Dose-Dependent Effects of <i>Astragalus membranaceus</i> Injection via Regulating Keap1-Nrf2-SOD Pathway in D-Galactose–Induced Aging Rats

Objective As a key brain region for regulating learning and memory, the hippocampus is closely related to cognitive impairment due to its functional decline. Therefore, it is of great significance to explore effective intervention measures to delay hippocampal aging. This study focused on the dose-dependent effects of Astragalus membranaceus (AM) injection at Zang-organ Shu acupoints on delaying hippocampal aging and its mechanism through the Keap1-Nrf2-SOD pathway. Materials and Methods The aging rat model was constructed using D-galactose (D-gal), and intervention with different doses of AM injection was performed. The dose–effect relationship and the effects on the key expression molecules of the Keap1-Nrf2-SOD signaling pathway were evaluated from multiple dimensions, including behavior, organ index, oxidative stress (OS) level, expression of hippocampal aging markers, and pathological changes in brain tissue. Results Treatment of AM injection at five Zang-organ Shu acupoints improved the brain index, reduced pathological damage, inhibited the expression of hippocampal aging markers p53 and p16, decreased OS levels, and enhanced motor and cognitive functions in the aging rat model. In terms of overall efficacy, the M-AM + D-gal group (2 ml/kg) had the best effect on enhancing the activity of ARE target genes. Conclusion AM injection at five Zang-organ Shu acupoints delays hippocampal aging effectively, possibly exerting its protective effects partially through modulation of the Keap1-Nrf2-SOD pathway, with the medium dose showing the best effect.