User:Growtab/Gingerol/Bibliography

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 in all zingerbraea family plant species and is found 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.

Physiological Effects

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. Many herbal products are untested for quality assurance, potency and effectiveness in clinical settings due to a lack of funding in western medical 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. This type of research is gaining momentum which is providing more funding for the exploration of physiological benefits on human subjects. Most research on 6-gingerol has been on either live mouse subjects or on cultured human tissue and may be used in the future to discuss possible applications for multi-target disease control.

In a pre-clinical meta-analysis of ginger compounds there were associated benefits of anticancer, anti-inflammatory, antioxidant and gastroprotective properties among many. These studies included mouse and human cell culture studies when analyzing data. As previously stated and confirmed through this analysis, there have been little clinical trials observed with ginger compounds. A study conducted using an African species of ginger discovered that gingerol compounds work in tandem with other phytochemicals in ginger when considering the anti-fungal capabilities. The African species tested higher in both gingerol and shogaol compounds than in the Indonesian relative. When tested for the anti-fungal properties the African ginger combated against 13 human pathogens at similar phytochemical concentrations and was three times more effective than the commercial Indonesian counterpart.

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.

Many studies have been conducted on gingerol and its effects on a wide range of cancers including leukemia, prostate, breast, skin, ovarian and colon. In a meta analysis observing many different phytochemical effects on prostate cancer, two specific studies using mice observed [6]-gingerol compounds inducing 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 with 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, targeting 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 cytotoxic activity . Cultured human breast cancer cells were subjected to various concentrations of [6]-gingerol to determine the impacts on live cells. 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, gingerol inhibited the cancer cells from invading and increasing in size. This study suggests the reason for keeping cancer cells from growing was due to a reduction in specific mRNA that transcribes for extracellular degrading enzymes called matrix metalloproteinases (MMP's). In a study using Human cells in vitro researchers looked at 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.

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 and Gingerol compounds increased glucose uptake in cells without the needed 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 mice . 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 dosage the more of an effect [6]-gingerol had.

The anti-oxidant properties of [6]-gingerol have been known to defends against Alzheimer’s. A study observed the molecular mechanisms responsible for the protection against DNA fragmentation and mitochondrial membrane potential breakdown of cells which suggests a neuroprotective support of gingerol. Suggests 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 oxidattion 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 in normal conditions these phytochemicals observable have anti-inflammatory and ant-oxidant qualities.

