Liver fibrosis is a wound healing response that occurs in the setting of chronic liver injury and is caused by imbalance in the synthesis and degradation of extracellular matrix （ECM）. If left untreated， it can progress to liver cirrhosis and hepatocellular carcinoma. The activation of hepatic stellate cell （HSC） is now well established as a central driver of liver fibrosis. The activated HSC will transform into myofibroblasts that produce ECM protein. Transforming growth factor-β₁ （TGF-β₁） can induce the activation of hepatic stellate cell （HSC）， and TGF-β₁/Smads signaling pathway is one of the important pathways to promote liver fibrosis. Non-coding RNA （ncRNA） does not encode proteins during the transcription but plays an important regulatory role in the post-transcriptional process of genes. Accumulating evidence shows that the occurrence of liver fibrosis is closely related to the abnormal expression of ncRNA which participates in the activation of HSC by regulating TGF-β₁ signal transduction and then affects the process of liver fibrosis. MiRNA-mediated TGF-β₁/Smads signaling pathway can not only promote liver fibrosis but also play a role in anti-fibrosis. Long non-coding RNA （lncRNA） not only promotes the development of liver fibrosis by binding to target genes but also enhances TGF-β₁ signal transduction by acting as competitive endogenous RNA. circular RNA （circRNA） acts as a ''sponge'' to regulate TGF-β₁/Smads pathway， thereby inhibiting HSC activation and exerting the anti-liver fibrosis effect. Chinese medicinal plays an essential part in the prevention and treatment of liver fibrosis， and the active components can inhibit TGF-β₁/Smads pathway by regulating the expression of miRNA， thus alleviating liver fibrosis. This article reviews the role and mechanism of miRNA-， lncRNA- and circRNA-mediated TGF-β₁/Smads signaling pathway in liver fibrosis and summarizes the anti-liver fibrosis effect of active components of Chinese medicinals by regulating miRNA-mediated TGF-β₁/Smads signaling pathway， which can serve as a reference for clinical treatment of liver fibrosis and the development of new drugs.

OBJECTIVE To investigate the effects of Isodon ternifolius extract on Toll -like receptor 4（TLR4）/nuclear factor - κB（NF-κB）/NOD-like receptor protein 3（NLRP3）pathway in hepatic stellate cells and hepatocytes . METHODS Using primary hepatic stellate cells and primary hepatocytes of rats as subjects ，inflammatory injury model was induced by lipopolysaccharide （LPS，100 ng/mL）. Using colchicine （1 μmol/L）as positive control and TLR 4 inhibitor（TAK-242，1 μmol/L）as reference ，the contents of transforming growth factor -β1（TGF-β1），α-smooth muscle actin （α-SMA），type Ⅰ collagen（COL-Ⅰ），COL-Ⅲ in the supernatant of hepatic stellate cells ，and the contents of alanine aminotransferase （ALT），aspartate aminotransferase （AST），interleukin-1β （IL-1β） and IL -18 in the supernatant of hepatocytes were detected after intervention with I. ternifolius extract（1 mg/mL）. The mRNA expressions of TLR 4，inhibitor α of NF -κB（IκBα），NF-κB p 65，NLRP3，Gasdermin D （GSDMD），apoptosis-associated speck -like protein containing CARD （ASC） and protein expressions of TLR 4， phosphorylated I κBα（p-IκBα），NF-κB p 65，NLRP3，GSDMD，ASC in the above cells were determined . RESULTS Compared with LPS model group ，the contents of TGF -β1，α-SMA， COL-Ⅰ and COL -Ⅲ in the supernatant of hepatic stellate cells and the contents of ALT ，AST，IL-1β and IL -18 in the supernatant of hepatocytes were significantly decreased ；the mRNA expressions of TLR 4，NF-κB p 65，NLRP3，GSDMD，ASC and the protein expressions of TLR 4，p-IκBα，NF-κB p 65，NLRP3，GSDMD，ASC in the two kinds of cells were significantly down - regulated，and the mRNA expression of I κBα was significantly up -regulated in all administration groups （P＜0.05）. Compared with TLR 4 inhibitor group ，the improvement of most of above indexes was more significant in the TLR 4 inhibitor+I. ternifolius extract group （P＜0.05）. CONCLUTIONS I. ternifolius extract could inhibit the activation of TLR 4/NF-κB/NLRP3 pathway， reduce the release of fibrosis factors and inflammatory factors ，alleviate the inflammatory injury of liver cells ，and inhibit the activation of hepatic stellate cells ，so as to protect liver cells and resist liver fibrosis .

Abstract OBJECTIVE To investigate the effect of isodon ternifolia-containing serum(ITS) on the activation of rat primary hepatic Kupffer cell(KC) induced by lipopolysaccharide(LPS) through TLR4/NF-κB/NLRP3 signal pathway. METHODS The primary KC of rats were isolated and cultured, and the primary KC induced by LPS were divided into blank control group, model control group, blank serum group, positive control group(colchicine containing serum group), ITS group, TLR4 blocker group and TLR4 blocker+ITS group. MTT assay was used to detect the effect of different concentrations of ITS on the proliferation activity of KC. The content of interleukin-1β(IL-1β), interleukin-18(IL-18), tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6) in KC supernatant were detected by ELISA. Fluorescence quantitative polymerase chain reaction(PCR), Western blotting and immunofluorescence were used to detect the expression of TLR4, nuclear factor κB inhibitor protein α(IκBα), cysteine protease-1(Caspase-1), NLRP3 mRNA and TLR4, IκBα, phosphorylated IκBα(p-IκBα), Caspase-1, NLRP3 and NF-κBp65 in KC. RESULTS Compared with the model control group, the contents of IL-1β, IL-18, TNF-α and IL-6 in the supernatant of KC and the expression of TLR4, IκB α, Caspase-1, NLRP3 mRNA and TLR4, IκBα, p-IκBα, Caspase-1, NLRP3, NF-κBp65 protein in the supernatant of KC in all drug groups were down-regulated or decreased(P<0.05 or P<0.01). Compared with TLR4 blocker group, the improvement of most of the above indexes in TLR4 blocker+ITS group was more obvious. CONCLUSION Isodon ternifolia may inhibit the activation of KC and reduce the expression and release of inflammatory factors by down-regulating TLR4/NF-κB/NLRP3 signal pathway, thus alleviating the inflammatory injury of liver.