Graptopetalum Paraguayense Ameliorates Chemical-Induced Rat Hepatic Fibrosis In Vivo and Inactivates Stellate Cells and Kupffer Cells In Vitro

• Published in: PloS one Vol. 8; no. 1; p. e53988
• Main Authors: Su, Li-Jen, Chang, Chia-Chuan, Yang, Chih-Hsueh, Hsieh, Shur-Jong, Wu, Yi-Chin, Lai, Jin-Mei, Tseng, Tzu-Ling, Huang, Chi-Ying F., Hsu, Shih-Lan
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 15.01.2013; Public Library of Science (PLoS)
• Subjects: Alanine; Alanine transaminase; Alcohol; Animals; Apoptosis; Apoptosis - drug effects; Aspartate; Aspartate transaminase; Bile; Bilirubin; Biology; Body Weight - drug effects; Breeding of animals; Carbon tetrachloride; CCL4 protein; Cell activation; Cell death; Chemical compounds; Collagen; Collagen (type I); Cytokines; Cytokines - biosynthesis; Dimethylnitrosamine; Dimethylnitrosamine - adverse effects; Disease Models, Animal; Drugs, Chinese Herbal - administration & dosage; Drugs, Chinese Herbal - pharmacology; Education; Ferns - chemistry; Fibrosis; Gastroenterology; Gene expression; Graptopetalum paraguayense; Health aspects; Hepatic Stellate Cells - drug effects; Hepatic Stellate Cells - metabolism; Hepatology; Herbal medicine; Hospitals; Hydroxyproline; Immunohistochemistry; Incubation; Inflammation - metabolism; Inflammation - pathology; Interleukin; Interleukin 10; Interleukin 6; Interleukins; Kupffer cells; Kupffer Cells - drug effects; Kupffer Cells - metabolism; Laboratory animals; Lipopolysaccharides; Liver; Liver - drug effects; Liver - pathology; Liver cirrhosis; Liver Cirrhosis - blood; Liver Cirrhosis - drug therapy; Liver Cirrhosis - metabolism; Liver diseases; Male; Medicine; Mitogens; Muscle proteins; Muscles; N-Nitrosodimethylamine; Nitric oxide; Oral administration; Organ Size - drug effects; Pharmacology; Plant Extracts - administration & dosage; Plant Extracts - pharmacology; Prothrombin; Rats; Rodents; Smooth muscle; Spleen - drug effects; Stellate cells; Thrombin; Toxins; Tumor necrosis factor-TNF; Taiwan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0053988

Graptopetalum paraguayense (GP) is a folk herbal medicine with hepatoprotective effects that is used in Taiwan. The aim of this study was to evaluate the hepatoprotective and antifibrotic effects of GP on experimental hepatic fibrosis in both dimethylnitrosamine (DMN)- and carbon tetrachloride (CCl(4))-induced liver injury rats. Hepatic fibrosis-induced rats were fed with the methanolic extract of GP (MGP) by oral administration every day. Immunohistochemistry, biochemical assays, and Western blot analysis were performed. The effects of MGP on the expression of fibrotic markers and cytokines in the primary cultured hepatic stellate cells (HSCs) and Kupffer cells, respectively, were evaluated. Oral administration of MGP significantly alleviated DMN- or CCl(4)-induced liver inflammation and fibrosis. High levels of alanine transaminase, aspartate transaminase, bilirubin, prothrombin activity and mortality rates also decreased in rats treated with MGP. There were significantly decreased hydroxyproline levels in therapeutic rats compared with those of the liver-damaged rats. Collagen I and alpha smooth muscle actin (α-SMA) expression were all reduced by incubation with MGP in primary cultured rat HSCs. Furthermore, MGP induced apoptotic cell death in activated HSCs. MGP also suppressed lipopolysaccharide-stimulated rat Kupffer cell activation by decreasing nitric oxide, tumor necrosis factor-α and interleukin-6 production, and increasing interleukin-10 expression. The results show that the administration of MGP attenuated toxin-induced hepatic damage and fibrosis in vivo and inhibited HSC and Kupffer cell activation in vitro, suggesting that MGP might be a promising complementary or alternative therapeutic agent for liver inflammation and fibrosis.