Lepidine potentiates the antidiabetic effect of metformin in nicotinamide/streptozotocin-induced diabetic male rats

Metformin is used as a first-line treatment of type 2 diabetes mellitus (T2DM) and is effective as monotherapy and in combination with other glucose-lowering medications. Lepidine, a natural product found in Lepidium sativum, had antidiabetic, antioxidant, anticancer, anti-inflammatory, and hypolipidemic effects. This study aimed to assess the effects of lepidine alone and in combination with metformin in nicotinamide (NA)/streptozotocin (STZ)-induced diabetic Wistar rats. T2DM was induced by intraperitoneal injection of NA 15 minutes before intraperitoneal injection of STZ. Diabetic rats were orally treated with lepidine (20 mg/kg body weight) and/or metformin (70 mg/kg body weight) every other day for four weeks. Both lepidine and metformin treated diabetic rats showed a significant decrease in fasting blood glucose (FBG), amelioration of serum lipid profile, increase in serum insulin, and C-peptide , and downregulation in the elevated serum tumour necrosis α (TNF-α) level in association with the improvement in the pancreatic islet integrity and function. In conclusion, the lepidine has potent anti-diabetic effects and may add more to the therapeutic value of metformin when the two agents are used in combination. However, further clinical studies on human beings with T2DM are required to assess the efficacy and safety of the combination of metformin and lepidine before its approval and therapeutic application.二甲双胍（Metformin）是2型糖尿病（type 2 diabetes mellitus, T2DM）的一线治疗药物，既可单药应用，也可与其他降糖药物联合使用，疗效确切。莱匹啶（Lepidine）是独行菜（Lepidium sativum）中分离得到的天然产物，具备抗糖尿病、抗氧化、抗肿瘤、抗炎及调血脂等多种药理活性。本研究旨在评估莱匹啶单用及与二甲双胍联用时，对烟酰胺（nicotinamide, NA）/链脲佐菌素（streptozotocin, STZ）诱导的糖尿病Wistar大鼠的干预效果。研究通过先腹腔注射烟酰胺、15分钟后再腹腔注射链脲佐菌素的方法构建2型糖尿病大鼠模型。造模成功的糖尿病大鼠隔日经口给药，分别给予莱匹啶（20 mg/kg体重）、二甲双胍（70 mg/kg体重），或二者联合给药，持续4周。实验结果表明，单用莱匹啶或二甲双胍，以及二者联合给药的糖尿病大鼠，其空腹血糖（fasting blood glucose, FBG）水平均显著降低，血清脂质谱得到改善，血清胰岛素及C肽水平升高，血清中升高的肿瘤坏死因子-α（tumour necrosis factor-α, TNF-α）水平得以下调，同时伴随胰岛完整性与功能的改善。综上，莱匹啶具有强效的抗糖尿病活性，与二甲双胍联用时可进一步提升后者的临床治疗价值。但仍需开展针对2型糖尿病患者的临床研究，以评估二者联合用药的有效性与安全性，方可推动其获批并应用于临床治疗。