PMID- 37544346 OWN - NLM STAT- MEDLINE DCOM- 20230918 LR - 20230918 IS - 1872-7573 (Electronic) IS - 0378-8741 (Linking) VI - 318 IP - Pt B DP - 2024 Jan 10 TI - Fuzheng Huayu recipe alleviates liver fibrosis via inhibiting NLRP3 inflammasome activation in macrophages. PG - 117001 LID - S0378-8741(23)00869-3 [pii] LID - 10.1016/j.jep.2023.117001 [doi] AB - ETHNOPHARMACOLOGICAL RELEVANCE: Fuzheng Huayu recipe (FZHY) is a commonly used Traditional Chinese Medicine formula for treating liver fibrosis in clinical settings. Despite its widespread use, the specific curative effects and underlying pharmacological mechanisms of FZHY in treating liver fibrosis are not yet fully understood. AIM AND STUDY: This study aims to investigate the antifibrotic mechanism of FZHY treatment by exploring its effects on the activation of NOD-like receptor protein 3 (NLRP3) inflammasome in macrophages. MATERIALS AND METHODS: In order to investigate the impact of FZHY on the activation and priming of NLRP3 inflammasome in clinical trials and animal experiments using immunohistochemistry and Western blotting. Twenty-four C57BL/6 mice were used to induce liver fibrosis by feeding a diet that contained 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC). To study inflammasome function, Lipopolysaccharide (LPS)/adenine triphosphate (ATP) induced NLRP3 inflammasome activation was induced in bone marrow-derived macrophages (BMDMs) isolated from wild mice. The effects of macrophage NLRP3 inflammasome activation on the function of hepatic stellate cells (HSCs) were explored by treating primary HSCs with preconditioned media from BMDMs culture. RESULTS: FZHY treatment resulted in the downregulation of NLRP3 protein expression and inhibition of its priming and activation in both human fibrotic livers and DDC-induced liver fibrosis. Furthermore, FZHY was observed to block the activation of the NLRP3 inflammasome pathway, which can lead to excessive inflammatory cytokine release in supernatants and cell lysates in response to LPS and ATP. Lastly, treatment with FZHY was able to inhibit the activation of HSCs induced by supernatants from macrophages. CONCLUSIONS: FZHY has been shown to potentially prevent NLRP3 inflammasome activation in macrophages which can result in the suppression of HSCs activation. Ultimately, these effects may lead to the improvement of liver fibrosis. The ability of FZHY to act on this novel mechanism represents an important aspect of its therapeutic potential for liver fibrosis. CI - Copyright (c) 2023 Elsevier B.V. All rights reserved. FAU - Ping, Dabing AU - Ping D AD - Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. FAU - Qi, Jingshu AU - Qi J AD - Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. FAU - Li, Meng AU - Li M AD - Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. FAU - Sun, Xin AU - Sun X AD - Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. FAU - Peng, Yuan AU - Peng Y AD - Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. Electronic address: pengyuan1026@126.com. FAU - Liu, Chenghai AU - Liu C AD - Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai, 201203, China; Key Laboratory of Liver and Kidney Diseases, Ministry of Education, Shanghai, 201203, China. Electronic address: chenghailiu@hotmail.com. LA - eng PT - Journal Article DEP - 20230806 PL - Ireland TA - J Ethnopharmacol JT - Journal of ethnopharmacology JID - 7903310 RN - 0 (fuzheng huayu) RN - 0 (Inflammasomes) RN - 0 (NLR Family, Pyrin Domain-Containing 3 Protein) RN - 0 (NLR Proteins) RN - 0 (Lipopolysaccharides) RN - 8L70Q75FXE (Adenosine Triphosphate) SB - IM MH - Mice MH - Humans MH - Animals MH - *Inflammasomes MH - *NLR Family, Pyrin Domain-Containing 3 Protein MH - NLR Proteins MH - Lipopolysaccharides MH - Mice, Inbred C57BL MH - Liver Cirrhosis/chemically induced/drug therapy/metabolism MH - Adenosine Triphosphate OTO - NOTNLM OT - FZHY OT - Liver fibrosis OT - Macrophages OT - NLRP3 COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2023/08/07 00:42 MHDA- 2023/09/18 12:43 CRDT- 2023/08/06 19:12 PHST- 2023/04/23 00:00 [received] PHST- 2023/07/26 00:00 [revised] PHST- 2023/08/02 00:00 [accepted] PHST- 2023/09/18 12:43 [medline] PHST- 2023/08/07 00:42 [pubmed] PHST- 2023/08/06 19:12 [entrez] AID - S0378-8741(23)00869-3 [pii] AID - 10.1016/j.jep.2023.117001 [doi] PST - ppublish SO - J Ethnopharmacol. 2024 Jan 10;318(Pt B):117001. doi: 10.1016/j.jep.2023.117001. Epub 2023 Aug 6.