Department of Geriatrics, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China.
Department of Gastroenterology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China.
J Ethnopharmacol. 2024 Jan 30;319(Pt 1):117195. doi: 10.1016/j.jep.2023.117195. Epub 2023 Sep 17.
Yuanzhi Powder (YZP) is a classical Chinese medicine prescription, which is suitable for the treatment of dementia by "dispelling phlegm and opening orifice". The therapeutic efficacy of YZP on Alzheimer's disease (AD) has been previously reported in our work. However, it remains unclear whether the neuroprotective effect of YZP is linked to β-amyloid(Aβ) clearance through cerebral lymphatic drainage.
The aim was to determine the protective efficacy of YZP against AD and investigate the potential mechanism for eliminating excessive Aβ deposition.
APP/PS1 mice were divided into four groups of 8 mice each: APP/PS1 group, DONE group, L-YZP group, and H-YZP group. Additionally, 8 wild-type littermates were assigned to the control group (WT group). After 8 weeks of consecutive intragastric administration, behavioral tests, including the open field test, novel object recognition test and Morris Water Maze test, were employed to assess the cognitive abilities of all groups of mice. Nissl staining, immunohistochemistry, and western blotting were utilized to evaluate clearance of excessive Aβ deposition and pathological changes. Furthermore, immunofluorescence was applied to visualize the drainage of the cerebral lymphatic system after fluorescent tracer injection in the cisterna magna.
The administration of YZP significantly attenuated cognitive deficits, cleared excessive Aβ deposition, and improved pathological damage in APP/PS1 mice. Furthermore, YZP effectively enhanced glymphatic system drainage by restoring AQP4 polarization and inhibiting reactive astrogliosis. Additionally, YZP facilitated the drainage of meningeal lymphatic vessels (MLVs) by augmenting their diameter and coverage. Lastly, YZP promoted the elimination of Aβ from the brain to deep cervical lymph nodes.
The administration of YZP may ameliorate the cognitive deficits and pathological damage in APP/PS1 mice by effectively clearing excessive Aβ deposition. The underlying mechanisms potentially involve Aβ clearance through the cerebral lymphatic system, which includes the glymphatic system and MLVs.
远志散（YZP）是一种经典的中药方剂，适用于通过“化痰开窍”治疗痴呆症。我们之前的工作已经报道了 YZP 对阿尔茨海默病（AD）的治疗功效。然而，YZP 的神经保护作用是否与通过脑淋巴引流清除β-淀粉样蛋白（Aβ）有关仍不清楚。
本研究旨在确定 YZP 对 AD 的保护作用，并探讨消除过量 Aβ沉积的潜在机制。
将 APP/PS1 小鼠分为四组，每组 8 只：APP/PS1 组、DONE 组、L-YZP 组和 H-YZP 组。此外，将 8 只野生型同窝仔鼠分配到对照组（WT 组）。连续灌胃 8 周后，采用旷场试验、新物体识别试验和 Morris 水迷宫试验评估各组小鼠的认知能力。尼氏染色、免疫组织化学和 Western blot 用于评估过量 Aβ沉积的清除和病理变化。此外，通过在枕骨大孔内注射荧光示踪剂，应用免疫荧光观察脑淋巴系统的引流情况。
YZP 的给药显著减轻了 APP/PS1 小鼠的认知障碍，清除了过量的 Aβ 沉积，并改善了病理损伤。此外，YZP 通过恢复 AQP4 极化和抑制反应性星形胶质细胞增生有效增强了糖质内淋巴系统的引流。此外，YZP 通过增加脑膜淋巴管（MLVs）的直径和覆盖范围促进了 MLVs 的引流。最后，YZP 促进了 Aβ从大脑向深部颈淋巴结的清除。
YZP 的给药可能通过有效清除过量的 Aβ 沉积来改善 APP/PS1 小鼠的认知障碍和病理损伤。其潜在机制可能涉及通过脑淋巴系统清除 Aβ，包括糖质内淋巴系统和 MLVs。
