Liang Junyi, Dong Xiaohong, Yang Jianshe, Hu Niyuan, Luo Xiaoting, Cong Shuyuan, Chen Jing, Zhao Weiming, Liu Bin
Heilongjiang University of Traditional Chinese Medicine, Harbin, Heilongjiang Province, China.
Heilongjiang Jiamusi Central Hospital, Jiamusi, Heilongjiang Province, China.
CNS Neurosci Ther. 2025 Jun;31(6):e70480. doi: 10.1111/cns.70480.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline and behavioral disturbances. Buyang Huanwu Decoction (BYHWD), a traditional Chinese herbal formulation, has demonstrated potential neuroprotective effects. This study aims to evaluate the therapeutic impact of BYHWD on cognitive impairments in 3×Tg mice and to investigate its underlying mechanism through modulation of the gut microbiota-C/EBPβ/AEP signaling pathway.
In two independent experiments, we assessed the effects of BYHWD and its derived fecal microbiota transplantation (FMT-BYHWD) on behavioral performance, neuropathological alterations, and signaling pathways in 3×Tg mice.
Treatment with BYHWD significantly improved cognitive function in 3×Tg mice and mitigated AD-like pathological changes. By suppressing the C/EBPβ/AEP signaling pathway, BYHWD reduced pathological Aβ plaque deposition, diminished tau hyperphosphorylation, and inhibited the release of pro-inflammatory cytokines. Further analysis revealed that BYHWD restored gut microbiota balance and suppressed the activation of the C/EBPβ/AEP pathway in the hippocampus. Moreover, transplanting FMT-BYHWD from BYHWD-treated mice to germ-free 3×Tg mice also ameliorated their cognitive deficits and AD-like pathology, suggesting that the anti-AD effects of BYHWD are mediated through the gut-brain axis by regulating the interplay between gut microbiota and the C/EBPβ/AEP signaling pathway.
This study uncovers the mechanism by which BYHWD improves cognitive deficits and neuropathological changes in 3×Tg mice via the gut-brain axis, mediated by the modulation of the gut microbiota-C/EBPβ/AEP signaling pathway, providing a novel therapeutic strategy for AD.
阿尔茨海默病（AD）是一种以认知衰退和行为障碍为特征的进行性神经退行性疾病。补阳还五汤（BYHWD），一种传统的中药配方，已显示出潜在的神经保护作用。本研究旨在评估补阳还五汤对3×Tg小鼠认知障碍的治疗效果，并通过调节肠道微生物群-C/EBPβ/AEP信号通路来探究其潜在机制。
在两项独立实验中，我们评估了补阳还五汤及其衍生的粪便微生物群移植（FMT-BYHWD）对3×Tg小鼠行为表现、神经病理学改变和信号通路的影响。
补阳还五汤治疗显著改善了3×Tg小鼠的认知功能，并减轻了类似AD的病理变化。通过抑制C/EBPβ/AEP信号通路，补阳还五汤减少了病理性Aβ斑块沉积，减少了tau蛋白过度磷酸化，并抑制了促炎细胞因子的释放。进一步分析表明，补阳还五汤恢复了肠道微生物群平衡，并抑制了海马体中C/EBPβ/AEP通路的激活。此外，将FMT-BYHWD从接受补阳还五汤治疗的小鼠移植到无菌3×Tg小鼠中也改善了它们的认知缺陷和类似AD的病理，这表明补阳还五汤的抗AD作用是通过调节肠道微生物群和C/EBPβ/AEP信号通路之间的相互作用，通过肠-脑轴介导的。
本研究揭示了补阳还五汤通过调节肠道微生物群-C/EBPβ/AEP信号通路，经肠-脑轴改善3×Tg小鼠认知缺陷和神经病理学变化的机制，为AD提供了一种新的治疗策略。
