title: The anti-fibrotic effect of betulinic acid is mediated through the inhibition of NF-κB nuclear protein translocation.
abstract: 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, 200mg/kg) twice weekly for 6weeks in Wistar rats. The administration of BA (20 or 50mg/kg) was started following TAA injections and was continued for 6 or 8weeks 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.
authors.affiliation: Key Laboratory for Natural Resource of Changbai Mountain & Functional Molecules, Ministry of Education, College of Pharmacy, Yanbian University, Yanji 133002, Jilin Province, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wan
authors.forename: Yan-Ling
authors.initials: YL
authors.lastname: Wu
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: Lian
authors.forename: Wen-Xue
authors.initials: WX
authors.lastname: Xie
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.forename: Bing-Qing
authors.initials: BQ
authors.lastname: Ouyang
authors.forename: Ting
authors.initials: T
authors.lastname: Bai
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.forename: Ning
authors.initials: N
authors.lastname: Yang
authors.forename: Ji-Xing
authors.initials: JX
authors.lastname: Nan
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006909:Hydroxyproline / Q000378:metabolism; D007150:Immunohistochemistry; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D008106:Liver Cirrhosis, Experimental / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D053978:Pentacyclic Triterpenes; D021381:Protein Transport / Q000187:drug effects; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013853:Thioacetamide; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D014315:Triterpenes / Q000494:pharmacology*; D000094062:Betulinic Acid
chemical_list: D000199:Actins; D006909:Hydroxyproline; D053509:Matrix Metalloproteinase 13; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D053978:Pentacyclic Triterpenes; D013853:Thioacetamide; D019715:Tissue Inhibitor of Metalloproteinase-1; D051197:Toll-Like Receptor 4; D014315:Triterpenes; D000094062:Betulinic Acid; C507781:Myd88 protein, rat; C495347:Tlr4 protein, rat; C498862:Acta2 protein, rat