Huangqi Gegen decoction ameliorates alcohol-induced cognitive dysfunction via attenuating oxidative stress and enhancing blood-brain barrier integrity in rats through the Keap۱-Nrf۲/HO-۱ signaling pathway

Objective(s): Chronic alcohol abuse causes cognitive deficits. Huangqi Gegen Decoction (HGD), a traditional Chinese herbal formula comprising Huangqi and Gegen, has been documented for its therapeutic efficacy in the treatment of alcoholic liver injury. However, its potential neuroprotective effects against alcohol-induced brain injury remain unexplored. This study aims to evaluate the neuroprotection of HGD on alcohol-induced cognitive dysfunction and the associated mechanism.Materials and Methods: Wistar rats were orally administered ۵۰% ethanol for ۱۰ weeks, followed by treatment with HGD at doses of ۱۶, ۳۲, or ۶۴ mg/kg/day for an additional ۶ weeks. The spatial learning and memory abilities of rats were assessed through the Morris Water Maze experiment. The pathological condition in the hippocampus was assessed using H&E and Nissl staining. Tight junction proteins, oxidative stress, and inflammation cytokines were measured by IF, ELISA, PCR, and western blot. The mRNA and protein expression of Keap۱, Nrf-۲, HO-۱, and NQO-۱ were tested by PCR and western blot.Results: Results showed that HGD effectively mitigated cognitive dysfunction and pathological changes in alcohol-induced rats while enhancing the expression of ZO-۱, Occludin, and Claudin-۵. Furthermore, HGD effectively mitigated oxidative stress by reducing levels of ROS and MDA, while elevating levels of SOD, CAT, and GSH-PX in brain tissue. Moreover, HGD significantly suppressed microglial activation and down-regulated expressions of IL-۱β, IL-۶, and TNF-α. Mechanistically, HGD remarkably up-regulated the expression of Nrf-۲, HO-۱, and NQO-۱ while down-regulating Keap۱ expression.Conclusion: These findings suggest that HGD may be a promising therapeutic agent for alleviating alcohol-induced cognitive dysfunction.

Keywords:

Alcohols , Blood-brain barrier , Cognitive dysfunction HuangQi , Oxidative stress , Pueraria