Phytomedicine : international journal of phytotherapy and phytopharmacology · 2026
Jieduquyuziyin prescription ameliorates systemic lupus erythematosus by targeting MAPK14 to inhibit SAA3-induced macrophage M1 polarization.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Lu Xinhui, Huang Yan, Liu Manchao, Xu Li, Chen Xi, Wei Yinghui, Zhou Yihan, Jin Hang, Lu Fengyu, Tang Yujun, Wen Chengping
Аннотация
BACKGROUND: Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease involving inflammatory macrophage polarization and hepatic acute-phase responses. Serum amyloid A3 (SAA3) is elevated in lupus-prone mice and may participate in the immune link between liver inflammation and macrophage responses. Jieduquyuziyin Prescription (JP) 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.
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.