Preclinical studies have shown that ginger extract and its constituents possess chemopreventive and antineoplastic properties in gastric cancer.

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Abstract​

Gastrointestinal (GI) cancer, a cancer of different organs of the digestive system, is one of the most common cancers around the world. The incidence and death rate of some of these cancers are very high. Although a large variety of chemotherapeutic agents have been introduced since the last few decades to combat GI cancer, most of them are very expensive and have side effects. Therefore, the compounds derived from natural sources, which are considered to be safe and cost effective, are needed. Ginger (Zingiber officinale) is one of the most widely used natural products consumed as a spice and medicine for treating nausea, dysentery, heartburn, flatulence, diarrhea, loss of appetite, infections, cough, and bronchitis. Experimental studies showed that ginger and its active components including 6-gingerol and 6-shogaol exert anticancer activities against GI cancer. The anticancer activity of ginger is attributed to its ability to modulate several signaling molecules like NF-κB, STAT3, MAPK, PI3K, ERK1/2, Akt, TNF-α, COX-2, cyclin D1, cdk, MMP-9, survivin, cIAP-1, XIAP, Bcl-2, caspases, and other cell growth regulatory proteins. In this review, the evidences for the chemopreventive and chemotherapeutic potential of ginger extract and its active components using in vitro, animal models, and patients have been described.

 

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1. Introduction​

The gastrointestinal (GI) tract is one of the important parts of the body. This tract starts from the mouth, includes esophagus, stomach, small and large intestine, and rectum, and finally ends with anus. The human GI tract is a single tube which is approximately nine meters long in relaxed condition [1]. Disorder in any part of the GI tract results in various malfunctions such as diseases of digestive system and cancer.

GI cancer is defined as the cancer of organs of the digestive system including the esophagus, gallbladder, liver, pancreas, stomach, small intestine, large intestine, rectum, and anus (Figure 1) [2]. The common risk factors for GI cancer include infection, smoking, drinking alcohol, high fat diet, age, race, gender, family history, and geographical location. The occurrence of GI cancer is very high in developed countries. In the United States, GI cancer accounts to 20 percent of all newly diagnosed cancer cases. Among different GI cancers, colorectal cancer is the most common cancer and is the second leading cause of death [3].

 

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Accumulated evidences revealed that changing lifestyle could prevent all these cancers. The major change in lifestyle which proves beneficial includes avoiding tobacco, increased ingestion of fruits and vegetables, moderate use of alcohol, caloric restriction, exercise, minimal meat consumption, intake of whole grains, proper vaccinations, and regular health checkups. The link between healthy diet and cancer has been revealed in numerous studies [4–7]. An inverse association between the consumption of fruits and vegetables and cancer risk was evident by an epidemiological study in Netherlands. It has been found that the consumption of 21 vegetables and 9 fruits decreased the tumor growth in urothelial cancer patients [8]. It has also been reported that Asians have lower incidence of cancer than the residents of Western countries, and the rate increases substantially among Asians who have migrated to the West (http://www.dietandcancerreport.org/?p=ER). Consumption of diet rich in plant products may be one of the important reasons for the low incidence of cancer in Asia. A wide variety of natural products containing anticancer properties have been reported in the literature. In this paper, the role of ginger and its active ingredients against GI cancer have been discussed as it has worldwide consumption as a spice.

 

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2. Ginger and Its Constituents​

Ginger (Zingiber officinale), a member of the Zingiberaceae family, is a popular spice used globally especially in most of the Asian countries [9]. Chemical analysis of ginger shows that it contains over 400 different compounds. The major constituents in ginger rhizomes are carbohydrates (50–70%), lipids (3–8%), terpenes, and phenolic compounds [10]. Terpene components of ginger include zingiberene, β-bisabolene, α-farnesene, β-sesquiphellandrene, and α-curcumene, while phenolic compounds include gingerol, paradols, and shogaol (Figure 2). These gingerols (23–25%) and shogaol (18–25%) are found in higher quantity than others. Besides these, amino acids, raw fiber, ash, protein, phytosterols, vitamins (e.g., nicotinic acid and vitamin A), and minerals are also present [11, 12].

[IMG alt="An external file that holds a picture, illustration, etc.
Object name is GRP2015-142979.002.jpg"]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4369959/bin/GRP2015-142979.002.jpg[/IMG]
Figure 2
Ginger, ginger rhizome, and its major active components: 6-gingerol, 6-shogaol, and 6-paradol.

