title: Artesunate alleviates hepatic fibrosis induced by multiple pathogenic factors and inflammation through the inhibition of LPS/TLR4/NF-κB signaling pathway in rats.
abstract: The current study was performed in order to explore the effect of artesunate (Art) on experimental hepatic fibrosis and the potential mechanism involved. Art, a water-soluble hemisuccinate derivative of artemisinin extracted from the Chinese herb Artemisia Annua, is a safe and effective antimalarial drug. Hepatic fibrosis was induced in SD rats by multiple pathogenic factors. Rats were treated concurrently with Art (28.8 mg/kg) given daily by oral gavage for 6 or 8 weeks to evaluate its protective effects. Our data demonstrated that Art treatment obviously attenuated hepatic fibrosis, characterized by less inflammatory infiltration and accumulation of extracellular matrix (ECM). Art remarkably decreased endotoxin, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) levels as well. Art significantly downregulated protein and mRNA expression of α-smooth muscle actin (α-SMA), toll-like receptors 4 (TLR4), myeloid differentiation factor 88 (MyD88) and transforming growth factor beta 1 (TGF-β1). Art also significantly inhibited the nuclear transcription factor kappa B p65 (NF-κB p65) translocation into the nucleus. In addition, there were no remarkable differences between the N group and the NA group. In conclusion, we found that Art could alleviate hepatic fibrosis induced by multiple pathogenic factors and inflammation through the inhibition of LPS/TLR4/NF-κB signaling pathway in rats, suggesting that Art may be a potential candidate for the therapy of hepatic fibrosis.
authors: Department of Pharmacology, Changzhi Medical College, Changzhi 046000, China.
authors: Lina
authors: L
authors: Lai
authors: Department of Microbiology and Immunology, Changzhi Medical College, Changzhi 046000, China.
authors: Yunxia
authors: Y
authors: Chen
authors: Department of Pathophysiology, Changzhi Medical College, Changzhi 046000, China.
authors: Xiaoxia
authors: X
authors: Tian
authors: Department of Physiology, Changzhi Medical College, Changzhi 046000, China.
authors: Xujiong
authors: X
authors: Li
authors: Department of Pharmacology, Changzhi Medical College, Changzhi 046000, China.
authors: Xiaojing
authors: X
authors: Zhang
authors: Department of Pharmacology, Changzhi Medical College, Changzhi 046000, China.
authors: Jingwen
authors: J
authors: Lei
authors: Undergraduate of Clinical Medicine Department, Changzhi Medical College, Changzhi 046000, China.
authors: Yanghui
authors: Y
authors: Bi
authors: Department of Pharmacology, Tianjin Medical University, TianJin 300070, China.
authors: Buwu
authors: B
authors: Fang
authors: Department of Pharmacology, Changzhi Medical College, Changzhi 046000, China. Electronic address: sxl33469399@126.com.
authors: Xiaoliang
authors: X
authors: Song
mesh_terms: D000818:Animals; D037621:Artemisinins / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000077332:Artesunate; D001835:Body Weight / Q000187:drug effects; D002251:Carbon Tetrachloride / Q000008:administration & dosage; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D004731:Endotoxins / Q000097:blood*; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000276:immunology; D009929:Organ Size / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors* / Q000276:immunology
chemical_list: D037621:Artemisinins; D004365:Drugs, Chinese Herbal; D004731:Endotoxins; D016328:NF-kappa B; D051197:Toll-Like Receptor 4; D000077332:Artesunate; D002251:Carbon Tetrachloride
keywords: Artesunate; Endotoxin; Hepatic fibrosis; Inflammation; Toll-like receptors