Chlorogenic acid (CGA) is a type of polyphenol with anti-inflammatory, antioxidant activities. Our previous studies showed CGA could efficiently inhibit carbon tetrachloride (CCl 4 )-induced liver fibrosis in rats. However, the specific underlying mechanism remains unclear. The aim of this study is to investigate the effects of CGA on liver inflammation and fibrosis induced by CCl 4 and whether they are related to inhibition of toll-like receptor 4 (TLR4) signaling pathway. Male Sprague-Dawley (SD) rats were administrated CCl 4 together with or without CGA for 8 weeks. Histopathological and biochemical analyses were carried out. The mRNA and protein expression levels of proinflammatory and profibrotic mediators were detected by RT-PCR and Western blot, respectively. The levels of serum proinflammatory cytokines were detected by ELISA. CGA significantly attenuated CCl 4 -induced liver damage and symptoms of liver fibrosis, accompanied by reduced serum transaminase levels, collagen I and α-smooth muscle actin (α-SMA) expression. As compared with the CCl 4 -treated group, the expression levels of TLR4, myeloid differentiation factor 88 (MyD88), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were reduced in the treatment group of CCl 4 and CGA, whereas bone morphogenetic protein and activin membrane-bound inhibitor (Bambi) expression was increased. CGA also suppressed CCl 4 induced nuclear factor-κB (NF-κB) activation. Moreover, the hepatic mRNA expression and serum levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) were significantly increased in CCl 4 -treated rats and attenuated by co-treatment with CGA. Our data indicate that CGA can efficiently inhibit CCl 4 -induced liver fibrosis in rats and the protective effect may be due to the inhibition of TLR4/MyD88/NF-κB signaling pathway.
Financed by the National Centre for Research and Development under grant No. SP/I/1/77065/10 by the strategic scientific research and experimental development program:
SYNAT - “Interdisciplinary System for Interactive Scientific and Scientific-Technical Information”.