 

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3. Use of Ginger as a Traditional Medicine​

Ginger has been used as a spice as well as medicine in India and China since ancient times. It was also known in Europe from the 9th century and in England from the 10th century for its medicinal properties [62]. Native Americans have also used wild ginger rhizome to regulate menstruation and heartbeat. Ginger is thought to act directly on the gastrointestinal system to reduce nausea. Therefore, it is used to prevent nausea resulting from chemotherapy, motion sickness, and surgery [63]. Ginger is known as a popular remedy for nausea during pregnancy [11]. Ginger is also used to treat various types of other GI problems like morning sickness, colic, upset stomach, gas, bloating, heartburn, flatulence, diarrhea, loss of appetite, and dyspepsia (discomfort after eating). According to Indian Ayurvedic medicinal system, ginger is recommended to enhance the digestion of food [59].
Besides these, ginger has been reported as a pain relief for arthritis, muscle soreness, chest pain, low back pain, stomach pain, and menstrual pain. It can be used for treating upper respiratory tract infections, cough, and bronchitis. As an anti-inflammatory agent, it is recommended for joint problems [12]. Fresh juice of ginger has been shown to treat skin burns. Active component of ginger is used as a laxative and antacid medication. It is also used to warm the body for boosting the circulation and lowering high blood pressure. Because of its warming effect, ginger acts as antiviral for treatment of cold and flu [64]. Ginger is also used as a flavoring agent in foods and beverages and as a fragrance in soaps and cosmetics [65].

 

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4. Role of Ginger and Its Constituents in Prevention and Treatment of Gastrointestinal Cancer​

Evidences from in vitro, animal, and epidemiological studies suggest that ginger and its active constituents suppress the growth and induce apoptosis of variety of cancer types including skin, ovarian, colon, breast, cervical, oral, renal, prostate, gastric, pancreatic, liver, and brain cancer. These properties of ginger and its constituents could be associated with antioxidant, anti-inflammatory, and antimutagenic properties as well as other biological activities [66]. In this review, focus has been laid solely on GI cancers to describe whether ginger and its active components exhibit chemopreventive and chemotherapeutic potential. The in vitro (Table 1), in vivo (Table 2), and clinical effects (Table 3) of ginger have also been described.

 

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4.1. Gastric Cancer​

Preclinical studies have shown that ginger extract and its constituents possess chemopreventive and antineoplastic properties in gastric cancer. In vitro study showed that 6-gingerol induces apoptosis of gastric cancer cells. It facilitates TNF-related apoptosis-inducing ligand- (TRAIL-) induced apoptosis by increasing caspase-3/7 activation. The induction of apoptosis by 6-gingerol was mediated through downregulation of cytosolic inhibitor of apoptosis (cIAP)-1 and inhibiting TRAIL-induced nuclear factor-kappaB (NF-κB) activation. Besides 6-gingerol, 6-shogaol also reduced the viability of gastric cancer cells by damaging microtubules [30]. When ginger extract was given to Sprague-Dawley rats having acetic acid-induced ulcers, it significantly reduced the gastric ulcer area. Ginger extract also attenuated elevated activities of xanthine oxidase and myeloperoxidase, as well as malondialdehyde (MDA) level in the ulcerated mucosa. Thus, ginger extract promotes ulcer healing by acting as an antioxidant and prevents gastric mucosal damage [46].

It is also reported to be effective in ameliorating the side effects of conventional therapeutic agents including γ-radiation, doxorubicin, and cisplatin by regulating P-glycoprotein [67]. Thus ginger extract exhibits chemosensitizing effects in certain neoplastic cells in vitro andin vivo. In support of this, another study showed that ginger reverses cisplatin-induced delay in gastric emptying indicating that ginger acts as an antiemetic for cancer chemotherapy [47]. Thus, it may be useful in improving the gastrointestinal side effects of cancer chemotherapy. Besides ginger, zerumbone (a sesquiterpene) derived from a subtropical gingerZingiber zerumbet Smith was also reported to have antitumor and anti-inflammatory properties in different cancers. In gastric cancer cell lines, zerumbone inhibited cell proliferation, VEGF expression, and NF-κB activation [28]. Thus, zerumbone acts as an antiangiogenic and antitumor drug in the treatment of gastric cancer.

 

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8. Conclusion​

Although the medicinal properties of ginger have been known for thousands of years, a significant number of in vitro, in vivo, and epidemiological studies further provide substantial evidence that ginger and its active compounds are effective against wide variety of human diseases including GI cancer. Ginger has been found to be effective against various GI cancers such as gastric cancer, pancreatic cancer, liver cancer, colorectal cancer, and cholangiocarcinoma. However, its anticancer effects on other GI cancers like duodenal, esophageal, anal, GI carcinoid tumor and pancreatic islet cell cancer have yet not been established. Therefore, efficacy of such potent agents on these cancers is warranted. Ginger and its polyphenols have been shown to target multiple signaling molecules that provide a basis for its use against multifactorial human diseases. Moreover, most of the known activities of ginger components are based only on in vitro and in vivo studies, except for a few clinical studies in human subjects. Therefore, more extensive and well-controlled human studies are required to demonstrate its efficacy as an anticancer agent, as it is a safe and cost-effective alternative.

 

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Moreover, most of the known activities of ginger components are based only on in vitro and in vivo studies, except for a few clinical studies in human subjects.

And they are on colorectal cancer because that’s one of the top most cancer in USA and uk.

 

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