Department of Pharmacy, 302 Hospital of People's Liberation Army, Beijing, People's Republic of China Chengde Medical University Chengde, Hebei, People's Republic of China Department of Health Statistics, Taishan Medical University, Taian, Shandong, People's Republic of China Animal Laboratory Center, 302 Hospital of People's Liberation Army, Beijing, People's Republic of China China Military Institute of Chinese Medicine, 302 Hospital of People's Liberation Army, Beijing, People's Republic of China
刊名
Journal of Ethnopharmacology
年份
2018
卷号
Vol.210
页码
232-241
ISSN
0378-8741
摘要
Ethnopharmacological relevance Liuweiwuling tablets contain a six-herb Chinese formula and are commonly prescribed to facilitate nourishment of the liver and kidneys, clear away toxic materials and activate blood circulation. Administration of LWWL is well known for its protective effects on the liver and its capacity to confer long-term stability in patients exhibiting reduced transaminase levels. Clinical studies have reported that LWWL can also be used for the treatment of liver fibrosis wit...更多
Ethnopharmacological relevance Liuweiwuling tablets contain a six-herb Chinese formula and are commonly prescribed to facilitate nourishment of the liver and kidneys, clear away toxic materials and activate blood circulation. Administration of LWWL is well known for its protective effects on the liver and its capacity to confer long-term stability in patients exhibiting reduced transaminase levels. Clinical studies have reported that LWWL can also be used for the treatment of liver fibrosis with associated treatment regimens resulting in a concomitant reduction in transforming growth factor β1 levels in the serum of patients with hepatic fibrosis. TGF-β1 plays a prominent role in stimulating liver fibrogenesis and this effect is mediated by myofibroblasts derived from hepatic stellate cells . It is likely that this phenomenon underpins the antifibrotic effects associated with LWWL. Aim The purpose of this study was to investigate the antifibrotic effects and mechanisms pertaining to LWWL. Methods Hepatic fibrosis was induced in rats following bile duct ligation . Rats that underwent BDL received daily gavage administration of colchicine , LWWL or PBS . Pathological changes in hepatic tissue were examined using hematoxylin and eosin and sirius red staining. Immunohistochemical analysis was performed to monitor α-SMA and type I collagen protein expression. Real-time quantitative reverse transcription polymerase chain reaction and Western blot analyses were used to monitor the expression of genes and proteins in the TGF-β/Smad signaling pathway, including TGF-β1, bone morphogenic protein and activin membrane-bound inhibitor , Smad3, phosphorylated Smad3 and Smad7. We also monitored the expression of genes and proteins in the nuclear factor-κB signaling pathway, including NF-κB p65, IκBα and phosphorylation of IκBα , tumor necrosis factor-alpha , interleukin 6 and interleukin 1β . Results LWWL dose-dependently inhibited BDL-induced liver injury and hepatic fibrosis in rats. Furthermore, LWWL reduced liver tissue collagen deposition, hydroxyproline content, liver dysfunction and α-SMA expression in BDL-induced hepatic fibrosis rats. Moreover, LWWL markedly prevented activation of the TGF-β/Smad signaling pathway by inhibiting expression of Smad2/3 and phosphorylation of Smad3, and upregulating the expression of Bambi and Smad7. In addition, LWWL regulated the expression of the inflammatory cytokines IL-1β, TNF-α and IL-6 by inhibiting the activation of NF-κB p65 and the phosphorylation of IκBα, and increasing the expression of IκBα. Conclusions LWWL can attenuate BDL-induced hepatic fibrosis in rats, and this effect may be due to modulation of the NF-κB-dependent inflammatory response and activation of HSC and TGF-β/Smad-mediated synthesis and degradation of Collagen I.收起
