Bioactive compounds and biological activity of ginger

Ginger has an abundant amount of biological compounds. Both fresh and dried gingers have a beneficial effect. It has popularity as spices all over the world. However, for the last century ginger, and ginger extracts have been acquired an interest in their medicinal properties. Ginger is being used for the medical care and avoidance of diseases in the past. Now it is considered a medicinal plant. Ginger has been showed to contribute as anti-carcinogenic, anti-diabetic, anti-tumor activity. It is also effective against pregnancy-induced nausea and vomiting and has proved for the treatment of motion sickness and arthritis. Numerous studies have taken place by an animal models for confirmation of ginger pharmacological activity. In this review, we focused on the ginger and its constituents and therapeutic activity of ginger extracts.


Introduction
Ginger (Zingiber officinale), which is prominent as spices globally, especially in the South East Asian countries.It is a perennial plant and particularly ginger rhizome is used as well as a functional food due to its potentiality in health [1].These are now cultivated prominently in India, Bangladesh, China, Australia, and Nigeria.In the South East Asian region fresh ginger is used for the flavor of cooked curry and meat.However, nowadays ginger is used for the flavor of bakery products, condiments, beverages, desserts, and various sauces.Also, the roots are peeled sometimes eaten raw, pickled, candy or dipped in chocolate.Moreover, it has been used in soaps and cosmetic worldwide.
For the medicinal purpose, ginger is being used from the ancient years.For instance, it is well documented in Sanskrit, Chinese and Greek history as well as Arabic and Roman literature [2].For the treatment of diarrhea, stomach aches, and nausea the ginger has been used according to the Asian practitioners.It was also recognized in Europe from the 9th century and in England from the 10th century for its medicinal use.Both conventional and traditional medicine is convinced of the therapeutic activity of ginger.
Ginger is preventive for digestive problems like indigestion, intestinal infections and different types of food poisoning.It has been seen to be active against vomiting related to pregnancy and in the arthritis treatment and to prevent travel sickness.Furthermore, fresh ginger is known to ubiquitous with digestive enzymes.It has been also applied for the remedy of skin burns.Moreover, boosting the circulation and lowering high blood pressure by warming the body is another usage of fresh ginger.From the ancient time, it has also popularity for their healing properties.So, this review focused on the active component of ginger extracts and the potential activity against harmful diseases.

Bioactive compounds of Ginger
The chemical studied of ginger found that it has over 400 different constituents.The major pungent compounds from the lipophilic rhizome extract have yielded potentially active gingerols, which can be converted to shogaols, zingerone and paradol (Figure 1).Dried or extracted products have a high amount of zingerone, and shogaols compared with fresh ginger.

6-gingerol
[6]-Gingerol is responsible for its characteristic aroma and taste.It was known as the most prominent active components such as anti-oxidant, anti-inflammatory, analgesic, and antipyretic properties in ginger with various pharmacological effects [7].It has been investigated that 6-gingerol induced apoptosis through the upregulation of the G1 cell cycle and NAG-1 arrest by downregulation of cyclin D1 [8].6-gingerol has been identified as having the anti-cancerous effects [9].It has a potential role in the suppression of the hyperproliferation, inflammatory processes, and transformation that engaged in various steps of angiogenesis and metastasis.For instance, through the activation of CD8+ T cells, it inhibited B16F10 melanoma cells of pulmonary metastasis in mice [10].Anti-tumoral activity showed by 6-gingerol through induction of reactive oxygen species (ROS) which, trigger p53 activation, apoptosis, and arrest the cell cycle [11].

Biological activities of Ginger compounds
Ginger has been used as an herbal remedy as described before.It is an important herbal medicine.From the last century, more research has been performed by ginger extracts from producing new avenue for identifying the treatment of harmful diseases.Ginger and its pungent isolated compounds are known to have many potent biological activities.It has the potentiality to modulate the enzymatic profile and act as the prevention of diseases.It possesses various medicinal activities including antiinflammation, anti-tumor, insect repellent, anti-bacterial, anti-mutagen, anti-carcinogenic and antioxidant properties.

Antioxidant activity
Ginger has potential antioxidant activity.It has been believed that ginger is a plant with a significant antioxidant compound which prevents various diseases.It has also an essential role in the decrement of lipid oxidation.For instance, inhibition of ascorbate/ferrous complex about rat liver microsomes generated lipid peroxidation [21].In addition, scavenging superoxide anion and hydroxyl radicals has been shown by ginger extract and gingerol.Moreover, after heating treatment ginger antioxidant activity unchanged [22].
It has been documented that the prevention of damaged macromolecules due to oxidative stress could be cured by ginger extracts and its derivatives [23].6-gingerol is identified as a powerful anti-oxidant compound combined with anti-inflammatory and anti-apoptotic action by in vivo and in vitro studies [24].

Neuroprotective activity
Ginger has neuroprotective activity owing to the phenolic and flavonoids compounds.Ginger extracts have been studied as a neuroprotective effect on monosodium glutamate-induced toxicity in the brain of the rat.In this article, the result showed that the ginger roots to extract has a significant role in neuroprotective role in this toxicity [25].It has experimented that with transient global ischemia through the inhibition of microglia by 6-shogaol showed the neuroprotective outcome as well [26].Sometimes for the brain damage has been occurred particularly for the diabetic patient.It has been identified that ginger might be a therapeutic alternative to the treatment of diabetic-induced damage in the brain [27].This finding has been also proved in the streptozotocininduced diabetic brain of rats.In addition, ginger extracts pre-treatment decreased the seizures' behavior in pentylenetetrazol receiving mice [28].

