Shobhaben Pratapbhai Patel School of Pharmacy and Technology Management, SVKM's NMIMS, V.L.Mehta road, Vile Parle (W), Mumbai 400056, India; SVKM's Dr. Bhanuben Nanavati College of Pharmacy, Vile Parle (W), Mumbai 400056, India.
Shobhaben Pratapbhai Patel School of Pharmacy and Technology Management, SVKM's NMIMS, V.L.Mehta road, Vile Parle (W), Mumbai 400056, India.
Life Sci. 2019 Feb 15;219:109-121. doi: 10.1016/j.lfs.2019.01.013. Epub 2019 Jan 11.
Diabetic nephropathy is the commonly developed complication of vasculature in type 2 diabetic patients. Chronic hyperglycemia leads to nephropathy in diabetics because of the formation of excessive reactive oxygen species and advanced glycation end products which is reflected in the form of glomerulosclerosis, tubular atrophy and interstitial fibrosis. As per the various reports reduction in SIRT1 expression in kidney tissue is key factor in the development of nephropathy in diabetes because its reduction in tissue is linked with excessive formation of ROS. Formononetin is a polyphenolic compound reported for its effect on SIRT1 and ROS.
Type 2 diabetes was induced in rats by diet modification using high fat diet for fifteen days prior to streptozotocin regimen (35 mg/kg, i.p.). Treatment of formononetin was started after confirmation of diabetes and continued for 16 weeks. Formononetin was administered orally to the diabetic animals at the dose of 10. 20 and 40 mg/kg.
Formononetin treatment for 16 week was able to control hyperglycemia and insulin resistance in diabetic animals. It has also been reduced triglyceride and cholesterol in blood. Formononetin treatment reduced blood concentration of creatinine, blood urea nitrogen and increased albumin concentration. Formononetin treatment also enhanced creatinine clearance in diabetic animals. Oxidative stress burden was also reduced significantly after formononetin treatment along with increased SIRT1 expression in kidney tissues of diabetic animals.
Formononetin is a potential molecule which increases the expression of SIRT1 in kidney tissue of diabetic. Thus formononetin is an effective molecule to control nephropathy in type 2 diabetes mellitus.
糖尿病肾病是 2 型糖尿病患者血管常见的并发症。慢性高血糖导致糖尿病患者发生肾病，原因是活性氧和晚期糖基化终产物的形成过多，这反映在肾小球硬化、肾小管萎缩和间质纤维化的形式中。根据各种报道，肾脏组织中 SIRT1 表达的减少是糖尿病肾病发展的关键因素，因为其组织中的减少与 ROS 的过度形成有关。芒柄花素是一种多酚化合物，因其对 SIRT1 和 ROS 的作用而被报道。
通过高脂肪饮食对大鼠进行 15 天的饮食修改，诱导 2 型糖尿病，然后进行链脲佐菌素方案（35mg/kg，ip）。在确认糖尿病后开始进行芒柄花素治疗，并持续 16 周。芒柄花素以 10、20 和 40mg/kg 的剂量口服给予糖尿病动物。
芒柄花素治疗 16 周可控制糖尿病动物的高血糖和胰岛素抵抗。它还降低了血液中的甘油三酯和胆固醇。芒柄花素治疗降低了糖尿病动物血液中肌酐、血尿素氮的浓度，并增加了白蛋白的浓度。芒柄花素治疗还提高了糖尿病动物的肌酐清除率。芒柄花素治疗后，氧化应激负担也显著降低，同时糖尿病动物肾脏组织中 SIRT1 的表达增加。
芒柄花素是一种潜在的分子，可增加糖尿病肾脏组织中 SIRT1 的表达。因此，芒柄花素是控制 2 型糖尿病肾病的有效分子。
