Tissue & cell · 2025
Modified Xuan-Bi-Qing-Ying decoction alleviates septic liver injury by regulating autophagy and apoptosis via HIF-1α signaling pathway.
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Yan Jing, Pan Yifeng, Liu Zhu, Chen Yulin, Hu Kai, Liu Yuanyuan, Wang Guangyao, Li Liqun, Xie Sheng
Аннотация
BACKGROUND: Xuan-Bi-Qing-Ying Decoction (XBQYD), a Traditional Chinese Medicine (TCM) formula modified based on clinical experience, has demonstrated efficacy and safety in the treatment of septic liver injury (SLI).
METHODS: The absorbed components of XBQYD were characterized in vivo using LC-MS/MS. A rat model of septic liver injury (SLI) was then established by cecal ligation and puncture. To evaluate the preventive efficacy of XBQYD, rats were pretreated with the formula for seven days prior to injury induction. Subsequently, we evaluated liver histopathology (HE staining), measured serum inflammatory cytokines (IL-1β, IL-6, TNF-α), oxidative stress markers (MDA, SOD) with commercial kits, and assessed liver function via biochemical analysis. To investigate the mechanism, network pharmacology was combined with Mendelian randomization (MR) analysis, which identified HIF1A as a core predicted target. Based on this prediction, the influence of XBQYD pretreatment on the HIF‑1α pathway was measured in liver tissue at both mRNA and protein levels, along with its downstream effects on autophagy and apoptosis. Finally, molecular docking and dynamics simulations were used to investigate potential direct interactions between key XBQYD constituents and HIF-1α.
RESULTS: A total of 22 bioactive components derived from XBQYD were identified in vivo. In SLI rats, pretreatment with XBQYD significantly mitigated liver histological damage, decreased pro-inflammatory cytokine levels and oxidative stress, and restored liver function. Network pharmacology revealed 233 intersecting targets of XBQYD and SLI. KEGG and PPI analyses highlighted the HIF-1 signaling pathway and 50 core targets, including HIF1A. MR analysis confirmed that HIF1A may increase the risk of sepsis and sepsis-related 28-day mortality. This preventive effect was associated with the inhibition of the HIF-1α pathway activation by XBQYD pretreatment, which correlated with enhanced autophagy and suppressed apoptosis. Molecular docking and dynamics simulations demonstrated stable interactions between key XBQYD constituents (Quercetin, Delphinidin, and Azaleatin) and HIF-1α.
CONCLUSION: Our study demonstrates that pretreatment with XBQYD exerts a preventive effect against SLI in rats by inhibiting the HIF-1α signaling pathway. These findings provide a mechanistic basis for considering XBQYD as a potential preventive strategy for SLI.
METHODS: The absorbed components of XBQYD were characterized in vivo using LC-MS/MS. A rat model of septic liver injury (SLI) was then established by cecal ligation and puncture. To evaluate the preventive efficacy of XBQYD, rats were pretreated with the formula for seven days prior to injury induction. Subsequently, we evaluated liver histopathology (HE staining), measured serum inflammatory cytokines (IL-1β, IL-6, TNF-α), oxidative stress markers (MDA, SOD) with commercial kits, and assessed liver function via biochemical analysis. To investigate the mechanism, network pharmacology was combined with Mendelian randomization (MR) analysis, which identified HIF1A as a core predicted target. Based on this prediction, the influence of XBQYD pretreatment on the HIF‑1α pathway was measured in liver tissue at both mRNA and protein levels, along with its downstream effects on autophagy and apoptosis. Finally, molecular docking and dynamics simulations were used to investigate potential direct interactions between key XBQYD constituents and HIF-1α.
RESULTS: A total of 22 bioactive components derived from XBQYD were identified in vivo. In SLI rats, pretreatment with XBQYD significantly mitigated liver histological damage, decreased pro-inflammatory cytokine levels and oxidative stress, and restored liver function. Network pharmacology revealed 233 intersecting targets of XBQYD and SLI. KEGG and PPI analyses highlighted the HIF-1 signaling pathway and 50 core targets, including HIF1A. MR analysis confirmed that HIF1A may increase the risk of sepsis and sepsis-related 28-day mortality. This preventive effect was associated with the inhibition of the HIF-1α pathway activation by XBQYD pretreatment, which correlated with enhanced autophagy and suppressed apoptosis. Molecular docking and dynamics simulations demonstrated stable interactions between key XBQYD constituents (Quercetin, Delphinidin, and Azaleatin) and HIF-1α.
CONCLUSION: Our study demonstrates that pretreatment with XBQYD exerts a preventive effect against SLI in rats by inhibiting the HIF-1α signaling pathway. These findings provide a mechanistic basis for considering XBQYD as a potential preventive strategy for SLI.