogen synthase kinase 3β (GSK-3β) and β-catenin pathway in A549 cell line
• to analyse the effects of 6-Shogaol (6-SG) on diabetic nephropathy (DN) in db/db mice

Definition

ChEBI:Gingerol is a beta-hydroxy ketone that is 5-hydroxydecan-3-one substituted by a 4-hydroxy-3-methoxyphenyl moiety at position 1; believed to inhibit adipogenesis. It is a constituent of fresh ginger. It has a role as an antineoplastic agent and a plant metabolite. It is a beta-hydroxy ketone and a member of guaiacols.

General Description

6-Gingerol is a naturally occurring plant phenoland an active pungent constituent found in the rhizome of ginger, which is known to possess anti-inflammatory, anti-tumor and antioxidant properties and can hence, serve as a potential candidate in the treatment of cancer.

Biological Activity

6-Gingerol is the major pharmacologically-active component of ginger. It is known to exhibit a variety of biological activities including anticancer, anti-inflammation, and anti-oxidation. 6-Gingerol has been found to possess anticancer activities via its effect on a variety of biological pathways involved in apoptosis, cell cycle regulation, cytotoxic activity, and inhibition of angiogenesis.

Biochem/physiol Actions

Bioactive compound found in ginger (Zingiber officinale) with antioxidant activity, which functions as an anti-inflammatory and antitumor agent. [6]-Gingerol down regulates proinflammatory cytokine release by macrophages. It has been shown to inhibit COX-2 expression by blocking the activation of p38 MAP kinase and NF-κB in phorbol ester-stimulated mouse skin.

Mechanism of action

6-Gingerol suppressed UVB-induced translocation of NF-κB from cytosol to nucleus via prevention of IκBα phosphorylation and COX-2 expression and transactivation in HaCaT cells in vitro. [6]-Gingerol suppressed COX-2 expression at mRNA and protein levels and translocation of NF-κB in UVB-irradiated skin of hairless mice. It suppressed TPA-induced COX-2 gene expression in the skin of mice by inhibiting the p38 MAP kinase-NF-κB signalling pathway. These findings suggest the chemopreventive effect of 6-Gingerol on UVB-induced skin disorders, including cancer. Jeong et al. found that 6-Gingerol inhibited the growth of colon cancer by inhibiting LTA4 hydrolase. 6-Gingerol suppressed PGE2 levels in IL-1β-stimulated human oral keratinocytes. Overall, these studies demonstrated that [6]-gingerol exerts anti-cancer and cancer-preventive activities by targeting the AA pathway.

Anticancer Research

6-Gingerol is a plant polyphenol and an active constituent of Zingiber officinale, which shows antioxidant, anti-inflammation, and antitumor properties. It has been reported to possess anti-cancer and chemopreventive potentials against several cancers, including skin, colorectal, gastrointestinal and pancreatic. It can inhibit NOS, TNF-α, and COX-2 enzymes, which are regulated by NF-κB. It hinders the cell growth of prostate, gastric, and breast cancer cells and suppresses the lung metastasis of B16F10 melanoma. It exhibits an antitumorigenic effect in human colorectal cancer cells via upregulating NSAID-activated gene-1 (NAG-1). Italters ERK1/2/JNK/AP1 pathway and induces apoptosis in colon cancer cells in acaspase-dependent manner. ROS levels were significantly increased in K562 and MOLT4 cells treated with gingerol, and apoptosis was induced in leukaemia cells by the mitochondrial pathway.

Synthesis

Method from CN201210553119.2:
1) Ginger is extracted with 80-95% ethanol under reflux and concentrated.
2) The extract is extracted with ethyl acetate. The solvent is removed under reduced pressure to give a crude gingerol extract.
3) Initial purification by silica gel column chromatography (eluted with petroleum ether-ethyl acetate mixtures), repeated to obtain purer 6-gingerol.
4) Final purification by preparative HPLC (methanol-water mobile phase). Evaporation yields high-purity 6-gingerol.