{"title":"Palmatine, an isoquinoline alkaloid from Phellodendron amurense Rupr., ameliorated gouty inflammation by inhibiting pyroptosis via NLRP3 inflammasome.","authors":"Yin-Jing Jiang, Yong-Hong Cheng, Hao-Qing Zhu, Yan-Ling Wu, Ji-Xing Nan, Li-Hua Lian","doi":"10.1016/j.jep.2024.119231","DOIUrl":null,"url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>Palmatine (Pal), derived from Daemonorops margaritae (Hance) Becc and Phellodendron amurense Rupr. is a natural isoquinoline alkaloid widely used in clearing heat and drying dampness, purging the pathogenic fire and removing symptoms, detoxifying toxins and healing sores.</p><p><strong>Aim of the study: </strong>Gout is a common metabolic inflammatory disease caused by the deposition of MSU crystals (MSU) in joints and non-articulation structures. Given the multiple toxic side effects of clinical anti-gout medications, there is a need to find a safe and effective alternative. We investigated the therapeutic effects of Pal on MSU crystal-induced acute gouty inflammation, targeting the NLRP3 inflammasome mediated pyroptosis.</p><p><strong>Materials and methods: </strong>In vitro, mouse peritoneal macrophages (MPM) and rat articular chondrocytes were stimulated with LPS plus MSU in the presence or absence of Palmatine. In vivo, arthritis models include the acute gouty arthritis model by injecting MSU crystals in the paws of mice and the air pouch acute gout model by injecting MSU crystals into the mouse subcutaneous tissue of the back. Expression of NLRP3 inflammasome activation and NETosis formation was determined by Western blot, ELISA kit, immunohistochemistry, and immunofluorescence. In addition, the anti-cartilage damage of Palmatine on MSU-induced arthritis mice were also evaluated.</p><p><strong>Results: </strong>Pal dose-dependently decreased levels of NLRP3 inflammasome activation related proteins NLRP3, ASC, caspase-1, IL-1β, HMGB1 and Cathepsin B. The NETosis protein levels of caspase-11, histone3, PR3 and PAD4 were remarkably reduced by Pal. Pal effectively blocked the activation of NLRP3 inflammasome, attenuated the caspase-11 mediated noncanonical NLRP3 inflammasome activation and intervened the formation of NETs, thereby inhibiting the pyroptosis. In vivo, Pal attenuated MSU-induced inflammation in gouty arthritis and protect the articular cartilage through inhibiting the pyroptosis of proteins NLRP3, ASC, caspase-1, IL-1β, HMGB1 and Cathepsin B, reducing levels of NETosis relevant proteins caspase-11, histone3, PR3 and PAD4 and up-regulating expression of protein MMP-3.</p><p><strong>Conclusion: </strong>Palmatine ameliorated gouty inflammation by inhibiting pyroptosis via NLRP3 inflammasome.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"119231"},"PeriodicalIF":4.8000,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of ethnopharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.jep.2024.119231","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
引用次数: 0
Abstract
Ethnopharmacological relevance: Palmatine (Pal), derived from Daemonorops margaritae (Hance) Becc and Phellodendron amurense Rupr. is a natural isoquinoline alkaloid widely used in clearing heat and drying dampness, purging the pathogenic fire and removing symptoms, detoxifying toxins and healing sores.
Aim of the study: Gout is a common metabolic inflammatory disease caused by the deposition of MSU crystals (MSU) in joints and non-articulation structures. Given the multiple toxic side effects of clinical anti-gout medications, there is a need to find a safe and effective alternative. We investigated the therapeutic effects of Pal on MSU crystal-induced acute gouty inflammation, targeting the NLRP3 inflammasome mediated pyroptosis.
Materials and methods: In vitro, mouse peritoneal macrophages (MPM) and rat articular chondrocytes were stimulated with LPS plus MSU in the presence or absence of Palmatine. In vivo, arthritis models include the acute gouty arthritis model by injecting MSU crystals in the paws of mice and the air pouch acute gout model by injecting MSU crystals into the mouse subcutaneous tissue of the back. Expression of NLRP3 inflammasome activation and NETosis formation was determined by Western blot, ELISA kit, immunohistochemistry, and immunofluorescence. In addition, the anti-cartilage damage of Palmatine on MSU-induced arthritis mice were also evaluated.
Results: Pal dose-dependently decreased levels of NLRP3 inflammasome activation related proteins NLRP3, ASC, caspase-1, IL-1β, HMGB1 and Cathepsin B. The NETosis protein levels of caspase-11, histone3, PR3 and PAD4 were remarkably reduced by Pal. Pal effectively blocked the activation of NLRP3 inflammasome, attenuated the caspase-11 mediated noncanonical NLRP3 inflammasome activation and intervened the formation of NETs, thereby inhibiting the pyroptosis. In vivo, Pal attenuated MSU-induced inflammation in gouty arthritis and protect the articular cartilage through inhibiting the pyroptosis of proteins NLRP3, ASC, caspase-1, IL-1β, HMGB1 and Cathepsin B, reducing levels of NETosis relevant proteins caspase-11, histone3, PR3 and PAD4 and up-regulating expression of protein MMP-3.
Conclusion: Palmatine ameliorated gouty inflammation by inhibiting pyroptosis via NLRP3 inflammasome.
期刊介绍:
The Journal of Ethnopharmacology is dedicated to the exchange of information and understandings about people''s use of plants, fungi, animals, microorganisms and minerals and their biological and pharmacological effects based on the principles established through international conventions. Early people confronted with illness and disease, discovered a wealth of useful therapeutic agents in the plant and animal kingdoms. The empirical knowledge of these medicinal substances and their toxic potential was passed on by oral tradition and sometimes recorded in herbals and other texts on materia medica. Many valuable drugs of today (e.g., atropine, ephedrine, tubocurarine, digoxin, reserpine) came into use through the study of indigenous remedies. Chemists continue to use plant-derived drugs (e.g., morphine, taxol, physostigmine, quinidine, emetine) as prototypes in their attempts to develop more effective and less toxic medicinals.