Liu Xingduo, Sun Chaoqun, Dai Yuqiong, Duan Feifei, He Tianzhen, Zhen Menglu, Liang Enxi, Zhang Shuting, Xia Yun, Hu Nianchun, Zhan Ruoting, Deng Dong, Liu Sijun
School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China.
Shenzhen Luohu Traditional Chinese Medicine Hospital, Shenzhen, China.
Front Microbiol. 2025 Jul 31;16:1620784. doi: 10.3389/fmicb.2025.1620784. eCollection 2025.
Alzheimer's disease (AD), a neurodegenerative disorders linked to gut microbiota dysbiosis, may benefit from Traditional Chinese Medicine (TCM) interventions.
Danggui Shaoyao San (DSS), a classic traditional Chinese Medicine (TCM) formula. This study investigated whether Danggui Shaoyao San and its disassembled prescriptions could improve cognitive deficits in APP/PS1 mice by modulating the structure of the gut microbiota, thereby providing a theoretical basis for AD treatment and the further development and application of Danggui Shaoyao San.
Forty APP/PS1 and eight C57BL/6 mice were divided into six groups: DSS (6.4 g/kg/d), QDW (4.6 g/kg/d), DW (1.8 g/kg/d), GV971 (positive control, 40 mg/kg/d), model (saline), and control (saline). After 60 days of treatment, the mice underwent behavioral testing in the open field, novel object recognition, and water maze. Gut microbiota composition, diversity, and function were then analyzed by 16S rRNA sequencing.
The results of Behavioral experiment indicate that Danggui Shaoyao San and its disassembled prescriptions can ameliorate spatial memory deficits (Morris water maze), enhance recognition memory (novel object recognition), and reduce anxiety-like behaviors (open field test), with the DSS group demonstrating the most pronounced effects. In addition, through 16S sequencing analysis we predicted DSS and its disassembled prescriptions reduced harmful bacteria (Firmicutes, Akkermansia) while increasing beneficial bacteria (Bacteroidetes, Bifidobacterium, Lactobacillus). DSS restored microbial diversity closest to healthy controls, evidenced by elevated Chao1/Shannon indices and reduced Simpson index. Beta diversity revealed structural divergence between treatment and model groups. Functional predictions highlighted enriched pathways (D-glutamine metabolism, bile acid biosynthesis) and suppressed antibiotic biosynthesis.
Danggui Shaoyao San and its disassembled prescriptions ameliorate AD-related cognitive impairment and gut dysbiosis, enhance microbial diversity, and modulate metabolic pathways, supporting their therapeutic potential via gut-brain axis regulation. This study elucidates the multi-target mechanisms of DSS in AD treatment, advancing TCM rationalization for neurodegenerative disorders.
阿尔茨海默病（AD）是一种与肠道微生物群失调有关的神经退行性疾病，可能受益于中医干预。
当归芍药散（DSS）是一种经典的中药方剂。本研究调查了当归芍药散及其拆方是否能通过调节肠道微生物群结构改善APP/PS1小鼠的认知缺陷，从而为AD治疗以及当归芍药散的进一步开发和应用提供理论依据。
将40只APP/PS1小鼠和8只C57BL/6小鼠分为六组：DSS组（6.4 g/kg/d）、QDW组（4.6 g/kg/d）、DW组（1.8 g/kg/d）、GV971组（阳性对照，40 mg/kg/d）、模型组（生理盐水）和对照组（生理盐水）。治疗60天后，对小鼠进行旷场、新物体识别和水迷宫行为测试。然后通过16S rRNA测序分析肠道微生物群的组成、多样性和功能。
行为实验结果表明，当归芍药散及其拆方可以改善空间记忆缺陷（莫里斯水迷宫），增强识别记忆（新物体识别），并减少焦虑样行为（旷场试验），其中DSS组效果最为显著。此外，通过16S测序分析，我们预测DSS及其拆方减少了有害细菌（厚壁菌门、阿克曼氏菌），同时增加了有益细菌（拟杆菌门、双歧杆菌属、乳酸杆菌属）。DSS恢复的微生物多样性最接近健康对照组，Chao1/香农指数升高和辛普森指数降低证明了这一点。β多样性揭示了治疗组和模型组之间的结构差异。功能预测突出了富集的途径（D-谷氨酰胺代谢、胆汁酸生物合成）和受抑制的抗生素生物合成。
当归芍药散及其拆方改善了与AD相关认知障碍和肠道菌群失调，增强了微生物多样性，并调节了代谢途径，支持其通过肠-脑轴调节的治疗潜力。本研究阐明了DSS在AD治疗中的多靶点机制，推动了中医对神经退行性疾病的合理化应用。
