棕榈碱是黄柏的一种异喹啉类生物碱。通过NLRP3炎性体抑制焦亡，改善痛风炎症。

IF 4.8 2区医学 Q1 CHEMISTRY, MEDICINAL

Journal of ethnopharmacology Pub Date : 2025-01-31 DOI:10.1016/j.jep.2024.119231

Yin-Jing Jiang , Yong-Hong Cheng , Hao-Qing Zhu , Yan-Ling Wu , Ji-Xing Nan , Li-Hua Lian

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引用次数: 0

摘要

民族药理学相关性：棕榈碱（Pal），来源于马菖蒲和黄柏。是一种天然异喹啉类生物碱，广泛应用于清热燥湿、泻火祛病、解毒疗疮。研究目的：痛风是一种常见的代谢性炎症性疾病，由MSU晶体（MSU）沉积在关节和非关节结构中引起。鉴于临床抗痛风药物的多重毒副作用，有必要找到一种安全有效的替代品。我们研究了Pal对MSU晶体诱导的急性痛风炎症的治疗作用，靶向NLRP3炎症小体介导的焦亡。材料和方法：在体外，用LPS加MSU刺激小鼠腹膜巨噬细胞（MPM）和大鼠关节软骨细胞，在存在或不存在Palmatine的情况下。在体内，关节炎模型包括在小鼠爪部注射MSU晶体的急性痛风性关节炎模型和在小鼠背部皮下组织注射MSU晶体的气囊急性痛风模型。采用Western blot、ELISA试剂盒、免疫组织化学和免疫荧光检测NLRP3炎症小体活化和NETosis形成的表达。此外，还评价了巴马汀对msu诱导的关节炎小鼠的抗软骨损伤作用。结果：Pal以剂量依赖性降低NLRP3炎性小体激活相关蛋白NLRP3、ASC、caspase-1、IL-1β、HMGB1和Cathepsin b的水平，Pal显著降低caspase-11、histone3、PR3和PAD4的NETosis蛋白水平，Pal有效阻断NLRP3炎性小体的激活，减弱caspase-11介导的非典型NLRP3炎性小体的激活，干预NETs的形成，从而抑制焦亡。在体内，Pal通过抑制NLRP3、ASC、caspase-1、IL-1β、HMGB1和Cathepsin B蛋白的凋亡，降低NETosis相关蛋白caspase-11、histone3、PR3和PAD4的水平，上调MMP-3蛋白的表达，减轻msu诱导的痛风性关节炎炎症，保护关节软骨。结论：巴马汀通过NLRP3炎性体抑制焦亡，改善痛风性炎症。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Palmatine, an isoquinoline alkaloid from Phellodendron amurense Rupr., ameliorated gouty inflammation by inhibiting pyroptosis via NLRP3 inflammasome

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Palmatine, an isoquinoline alkaloid from Phellodendron amurense Rupr., ameliorated gouty inflammation by inhibiting pyroptosis via NLRP3 inflammasome

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.

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来源期刊

Journal of ethnopharmacology 医学-全科医学与补充医学

CiteScore

10.30

自引率

5.60%

发文量

967

审稿时长

77 days

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.