Phytomedicine : international journal of phytotherapy and phytopharmacology · 2025
10-hydroxydec-2-enoic acid alleviates post-myocardial infarction inflammation and oxidative stress by modulating the TLR4 signaling axis.
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Zhao Ruyi, Xie Yuting, Xu Kangmin, Liu Yue, Chen Ruping, Zhao Shengnan, Zhou Zengxian, Xie Zhuohui, Jiang Yuxiao, Lin Fenfen, Zhu Jinwei, Chen Gaozhi
Аннотация
BACKGROUND: 10-Hydroxydec-2-enoic acid (10-HDA) is a royal jelly-specific fatty acid endowed with strong anti-inflammatory and antioxidant potential. However, its protective role in myocardial infarction (MI)-induced cardiac injury remains unclear.
PURPOSE: The present study sought to clarify whether 10-HDA mitigates MI-induced cardiac injury via regulation of the TLR4/MyD88/NF-κB pathway-a key innate immune inflammatory mediator.
METHODS: For in vivo and in vitro assessment of 10-HDA's cardioprotection, we utilized a murine MI model and hypoxic neonatal rat cardiomyocytes (NRCMs). Cardiac function, histology, inflammatory cytokines, and oxidative stress markers were evaluated. To examine TLR4/MyD88/NF-κB pathway modulation, Western blotting, immunofluorescence, and co-immunoprecipitation were employed. TLR4 dependence of 10-HDA was verified using the specific inhibitor TAK242. Furthermore, the regulatory effect of 10-HDA on macrophage-mediated myocardial inflammatory injury was evaluated a conditioned medium experiment.
RESULTS: 10-HDA improved cardiac function in MI mice in a dose-dependent manner, accompanied by significant reductions in cardiomyocyte hypertrophy, cardiac fibrosis, inflammatory cell infiltration, and oxidative stress. Similar protective effects were observed in hypoxia-treated NRCMs. At the mechanistic level, 10-HDA suppressed MI- or hypoxia-induced TLR4 and MyD88 upregulation, decreased IκBα phosphorylation and degradation, prevented NF-κB nuclear translocation, and downregulated pro-inflammatory cytokine expression. Co-immunoprecipitation assay confirmed reduced TLR4-MyD88 interaction. Moreover, results from TAK242 intervention demonstrated that 10-HDA mediates its cardioprotective effects primarily via inhibition of the TLR4/MyD88/NF-κB pathway.
CONCLUSIONS: 10-HDA protects against MI-induced cardiac injury by inhibiting TLR4/MyD88/ NF-κB pathway to reduce myocardial inflammation and oxidative stress.
PURPOSE: The present study sought to clarify whether 10-HDA mitigates MI-induced cardiac injury via regulation of the TLR4/MyD88/NF-κB pathway-a key innate immune inflammatory mediator.
METHODS: For in vivo and in vitro assessment of 10-HDA's cardioprotection, we utilized a murine MI model and hypoxic neonatal rat cardiomyocytes (NRCMs). Cardiac function, histology, inflammatory cytokines, and oxidative stress markers were evaluated. To examine TLR4/MyD88/NF-κB pathway modulation, Western blotting, immunofluorescence, and co-immunoprecipitation were employed. TLR4 dependence of 10-HDA was verified using the specific inhibitor TAK242. Furthermore, the regulatory effect of 10-HDA on macrophage-mediated myocardial inflammatory injury was evaluated a conditioned medium experiment.
RESULTS: 10-HDA improved cardiac function in MI mice in a dose-dependent manner, accompanied by significant reductions in cardiomyocyte hypertrophy, cardiac fibrosis, inflammatory cell infiltration, and oxidative stress. Similar protective effects were observed in hypoxia-treated NRCMs. At the mechanistic level, 10-HDA suppressed MI- or hypoxia-induced TLR4 and MyD88 upregulation, decreased IκBα phosphorylation and degradation, prevented NF-κB nuclear translocation, and downregulated pro-inflammatory cytokine expression. Co-immunoprecipitation assay confirmed reduced TLR4-MyD88 interaction. Moreover, results from TAK242 intervention demonstrated that 10-HDA mediates its cardioprotective effects primarily via inhibition of the TLR4/MyD88/NF-κB pathway.
CONCLUSIONS: 10-HDA protects against MI-induced cardiac injury by inhibiting TLR4/MyD88/ NF-κB pathway to reduce myocardial inflammation and oxidative stress.