Scoparone alleviates hepatic fibrosis by inhibiting the TLR‐4/NF‐κB pathway

Abstract

The aim of this study was to investigate the role of scoparone (SCO) in hepatic fibrosis. For this, we conducted in vivo and in vitro experiments. In vivo rats that were divided into six groups, control, carbon tetrachloride, and colchicine, as well as SCO groups, SCO50, SCO100, and SCO200 treated with 50, 100, and 200 mg/kg SCO doses, respectively. Furthermore, SCO was shown to inhibit Toll‐like receptor‐4 (TLR‐4)/nuclear factor kappa‐B (NF‐κB; TLR‐4/NF‐κB) signals by inhibiting TLR‐4, which in turn downregulates the expression of MyD88, promotes NF‐κB inhibitor‐α, NF‐κB inhibitor‐β, and NF‐κB inhibitor‐ε activation, while inhibiting NF‐κB inhibitor‐ζ. Subsequently, the decrease of phosphorylation of nuclear factor‐κB levels leads to the downregulation of the downstream inflammatory factors' tumor necrosis factor‐alpha (TNF‐α), interleukin‐6 (IL‐6), and IL‐1 beta, thus weakening hepatic fibrosis. Notably, the SCO200 treated group presented the most significant improvement. Hence, we conclude that SCO alleviates hepatic fibrosis by inhibiting TLR‐4/NF‐κB signals.

Lidocaine attenuates CFA‑induced inflammatory pain in rats by regulating the MAPK/ERK/NF‑κB signaling pathway

“…Inactivated NF-κB is located in the cytoplasm, but when cells are stimulated by cytokines, NF-κB then translocates into the nucleus to activate gene transcription ( 40 ). Studies have previously shown that NF-κB can promote the expression of inflammatory factors IL-1, TNF-α and IL-6 during hepatic fibrosis ( 41 , 42 ). In the present study, western blotting results showed that injection of CFA increased ERK1/2 and p65 protein phosphorylation but lidocaine treatment reversed this.…”

Effects of scoparone on non-alcoholic fatty liver disease revealed by RNA sequencing

“…Other studies suggested that SCO also mitigate hepatic steatosis and fibrosis in NAFLD mice induced by choline deficiency diet (7), which means SCO maybe improve NAFLD by regulating lipid metabolism. Furthermore, our preliminary study also confirmed that SCO could downregulate the expressions of alanine aminotransferase (ALT), aspartate aminotransferase (AST), g-glutamyl transferase (g-GT) in serum, effectively improving liver damage (8). Up till now, although some drugs (such as vitamin E, statins and metformin) have been tried to treat NAFLD, the efficacy is limited (9)(10)(11).…”

“…The HFD + SCO 60 group, HFD + SCO 120 group and HFD + Silymarin group were administered intragastrically with SCO (60 mg/kg, 120 mg/kg) and Silymarin (150 mg/kg) for 4 weeks (Figure 1), respectively. The dose of SCO was according to other studies and our previous studies with some adjustments (7,8). At the end of the 12th week, all mice were fasted overnight.…”

Lipidomics Revealed Alteration of the Sphingolipid Metabolism in the Liver of Nonalcoholic Steatohepatitis Mice Treated with Scoparone

“…Scoparone, a biologically active ingredient obtained from the Chinese medicinal Artemisia capillaris Thunb, has a wide range of pharmacological effects, such as hypolipidemic and anti-inflammatory properties . In a methionine–choline deficient (MCD) diet-induced NASH mice model, scoparone caused a significant improvement in liver inflammation, steatosis, and fibrosis. , Amelioration of NASH symptoms could be achieved by scoparone through enhanced autophagy in macrophages . Scoparone functioned by inactivating the TGF-β/Smad signaling pathway, thereby significantly inhibiting hepatic stellate cells (HSCs) activation and proliferation to prevent hepatic fibrosis .…”

“…16 In a methionine−choline deficient (MCD) diet-induced NASH mice model, scoparone caused a significant improvement in liver inflammation, steatosis, and fibrosis. 17,18 Amelioration of NASH symptoms could be achieved by scoparone through enhanced autophagy in macrophages. 19 prevent hepatic fibrosis.…”