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

Abstract

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.

• Authors: Shao-Peng Lin, Lidong Zhu, Hongjian Shi, Shan Ye, Qi Li, Xiaofang Yin, Qiangda Xie, Qizhong Xu, Jue-Xian Wei, Fen Mei, Yongcheng Zhu, Pei-Yi Lin, Xiao-Hui Chen
• Journal: Phytomedicine : international journal of phytotherapy and phytopharmacology (Phytomedicine) Vol. 121 Pg. 155119 (Dec 2023) ISSN: 1618-095X [Electronic] Germany
• PMID: 37801894 (Publication Type: Journal Article)
• Copyright: Copyright © 2023. Published by Elsevier GmbH.

Chemical References

• puerarin
• Tumor Necrosis Factor-alpha
• Interleukin-6
• Lipopolysaccharides
• Anti-Inflammatory Agents

Topics

• Mice
• Animals
• Sepsis-Associated Encephalopathy (drug therapy, metabolism)
• Tumor Necrosis Factor-alpha (metabolism)
• Interleukin-6 (metabolism)
• Microglia
• Lipopolysaccharides (pharmacology)
• Anti-Inflammatory Agents (pharmacology, metabolism)