Search JIM Advanced Search

Journal of Integrative Medicine ›› 2019, Vol. 17 ›› Issue (6): 446-454.doi: 10.1016-j.joim.2019.10.001

Previous Articles     Next Articles

Opening of liver mitochondrial permeability transition pore in streptozotocin-induced diabetic rats and its inhibition by methanol fraction of Ficus mucoso (Welw) root bark

Olubukola Titilope Oyebode, Foluso Olayemi Ogunbiyi, Olufunso Olabode Olorunsogo   

  1. Laboratories for Biomembrane Research and Biotechnology, Department of Biochemistry, Faculty of Basic Medical Sciences, College of Medicine, University of Ibadan, Ibadan, 200284, Nigeria
  • Online:2019-11-10 Published:2019-11-15

Objective: 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.
Methods: 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 (50mg/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.
Results: 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.
Conclusion: 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

Key words: Mitochondria, Ficus mucoso, Permeability transition, Cytochrome C

[1] Victor Abou Nehmi Filho, Gilson Masahiro Murata, Ruan Carlos Macêdo de Moraes, Gabriely Cristina Alves Lima, Danielle Araujo de Miranda, Katrin Radloff, Raquel Galvão Figuerêdo Costa, Joyce de Cassia Rosa de Jesus, Jéssica Alves De Freitas, Nayara Izabel Viana, Ruan Pimenta, Katia Ramos Moreira Leite, José Pinhata Otoch, Ana Flávia Marçal Pessoa. A novel supplement with yeast β-glucan, prebiotic, minerals and Silybum marianum synergistically modulates metabolic and inflammatory pathways and improves steatosis in obese mice. Journal of Integrative Medicine, 2021, 19(5): 439-450.
[2] Shriniwas S. Basaiyye, Sanjay Kashyap, Kannan Krishnamurthi, Saravanadevi Sivanesan. Induction of apoptosis in leukemic cells by the alkaloid extract of garden cress (Lepidium sativum L.). Journal of Integrative Medicine, 2019, 17(3): 221-228.
[3] Jesmin Mondal, Jayeeta Das, Rajesh Shah, Anisur Rahman Khuda-Bukhsh. A homeopathic nosode, Hepatitis C 30 demonstrates anticancer effect against liver cancer cells in vitro by modulating telomerase and topoisomerase II activities as also by promoting apoptosis via intrinsic mitochondrial pathway. Journal of Integrative Medicine, 2016, 14(3): 209-218.
[4] Dao-fang Ding, Xiao-feng Li, Hao Xu, Zhen Wang, Qian-qian Liang, Chen-guang Li, Yong-jun Wang. Mechanism of resveratrol on the promotion of induced pluripotent stem cells. Journal of Chinese Integrative Medicine, 2013, 11(6): 389-396.
[5] Yue-hua Wang, Xiao-li He, Xiao-xiu Li, Hai-lin Qin, Guan-hua Du . Effects of the effective component group of Chinese herbal medicine Xiaoxuming Decoction on brain mitochondria in rats with chronic cerebral ischemia. Journal of Chinese Integrative Medicine, 2012, 10(5): 569-576.
[6] Min Zhu , Mi Zhou , Ying Shi , Wen-wei Li. Effects of echinacoside on MPP+-induced mitochondrial fragmentation, mitophagy and cell apoptosis in SH-SY5Y cells. Journal of Chinese Integrative Medicine, 2012, 10(12): 1427-1432.
[7] Xiao-ping Huang , Xiao-dan Liu , Chang-qing Deng . Effects of the combination of active component extracts from Astragalus membranaceus and Panax notoginseng on apoptosis, reactive oxygen species and mitochondrial membrane potential of PC12 cells with oxidative injury. Journal of Chinese Integrative Medicine, 2012, 10(10): 1127-1134.
[8] Bin Cheng, Xin Wang, Lei Wang, Kai Cao, Lei Duan, Feng-tao Li. Changes of mitochondrial apoptosis in spinal cord ischemia-reperfusion injury and the effects of Herba Erigerontis Breviscapi Injection preconditioning intervention in rabbits. Journal of Chinese Integrative Medicine, 2009, 7(9): 842-847.
[9] Zhi-jun Dai, Xi-jing Wang, Qian Xue, Zong-zheng Ji, Xiao-xu Liu, Hua-feng Kang, Hai-tao Guan, Xiao-bin Ma, Hong-tao Ren. Effects of Scutellaria Barbata drug-containing serum on apoptosis and mitochondrial transmembrane potential of hepatoma H22 cells. Journal of Chinese Integrative Medicine, 2008, 6(8): 821-826.
