کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2580853 | 1130161 | 2012 | 9 صفحه PDF | دانلود رایگان |
The purpose of the study was to investigate the anti-fibrotic effect and the potential mechanisms of action of betulinic acid (BA) against hepatic fibrosis in vivo and in vitro. BA is an active compound isolated from the bark of the birch tree Betula spp. (Betulaceae). Liver fibrosis was induced by intraperitoneal injections of thioacetamide (TAA, 200 mg/kg) twice weekly for 6 weeks in Wistar rats. The administration of BA (20 or 50 mg/kg) was started following TAA injections and was continued for 6 or 8 weeks to evaluate both the preventive and the protective effects. BA demonstrated great efficacy in preventing and curing hepatic fibrosis via attenuating the TAA-mediated increases in liver tissue hydroxyproline and α-smooth muscle actin (α-SMA). In vitro, BA effectively decreased the HSC-T6 cell viability induced by TNF-α and showed low toxicity in normal human chang liver cells. Moreover, BA significantly attenuated the expression of α-SMA and tissue inhibitor of metalloproteinase-1 (TIMP-1) and increased the levels of matrix metalloprotease (MMP)-13. BA also inhibited the expression of Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88) and the activation of nuclear factor-κB (NF-κB) in a time-dependent manner. This study provides evidence that BA exerts a significant anti-fibrosis effect by modulating the TLR4/MyD88/NF-κB signaling pathway.
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► We investigate the anti-fibrosis mechanism of betulinic acid in vivo and in vitro.
► Betulinic acid decreased activated HSC-T6 cell viability and induced HSC apoptosis.
► Betulinic acid suppressed the expression of TLR4/MyD88 and the activation of NF-κB.
Journal: Chemico-Biological Interactions - Volume 195, Issue 3, 5 February 2012, Pages 215–223