【摘 要】
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OBJECTIVE Thymoquinone (TQ) is the major active compound derived from the medicinal Nigella sativa.It has been shown to exert anti-neoplastic and anti-inflammatory effects.In the present study, we inv
【机 构】
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Key Laboratory for Natural Resource of Changbai Mountain & Functional Molecules, Ministry of Educati
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OBJECTIVE Thymoquinone (TQ) is the major active compound derived from the medicinal Nigella sativa.It has been shown to exert anti-neoplastic and anti-inflammatory effects.In the present study, we investigated the anti-fibrosis effects and mechniasm of TQ in lipopolysaccharide (LPS)-stimulated hepatic stellate cells (HSCs).METHODS HSCs were treated with or without TQ (3.125, 6.25, 12.5, 25 μmol· L-1), with or without pre-treatment of lipoopolysaccharide (LPS) (1 μg· ml-1).The viability of the cells was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenylte-trazolium bromide (MTT) assay.The effect of TQ on the expression of CD14, toll-like receptor 4 (TLR4), the smooth muscle α-actin (α-SMA), Collagen-Ⅰ , TGF-beta activated kinase 1 (TAK 1) phosphorylation was analysed by Western blotting analysis.The effect of TQ on LPS-induced activation and nuclear translocation of NF-kB was examined by Western blotting analysis.RESULTS Our data demonstrated that Thymoquinone showed no cytotoxity on HSCs.We found that TQ activation caspase and PARP cleavage and induced the apoptotic of HSCs.TQ blocked α-SMA, collagen-Ⅰ , CD14, TLR4 expression in a concentration-dependent manner.TQ significantly inhibited TAK 1 phosphorylation and the expression of NF-κB p65 in a time-dependent manner.The results also show that TQ blocked CD14 and TLR4 expression 24 h after LPS stimulation.Furthermore, TQ significantly inhibited TAK 1 phosphorylation 30 min after LPS stimulation.TQ inhibited the activation of NF-κB p65 induced by LPS, associated with the abrogation of IκB-αdegradation, with decrease in nuclear p65 protein levels.Therefore, TQ inhibit LPS-induced TLR4 signaling by blocking NF-κB activation in HSCs.CONCLUSION Our data demonstrate that TQ suppressed LPS-induced TLR4 expression via inhibiting the activation of NF-κB and TAK1 phosphorylation in HSCs.TQ represent a potential clinically valuable agent for anti-fibrosis.
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