Soetikno Vivian, Murwantara Andriyani, Andini Prisma, Charlie Fabrian, Lazarus Gilbert, Louisa Melva, Arozal Wawaimuli
Department of Pharmacology and Therapeutics, Faculty of Medicine, Universitas Indonesia, Jakarta, 10430, Indonesia.
Graduate Course, Faculty of Medicine, Universitas Indonesia, Jakarta 10430, Indonesia.
J Exp Pharmacol. 2020 Jan 28;12:27-38. doi: 10.2147/JEP.S233111. eCollection 2020.
The aim of present study was to analyze the effect of alpha-mangostin on cardiac hypertrophy and fibrosis and biochemical parameters in high-fat/high-glucose diet and low-dose streptozotocin injection (HF/HG/STZ)-induced type 2 diabetic rats.
Diabetes was induced in male Wistar rats by giving a combination of high-fat/high-glucose (HF/HG) diet for 3 weeks and followed by low-dose streptozotocin intraperitoneal injection (STZ; 35 mg/kg) at Week-3 and the HF/HG diet was continued until 8 weeks. The diabetic rats were then divided into four groups (each, n=6): untreated diabetic group (HF/HG/STZ); diabetic group treated with metformin 200 mg/kg/day (HF/HG/STZ+Metformin); diabetic group treated with alpha-mangostin 100 mg/kg/day (HF/HG/STZ+AM100); and diabetic group treated with alpha-mangostin 200 mg/kg/day (HF/HG/STZ+AM200) and all were given by oral gavage for 8 weeks. We also included a control group (C) treated with AM200 (C+AM200). The role of alpha-mangostin was assessed through its effect on blood glucose levels, HOMA-IR, blood pressure, body weight, pro-inflammatory cytokines in cardiac tissue, serum aminotransferases (ALT and AST), lipid profiles (cholesterol and triglyceride), blood urea nitrogen (BUN), uric acid, cardiac hypertrophy and fibrosis.
Diabetic rats treated with alpha-mangostin in both doses for 8 weeks showed decrease in blood glucose levels, HOMA-IR, and blood pressure. Alpha-mangostin treatment also prevented HF/HG/STZ-induced changes in the activities of ALT, AST, BUN, uric acid, lipid profiles, and pro-inflammatory cytokines, which were comparable with the standard drug metformin, while alpha-mangostin did not show any significant effects on control rats (p>0.05). The cardiac hypertrophy and fibrosis were also attenuated in diabetic rats treated with alpha-mangostin in both doses.
These data suggest that administration of alpha-mangostin can effectively attenuate diabetes-induced alteration in cardiac hypertrophy and fibrosis as well as biochemical parameters in HF/HG/STZ rats.
本研究旨在分析α-山竹黄酮对高脂/高糖饮食联合低剂量链脲佐菌素注射(HF/HG/STZ)诱导的2型糖尿病大鼠心脏肥大、纤维化及生化参数的影响。
对雄性Wistar大鼠给予高脂/高糖(HF/HG)饮食3周,然后在第3周腹腔注射低剂量链脲佐菌素(STZ;35mg/kg)诱导糖尿病,持续给予HF/HG饮食至8周。然后将糖尿病大鼠分为四组(每组n=6):未治疗的糖尿病组(HF/HG/STZ);用二甲双胍200mg/kg/天治疗的糖尿病组(HF/HG/STZ+二甲双胍);用α-山竹黄酮100mg/kg/天治疗的糖尿病组(HF/HG/STZ+AM100);用α-山竹黄酮200mg/kg/天治疗的糖尿病组(HF/HG/STZ+AM200),均通过灌胃给药8周。我们还纳入了用AM200治疗的对照组(C)(C+AM200)。通过α-山竹黄酮对血糖水平、胰岛素抵抗指数(HOMA-IR)、血压、体重、心脏组织中的促炎细胞因子、血清转氨酶(ALT和AST)、血脂谱(胆固醇和甘油三酯)、血尿素氮(BUN)、尿酸、心脏肥大和纤维化的影响来评估α-山竹黄酮的作用。
用两种剂量的α-山竹黄酮治疗8周的糖尿病大鼠血糖水平、HOMA-IR和血压均降低。α-山竹黄酮治疗还预防了HF/HG/STZ诱导的ALT、AST、BUN、尿酸、血脂谱和促炎细胞因子活性的变化,这与标准药物二甲双胍相当,而α-山竹黄酮对对照大鼠未显示任何显著影响(p>0.05)。用两种剂量的α-山竹黄酮治疗的糖尿病大鼠心脏肥大和纤维化也得到减轻。
这些数据表明,给予α-山竹黄酮可有效减轻糖尿病诱导的HF/HG/STZ大鼠心脏肥大、纤维化及生化参数的改变。