Cheng Xiaorui, Huang Yan, Zhang Yongxiang, Zhou Wenxia
Beijing Institute of Pharmacology and Toxicology, Beijing, China; State Key Laboratory of Toxicology and Medical Countermeasures, Beijing, China.
Beijing Institute of Pharmacology and Toxicology, Beijing, China; State Key Laboratory of Toxicology and Medical Countermeasures, Beijing, China.
Adv Pharmacol. 2020;87:159-177. doi: 10.1016/bs.apha.2019.10.005. Epub 2020 Jan 3.
LW-AFC is a new formula derived from the Liuwei Dihuang decoction, a classical traditional Chinese medicine prescription. Based on our research, LW-AFC is a promising drug for Alzheimer's disease (AD). The studies were conducted primarily in two typical AD mouse models: SAMP8 and APP/PS1 mice. The results showed that LW-AFC could improve many cognitive behaviors, such as spatial learning and memory ability, passive and active avoidance response, and object recognition memory capability. In addition, LW-AFC could also alleviate the AD-like pathology in animal models, such as neuron loss and Aβ deposition. Subsequent studies found that LW-AFC could rebalance hypothalamic-pituitary-adrenal (HPA) axis and hypothalamic-pituitary-gonadal (HPG) axis, and modulate the disturbance of immune system and gut flora. These data suggested that the anti-AD effects of LW-AFC might be mainly via modulating the neuroendocrine immunomodulation (NIM) network. As inhibiting the immune function by immunosuppressant could abolish the protective effects of LW-AFC against long-term potentiation (LTP) impairment model, it is likely that LW-AFC balancing the NIM network is initiated by modulating the immune system.
六味地黄活性成分复方(LW-AFC)是一种源自经典中药方剂六味地黄丸的新配方。基于我们的研究,LW-AFC是一种有前景的治疗阿尔茨海默病(AD)的药物。这些研究主要在两种典型的AD小鼠模型中进行:SAMP8和APP/PS1小鼠。结果表明,LW-AFC可以改善多种认知行为,如空间学习和记忆能力、被动和主动回避反应以及物体识别记忆能力。此外,LW-AFC还可以减轻动物模型中的AD样病理变化,如神经元丢失和Aβ沉积。随后的研究发现,LW-AFC可以重新平衡下丘脑-垂体-肾上腺(HPA)轴和下丘脑-垂体-性腺(HPG)轴,并调节免疫系统和肠道菌群的紊乱。这些数据表明,LW-AFC的抗AD作用可能主要通过调节神经内分泌免疫调节(NIM)网络来实现。由于免疫抑制剂抑制免疫功能可以消除LW-AFC对长时程增强(LTP)损伤模型的保护作用,因此LW-AFC平衡NIM网络很可能是通过调节免疫系统来启动的。