Artesunate alleviates hepatic fibrosis induced by multiple pathogenic factors and inflammation through the inhibition of LPS/TLR4/NF-kappa B signaling pathway in rats

作者：Lai, Lina; Chen, Yunxia; Tian, Xiaoxia; Li, Xujiong; Zhang, Xiaojing; Lei, Jingwen; Bi, Yanghui; Fang, Buwu; Song, Xiaoliang^*

来源：European Journal of Pharmacology, 2015, 765: 234-241.

DOI：10.1016/j.ejphar.2015.08.040

• Artesunate
• Hepatic fibrosis
• Inflammation
• Endotoxin
• Toll-like receptors

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-alpha (TNF-alpha), and interleukin-6 (IL-6) levels as well. Art significantly downregulated protein and mRNA expression of a-smooth muscle actin (alpha-SMA), toll-like receptors 4 (TLR4), myeloid differentiation factor 88 (MyD88) and transforming growth factor beta 1 (TGF-beta 1). Art also significantly inhibited the nuclear transcription factor kappa B p65 (NF-kappa B 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-kappa B signaling pathway in rats, suggesting that Art may be a potential candidate for the therapy of hepatic fibrosis.

• 出版日期2015-10-15
• 单位天津医科大学; 长治医学院