Puerarin prevents sepsis-associated encephalopathy by regulating the AKT1 pathway in microglia.

BACKGROUND: Previous studies have reported that puerarin possesses cardioprotective, vasodilatory, anti-inflammatory, anti-apoptotic, and hypoglycemic properties. However, the impact of puerarin on sepsis-associated encephalopathy (SAE) remains unexplored. In this study, we explored whether puerarin can modulate microglia-mediated neuroinflammation for the treatment of SAE and delved into the underlying mechanisms. METHODS: We established a murine model of SAE through intraperitoneal injection of lipopolysaccharide (LPS). The puerarin treatment group received pretreatment with puerarin. For in vitro experiments, BV2 cells were pre-incubated with puerarin for 2 h before LPS exposure. We employed network pharmacology, the Morris Water Maze (MWM) test, Novel Object Recognition (NOR) test, immunofluorescence staining, enzyme-linked immunosorbent assay (ELISA), Western blotting, and quantitative real-time PCR (qRT-PCR) to elucidate the molecular mechanism of underlying puerarin's effects in SAE treatment. RESULTS: Our findings demonstrate that puerarin significantly reduced the production of inflammatory cytokines (TNF-α and IL-6) in the peripheral blood of LPS-treated mice. Moreover, puerarin treatment markedly ameliorated sepsis-associated cognitive impairment. Puerarin also exhibited inhibitory effects on the release of TNF-α and IL-6 from microglia, thereby preventing hippocampal neuronal cell death. Network pharmacology analysis identified AKT1 as a potential therapeutic target for puerarin in SAE treatment. Subsequently, we validated these results in both in vitro and in vitro experiments. Our study conclusively demonstrated that puerarin reduced LPS-induced phosphorylation of AKT1, with the AKT activator SC79 reversing puerarin's anti-inflammatory effects through the activation of the AKT1 signaling pathway. CONCLUSION: Puerarin exerts an anti-neuroinflammatory effect against SAE by modulating the AKT1 pathway in microglia.

Xuanbai Chengqi decoction plus Western Medicine in treatment of severe pneumonia with symptom pattern of phlegm-heat obstructing lung: a Meta-analysis.

OBJECTIVE: To evaluate the effectiveness and safety of Xuanbai Chengqi decoction (, XBCQD) plus Western Medicine (WM) in treatment of severe pneumonia with symptom pattern of phlegm-heat obstructing lung. METHODS: Randomized controlled trials (RCTs) investigating the effect of XBCQD on severe pneumonia with symptom pattern of phlegm-heat obstructing lung, were included in this study. Seven electronic databases were searched up to March 2019. Meta-analysis was conducted by Review Manager 5.3 software. Risk ratio (RR) and mean difference (MD) with 95% confidence interval (CI) were used as effect estimation. RESULTS: Eleven RCTs were included, involving 992 participants. Meta-analysis showed that XBCQD combined with WM achieved better effectiveness than WM alone in terms of total effective rate [RR = 1.23, 95%CI (1.16, 1.30)], clinical pulmonary infection score [CPIS, MD = -2.02, 95%CI (-2.42, -1.63)], acute physiology and chronic health evaluation Ⅱ [APACHEⅡ, MD = -6.81, 95% CI (-8.26, 5.37)], mechanical ventilation time [MD = -101.41, 95%CI (-140.47, -62.34)], and lactic acid content in arterial blood [MD = -2.41, 95%CI (-2.64, -2.18)]. CONCLUSION: XBCQD combined with WM had better benefit than WM alone to the patients of severe pneumonia with the symptom pattern of phlegm-heat obstructing lung. However, due to low quality of the included studies, more rigorously designed studies were required to further evaluate the effectiveness and safety of XBCQD in the treatment of severe pneumonia with symptom pattern of phlegm-heat obstructing lung.