Introduction
Ginger [root/rhizome of the plant]- Zingiber officinale is one of the most commonly used dietary condiments and widely used in traditional folk medicine, science for a long time and is considered a potential chemo preventive agent [1]. Also, for treating nausea, dysentery, heartburn, flatulence, diarrhea, loss of appetite, infections, bronchitis, colds, arthritis, migraines, and hypertension. Indians and Chinese have offered Ginger as a tonic root for over 5000 years to treat many diseases.
Active components of Ginger
The unique spicy aroma of Ginger is mainly due to the ketones, principally gingerols, the primary component. A large number of analytical methods have identified at least 115 components in fresh and dried ginger varieties. Gingerols are the main ingredients of fresh Ginger and are slightly reduced in dried Ginger. In contrast, the concentrations of shogaols, which are the main dehydration products of gingerol., they are more common in dried Ginger than in fresh Ginger [2]. At the minimum, 31 gingerol-associated compounds were recognized from the methanolic crude extracts of fresh ginger rhizome [3]. Ginger has bioactive compounds [4], [6], [8], [10]-gingerol, [6]-paradol, [6], [14]-shogaol, 1-dehydro- [10]-gingerdione, [10]-gingerdione, hexahydrocurcumin, gingerenone A, 1,7-bis-(4′ hydroxyl-3′ methoxyphenyl)- 5-methoxyhepthan- 3-one, and methoxy- [10]-gingerol, tetrahydrocurcumin [4]. It is observed that the proportion of each component depends on the place of origin, commercial processor, and condition of the Ginger, i.e., fresh, dried, or processed [5].
Ginger and Cancer
A lot of reviews are done on several aspects of the chemo preventive properties of Ginger [6] mainly focused on several forms of Ginger from crude or partially purified to ginger extracts like gingerols, particularly [6]-gingerol; shogaols specifically [6]-shogaol; and zerumbone(a sesquiterpene compound acquired from Ginger) to several minor metabolite compounds.
The anti-cancer activities of [6] gingerol and zerumbone have been linked to their antioxidant activities. Several components of Ginger have been reported to have potent carcinogenic effects based on their ability to inhibit the TPA-induced Epstein-Barr virus (EBVEA) early antigen on Raji cells [7].
Also, a lot of studies has been conducted to investigate the effectiveness of Ginger in preventing cancer or suppressing the growth of the tumour in different cancer types like lymphoma, colorectal cancer, breast cancer, skin cancer, liver cancer, bladder cancer by mechanisms like apoptosis, reducing cell proliferation, cell-cycle arrest, and suppressing activator protein (AP-1) & NF-κB/COX-2 signaling pathways.
Zerumbone suppressed the expression of several Nrf2/ARE-dependent phase II enzyme genes, like Y-glutamyl-cysteine synthetase, glutathione peroxidase, and heme oxygenase-1 [8], decreased the TPA-induced hydrogen peroxide formation [9], suppress the NF-κB(signaling pathway) activation influenced by numerous stimuli like tumour necrosis factor (TNF), cigarette smoke condensate, and hydrogen peroxide [10]. Zerumbone has been reported to downregulate CXC chemokine receptor 4 (CXCR4), which is profoundly expressed in numerous tumours, like breast cancer, ovarian cancer, prostate cancer, gastrointestinal cancer, head and neck cancer, bladder cancer, brain cancer, and melanoma tumours [11], concluding that zerumbone is a potential cancer tumour suppressor as it is efficient in suppressing CXCR4, Y-glutamyl-cysteine synthetase, glutathione peroxidase, and heme oxygenase-1 in different types of cancers.
It has been observed that [6]-gingerol suppresses the Reactive oxygen species (ROS) that invades the AH109A cells (ascites hepatoma) by subduing the peroxide levels [12]. [6]-gingerol has been shown to be a highly effective agent against skin cancer in the two-stage initiation-promoting mouse skin model in in-vivo as an anticancer agent [13]. It has been observed that ginger extract and, in particular [6]-gingerol effectively reduced the proliferation of YYT colon cancer cells (a cell line) and the angiogenic activity in immortalized MS1 endothelial cells [14]. Also [6]-gingerol can inhibit the proliferation and invasion by S-phase arrest of AH109A cells [15]; also it induces cell-cycle arrest, suppresses the growth of human pancreatic adenocarcinoma (HPAC) cells, human pancreatic cancer cell lines, that is inducing apoptosis in p53-mutant cells and induced arrest, but not apoptosis, in p53-expressing cells [16]; suppress proliferation and inducing apoptosis of G1 cell-cycle arrest in several colorectal cell lines, including SW480, HCT116, HT29, Caco2, and LoVo cells by decreasing the cyclin D1(proto-oncoprotein that is overexpressed in cancer)[17].
