Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad, Pakistan.
Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad, Pakistan.
Biomed Pharmacother. 2021 Jun;138:111411. doi: 10.1016/j.biopha.2021.111411. Epub 2021 Mar 9.
Diabetes is a complex endocrine and metabolic disorder. Continentalic acid is a natural drug product found in roots of Aralia continentalis (family Araliaceae), which used in traditional medicine for treatment of rheumatic arthritis, lumbag, lameness, inflammation, gastritis, nephritis and diabetes mellitus.
This study is aim to investigate the continentalic acid anti-diabetic potential.
In-silico, in-vitro, in-vivo and molecular techniques were used to investigate various effects of continentalic acid by Auto Doc Vina, α-amylase and α-glucosidase inhibitory assay and alloxan-induced diabetes rats model.
In-silico results revealed that continentalic acid exhibits binding energy values of - 5 to - 9.3Kcal/mol against selected targets. In-vitro assay showed that continentalic acid caused α-amylase and α-glucosidase enzymes inhibition. In-vivo finding exhibits that continentalic acid (50 mg/kg) decreased blood glucose level, body weight, oral glucose tolerance overload, glycosylated hemoglobin, triglycerides, total cholesterol, low density lipoprotein, aspartate transaminase, aspartate aminotransferase, alkaline phosphate, total bilirubin and increased high density lipoprotein (P < 0.05, P < 0.01, P < 0.001 vs. diabetic control group). In animals pancreas and liver tissues, continentalic acid enhanced glutathione-s-transferase, reduced glutathione, catalase and decreased lipid hydroperoxide level, improved cellular architecture in histopathological examination and decrease expression of inflammatory markers: cyclooxygenase 2, tumor necrosis factor alpha, phosphorylated-nuclear factor kappa B, prostaglandins E, interleukin-18 and increased heme oxygenase-1, as evidenced in immunohistochemistry and enzyme-linked immunosorbent assay molecular investigations.
This study shows that continentalic acid exhibited binding affinities against the different targets and anti-diabetic action, mediated possibly through α-amylase and α-glucosidase inhibition, anti-hyperlipidemic, hepatoprotection, antioxidant and anti-inflammatory pathways.
糖尿病是一种复杂的内分泌和代谢紊乱。大陆酸是从五加科楤木属植物楤木的根中提取的天然药物，用于治疗风湿性关节炎、腰痛、跛行、炎症、胃炎、肾炎和糖尿病。
本研究旨在探讨大陆酸的抗糖尿病作用。
采用 Auto Doc Vina、α-淀粉酶和α-葡萄糖苷酶抑制试验及链脲佐菌素诱导糖尿病大鼠模型，研究大陆酸的各种作用。
计算机模拟结果显示，大陆酸对选定靶点的结合能值为-5 至-9.3Kcal/mol。体外试验表明，大陆酸可抑制α-淀粉酶和α-葡萄糖苷酶。体内研究结果表明，大陆酸（50mg/kg）可降低血糖水平、体重、口服糖耐量负荷、糖化血红蛋白、甘油三酯、总胆固醇、低密度脂蛋白，增加高密度脂蛋白（P<0.05，P<0.01，P<0.001 与糖尿病对照组相比）。在动物的胰腺和肝脏组织中，大陆酸增强了谷胱甘肽-S-转移酶、还原型谷胱甘肽、过氧化氢酶的水平，降低了脂质过氧化物的水平，改善了组织病理学检查中的细胞结构，并降低了炎症标志物：环氧化酶 2、肿瘤坏死因子-α、磷酸化核因子-κB、前列腺素 E、白细胞介素-18 的表达，增加血红素加氧酶-1 的表达，这些都在免疫组织化学和酶联免疫吸附试验分子研究中得到了证实。
本研究表明，大陆酸对不同靶点具有结合亲和力，并具有抗糖尿病作用，可能通过抑制α-淀粉酶和α-葡萄糖苷酶、抗高血脂、肝保护、抗氧化和抗炎途径发挥作用。
