User:Growtab/Gingerol

Gingerol, properly known as [6]-gingerol, is a phenol phytochemical compound found in fresh ginger that activates spice receptors on the tongue. Molecularly, gingerol is similar to capsaicin and piperine which are alkaloids though the bioactive pathways are unconnected. These other compounds are what gives chilli peppers and black pepper their respective spiciness. Gingerol is normally found as a pungent yellow oil in the fresh ginger rhizome but also can form a low-melting crystalline solid. This chemical compound is found in all Zingiberaceae family plant species and is in high concentrations in the grains of paradise as well as an African Ginger species.

Cooking ginger transforms gingerol via a reverse aldol reaction into zingerone, which is less pungent and has a spicy-sweet aroma. When ginger is dried or mildly heated, gingerol undergoes a dehydration reaction forming shogaols, which are about twice as pungent as gingerol. This explains why dried ginger is more pungent than fresh ginger.

Ginger also contains [8]-gingerol, [10]-gingerol, and [12]-gingerol, collectively deemed gingerols.

Physiologic Potential

In a pre-clinical meta-analysis of gingerol compounds there were associated physiological benefits of anticancer, anti-inflammatory, anti-fungal, antioxidant, neuroprotective and gastroprotective properties which include studies in-vitro and in-vivo. A few in-vivo studies have proposed that gingerols facilitate healthy glucose regulation for diabetics. Many studies have been around the effects of gingerols on a wide range of cancers including leukemia, prostate, breast, skin, ovarian, lung, pancreatic and colorectal. There has not been much clinical testing to observe gingerols physiological impacts in humans.

While many of the chemical mechanisms associated with the effects of gingerols on cells have been thoroughly studied, few have been in a clinical setting. This is due to the high variability in natural phytochemicals and the lack of efficacy in research . Most herbal medicine, which include gingerols, are under the restrictions of the Food and Drug Administration in the United States and experimental methods have not held up to scrutiny which has decreased the value in phytochemical research. Herbal medicine is untested for quality assurance, potency and effectiveness in clinical settings due to a lack of funding in western medical research. Most research on [6]-Gingerol has been on either mouse subjects (in-vivo) or on cultured human tissue (in-vitro) and may be used in the future to discuss possible applications for multi-target disease control.

An investigation scrutinizing gingerols anti-fungal capabilities remarked that an African species of ginger tested higher in both gingerol and shogaol compounds than in the more commonly cultivated Indonesian relative. When tested for the anti-fungal properties the African ginger combated against 13 human pathogens and was three times more effective than the commercial Indonesian counterpart. It is thought that gingerol compounds work in tandem with the other phytochemicals present including shogaols, paradols and zingerone.

A few established cellular pathways effected by [6]-gingerol that result in apoptosis of a cancerous cell. ABBREVIATIONS: 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.

In a meta analysis looking at many different phytochemical effects on prostate cancer, two specific studies using mice observed [6]-gingerol compounds induced apoptosis in cancer cells by interfering with the mitochondrial membrane. There were also observed mechanisms associated with the disruption of G1 phase proteins to stop the reproduction of cancer cells which is also an associated benefit of other relevant anticancer studies. The main function of gingerol phytochemicals on cancer cells seems to be protein disruption. The anti-carcinogenic activity of [6]-gingerol and [6]-paradol was analysed in a study observing the cellular mechanisms associated with mouse skin cancer which targeted the activator proteins associated with tumor initiation. Gingerol compound inhibited the transformation of normal cells into cancer cells by blocking AP-1 proteins and when cancer did develop paradol encouraged apoptosis due to its cytotoxic activity . Cultured human breast cancer cells were subjected to various concentrations of [6]-gingerol to determine the impacts on live cells. These concentration dependent results concluded that there was no impact at 5 μM but a reduction of 16% occurred at 10 μM. [6]-gingerol targeted three specific proteins in breast cancer cells that encourage them to metastasis and while adhesion remained relatively unchanged, [6]-gingerol inhibited the cancer cells from invading and increasing in size. This study suggests the reason cancer cells were kept from growing was due to a reduction in specific mRNA that transcribes for extracellular degrading enzymes called matrix metalloproteinases (MMP's). An examination using Human cells in-vitro displayed gingerols capabilities in combating oxidative stress. The results concluded that gingerol had anti-inflammatory effects though shogaol showed the most promising effects combating free radicals. There was an inverted dose- concentration response and as dosage concentration increased the amount of free radicals in cells decreased.

Cisplatin is a chemotherapy drug that if used in high dosages causes renal failure which is considered a limiting factor for this life saving drug. By using [6]-gingerol it prevented the occurrence of renal failure in rats. [6]-gingerol improved glutathione production in dose-dependent results which suggested that the higher a dosage the more of an effect [6]-gingerol had.

Gingerol compounds are known to help in diabetic patients because of the toxicity regulation factors including anti-inflammatory and glutathione activity. Anti-hyperglycaemic effects were studied in diabetic and severely obese mice. Gingerol compounds increased glucose uptake in cells without the need of a synthetic insulin activator, while also increase fasting glucose and decreasing glucose tolerance. In a different study the exact metabolic mechanisms associated with the physiological benefits of gingerol phytochemicals concluded that there was increased enzyme activity (CAT) and glutathione production while decreasing lipoprotein cholesterol and improving glucose tolerance in mice. Cardio-arrhythmia is a common side effect of diabetic patients and the anti-inflammatory effects of gingerol suppressed the risks by lowering blood glucose levels in-vivo .

The anti-oxidant properties of [6]-gingerol have been known to defend against Alzheimer’s. A study observed the molecular mechanisms responsible for the protection against DNA fragmentation and mitochondrial membrane potential deterioration of cells which suggests a neuroprotective support of gingerol. This study indicates that ginger up-regulates glutathione production in cells, including nerve cells, through anti-oxidative properties which decreases the risk of Alzheimer's in Human neuroblastoma cells and mouse hippocampal cells.

While many studies suggest the low risk of using ginger phytochemicals to combat oxidation damage to cells, there are a few studies that suggest potential genotoxic effects. In one study too high of a dose to human hepatoma cells resulted in DNA fragmentation, chromosomal damage and organelle membrane instability which could result in apoptotic behavior. There are some pro-oxidant behaviors to gingerol compounds when the concentration reaches high levels although also considered, in normal conditions these phytochemicals observed have anti-inflammatory and ant-oxidant qualities. In another study [6]-Gingerol notably inhibited the metabolic rate of rats when given an intraperitoneal injection which induced a hypothermic reaction though, when consumed orally in excess there were no changes in body temperature.