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Phillygenin inhibits LPS-induced activation and inflammation of LX2 cells by TLR4/MyD88/NF-kappa B signaling pathway

作者 Hu, Naihua; Wang, Cheng; Dai, Xuyang; Zhou, Mengting; Gong, Lihong; Yu, Lingyuan; Peng, Cheng; Li, Yunxia

期刊 JOURNAL OF ETHNOPHARMACOLOGY , FEB 10 2020,:248

DOI 10.1016/j.jep.2019.112361 PubMed 31683033

摘要 Ethnopharmacological relevance:: The traditional Chinese medicine Forsythiae Fructus is the dried fruit of Forsythia suspensa (Thunb.) Vahl. It is commonly used to clear heat and detoxify, reduce swelling and disperse knot, and evacuate wind and heat.Aim of the study:: Inflammation is involved in liver fibrosis. Phillygenin (PHI) is a kind of lignans extracted and separated from Forsythiae Fructus, which has been reported to have a good anti-inflammatory effect. Therefore, we aimed to explore whether PHI has a therapeutic effect on liver fibrosis caused by inflammation.Materials and methods:: Firstly, the induction of the LX2 cells inflammatory model and fibrosis model by LPS with different concentrations were studied. Then, high, medium and low doses PHI was given for intervention therapy. The secretion of IL-6, IL-1 beta and TNF-alpha inflammatory factors were detected by ELISA kit, and the expression of collagen I and alpha-SMA was detected by Western blot and RT-qPCR. The possible mechanism of PHI on TLR4/MyD88/NF-kappa B signal pathway was studied by computer-aided drug design software and the results were further verified by Western blot and RT-qPCR experiments.Results:: The results showed that LPS could promote the expression of IL-6, IL-1 beta and TNF-alpha and the expression of collagen I and alpha-SMA, indicating that LPS could induce inflammation and fibrosis in LX2 cells. PHI could inhibit LX2 cell activation and fibrotic cytokine expression by inhibiting LPS-induced pro-inflammatory reaction. Molecular docking results showed that PHI could successfully dock with TLR4, MyD88, IKK beta, p65, I kappa B alpha, and TAK1 proteins. Subsequently, Western blot and qPCR results further proved that PHI could inhibit the proteins expression in TLR4/MyD88/NF-kappa B signal pathway which were consistent with the molecular docking results.Conclusion: PHI can inhibit LPS-induced pro-inflammatory reaction and LX2 cell activation through TLR4/MyD88/NF-kappa B signaling pathway, thereby inhibiting liver fibrosis.

涉及物种 连翘 Forsythia suspensa