Xing-Xin Yang1, Xi Wang1, Ting-Ting Shi2, Jin-Cai Dong1, Feng-Jiao Li1, Lin-Xi Zeng1, Min Yang1, Wen Gu1, Jing-Ping Li1, Jie Yu3. 1. College of Pharmaceutical Science, Yunnan University of Chinese Medicine, 1076 Yuhua Road, Kunming, 650500, China; Kunming Key Laboratory for Metabolic Diseases Prevention and Treatment by Chinese Medicine, 1076 Yuhua Road, Kunming, 650500, China. 2. Department of Pharmaceutical Preparation, The Xixi Hospital of Hangzhou Affiliated to Zhejiang University of Traditional Chinese medicine, Hangzhou, 310023, China. 3. College of Pharmaceutical Science, Yunnan University of Chinese Medicine, 1076 Yuhua Road, Kunming, 650500, China; Kunming Key Laboratory for Metabolic Diseases Prevention and Treatment by Chinese Medicine, 1076 Yuhua Road, Kunming, 650500, China. Electronic address: cz.yujie@gmail.com.
Abstract
BACKGROUND: Mitochondrial dysfunction is an important mechanism of non-alcoholic fatty liver disease (NAFLD). Developing mitochondrial regulators/nutrients from natural products to remedy mitochondrial dysfunction represent attractive strategies for NAFLD therapy. In China, Polygonatum kingianum (PK) has been used as a herb and food nutrient for centuries. So far, studies in which the effects of PK on NAFLD are evaluated are lacking. Our study aims at identifying the effects and mechanism of action of PK on NAFLD based on mitochondrial regulation. METHODS: A NAFLD rat model was induced by a high-fat diet (HFD) and rats were intragastrically given PK (1, 2 and 4 g/kg) for 14 weeks. Changes in body weight, food intake, histological parameters, organ indexes, biochemical parameters and mitochondrial indicators involved in oxidative stress, energy metabolism, fatty acid metabolism, and apoptosis were investigated. RESULTS: PK significantly inhibited the HFD-induced increase of alanine transaminase, aspartate transaminase, total cholesterol (TC), and low density lipoprotein cholesterol in serum, and TC and triglyceride in the liver. In addition, PK reduced high density lipoprotein cholesterol and liver enlargement without affecting food intake. PK also remarkably inhibited the HFD-induced increase of malondialdehyde and the reduction of superoxide dismutase, glutathione peroxidase, ATP synthase, and complex I and II, in mitochondria. Moreover, mRNA expression of carnitine palmitoyl transferase-1 and uncoupling protein-2 was significantly up-regulated and down-regulated after PK treatment, respectively. Finally, PK notably inhibited the HFD-induced increase of caspase 9, caspase 3 and Bax expression in hepatocytes, and the decrease of expression of Bcl-2 in hepatocytes and cytchrome c in mitochondria. CONCLUSION: PK alleviated HFD-induced NAFLD by promoting mitochondrial functions. Thus, PK may be useful mitochondrial regulators/nutrients to remedy mitochondrial dysfunction and alleviate NAFLD.
BACKGROUND:Mitochondrial dysfunction is an important mechanism of non-alcoholic fatty liver disease (NAFLD). Developing mitochondrial regulators/nutrients from natural products to remedy mitochondrial dysfunction represent attractive strategies for NAFLD therapy. In China, Polygonatum kingianum (PK) has been used as a herb and food nutrient for centuries. So far, studies in which the effects of PK on NAFLD are evaluated are lacking. Our study aims at identifying the effects and mechanism of action of PK on NAFLD based on mitochondrial regulation. METHODS: A NAFLD rat model was induced by a high-fat diet (HFD) and rats were intragastrically given PK (1, 2 and 4 g/kg) for 14 weeks. Changes in body weight, food intake, histological parameters, organ indexes, biochemical parameters and mitochondrial indicators involved in oxidative stress, energy metabolism, fatty acid metabolism, and apoptosis were investigated. RESULTS:PK significantly inhibited the HFD-induced increase of alanine transaminase, aspartate transaminase, total cholesterol (TC), and low density lipoprotein cholesterol in serum, and TC and triglyceride in the liver. In addition, PK reduced high density lipoprotein cholesterol and liver enlargement without affecting food intake. PK also remarkably inhibited the HFD-induced increase of malondialdehyde and the reduction of superoxide dismutase, glutathione peroxidase, ATP synthase, and complex I and II, in mitochondria. Moreover, mRNA expression of carnitine palmitoyl transferase-1 and uncoupling protein-2 was significantly up-regulated and down-regulated after PK treatment, respectively. Finally, PK notably inhibited the HFD-induced increase of caspase 9, caspase 3 and Bax expression in hepatocytes, and the decrease of expression of Bcl-2 in hepatocytes and cytchrome c in mitochondria. CONCLUSION:PK alleviated HFD-induced NAFLD by promoting mitochondrial functions. Thus, PK may be useful mitochondrial regulators/nutrients to remedy mitochondrial dysfunction and alleviate NAFLD.
Authors: Hassan Reda Hassan Elsayed; Mohammad El-Nablaway; Basma Adel Khattab; Rania N Sherif; Wagdi Fawzy Elkashef; Asim Mohammed Abdalla; Eman Mohammad El Nashar; Mostafa Mohammed Abd-Elmonem; Randa El-Gamal Journal: J Histochem Cytochem Date: 2021-08-27 Impact factor: 4.137
Authors: Wolfgang Marx; Melissa Lane; Meghan Hockey; Hajara Aslam; Michael Berk; Ken Walder; Alessandra Borsini; Joseph Firth; Carmine M Pariante; Kirsten Berding; John F Cryan; Gerard Clarke; Jeffrey M Craig; Kuan-Pin Su; David Mischoulon; Fernando Gomez-Pinilla; Jane A Foster; Patrice D Cani; Sandrine Thuret; Heidi M Staudacher; Almudena Sánchez-Villegas; Husnain Arshad; Tasnime Akbaraly; Adrienne O'Neil; Toby Segasby; Felice N Jacka Journal: Mol Psychiatry Date: 2020-11-03 Impact factor: 15.992
Authors: Javad Habibi; Dongqing Chen; Jack L Hulse; Adam Whaley-Connell; James R Sowers; Guanghong Jia Journal: Am J Physiol Regul Integr Comp Physiol Date: 2022-02-02 Impact factor: 3.619