Authors
Song-Fan Wang, Ying-Yi Jiang, Xing-Yuan Li, Xiao-Hui Li, Jian-Ru Wang
Published in
Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica. Volume 51. Issue 13. Pages 3809-3817.
Abstract
To investigate whether the anti-atherosclerotic(AS) effect of Huanglian Jiedu Decoction(HLJDD) is associated with activation of extracellular signal-regulated kinase 5(ERK5) and the consequent improvement of microtubule-associated protein 1 light chain 3(LC3)-associated phagocytosis(LAP) dysfunction in macrophages. RAW264.7 cells were randomly divided into the normal control group, oxidized low-density lipoprotein(ox-LDL) group, HLJDD group, simvastatin(simva) group, and RAW264.7-ERK5 gene knockout(ERK5-KO) group. According to the experimental protocol, cells in each group were treated for 24 h with normal control rat serum, ox-LDL, HLJDD-containing serum, or simva-containing serum. Apoptotic Jurkat cells were added to each group and co-cultured for 90 min. After removal of the supernatant, LC3-Ⅱ labeling was performed to observe LAPosomes in macrophages, and the clearance of apoptotic Jurkat cells was assessed. The expression levels of phosphorylated(p)-ERK5, ERK5, LAP-related signaling molecules [T-cell immunoglobulin and mucin-domain-containing molecule-4(TIM-4), vacuolar protein sorting 34(VPS34), Beclin-1, RUN domain Beclin-1-interacting and cysteine-rich domain-containing protein(Rubicon), autophagy-related protein 5(ATG5), and autophagy-related protein 7(ATG7)], pro-inflammatory cytokines [interleukin-1β(IL-1β), interleukin-6(IL-6)], and anti-inflammatory cytokines [interleukin-10(IL-10), transforming growth factor-β(TGF-β)] were measured. RESULTS:: showed that, compared with the control group, the ox-LDL group exhibited decreased LAPosome percentage and reduced clearance of apoptotic cells, downregulated expression of p-ERK5, TIM-4, VPS34, Beclin-1, Rubicon, ATG5, and ATG7, increased IL-1β and IL-6 levels, and no significant changes in IL-10 or TGF-β expression. Compared with the ox-LDL group, the HLJDD and simva groups showed increased LAPosome percentage and enhanced apoptotic cell clearance, upregulated expression of p-ERK5, TIM-4, VPS34, Beclin-1, Rubicon, ATG5, and ATG7, decreased IL-1β and IL-6 levels, and increased IL-10 and TGF-β expression. Compared with the HLJDD group, the ERK5-KO group exhibited significantly reduced expression of ERK5 and p-ERK5, and all other indicators were reversed. In conclusion, HLJDD may ameliorate macrophage LAP dysfunction and exert anti-AS effects by activating ERK5.
PMID:
42543371
Bibliographic data and abstract were imported from PubMed on 03 Aug 2026.
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