The anti-hepatic fibrosis effects of chlorogenic acid extracted from Artemisia Capillaris Herba on CCl4-induced mice via regulating TGF-β1/smad3 pathway

Abstract

IntroductionArtemisia Capillaris Herba, a famous traditional Chinese medicine, is effective for the treatment of hepatic fibrosis(HF) in clinical applications. Research has confirmed that chlorogenic acid (CA), an organic acid compound was extracted from Artemisia Capillaris Herba, could reduce the hepatocyte injury induced by HF, however, its mechanism of anti-HF is still unclear, and we investigated whether CA could help treating HF mice. MethodsIn this study, we evaluated the therapeutic effect of CA on HF mice induced by CCl4, which was extracted from Artemisia Capillaris Herba and identified by 1H NMR and 13C NMR spectroscopy. Seventy two NIH mice were divided into following groups: normal group, model group, low, medium and high dose of CA groups (7.5, 15, 30 mg/kg) and colchicine (Colc)-positive control group (0.2 mg/kg). All mice were injected 40% CCl4 for 8 weeks with a 24 h interval except normal mice. Each drug group and Colc group were given intragastric administration for 40 days while modeling. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), collage IV (Col-IV), hyaluronic acid (HA), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), procollagen typeⅢ (PC-Ⅲ), malondialdehyde (MDA) and laminin (LN) levels were detected by ELISA, samd3 and TGF-β1 were examined by immunohistochemistry and western blotting and the liver and kidney tissues were observed by HE. ResultsAt the end of administrations, the body weight of mice was decreased and the levels of ALT, AST, Col-IV, HA, IL-6, TNF-α, LN, PC-III, and MDA were increased in the HF modle mice compared with that of normal mice. Compared with the HF mice only, treatment with CA significantly decreased the levels of ALT, AST, Col-IV, HA, IL-6, TNF-α, LN, PC-III, and MDA. The HE staining results showed that the hepatic and nephritic injury were significantly alleviated after CA treatment. And the smad3 and TGF-β1 expression were inhibited in the CA-treated mice in comparison with the model mice. ConclusionConclusively, CA treatment could attenuate HF through the regulation of TGF-β1/smad3 pathway, suggesting that CA may be an effective component of Artemisia Capillaris Herba in the treatment of HF.