Tian Jin, Huo Ran, Wang Yixuan, Wang Jiepeng, Fang Fang, Fang Chaoyi
Hebei University of Chinese Medicine, Shijiazhuang, Hebei 050200, China.
Hebei Key Laboratory of Integrated Chinese and Western Medicine for Lung Disease Research, Shijiazhuang, Hebei 050091, China.
Biol Pharm Bull. 2025;48(5):523-536. doi: 10.1248/bpb.b24-00524.
Astragalus polysaccharide (APS) is a biologically active water-soluble polysaccharide extracted from stems or roots, which has been proven to have antiaging effects. The aim of this study was to investigate the effects of APS on cognitive function in d-galactose (d-gal)-induced aging rats and explore the potential underlying molecular mechanisms. The rats were induced to age by intraperitoneal injection with 400 mg/kg/d d-gal for 8 weeks. Aging of rats was assessed through the Morris water maze test, step-down test, open field test, and grip strength test. Pathological changes in the hippocampal CA3 and CA1 regions were determined by Hematoxylin and eosin and Nissl staining. The superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), and total antioxidant capacity (T-AOC) in the serum were measured. Telomere length, dual oxidase 1 (Duox1), dual oxidase 2 (Duox2), peroxiredoxin 1 (Prdx1), p21, p16, p53, telomerase reverse transcriptase (TERT), phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), nicotinamide phosphoribosyl transferase (NAMPT), and sirtuin 1 (SIRT1) were detected via real-time PCR, Western blotting, and immunohistochemical staining. The results indicated that APS ameliorated the general status in d-gal-induced aging rats, mitigated neuronal degeneration in the CA3 and CA1 regions, reduced the oxidative stress levels, modulated senescence-related β-GAL and protein expression, and maintained telomere length. Furthermore, APS significantly reduced p53 expression and increased p-PI3K, p-AKT, NAMPT, SIRT1, and TERT expression. Therefore, d-gal-induced aging and cognitive impairment in rats can be prevented by APS, likely through regulation of the TERT/p53 signaling axis via the PI3K/Akt and NAMPT/SIRT1 signaling pathways.
黄芪多糖（APS）是一种从茎或根中提取的具有生物活性的水溶性多糖，已被证明具有抗衰老作用。本研究旨在探讨APS对d-半乳糖（d-gal）诱导的衰老大鼠认知功能的影响，并探索其潜在的分子机制。通过腹腔注射400mg/kg/d的d-gal，连续8周诱导大鼠衰老。通过莫里斯水迷宫试验、跳台试验、旷场试验和握力试验评估大鼠的衰老情况。采用苏木精-伊红染色和尼氏染色法观察海马CA3和CA1区的病理变化。检测血清中超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-Px）、丙二醛（MDA）和总抗氧化能力（T-AOC）。通过实时荧光定量PCR、蛋白质免疫印迹法和免疫组织化学染色检测端粒长度、双氧化酶1（Duox1）、双氧化酶2（Duox2）、过氧化物酶1（Prdx1）、p21、p16、p53、端粒酶逆转录酶（TERT）、磷脂酰肌醇3激酶（PI3K）、蛋白激酶B（AKT）、烟酰胺磷酸核糖转移酶（NAMPT）和沉默信息调节因子1（SIRT1）。结果表明，APS改善了d-gal诱导的衰老大鼠的一般状态，减轻了CA3和CA1区的神经元变性，降低了氧化应激水平，调节了衰老相关的β-半乳糖苷酶和蛋白质表达，并维持了端粒长度。此外，APS显著降低p53表达，增加p-PI3K、p-AKT、NAMPT、SIRT1和TERT表达。因此，APS可能通过PI3K/Akt和NAMPT/SIRT1信号通路调节TERT/p53信号轴，从而预防d-gal诱导的大鼠衰老和认知障碍。
