Effect and mechanism of Bidens pilosa decoction on non-alcoholic fatty liver disease induced by high fat and high glucose in mice
【Abstract】This study aimed to investigate the effect and possible mechanism of Bidens pilosa decoction on non-alcoholic fatty liver disease (NAFLD) induced by high-fat and high-glucose diet in mice. Balb/c mice were randomly divided into normal group, model group, metformin (200 mg·kg−1) treatment group, B. pilosa decoction (10 g·kg−1) treatment group, and combination treatment of metformin and B. pilosa decoction (100 mg·kg−1 + 5 g·kg−1) group. Except for the normal group, mice in other four groups were fed with high-fat and high-glucose diet for eight weeks to establish NAFLD model. After four weeks of treatment, blood was collected from the eyeballs, and the mice were sacrificed. Then the relevant indicators were detected. The results showed that compared with the model group, blood lipid and blood glucose levels of each treatment group were significantly decreased (P < 0.05); HE staining results showed that liver pathological damage in each treatment group was significantly improved; oil red O staining results showed that fat distribution in each treatment group significantly reduced (P < 0.01); immunohistochemical staining showed that the expression of glucose-regulated protein78 (GRP78) in liver tissues of each treatment group was also significantly reduced (P < 0.01); Western blot results showed that endoplasmic reticulum (ER) stress signaling pathway-related factors GRP78, phosphorylated-protein kinase R-like ER kinase (p-PERK), eukaryotic translation-initiation factor 2α (eIF2α), activating transcription factor 4 (ATF4), C/EBP homologous protein (Chop), inositol requiring 1α (IRE1α), and cleaved-cysteinyl aspartate specific proteinase 12 (cleaved-caspase-12) were significantly reduced (P < 0.01). The results of the combination treatment group were better than those of the single drug treatment group. These results showed that B. pilosa decoction had the effect in improving non-alcoholic fatty liver, and its mechanism may be related to the down-regulation of the expression of ER stress-related factors, and the reduction of the apoptosis of hepatocytes caused by ERS and the down-regulation of blood lipid and blood glucose levels.
【Keywords】 Bidens pilosa decoction; metformin; high fat and high glucose; non-alcoholic fatty liver disease (NAFLD); endoplasmic reticulum stress (ERS);
(Translated by XING Y)
 DING J, ZHANG B, WANG P J, et al. Analysis on mechanisms and medication rules of herbal prescriptions for nonalcoholic fatty liver disease based on methods of data mining and biological information [J]. China Journal of Chinese Materia Medica, 2019, 44 (8): 1689 (in Chinese).
 WANG Y J, LU C, YAO D K. 非酒精性脂肪肝病的药物治疗研究进展 [J]. International Journal of Digestive diseases, 2018, 38 (4): 233 (in Chinese).
 YUE L N, FU P. 非酒精性脂肪肝的中西医研究进展 [J]. World Latest Medicine Information, 2019, 19 (92): 118 (in Chinese).
 PAN Y T, XU F Y, YU X Z, et al. Research progress on therapeutic targets of active components in Chinese herbs for treatment of nonalcoholic fatty liver disease [J]. China Journal of Chinese Materia Medica, 2017, 42 (6): 1109 (in Chinese).
 LV B W, FENG C Q, SUN J G. Intervention effect of Bushen Jiangzhuoyin on insulin resistance on rat nonalcoholic fatty liver disease [J]. China Journal of Experimental Traditional Medical Formulae, 2018, 24 (12): 107 (in Chinese).
 YANG J Y, SHI S H, MA W, et al. Effect of Fuzi Lizhong decoction in reducing fiver injury of rats with non-alcoholic fatty liver via activating AMPK and suppressing NF-κBp65 pathway [J]. China Journal of Chinese Materia Medica, 2018, 43 (15): 3176 (in Chinese).
 NGUYEN T H G, CHEN N, HUANG W S, et al. Antihypertensive effect of aqueous extracts from Bidens bipinnata L. in rats and its mechanism [J]. Journal of Guangxi Medical University, 2017, 34 (2): 177 (in Chinese).
 KARLA MARIELA H S, LETICIA G S C, JULIETA L H, et al. Antimycobacterial and hypolipemiant activities of Bidens odorata (Cavanilles) [J]. J Ethnopharmacol, 2018, 222: 159.
 SHEN Y W, SUN Z L, SHI P Y, et al. Anticancer effect of petroleum ether extract from Bidens pilosa L and its constituent’s analysis by GC-MS [J]. J Ethnopharmacol, 2018, 217: 126.
 WANG B Q, ZHAO J N, ZHANG Y, et al. Advances in Pharmacological Effects of Biden spilosa L [J]. Guiding Journal of Traditional Chinese Medicine and Pharmacology, 2019, 25 (18): 100 (in Chinese).
 LAU J K, ZHANG X, YU J. Animal models of non-alcoholic fatty liver disease: current perspectives and recent advances [J]. Pathology, 2017, 24 (1): 36.
 ZHAO Y F, GAO Y, WU X F, et al. Protective effect of earthworm active ingredients against endoplasmic reticulum stress-induced acute liver injury in mice [J]. China Journal of Chinese Materia Medica, 2017, 42 (6): 1183 (in Chinese).
 ZHANG C, SHENG L, YANG T, et al. Effects of ellagic acid on inflammation and oxidative stress induced by AKT gene transfection in mice with fatty liver disease [J]. China Journal of Chinese Materia Medica, 2019, 44 (9): 1869 (in Chinese).
 LI Y, CAO M Q, TAO W C, et al. Effect of Huangqisan on endoplasmic reticulum stress signaling pathway in liver tissues of high-fat diet-induced obese rats [J]. China Journal of Experimental Traditional Medical Formulae, 2019, 25 (21): 6 (in Chinese).
 ZHENG Z, SHANG Y X, TAO J H, et al. Endoplasmic reticulum stress signaling pathways: activation and diseases [J]. Curr Protein Pept Sci, 2019, 20 (9): 935.
 HUANG S J, XING Y Y, LIU Y. Emerging roles for the ER stress sensor IRE1α in metabolic regulation and disease [J]. J Biol Chem, 2019, 294 (49): 18726.
 SANKRITYAYAN H, OZA M J, KULKARNI Y A, et al. ER stress response mediates diabetic microvascular complications [J]. Drug Discov Today, 2019, 24 (12): 2247.
 PAN S G. 二甲双胍联合双歧杆菌三联活菌对非酒精性脂肪肝病患者生化指标及氧化应激的影响 [J]. Journal of Practical Medical Techniques, 2019, 26 (6): 738 (in Chinese).