School of Pharmacy, Faculty of Health and Medical Sciences, Taylor's University, Subang Jaya, Malaysia; Akhtar Saeed College of Pharmacy, Canal Campus, Lahore, Pakistan.
School of Pharmacy, Monash University Malaysia, Jalan Lagoon Selatan, 47500 Bandar Sunway, Selengor, Malaysia.
Life Sci. 2022 Jan 15;289:120232. doi: 10.1016/j.lfs.2021.120232. Epub 2021 Dec 15.
Type 2 diabetes mellitus (T2DM) is a worldwide health issue primarily due to failure of pancreatic β-cells to release sufficient insulin.
The present work aimed to assess the antidiabetic potential of arjunolic acid (AA) isolated from Terminalia arjuna in type 2 diabetic rats.
After extraction, isolation and purification, AA was orally administered to type 2 diabetic Sprague Dawley rats to investigate antidiabetic effect of AA.
T2DM was induced via single intraperitoneal injection of streptozotocin-nicotinamide (STZ-NIC) in adult male rats. After 10 days, fasting and random blood glucose (FBG and RBG), body weight (BW), food and water intake, serum C-peptide, insulin and glycated hemoglobin (HbA1c) was measured to confirm T2DM development. Dose dependent effects of orally administered AA (25 and 50 mg/kg/day) for 4 weeks was investigated by measuring BW variation, fasting and postprandial hyperglycemia, oral glucose tolerance test (OGTT), and levels of serum HbA1c, serum total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL), high density lipoprotein (HDL), serum and pancreatic C-peptide, insulin, growth differentiation factor 15 (GDF-15), serum and pancreatic inflammatory cytokines.
The oral administration of AA in preclinical model of T2DM significantly normalized FBG and RBG, restored BW, controlled polyphagia, polydipsia and glucose tolerance. In addition, AA notably reduced serum HbA1c, TC, TG, LDL with non-significant increase in HDL. On the other hand, significant increase in serum and pancreatic C-peptide and insulin was observed with AA treatment, while serum and pancreatic GDF-15 were non-significantly altered in AA treated diabetic rats. Moreover, AA showed dose dependent reduction in serum and pancreatic proinflammatory cytokines including TNF-α, IL-1β and IL-6.
For the first time our findings highlighted AA as a potential candidate in type 2 diabetic conditions.
2 型糖尿病(T2DM)是一个全球性的健康问题,主要是由于胰腺β细胞不能释放足够的胰岛素。
本研究旨在评估从诃子中分离得到的齐墩果酸(AA)在 2 型糖尿病大鼠中的降血糖作用。
在提取、分离和纯化后,将 AA 口服给予 2 型糖尿病 Sprague Dawley 大鼠,以研究 AA 的降血糖作用。
通过单次腹腔注射链脲佐菌素-烟酰胺(STZ-NIC)诱导成年雄性大鼠 2 型糖尿病。10 天后,测量空腹和随机血糖(FBG 和 RBG)、体重(BW)、食物和水的摄入、血清 C 肽、胰岛素和糖化血红蛋白(HbA1c),以确认 T2DM 的发展。通过测量 BW 变化、空腹和餐后高血糖、口服葡萄糖耐量试验(OGTT)以及血清 HbA1c、血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL)、高密度脂蛋白(HDL)、血清和胰腺 C 肽、胰岛素、生长分化因子 15(GDF-15)、血清和胰腺炎症细胞因子的水平,研究 AA(25 和 50mg/kg/天)口服给药 4 周的剂量依赖性效应。
AA 在 2 型糖尿病的临床前模型中的口服给药显著使 FBG 和 RBG 正常化,恢复 BW,控制多食、多饮和葡萄糖耐量。此外,AA 显著降低了血清 HbA1c、TC、TG、LDL,而 HDL 无显著增加。另一方面,AA 治疗后观察到血清和胰腺 C 肽和胰岛素显著增加,而 AA 治疗的糖尿病大鼠的血清和胰腺 GDF-15 无显著变化。此外,AA 显示出剂量依赖性降低血清和胰腺促炎细胞因子,包括 TNF-α、IL-1β 和 IL-6。
我们的研究结果首次强调了 AA 作为 2 型糖尿病的潜在候选药物。