Ephedra Sinica Extract Ameliorates Cognitive Function in Rats with Alzheimer's Disease by Modulating Neuroinflammation through NLRP3

Background: Ephedra sinica extract (ESE) exhibits anti-inflammatory, antioxidant, and neuroprotective effects. Previous studies have reported the efficacy of ESE against Alzheimer's disease (AD). Nevertheless, its mechanism is still a mystery. This research aimed to explore the effect of ESE on AD from the perspective of neuroinflammation and oxidative damage.Methods: An AD rat model was built by injecting 10 mu g of amyloid-beta peptide (A beta(1-42)) into the bilateral hippocampus CA1 region. Subsequently, the AD rats received intragastric administration of 100, 200, or 300 mg/kg of ESE for 4 weeks. The effects of ESE on the cognitive performance of AD rats were studied through passive avoidance and Morris water maze tests. The concentrations of inflammatory factors (Interleukin-1 beta (IL-1 beta), IL-6, and tumor necrosis factor-alpha (TNF-alpha)) and oxidative factors [glutathione (GSH), malondialdehyde (MDA) and nitric oxide (NO)] in rat hippocampal tissue were measured with corresponding biochemical kits, and NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome-associated protein expression levels in rat hippocampal tissue were measured by Western blot.Results: The behavioral tests confirmed that ESE ameliorated the cognitive dysfunction of AD rats (p < 0.05 and p < 0.01). ESE treatment significantly lowered the concentration of all inflammatory factors (IL-1 beta, IL-6, and TNF-alpha) and oxidative factors (MDA and NO) (p < 0.05 and p < 0.01), whereas it increased the levels of GSH in the hippocampus of the AD rats (p < 0.05). Additionally, inhibition of NLRP3 inflammasome-associated protein expression was observed after ESE administration (p < 0.05 and p < 0.01).Conclusion: ESE ameliorates AD rats' cognitive dysfunction by reducing neuroinflammation and oxidative stress.