B. Phytochemicals to prevent diabetes
Curcumin is a phytochemical found abundant in the plant. In acidic solutions (pH <7.4) it turns yellow, whereas in basic (pH > 8.6) solutions it turns bright red. Diabetic nephropathy is a debilitating disease that leads to end-stage renal failure in the Western world. According to the study by University of Western Ontario, diabetes-induced upregulation of vasoactive factors (endothelial nitric oxide synthase and endothelin-1), transforming growth factor-beta1 and extracellular matrix proteins (fibronectin and extradomain-B-containing fibronectin) in the kidneys. These changes were associated with increased oxidative stress, mesangial expansion, and p300 and nuclear factor-kappaB activity that were prevented with curcumin treatment(54). Other suggested that dietary curcumin admixture ameliorated diabetes in high-fat diet-induced obese and leptin-deficient ob/ob male C57BL/6J mice as determined by glucose and insulin tolerance testing and hemoglobin A1c percentages. Curcumin treatment also significantly reduced macrophage infiltration of white adipose tissue, increased adipose tissue adiponectin production, and decreased hepatic nuclear factor-kappaB activity, hepatomegaly, and markers of hepatic inflammation(55).
Gallocatechin, containing catechin is phytochemicals of Flavan-3-ols, in the group of Flavonoids (polyphenols), found abundantly in green tea, almonds, black diamond plums, black tea, cocoa beans, Fuji apples, golden delicious apple, etc,. In the observation of Terminalia sericea stem bark extract and theirs effect against alpha-glucosidase and alpha-amylase enzymes, found that four known compounds namely beta-sitosterol (1), beta-sitosterol-3-acetate (2), lupeol (3), and stigma-4-ene-3-one (4), in addition to two inseparable sets of mixtures of isomers [epicatechin-catechin (M1), and gallocatechin-epigallocatechin (M2). 1 and 3 showed the best inhibitory activity on alpha-glucosidase (IC50:54.5 and 66.5 microM). Bio-evaluation of the inhibitory activity of the purified compounds on alpha-amylase showed that 3 and 1 exhibited IC50 values of 140.7 and 216.02 microM, respectively against alpha-amylase, according to "Antidiabetic activity of Terminalia sericea constituents" by Nkobole N, Houghton PJ, Hussein A, Lall N.(56).
Others, suggested that green tea (400 and 800 mg EGCG as PPE; ~5-10 cups) supplementation for 2 months had suggestive beneficial effects on LDL cholesterol concentrations and glucose-related markers, according to "Effect of 2-month controlled green tea intervention on lipoprotein cholesterol, glucose, and hormonal levels in healthy postmenopausal women" by Wu AH, Spicer D, Stanczyk FZ, Tseng C, Yang CS, Pike MC.(57)
Resveratrol is a phytochemical in the class of Stilbenoids, found abundantly in skins and seed of grape wine, nuts, peanuts, etc. In the evaluation of resveratrol, a polyphenolic SIRT1 activator and its SIRT1 activation in an in vitro fluorescent based assay (EC(50) : 7 μM) and the efficacy of resveratrol was also evaluated in ob/ob mice for its antidiabetic and associated metabolic effects, found that a significant improvement observed in the glucose excursion in the oral glucose tolerance test performed for 120 min; although an insignificant improvement in the triglycerides, total cholesterol, adiponectin and free fatty acid levels was observed at different doses of resveratrol tested. The present findings suggest that resveratrol is an antihyperglycemic agent and drugs similar to resveratrol can be considered as an effective therapeutic adjuvant for the current treatment of diabetes mellitus, according to "Antidiabetic activity of resveratrol, a known SIRT1 activator in a genetic model for type-2 diabetes" bySharma S, Misra CS, Arumugam S, Roy S, Shah V, Davis JA, Shirumalla RK, Ray A.(58).
