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作者

Xinhui Lu Yan Huang Manchao Liu Li Xu Xi Chen Yinghui Wei Yihan Zhou Hang Jin Fengyu Lu Yujun Tang Chengping Wen

作者单位

⁶School of Public Health, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, 250117, China ¹Key Laboratory of Chinese Medicine Rheumatology of Zhejiang Province, College of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou, 310053, China ⁴Jinhua Academy, Zhejiang Chinese Medical University, Jinhua, China ²These authors contributed equally to this study. ⁵Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, 310022, China ³Department of Anesthesiology, Zhejiang Cancer Hospital, Laboratory of Anesthesia and Perioperative Medicine, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, 310022, China ⁷Innovative Research Center for Basic Medicine on Autoimmune Diseases of Ministry of Education, Hangzhou, China

刊名

Phytomedicine

年份

2026

卷号

Vol.160

页码

158659

ISSN

0944-7113

关键词

Systemic lupus erythematosus Jieduquyuziyin prescription Mapk14 Serum amyloid a3 Macrophage polarization

摘要

Background Systemic lupus erythematosus is a heterogeneous autoimmune disease involving inflammatory macrophage polarization and hepatic acute-phase responses. Serum amyloid A3 is elevated in lupus-prone mice and may participate in the immune link between liver inflammation and macrophage responses. Jieduquyuziyin Prescription is a traditional formula used clinically for SLE, but its chemical basis and SAA3-related immunomodulatory mechanisms remain incompletely defined. Purpose This study in...更多

Background Systemic lupus erythematosus is a heterogeneous autoimmune disease involving inflammatory macrophage polarization and hepatic acute-phase responses. Serum amyloid A3 is elevated in lupus-prone mice and may participate in the immune link between liver inflammation and macrophage responses. Jieduquyuziyin Prescription is a traditional formula used clinically for SLE, but its chemical basis and SAA3-related immunomodulatory mechanisms remain incompletely defined. Purpose This study investigated the effects of JP on SLE-related inflammatory phenotypes, hepatocyte SAA3 expression, and macrophage MAPK14/p38-related M1 polarization responses, and examined the interaction between representative JP constituents and MAPK14. Methods MRL/Lpr mice were used to evaluate the in vivo effects of JP. LC-MS and HPLC were used for chemical characterization. Network pharmacology, primary splenic macrophages, primary hepatocytes, and macrophage-naive CD4⁺ T cell co-culture systems were used to characterize JP-associated immune responses. Western blotting, flow cytometry, ELISA, and immunofluorescence were performed to assess p38 phosphorylation, macrophage polarization, cytokines, and SAA3. Molecular docking, SPR, molecular dynamics simulations, and ADP-Glo™ kinase assay were used to evaluate MAPK14 binding and kinase activity modulation by representative constituents. Results JP treatment improved survival and renal-related indices in MRL/Lpr mice, accompanied by lower serum SAA3 levels, reduced splenic F4/80⁺ CD86⁺ macrophages, and decreased F4/80/iNOS signals. JP-medicated serum reduced SAA3-induced p38 phosphorylation, iNOS expression, and IL-6 and IL-1β release, while increasing Arg-1 expression and F4/80⁺ CD206⁺ cells. JP-medicated serum also reduced IL-6-induced SAA3 expression in hepatocytes. In co-culture, systems containing SAA3-treated macrophages showed increased CD4⁺ IL-17A⁺ cells and IL-17 levels, whereas JP treatment reduced these readouts. Hesperidin, glycyrrhizic acid, and paeoniflorin were detected in JP decoction and JP-medicated serum and generated measurable binding responses to MAPK14. The three-compound mixture and individual constituents reduced recombinant MAPK14 kinase activity, with stronger activity observed for the mixture. Conclusion JP treatment was associated with reduced hepatocyte SAA3 expression, attenuated macrophage MAPK14/p38-related M1 inflammatory responses, and decreased Th17-associated inflammatory indices. MAPK14 may serve as a mechanistically relevant molecular node engaged by representative JP constituents, providing experimental support for JP-mediated regulation of SLE-related inflammatory networks.收起

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