Garlic Polyphenols: A Diet Based Therapy

Garlic has been used as medicinal herb due to their therapeutic activities. These activities are linked with presence of bioactive compounds such as diallyl trisulfide (DATS), allicin, diallyl sulfide (DAS), Allyl mercaptan (AM), and diallyl disulfide (DADS). The current review article summarized the chemo-preventive role of garlic along with their bioactive compounds against different human cancers including colon, liver, breast, pancreatic and gastric cancer, pancreatic cancer. They also have been working as to restrain the different cancer stages such as initial, promotion and progression stages. Garlic polyphenols lower the blood glucose level through various pathways such as prevention from the damage of β-cells, lower the insulin resistance, enhance the insulin sensitivity and secretion, and suppress the activities of glucosidase enzymes. Further, they also suppress the lipid peroxidation, nitric oxide synthetase activity, epidermal growth factor (EGF) receptor, protein kinase c, enzyme activity, survival signaling (IKK, NIK and AKT), NF-kB activity, and cell cycle regulation. In addition, more researchers by the researchers open the new horizons in the field of medicine.


Health Perspectives
Anticancer Role: Garlic and garlic oil have been found to provide significant protection against N-nitrosodiethylamine-induced hepatocarcinogenesis. Garlic contains fat and water soluble sulfur compounds that exhibits the anti-cancer mechanisms through the ameliorating oxidative stress, improving immune function, and inhibiting metabolic carcinogenic activation [10]. A group of peers, Choi and Park [11] determined that garlic oil has anticancer role by inducing apoptosis, inhibiting differentiation & tumor angiogenesis and reversing multidrug resistance. Garlic is a potential phytochemical candidate against colon cancer cells, glioblastoma cells and hepato carcinoma cells. It induces apoptosis mechanism in different cancer cells. Allicin, which is the most abundant component in garlic, could induce autophagic cell death in Hep G2 cells [12]. skin papillomagenesis [14]. It up-regulates the carcinogenesis progression and down-regulates the lipid peroxides, as well as also modulates PI3K/Akt signaling pathways and the p53 in the skin papilloma cells [15]. Similarly, in another study conducted by Cherng et al. [16], they investigated that supplementation of DAS significantly decreased the expression of apoptotic sunburn cells, DATS, AM, and DAS show the hypoglycemic action that augmented the hepatic metabolism, and insulin release [26]. Allicin controls the blood glucose level in serum and alters the activities of liver hexokinase glucose-6-phosphatase and haemoglobin coenzyme-A reductase in rabbits. It significantly increases the free amino acids and liver glycogen that lower the liver serum proteins, triglycerides level (aorta and liver) and fasting blood sugar (FBS) as compared to high sucrose-fed diet rabbits [1].
The supplementation of diallylthiosulfinate and S-methyl cysteine sulfoxide (SMCS) to alloxan diabetic rats that activates 3-hydroxy-3-methyl-glutaryl (HMG) Co-A reductase, hexokinase, glucose-6-phosphatase, and lecithin-cholesterol acyltransferase (LCAT) enzymes [27]. Padiya et al. [28] also determined the hypoglycaemic effect of garlic that enhanced the insulin sensitivity and lowered the body weight gain in fructose fed rats. The previous findings of Osman et al. [29], they reported that daily intra- Antimicrobial Activity: Antimicrobial drugs have failed to provide response to micro-organisms due to their expensive prices, side effects and greater risk of death [31]. The garlic containing extracts show antimicrobial activity against different types of bacteria such as gram positive (A streptococcus, s. pneumonia group, s. aureus and bacillus anthrax) and gram negative (salmonella species, citrobacter enterobacter, kilabsella and E. coli) [32]. Hindi [33] reported that thiosulfinates in garlic are responsible for the antimicrobial activity in rats. Allicin also exhibits the antibacterial action against some fish pathogenic bacteria.
Cardiovascular Role: Allicin, DATS, DADS and AM polyphenols perform their antioxidant mechanism and prevent from cardiovascular disease by enhancing fibrinolytic antioxidant activity, inhibiting platelet aggregation, reducting serum lipids and blood pressure levels [35]. The previous findings of Thomson et al. [36] reported that single intravenous dose of garlic extract (10-100mg/kg) dose-dependently suppressed the blood thromboxane B2 concentration in rats. Garlic also up-regulates the cellular glutathione levels in vascular endothelial cells and prevents endothelial dysfunction. The prophylactic supplementation of aged garlic extract prior to ischemia reperfusion suppresses the production of free radicals and prevent from the depletion of glutathione antioxidant enzyme. Similarly, they also suppress the fibrosis development in kidney and liver organs by inhibiting the neutrophil migration. Allicin and DATS suppress the angiotensin converting enzyme activity that lowered the blood pressure and cardio-protective effect in kidney and liver. The aged garlic extract (AGE) reduces the pulse pressure (PP) and improves the pliability of the artery. Additionally, they lower the deleterious effects that produce the papilloma in the forestomach, lower erythrocytes and enhance reticulocytes [37].

Blood Coagulation, Fibrinolysis and Circulatory Effects:
In oxidized erythrocytes of rats, the supplementation of aged garlic extract has been found to enhance the blood circulation via preventing hemolysis and lipid peroxidation. Allicin, AM improve the erythrocytes fluidity, whereas unable to protect the erythrocytes from t-butyl hydroperoxide-induced hemolysis [38]. They also modulate the production and function of both constricting factors (endothelin-1) and endothelium-derived relaxing factor (NO) in pulmonary arteries of mice [39]. Garlic juice and g-glutamylcysteines have been proved to show the beneficial effects on heart rate and may lower the blood pressure through inhibiting angiotensin-converting enzyme in vitro [40].
Immunomodulatory Activity: Aged garlic extract, and their bioactive components exhibit the immunomodulatory properties due to presence of organosulfur compounds. The concentration of garlic extract is dominantly effective on IL-2 and INF-γ gene expression of stimulated lymphocytes. These compounds also reduce the macrophage infection through the induction of NO production in vitro [41]. Allicin prevents from the immunemediated liver damage of T cells of mice and as well as also inhibit the NF-kappa B activation. A group of researchers [42], they investigated that allicin supplementation prevented from the intestinal inflammation though inhibitory effect on peripheral blood, and intestinal epithelial cells [42].
Antiallergic Role: Allergic responses are the activation of FceRI receptor on the plasma membrane of mast and basophilic cells is known to liberate the b-hexosaminidase, histamine, cytokines, prostaglandins and leukotrienes allergic mediators. Likewise, arachidonic acid metabolites such as prostaglandins and leukotrienes cause acute and chronic allergic inflammatory reactions [43]. Supplementation of allicin and AM can inhibit the passive cutaneous anaphylaxis (PCA) and immunoglobulin E-mediated aller-gic response in RBL-2H3 cells. Similarly, ethyl acetate extract of garlic polyphenols inhibits the release of TNF-a and b-hexosaminidase.

Conclusion
Garlic is mainly used as commodity worldwide for its health promoting perspectives in human such as prevention from cancer insurgence and diabetes, lowering the cardiovascular complications, allergy responses, and aging. Bioactive compounds from garlic exert anti-carcinogenic potential target multiple pathways, inclusive of the cell cycle, apoptotic cell death and angiogenic pathway. The active form of alliinase enzyme can be stabilized into biocompatible materials such as alginate beads and layered double hydroxides.
This review encompasses the multiple health effects of garlic and its bio-active constituents with references to health perspectives.