A study shows that [6]-shogaol, an alkanone from ginger, exhibited the most effective cytotoxicity activity against human tumour cells like SK-OV-3, A549, HCT15, and SK-MEL-2, compared to the [4]-, [6]-, [8]-, and [10]-gingerols, also inhibited proliferation of numerous transgenic ovarian cancer cell lines, like C1 and C2, in the mouse [18], it has also inhibited the growth and induce apoptosis in COLO 205(colon cancer cells) cells by activation of caspase-3, -8, and -9, resulting in upregulation of proapoptotic Bax, downregulation of antiapoptotic Bcl2, the release of mitochondrial cytochrome c[19], It has also subdued the viability of gastric cancer cells by inducing mitotic arrest and damaging the microtubules [20]. It is observed in in-silico prediction (reverse docking approach) that [6]-gingerol can target leukotriene A4 hydrolase (LTA4H) protein which is a consistent target for cancer therapy [21].
Concluding the above observed and recorded studies, the widely studied bioactive components of ginger, the gingerols, shogaols, and zerumbone, can be considered potent anticancer/antineoplastic agents.
Other therapeutic effects of ginger
Ginger is said to have many powerful medicinal and preventive effects and has been used to treat hundreds of diseases for thousands of years, from colds to cancer. Ginger is known as an antioxidant, antinausea compound, anti-inflammatory agent, and anticancer agent.
Antioxidant properties of ginger: A study reported that ginger extracts decreasing age-related oxidative stress markers [22] and has suggested protecting against ethanol-induced hepatotoxicity by suppressing oxidative sequelae in ethanol-treated rats [23]. The rhizome of ginger has a high level (3.85 mmol/100 g) of total antioxidants, transcended only by some types of berries and pomegranate [24]. It has been reported that ginger extract can suppress Nitric oxide that is produced in response to various stresses and also reduce peroxynitrite mediated oxidative damage [25].
Anti-inflammatory properties of ginger: The dried ginger extract and dried gingerol enriched extract were observed to have analgesic and potent anti-inflammatory effects [26]. The anti-inflammatory outcomes of ginger are probably associated with its capacity to inhibit prostaglandin and leukotriene biosynthesis [27].
Ginger as an antinausea agent: Ginger’s carminative(herbal) effect helps in breaking and expelling the intestinal gas. A clinical study showed that Ginger is more effective than dimenhydrinate (Dramamine) or placebo for preventing or reducing seasickness [28]. Also, some studies showed consuming ginger helped with morning sickness (nausea and vomiting) in pregnant women at early stages only due to side effects [29]. Although the exact antiemetic mechanism is unknown, some data showed that inhibiting serotonin receptors exercises ginger’s antiemetic effect [30]. Ginger extract, named Gingerol, is used to reduce vomiting and nausea due to cisplatin (a platinum-based cancer drug) [31]. Ginger is recommended for alleviating nausea and vomiting associated with pregnancy, chemotherapy, and specific surgical procedures as antinausea agent extracts.
Role of ginger in prevention of Cardiovascular and other diseases: A study showed the antiplatelet, anti-inflammatory, antioxidant, hypolipidemic, and hypotensive effects of ginger to treat numerous aspects of cardiovascular diseases [32]. A study showed that aqueous ginger extract (dose-dependent manner) could reduce atrial blood extract pressure extracts [33]. A double-blinded, controlled clinical trial study reported that administration of 3 g/day in 1-g capsule 3xd of powdered ginger prominently reduced lipid levels [34].
Administration of ginger extract has shown a reduction of lipid levels, body weight, hyperglycemia, hyperinsulinemia corresponding to insulin resistance [35], suggesting that ginger can be a potent of managing effects of diabetes.
Dried ginger may also have beneficial outcomes in treating dementia, such as Alzheimer’s disease[36].
Risk factors and side effects
Side effects include heartburn, skin irritation, redness and swelling. The components of Ginger may interact with some drugs like blood thinners, NSAIDs (nonsteroidal anti-inflammatory drugs), bleeding disorders, and pregnant women other than in the early stages of gestation might be at risk.
