title: The protective effects of Acanthus ilicifolius alkaloid A and its derivatives on pro- and anti-inflammatory cytokines in rats with hepatic fibrosis.
abstract: This study was designed to investigate the protective effects of Acanthus ilicifolius alkaloid A [4-hydroxy-2-benzoxazolone (HBOA)] and its acetylated derivatives including 4-acetoxy-2-benzoxazolone (TC-2) and 3-acetyl-4-acetoxy-2-benzoxazolone (TC-3) on carbon tetrachloride (CCl4 )-induced liver fibrosis in rats. Sprague-Dawley rats were given CCl4 twice per week for 8 weeks to induce liver fibrosis. Then, they were treated with HBOA, TC-2, and TC-3 daily for 4 weeks, respectively. The serum indicators including total protein (TP), albumin (Alb), globulin, hyaluronic acid (HA), and laminin (LN) were measured by commercial kits. The messenger ribonucleic acid expression of adiponectin, peroxisome proliferator-activated receptor-γ (PPAR-γ), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), transforming growth factor-β1 (TGF-β1 ) and Toll-like receptor 4 (TLR4 ) was determined by reverse-transcriptase -PCR. The proteins of adiponectin, TGF-β1 , α-smooth muscle actin (α-SMA), and TLR4 were also detected by the immunohistochemical assay. The results showed that HBOA, TC-2, and TC-3 significantly attenuated the fibrotic degree induced by CCl4 as evidenced by higher levels of TP, Alb, adiponectin, and PPAR-γ, which in turn decreased the proliferation of hepatic stellate cells. Moreover, those drugs markedly decreased the levels of HA, LN, TNF-α, IL-6, TGF-β1 , α-SMA, and TLR4 . Our study indicates that HBOA, TC-2, and TC-3 have beneficial effects against liver fibrosis, and the mechanisms may be related to the inhibition of inflammatory response.
authors.affiliation: Department of Pharmacology, Guangxi Medical University, Nanning, People's Republic of China.
authors.forename: Kyi Kyi
authors.initials: KK
authors.lastname: Wai
authors.affiliation: Department of Pharmacology, Guangxi Medical University, Nanning, People's Republic of China.
authors.forename: Yinge
authors.initials: Y
authors.lastname: Liang
authors.affiliation: Department of Pharmacology, Guangxi Medical University, Nanning, People's Republic of China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Pharmacology, Guangxi Medical University, Nanning, People's Republic of China.
authors.forename: Liping
authors.initials: L
authors.lastname: Cai
authors.affiliation: Department of Pharmacology, Guangxi Medical University, Nanning, People's Republic of China.
authors.forename: Chunhong
authors.initials: C
authors.lastname: Liang
authors.affiliation: Department of Pharmacology, Guangxi Medical University, Nanning, People's Republic of China.
authors.forename: Lin
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, Guangxi Medical University, Nanning, People's Republic of China.
authors.forename: Xing
authors.initials: X
authors.lastname: Lin
authors.affiliation: Department of Inorganic Chemistry and Physical Chemistry, Guangxi Medical University, Nanning, People's Republic of China.
authors.forename: Huahui
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Pharmacology, Guangxi Medical University, Nanning, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Lin
mesh_terms: D027901:Acanthaceae / Q000737:chemistry*; D000470:Alkaloids / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D002252:Carbon Tetrachloride Poisoning / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D016207:Cytokines / Q000378:metabolism*; D055166:Hepatic Stellate Cells / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D008297:Male; D051381:Rats
chemical_list: D000470:Alkaloids; D016207:Cytokines
keywords: 4-hydroxy-2-benzoxazolone; CCl4; anti-inflammatory cytokines; hepatic fibrosis; proinflammatory cytokines