Genistein is a phytochemical in the Isoflavones, belonging to the group of Flavonoids (polyphenols), found abundantly in food of the family of legumes, soy, alfalfa sprouts, red clover, chickpeas, peanuts, etc,. In the investigation of the effect of genistein on beta-cell proliferation and cellular signaling related to this effect and further determined its antidiabetic potential in insulin-deficient diabetic mice, found that genistein induced protein expression of cyclin D1, a major cell-cycle regulator essential for beta-cell growth. Dietary intake of genistein significantly improved hyperglycemia, glucose tolerance, and blood insulin levels in streptozotocin-induced diabetic mice, concomitant with improved islet beta-cell proliferation, survival, and mass. These results demonstrate that genistein may be a natural antidiabetic agent by directly modulating pancreatic beta-cell function via activation of the cAMP/PKA-dependent ERK1/2 signaling pathway, according to "Genistein induces pancreatic beta-cell proliferation through activation of multiple signaling pathways and prevents insulin-deficient diabetes in mice" by Fu Z, Zhang W, Zhen W, Lum H, Nadler J, Bassaganya-Riera J, Jia Z, Wang Y, Misra H, Liu D.(59).
5. Gallic acid
Gallic acid is a phytochemical in the class of Phenolic acids, found abundantly in tea, mango, strawberries, rhubarb, soy, etc,. In the review of 1, 2, 3, 4, 6-penta-O-galloyl-beta-D-glucose (PGG) is a polyphenolic compound highly enriched in a number of medicinal herbals, indicated that Chemically and functionally, PGG appears to be distinct from its constituent gallic acid or tea polyphenols. For anti-cancer activity, three published in vivo preclinical cancer model studies with PGG support promising efficacy to selectively inhibit malignancy without host toxicity. Potential mechanisms include anti-angiogenesis; anti-proliferative actions through inhibition of DNA replicative synthesis, S-phase arrest, and G(1) arrest; induction of apoptosis; anti-inflammation; and anti-oxidation. Putative molecular targets include p53, Stat3, Cox-2, VEGFR1, AP-1, SP-1, Nrf-2, and MMP-9. For anti-diabetic activity, PGG and analogues appear to improve glucose uptake, according to "Anti-cancer, anti-diabetic and other pharmacologic and biological activities of penta-galloyl-glucose" by Zhang J, Li L, Kim SH, Hagerman AE, Lü J(60).
6. Cinnamic acid
Cinnamic acid is a phytochemical in the class of Hydroxycinnamic acids, found abundantly in cinnamon, aloe. etc,. in the elucidation of the mechanisms by which p-Methoxycinnamic acid (p-MCA), a cinnamic acid increases [Ca2+]i and insulin secretion in INS-1 cells. p-MCA (100 μM) increased [Ca2+]i in INS-1 cells, found that p-MCA enhanced glucose-, glibenclamide-induced insulin secretion whereas it also potentiated the increase in insulin secretion induced by arginine, and Bay K 8644, an L-type Ca2+ channel agonist. Taken together, our results suggest that p-MCA stimulated insulin secretion from pancreatic β-cells by increasing Ca2+ influx via the L-type Ca2+ channels, but not through the closure of ATP-sensitive K+ channels, according to “Mechanisms of p-methoxycinnamic acid-induced increase in insulin secretion” by Adisakwattana S, Hsu WH, Yibchok-anun S.(61).
Alliin (S-allyl-L-cysteine-S-oxide) is a phytochemical compound sulfoxide,. a derivative of the amino acid cysteine, belonging to the class of sulfur compounds, found abundantly in fresh garlic and onion.
In comparison of the production and therapeutic efficiency of alliin extracted from garlic leaves of plants grown under ex situ and in situ conditions, found that Alliin production noted ~50% enhancement in leaves from plants grown under in situ conditions. Serum glucose, triglycerides, total lipids, total cholesterol, low-density lipoprotein (LDL)-, and very low-density lipoprotein (VLDL)-cholesterol in diabetic rats treated with alliin produced from in situ grown plants noted significant reduction of ~54%, 15%, 14%, 20%, 24%, and 15%, while 35%, 14%, 10%, 12%, 17% and 11% reduction was noted in diabetic rats treated with alliin produced from ex situ grown plants in comparison with those administered with distilled water. High-density lipoprotein (HDL)-cholesterol did not show any significant change. Leaf extract of plants lowered serum enzyme levels (alkaline phosphatase, aspartate aminotransferase, and alanine aminotransferase) toward the norm better than glibenclamide, according to “Alliin obtained from leaf extract of garlic grown under in situ conditions possess higher therapeutic potency as analyzed in alloxan-induced diabetic rats” by Nasim SA, Dhir B, Kapoor R, Fatima S, Mahmooduzzafar, Mujib A.(62).
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