Akhtar Nosheen, Jafri Laila, Green Brian D, Kalsoom Saima, Mirza Bushra
Department of Molecular Medicine, National University of Medical Sciences, Rawalpindi, Pakistan.
Department of Biochemistry, Bahauddin Zakariya University, Multan, Pakistan.
Front Pharmacol. 2018 Nov 27;9:1376. doi: 10.3389/fphar.2018.01376. eCollection 2018.
Type 2 diabetes is a metabolic disorder, characterized by hyperglycemia and glucose intolerance. Natural products and its derived active compounds may be achievable alternatives for the treatment of type 2 diabetes. In present study we investigated the antidiabetic potential of and isolated bioactive compounds i.e., Plectranthoic acid A (PA-A) and 3,4,5,7-Flavantetrol (FL). Anti-hyperglycemic potential was evaluated α-glucosidase, α-amylase and dipeptidyl peptidase 4 (DPP-4) assays. 5'AMP-activated kinase (AMPK) activation potential was assessed by using primary hepatocytes. Distribution of PA-A in different parts of was evaluated by using rapid high-performance liquid chromatography (HPLC). Ethyl acetate fraction (FME) exhibited significant inhibition of α-glucosidase, α-amylase, and DPP-4, therefore, was selected for isolation of bioactive compounds. Among isolated compounds PA-A was more potent and possessed pleotropic inhibitory activity with IC values of 39.5, 55.5, and 51.4 μM against α-glucosidase, α-amylase, and DPP-4, respectively. Our results showed that PA-A is also a potent activator of AMPK which is a central hub of metabolic regulation. Molecular docking studies confirmed the activity of PA-A against α-glucosidase, α-amylase, and DPP-4. Rapid HPLC method revealed that maximum concentration of PA-A is present in the stem (2.25 μg/mg dry weight) of . Both and studies proposed that and its isolated compound PA-A could be an important natural source for alleviating the symptoms of type 2 diabetes mellitus and we suggest that PA-A should be explored further for its ultimate use for the treatment of type 2 diabetes.
2型糖尿病是一种代谢紊乱疾病,其特征为高血糖和葡萄糖不耐受。天然产物及其衍生的活性化合物可能是治疗2型糖尿病的可行替代方案。在本研究中,我们研究了[植物名称未给出]及其分离出的生物活性化合物即水苏酸A(PA-A)和3,4,5,7-四羟基黄酮(FL)的抗糖尿病潜力。通过α-葡萄糖苷酶、α-淀粉酶和二肽基肽酶4(DPP-4)测定评估其降血糖潜力。使用原代肝细胞评估5'AMP激活蛋白激酶(AMPK)的激活潜力。通过快速高效液相色谱(HPLC)评估PA-A在[植物名称未给出]不同部位的分布。乙酸乙酯馏分(FME)对α-葡萄糖苷酶、α-淀粉酶和DPP-4表现出显著抑制作用,因此被选用于分离生物活性化合物。在分离出的化合物中,PA-A活性更强,对α-葡萄糖苷酶、α-淀粉酶和DPP-4的IC值分别为39.5、55.5和51.4μM,具有多效抑制活性。我们的结果表明,PA-A也是AMPK的有效激活剂,而AMPK是代谢调节的核心枢纽。分子对接研究证实了PA-A对α-葡萄糖苷酶、α-淀粉酶和DPP-4的活性。快速HPLC方法显示,PA-A的最大浓度存在于[植物名称未给出]的茎中(2.25μg/mg干重)。[植物名称未给出]和[研究名称未给出]均表明,[植物名称未给出]及其分离出的化合物PA-A可能是缓解2型糖尿病症状的重要天然来源,我们建议进一步探索PA-A用于治疗2型糖尿病的最终用途。