Laboratories for Biomembrane Research and Biotechnology, Department of Biochemistry, Faculty of Basic Medical Sciences, College of Medicine, University of Ibadan, Ibadan 200284, Nigeria.
Laboratories for Biomembrane Research and Biotechnology, Department of Biochemistry, Faculty of Basic Medical Sciences, College of Medicine, University of Ibadan, Ibadan 200284, Nigeria.
J Integr Med. 2019 Nov;17(6):446-454. doi: 10.1016/j.joim.2019.10.001. Epub 2019 Oct 16.
Several pathologies arise from the inappropriate opening of the mitochondrial permeability transition (mPT) pore. In this regard, inhibition of mPT pore represents a cytoprotective approach to preserve mitochondrial function for treatment of diseases characterized by excessive tissue wastage such as diabetes mellitus. The aim of this study, therefore, was to study the effects of fractions of Ficus mucoso, a medicinal plant used in the traditional treatment of diabetes, on mPT pore in normal and streptozotocin (STZ)-induced diabetic rat liver.
Different solvent fractions of the crude methanol extract of F. mucoso were obtained by vacuum liquid chromatography and were tested on the mPT pore. Of all the fractions tested, methanol fraction of F. mucoso (MFFM) was the most potent and was used for in vivo studies. Diabetes mellitus was induced by a single intraperitoneal injection of 60 mg/kg STZ, while treatment lasted for 14 d. In vivo, 30 male Wistar rats were divided into five groups: A, normo-glycemic control (distilled water); B, STZ (65 mg/kg; diabetic control); C, STZ + MFFM (25 mg/kg); D, STZ + MFFM (50 mg/kg); E, STZ + glibenclamide (5 mg/kg). The mPT, mitochondrial ATPase activity, lipid peroxidation and cytochrome c release were assessed spectrophotometrically while blood glucose levels were monitored using glucometer.
In vitro, the solvent fractions of F. mucoso, at all concentrations tested, had no effect on the mPT pore, in the absence of calcium, with no significant release of cytochrome c. Interestingly, calcium-dependent pore opening was inhibited by all solvent fractions of F. mucoso, with the MFFM having the highest inhibitory effect of 83% at 3 mg/mL. Induction of opening of the mPT pore, significant (P < 0.001) enhancement of mitochondrial ATPase activity and elevated malondialdehyde (MDA) levels in STZ-induced diabetes were significantly (P < 0.001) reversed by MFFM and were comparable with the effects of glibenclamide, a standard antidiabetic drug. Also, treatment with MFFM at different doses significantly (P < 0.001) reduced high serum blood glucose compared to the diabetic control.
F. mucoso could be useful in therapeutic management of diabetes mellitus given its ability to prevent excessive tissue wastage via inhibition of pore opening, and reduction in levels of MDA and serum blood glucose.
线粒体通透性转换（mPT）孔的不当开放会引发多种疾病。因此，抑制 mPT 孔的开放是保护线粒体功能的细胞保护方法，可用于治疗以过度组织消耗为特征的疾病，如糖尿病。因此，本研究旨在研究药用植物榕树叶的不同溶剂提取物对正常和链脲佐菌素（STZ）诱导的糖尿病大鼠肝线粒体通透性转换孔的影响。
通过真空液相色谱法从榕树叶粗甲醇提取物中获得不同溶剂级分，并在 mPT 孔上进行测试。在所测试的所有级分中，榕树叶甲醇级分（MFFM）最有效，并用于体内研究。糖尿病通过单次腹腔注射 60mg/kg STZ 诱导，治疗持续 14 天。在体内，将 30 只雄性 Wistar 大鼠分为五组：A、正常血糖对照（蒸馏水）；B、STZ（65mg/kg；糖尿病对照）；C、STZ+MFFM（25mg/kg）；D、STZ+MFFM（50mg/kg）；E、STZ+格列本脲（5mg/kg）。使用分光光度法评估 mPT、线粒体 ATP 酶活性、脂质过氧化和细胞色素 c 释放，同时使用血糖仪监测血糖水平。
在体外，榕树叶的溶剂级分在测试的所有浓度下均不影响无钙条件下的 mPT 孔，且细胞色素 c 无明显释放。有趣的是，所有榕树叶溶剂级分均抑制钙依赖性孔开放，MFFM 在 3mg/ml 时抑制作用最高，为 83%。STZ 诱导的糖尿病中 mPT 孔的开放、线粒体 ATP 酶活性的显著（P<0.001）增强和丙二醛（MDA）水平的升高均被 MFFM 显著（P<0.001）逆转，与标准抗糖尿病药物格列本脲的作用相当。此外，MFFM 以不同剂量治疗可显著（P<0.001）降低高血清血糖水平，与糖尿病对照组相比。
鉴于榕树叶具有通过抑制孔开放、降低 MDA 和血清血糖水平来防止过度组织消耗的能力，它可能对糖尿病的治疗管理有用。