Bibliography

• Study using Human cells in vitro looking at oxidation stress and anti-inflamatory effects of ginger phytochemicals including gingerol. Though shogol showed the most promising effects combating free radicals with [6]-gingerol close behind. There was an inverted dose- concentration response that showed as dosage concentration increased the amount of free radicals in cells decreased. This is a suggestion that ginger compounds inhibit oxidative stress.
• Meta analysis looking at many different phytochemicals effect on prostate cancer. Specific study using mice observed gingerol compounds inducing apoptosis by interfering with the mitochondrial membrane and also stopping reproduction. This analysis doesn't go into much detail although could be used as a comparative study for related compound to ginger like capcaisin.
• Used to balance out the benefits of gingerol this study suggests that too high of dosage has negative side effects to Human hepatoma cells. This study observed many genotoxic effects including DNA fragmentation, chromosomal damage and organelle membrane instability. This study suggests that gingerol contains pro-oxidant qualities though it does not disregard the other anti-inflammatory or anti-oxidant aspects.
• Cultured human breast cancer cells were subjected to various concentrations of [6]-gingerol to determine the impacts on live cells. Concentration dependent results concluded that there was no impact at 5 μM but reduction of 16% occurred at 10 μM. [6]-gingerol targeted 3 specific proteins in breast cancer cells that encourage them to metastasis. While adhesion remained relatively unchanged, gingerol inhibited the cancer cells from invading and increasing in size. This study suggests the reason for keeping cancer cells from growing was due to a reduction in specific mRNA that transcribes for extracellular degrading enzymes called MMP's.
• Molecular mechanisms associated with anticarcinogentic activity in mice skin cancer of two phytochemicals in ginger, [6]-gingerol and [6]-paradol. Specifically researching activator proteins associated with tumor production. This study is a suggestion that the gingerol compound inhibited the transformation of normal cells into cancer cells by blocking AP-1 proteins and when cancer did develop paradol encouraged apoptosis.
• Studied human leukemia cells subjected to [6]-gingerol. Specifically looked at apoptosis and cytotoxic activity of ginger compound. Analyzed determinant factors that enhanced the effects of ginger compounds and the biochemical reactions occurring. Another study that concludes that ginger compounds reduce AP-1 proteins and encourage apoptosis in cancer cells.
• 3 specific compounds of an African ginger species was discovered to have anti-fungal capabilities. Held up against and destroyed 13 human pathogens in a lab setting. The species of ginger was specific to Africa and had higher rates of anti-fungal properties than standard ginger due to the complex phytochemicals present. The suggestion is that a blend of chemicals is what lead to such a positive anti-fungal effect, where as pure gingerol did not have the same results.
• Ginger prevents cancer and initiates apoptosis in colon which was understood by the research presented here. Specifically, suppressed G1 initiation in cell cycle and an up-regulation of NAG-1 proteins to prevent reproduction of colon cancer cells. In depth mechanisms associated with [6]-gingerols capabilities are discussed and analysed through human cell cultures.
• Another anticancer study outlining the benefits to ginger in ovarian cancer cells. Specific to lab setting and not known in control human studies. Suggestions of decreased transcription and translation of angiogenic factors.
• Pre-clinical meta-analysis of ginger compounds associated with anticancer, anti-inflammatory, antioxidant and gastroprotective properties. Includes mouse studies and human cell culture studies when doing the review. Little clinical trials have been observed with ginger compounds.
• As a specific interest of mine, gastrointestinal systems are protected by ginger compounds and can reverse cancer by apoptosis. Though the focus instead was not [6]-gingerol but [6]-shogaol, a chemical compound in ginger that is created from gingerols as ginger is heated or dried. Apoptosis occurred due to shogaols microtubule damaging effects.
• Studies human pancreatic cancer cells and the effects of ginger causing apoptosis through the same mechanism of G1 cell arrest.
• Anti-hyperglycaemic effects were studied in diabetic and severely obese mice. Gingerol increased glucose uptake in cells without the needed insulin activator. It also increase fasting glucose while decreasing glucose tolerance. The use of this study is in the form of an abstract and not the full paper, which may change the ability to use as a research citation.
• Study uses mice to analyze the effects of [6]-gingerol on diabetes and what metabolic pathways are affected. Increases in enzyme activity (CAT) and glutathione production while decreasing lipoprotein cholesterol and improved glucose tolerance in mice. More research outlining the beneficial effects of [6]-gingerol
• Study concluded that antioxidant properties of [6]-gingerol suppressed risks associated with cardio-arrhythmia in diabetic mice. By orally feeding rats many times a day and then testing blood glucose levels after 8 weeks, there was an increase in blood glucose level.
• [6]-gingerol defends against Alzheimer’s through antioxidant properties. This study observed the molecular mechanisms responsible for the protection against DNA fragmentation and mitochondrial membrane potential breakdown of cells which suggests a neuroprotective support of gingerol. Suggests that ginger upregulates glutathione production in cells, including nerve cells, through antioxidative properties which decreases the risk of Alzheimers in Human neuroblastoma cells and mouse hippocampal cells.
• Cisplatin is a chemotherapy drug that if used in high dosages causes renal failure. This is a limiting factor for this life saving drug and by using [6]-gingerol it prevented the occurrence of renal failure in rats. Gingerol improved glutathione production which binds to toxins and excretes them safely through the bowels. This study was very dose dependent which suggested that the higher dosage the more of an effect gingerol had.