hyperoside and Diabetes-Mellitus--Type-2

Literature findings have instituted the role of hyperglycemia-induced oxidative stress and inflammation in the pathogenesis of cognitive derangement in diabetes mellitus (DM). Hyperoside (HYP) is a flavanone glycoside reported to possess diverse pharmacological benefits such as antioxidant and anti-inflammatory properties. The study explored whether HYP could mitigate DM-induced cognitive dysfunction and further elucidate on potential molecular mechanism in rats.. Streptozotocin/high-fat diet-induced diabetic rats were treated orally with HYP (50, 200 and 400 mg/kg/day) for six consecutive weeks. The blood glucose and serum insulin levels, Morris water maze test, intraperitoneal glucose tolerance test, and brain acetylcholinesterase (AChE) activity were determined. The brain expression of inflammatory nuclear factor-kappa B (NF-κB), tumour necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6), as well as superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), total antioxidant capacity (TAC), malondialdehyde (MDA), lipid profile and caspase-3 activity were estimated.. DM evoked hyperlipidemia, hypoinsulinemia, cognitive dysfunction by markedly increased AChE and reduction in learning and memory capacity. Brain activities of SOD and CAT, and levels of TAC and GSH were considerably depressed, whereas levels of IL-1β, IL-6, TNF-α, NF-κB, caspase-3 and MDA were prominently increased. Interestingly, the HYP treatment dose-dependently abrogated the altered cognitive and biochemical parameters.. The results suggested that hyperoside prevents DM-induced cognitive dysfunction, neuroinflammation and oxidative stress via antioxidant, anti-inflammatory and antiapoptotic mechanisms in rats.

Topics: Acetylcholinesterase; Animals; Anti-Inflammatory Agents; Antioxidants; Caspase 3; Cognitive Dysfunction; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Hippocampus; Interleukin-6; Neuroinflammatory Diseases; NF-kappa B; Oxidative Stress; Quercetin; Rats; Superoxide Dismutase; Tumor Necrosis Factor-alpha

Type 2 diabetes mellitus (T2DM) is characterized by peripheral insulin resistance and insufficient insulin secretion caused by pancreatic β-cell dysfunction. Excessive production of reactive oxygen species (ROS) and activation of caspases in mitochondria inhibit insulin secretion and promote apoptosis of pancreatic β-cells. Studies have demonstrated that positive correlation between the consumption of flavonoid-rich diets and diabetes prevention. Zanthoxylum bungeanum leaves have been used as food for a long time and are rich in flavonoids with strong radical scavenging abilities. We and others have identified hyperoside as the major bioactive component of total flavonoids exacted from Zanthoxylum bungeanum leaves. We hypothesize that hyperoside from Z. bungeanum leaves (HZL) may prevent T2DM by inhibiting excessive ROS formation and reducing pancreatic β-cells apoptosis. In current study, HZL was administered to high fat diet and alloxan-induced diabetic mice, and appeared to significantly ameliorate the damage of glucose metabolism and insulin secretion as well as restore the structural integrity of pancreas, and inhibit β-cell apoptosis. Pancreatic antioxidant enzyme activities were also restored by HZL supplementation. In cultured MIN6 cells, which produce and secret insulin, HZL treatment restored insulin secretion through inhibiting the expression of TXNIP and lowering intracellular calcium concentration. These observations mechanistically linked the beneficial effects of HZL with the regulation on cellular redox status and mitochondrial function. Taken together, our findings suggest that HZL has protective effect on pancreatic β-cell function and may be a beneficial nutritional supplementation for prevention and adjuvant therapy of T2DM.

Topics: Animals; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Insulin; Insulin Secretion; Insulin-Secreting Cells; Mice; Mitochondria; Oxidation-Reduction; Plant Leaves; Quercetin

In Chinese traditional medicine, Agrimonia pilosa Ledeb (APL) exhibits great effect on treatment of type 2 diabetes mellitus (T2DM), however its mechanism is still unknown. Considering that T2DM are correlated with postprandial hyperglycemia and oxidative stress, we investigated the α-glucosidase inhibitory activity and the antioxidant activity of flavonoid compound (FC) and triterpenoid compound (TC) from APL.. Entire plants of APL were extracted using 95% ethanol and 50% ethanol successively. The resulting extracts were partitioned and isolated by applying liquid chromatography using silica gel column and Sephadex LH 20 column to give FC and TC. The content of total flavonoids in FC and the content of total triterpenoids in TC were determined by using UV spectrophotometry. HPLC analysis was used to identify and quantify the monomeric compound in FC and TC. The α-glucosidase inhibitory activities were determined using the chromogenic method with p-nitrophenyl-α-D-glucopyranoside as substrate. Antioxidant activities were assessed through three kinds of radical scavenging assays (DPPH radical, ABTS radical and hydroxyl radical) & β-carotene-linoleic acid assay.. The results indicate FC is abundant of quercitrin, and hyperoside, and TC is abundant of 1β, 2β, 3β, 19α-tetrahydroxy-12-en-28-oic acid (265.2 mg/g) and corosolic acid (100.9 mg/g). The FC & the TC have strong α-glucosidase inhibitory activities with IC50 of 8.72 μg/mL and 3.67 μg/mL, respectively. We find that FC show competitive inhibition against α-glucosidase, while the TC exhibits noncompetitive inhibition. Furthermore, The FC exhibits significant radical scavenging activity with the EC50 values of 7.73 μg/mL, 3.64 μg/mL and 5.90 μg/mL on DPPH radical, hydroxyl radical and ABTS radical, respectively. The FC also shows moderate anti-lipid peroxidation activity with the IC50 values of 41.77 μg/mL on inhibiting β-carotene bleaching.. These results imply that the FC and the TC could be responsible for the good clinical effects of APL on T2MD through targeting oxidative stress and postprandial hyperglycaemia. So APL may be good sources of natural antioxidants and α-glucosidase inhibitors exhibiting remarkable potential value for the therapy of T2DM.

Topics: Agrimonia; alpha-Glucosidases; Antioxidants; beta Carotene; Chromatography, High Pressure Liquid; Diabetes Mellitus, Type 2; Flavonoids; Free Radical Scavengers; Glucosides; Glycoside Hydrolase Inhibitors; Hyperglycemia; Kinetics; Lipid Peroxidation; Oxidation-Reduction; Oxidative Stress; Plant Extracts; Postprandial Period; Quercetin; Triterpenes