Geriatric Department, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 610072, P.R. China.
Department of Chinese Internal Medicine, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 610072, P.R. China.
Mol Med Rep. 2021 Apr;23(4). doi: 10.3892/mmr.2021.11918. Epub 2021 Feb 19.
Yuan‑zhi‑san (YZS) is a classic type of Traditional Chinese Medicine, which has been reported to aid in the treatment of Alzheimer's disease (AD). The present study aimed to investigate the effects of YZS on tau protein aggregation, a hallmark of AD pathology, and its possible mechanisms. The results demonstrated that YZS improved learning and memory abilities, and decreased the severity of AD pathology in β‑amyloid (Aβ)‑induced AD rats. Moreover, YZS administration inhibited the hyperphosphorylation of tau protein at Ser199 and Thr231 sites. Several vital enzymes in the ubiquitin‑proteasome system (UPS), including ubiquitin‑activating enzyme E1a/b, ubiquitin‑conjugating enzyme E2a, carboxyl terminus of Hsc70‑interacting protein, ubiquitin C‑236 terminal hydrolase L1 and 26S proteasome, were all significantly downregulated in AD rats, which indicated an impaired enzymatic cascade in the UPS. In addition, it was identified that YZS treatment partly increased the expression levels of these enzymes in the brains of AD rats. In conclusion, the present results suggested that YZS could effectively suppress the hyperphosphorylation of tau proteins, which may be partially associated with its beneficial role in restoring functionality of the UPS.
元智散（YZS）是一种经典的中药，据报道可辅助治疗阿尔茨海默病（AD）。本研究旨在探讨 YZS 对 AD 病理标志性蛋白tau 蛋白聚集的影响及其可能的机制。结果表明，YZS 可改善学习记忆能力，并降低β-淀粉样蛋白（Aβ）诱导的 AD 大鼠 AD 病理的严重程度。此外，YZS 给药可抑制 tau 蛋白 Ser199 和 Thr231 位点的过度磷酸化。泛素-蛋白酶体系统（UPS）中的几种重要酶，包括泛素激活酶 E1a/b、泛素结合酶 E2a、Hsc70 相互作用蛋白羧基末端、泛素 C-236 末端水解酶 L1 和 26S 蛋白酶体，在 AD 大鼠中均显著下调，表明 UPS 中的酶级联反应受损。此外，研究还发现 YZS 治疗可部分增加 AD 大鼠大脑中这些酶的表达水平。综上所述，本研究结果表明，YZS 可有效抑制 tau 蛋白的过度磷酸化，这可能与其恢复 UPS 功能的有益作用部分相关。
