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.
Department of Pharmaceutical Preparation, The Xixi Hospital of Hangzhou Affiliated to Zhejiang University of Traditional Chinese medicine, Hangzhou, 310023, China.
Biomed Pharmacother. 2019 Sep;117:109083. doi: 10.1016/j.biopha.2019.109083. Epub 2019 Jul 4.
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.
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.
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.
PK alleviated HFD-induced NAFLD by promoting mitochondrial functions. Thus, PK may be useful mitochondrial regulators/nutrients to remedy mitochondrial dysfunction and alleviate NAFLD.
线粒体功能障碍是非酒精性脂肪性肝病（NAFLD）的一个重要机制。从天然产物中开发线粒体调节剂/营养素来纠正线粒体功能障碍，为 NAFLD 的治疗提供了有吸引力的策略。在中国，黄精（PK）已被用作草药和食物营养物质数百年。到目前为止，还缺乏评估 PK 对 NAFLD 影响的研究。我们的研究旨在基于线粒体调节，确定 PK 对 NAFLD 的作用机制和效果。
采用高脂肪饮食（HFD）诱导 NAFLD 大鼠模型，连续灌胃给予 PK（1、2 和 4g/kg）14 周。观察体重、摄食量、组织学参数、器官指数、生化指标和氧化应激、能量代谢、脂肪酸代谢和细胞凋亡相关的线粒体指标的变化。
PK 显著抑制 HFD 诱导的血清丙氨酸转氨酶、天冬氨酸转氨酶、总胆固醇（TC）和低密度脂蛋白胆固醇升高，以及肝脏 TC 和甘油三酯升高。此外，PK 降低了高密度脂蛋白胆固醇和肝脏肿大，而不影响摄食量。PK 还显著抑制 HFD 诱导的丙二醛升高和超氧化物歧化酶、谷胱甘肽过氧化物酶、ATP 合酶以及复合物 I 和 II 降低。此外，PK 处理后肉碱棕榈酰转移酶-1 和解偶联蛋白-2 的 mRNA 表达显著上调和下调。最后，PK 显著抑制 HFD 诱导的肝细胞中 caspase 9、caspase 3 和 Bax 表达增加，以及肝细胞中 Bcl-2 和线粒体中细胞色素 c 表达降低。
PK 通过促进线粒体功能缓解 HFD 诱导的 NAFLD。因此，PK 可能是一种有用的线粒体调节剂/营养素，可纠正线粒体功能障碍并缓解 NAFLD。