Anti-emetic activity
As earlier mentioned ginger juice is used for motion sickness as because of its central and peripheral anticholinergic and antihistaminic effects.Gingerols, shogaols, and galanolactone and diterpenoid of ginger extract may reduce nausea and vomiting [29].For example, it has been proved by the animal model that it has anti-serotoninergic and 5-HT3 receptors antagonism, which showed an important function in the etiology of postoperative vomiting and nausea [30].Ginger has been tested for a double-blind, placebo-controlled trial to manage nausea and vomiting in cancer patients [31].

Anti-inflammatory activity
Ginger and its components show a prominent role as anti-inflammatory processes.For instance, it has experimented that ginger oil (33 mg/kg), oral administration to rats for 26 days which reduced the paw and joint swelling related with acute chronic adjuvant arthritis [32].For investigating the anti-inflammatory effect, in the cell wall of streptococcal induced rheumatoid arthritis model in female Lewis arthritis ginger essential oil has been applied by oral dose.It has been shown that it inhibited acute joint pain [33].Moreover, inhibition of cyclooxygenase (COX) and inhibition of nuclear cause NF-kappaB (κB) has been studied in vitro, which is shown to have anti-inflammatory effects [3].In addition, ginger extracts have shown that it can help from relief to the pain of osteoarthritis in the knee [34].It is also reduced the pain of rheumatoid arthritis by improving the joint movement as well.

Hepatoprotective activity
Ginger extracts have a significant hepatoprotective effect.Alcoholic liver disease is common due to heavy alcohol intake and alcoholism ranks as one of the major health problems.It has been investigated that ginger has a protective effect on rat against the carbon tetrachloride-induced hepatotoxicity.Furthermore, liver cirrhosis induced by carbon tetrachloride in rats has been identified to have protective effects on ginger [35].Ginger extracts also increased the antioxidant enzyme in the liver.For instance, for the prevention of acetaminophen-induced hepatotoxicity aqueous extract of ginger (200, 400 mg/kg before acetaminophen) can be used [23].

Anti-ulcer activity
Anti-ulcer compounds have been found from the ginger.Anti-ulcer activity of 6-gingesulfonic acid and three mono acyldigalactosylglycerols, ginger glycolipids A, B, and C has been proved.In other words, the effect of anti-ulcer activity has been identified by experiment gastric ulcer animal models [36].In addition, the potential thromboxane synthetase inhibition is the main reason for the anti-ulcer activity of ginger [37].The main part of ginger such as [6]-shogaol and [6]-gingerol helps to suppressed gastric contraction in situ doing this [6]-shogaol was more intensive than other compounds.Further, chronic myeloid leukemia cell line K562 has been suppressed by ginger whole extracts [38].

Anti-biotic activity
Together with the leaf and root extract of ginger showed anti-bacterial activity.In addition, it can be used as conventional antibiotics to fight against infections.For instance, the more antibacterial activity against Staphylococcus aureus and Streptococcus pyogenes has been seen in ginger extracts [39].In addition, 10% of ethanol ginger extract was investigated to have antimicrobial action against microorganisms [40].Ginger extracted essential oil and oleoresin showed potential antimicrobial activity [41].

Anti-mutagenic and anti-cancer activity
Ginger also worked as an anti-tumor activity by modulating of genetic pathways.It helps for the activation of suppressing gene of the tumor.Furthermore, inhibition of vascular endothelial growth factor and modulation of apoptosis can be done by ginger.For instance, it has been identified that the terpenoids, compound of ginger has been induced apoptosis in endometrial cancer cells via the activation of tumor protein p53 [42].It has been discovered that for the treatment of prostate cancer whole ginger extract has been proved in vitro and in vivo experiment [43].On the other hand, ginger extract (100 mg/kg body weight) treatment expressed the highest performance of TNF-α in rats' liver cancer blockage [44].Moreover, ginger has an anti-cancer effect against pancreatic cancer [45].It has experimented with the anti-carcinogenic effect of breast cancer [46].

Anti-diabetic activity
Diabetes endocrine dysfunctions are characterized by defects in insulin secretion or action of a human.The prevalence of diabetes is on the inflation in accordance with the World Health Organization.Ginger is recommended as a potential drug in the treatment of diabetes.Ginger and their components showed a crucial role in the control of diabetes and its complications to antihyperglycemic effect.Ginger is also worked for reducing the sugar level for the diabetic patient and also reduced the cholesterol levels in the blood.For instance, an ethanol extract from ginger reduced the blood glucose level [47].The antihyperglycaemic effects of ginger have been experimented in vitro and in vivo on cell successfully.

Conclusion
Ginger is known as spices in the different communities throughout the world.Ginger rhizome and extracts have a huge source of pharmacological values.It has been discussed that ginger has various biological compounds, but the effects of 6gingerol and 6-shogaol compounds have more essential than other compounds.However, other compounds should be elucidated over that compound like terpenoids and phenolic content.The majority of experiments have been focused on analgesic effects, anti-vomiting and anti-emetic of ginger extracts.It has been paved the way for the researcher to find herbal medicine which has rather fewer side-effects than other medicine.Therefore, future research should be based on other types of therapeutic activity of ginger extracts.