[10] Shi-lin Huang, Nan-nan Chen, Yang Xiang, Chen Zhang, Li Zhang, De-jie Zhang. Effects of psoralen with long wave ultraviolet light on apoptosis and mitochondrial membrane potential in K562 cells. Journal of Chinese Integrative Medicine, 2008, 6(12): 1259-1262.
[11] Xue-mei Liu, Qi-fu Huang, Yun-ling Zhang, Jin-li Lou, Hong-sheng Liu, Hong Zheng. Effects of Tribulus terrestris L. saponion on apoptosis of cortical neurons induced by hypoxia-reoxygenation in rats. Journal of Chinese Integrative Medicine, 2008, 6(1): 45-50.
[12] Chen Zhang, Bai Li, Shu-qin Lu, Yong Li, Yong-hua Su, Chang-quan Ling. Effects of melittin on expressions of mitochondria membrane protein 7A6, cell apoptosis-related gene products Fas and Fas Ligand in hepatocarcinoma cells. Journal of Chinese Integrative Medicine, 2007, 5(5): 559-563.
[13] Jin-jun Cheng, Yuan-shan Zeng, Yi Xiong, Wei Zhang, Sui-jun Chen, Zhi-qiang Zhong. Ganoderma spores may regulate the levels of mitochondria-related molecular substances in hippocampus of young rats birthed by rats with gestational hypertension. Journal of Chinese Integrative Medicine, 2007, 5(3): 322-327.
[14] Jian-xiong Zhao, Fu-lian Guo, De-cheng Bai, Xue-xi Wang. Effects of Fuzheng Yiliu Granules on apoptotic rate and mitochondrial membrane potential of hepatocellular carcinoma cell line H22 from mice. Journal of Chinese Integrative Medicine, 2006, 4(3): 271-274.
[15] Lei Wang, Guang Ji, Wei Zhang, Lian-jun Xing, Pei-yong Zheng. Hepatic stellate cell apoptosis and mitochondrion. Journal of Chinese Integrative Medicine, 2005, 3(2): 144-148.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
[1] Jin-rong Fu. Establishment of multivariate diagnosis and treatment system of modern gynecology of traditional Chinese medicine. Journal of Chinese Integrative Medicine, 2008, 6(1): 22-24
[2] Hao Li, Ming-jiang Yao, Wen-ming Zhao, Jie Guan, Lin-lin Cai, Ling Cui. A randomized, controlled, double-blind trial of Huannao Yicong capsule in senile patients with mild cognitive impairment. Journal of Chinese Integrative Medicine, 2008, 6(1): 25-31
[3] Zhi-chun Jin. Problems in establishing clinical guideline for integrated traditional Chinese and Western medicine. Journal of Chinese Integrative Medicine, 2008, 6(1): 5-8
[4] SUN Ming-yu, ZUO Jian, DUAN Ji-feng, HAN Jun, FAN Shi-ming, ZHANG Wei, ZHU Li-fang, YAO Ming-hui. Antitumor activities of kushen flavonoids in vivo and in vitro. Journal of Chinese Integrative Medicine, 2008, 6(1): 51-59
[5] Min Cheng, Qiong Feng, Shu-wen Qian, Hui Gao, Cui-qing Zhu. Preliminary assay of p-amyloid binding elements in heart-beneficial recipe. Journal of Chinese Integrative Medicine, 2008, 6(1): 68-72
[6] Ning-qun Wang, Liang-duo Jiang, Zong-xing Li. Research progress in asthma-related quality of life. Journal of Chinese Integrative Medicine, 2008, 6(1): 93-97
[7] Jing-yuan Mao, Chang-xiao Liu, Heng-he Wang, Guang-li Wei , Zhen-peng Zhang, Jie Xing, Wang Xian liang , Ying-fei Bi . Effects of Shenmai Injection on serum concentration and pharmacokinetics of digoxin in dogs with heart failure. Journal of Chinese Integrative Medicine, 2010, 8(11): 1070-1074
[8] Zhi-mei Wang, Bin Zhang. A study on translation of ellipses in Huangdi Neijing from perspective of hermeneutic theory. Journal of Chinese Integrative Medicine, 2010, 8(11): 1097-1100
[9] Gui Yu, Jie Wang. Thinking on building the network cardiovasology of Chinese medicine. Journal of Chinese Integrative Medicine, 2012, 10(11): 1206-1210
[10] Pedro Saganha João, Doenitz Christoph, Greten Tobias, Efferth Thomas, J. Greten Henry. Qigong therapy for physiotherapists suffering from burnout: a preliminary study. Journal of Chinese Integrative Medicine, 2012, 10(11): 1233-1239