U-Shaped Dose-Dependent Modulation of Macrophages by Ginkgolide B Mitigates Systemic Inflammation in Septic Rats

银杏内酯B对巨噬细胞的U型剂量依赖性调节可减轻脓毒症大鼠的全身炎症反应

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Abstract

OBJECTIVES: This study delineates the U-Shaped Dose-Dependent Modulation of Ginkgolide B (GB) on macrophage function, highlighting its capacity to enhance bacterial phagocytosis and attenuate systemic inflammation in sepsis. METHODS: RAW264.7 cells were co-cultured with GB, and flow cytometry was used to assess macrophage phagocytosis and polarization. Rats were divided into five groups: Healthy, cecal ligation and puncture (CLP), and three GB treatment groups. Survival was monitored over 7 days, and arterial blood was analyzed to assess acidosis. Histological examination was performed to evaluate organ damage, while ELISA measured inflammatory factors in blood and peritoneal lavage fluid (PLF). Finally, bacterial colony counts in the PLF were analyzed to assess peritoneal macrophage bacterial clearance capacity. RESULTS: GB co-culture enhanced macrophage bacterial phagocytosis. GB treatment alleviated acidosis and improved survival in septic rats. It also reduced pro-inflammatory cytokines TNF-α and IL-6 while increasing anti-inflammatory IL-10 levels. GB injection decreased bacterial load in the PLF, indicating enhanced macrophage bacterial clearance. CONCLUSION: GB enhances macrophage phagocytic activity, improves bacterial clearance, increases the survival rate of septic rats, and reduces systemic inflammation.

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