通过改善白质损伤，GJ-4 对血管性痴呆认知障碍的神经保护作用。
Neuroprotective effect of GJ-4 against cognitive impairments in vascular dementia by improving white matter damage.
机构信息
State Key Laboratory of Bioactive Molecules and Druggability Assessment; Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research; Institute of Traditional Chinese Medicine & Natural Products, College of Pharmacy; Jinan University, Guangzhou, 510632, People's Republic of China; University of Michigan Life Sciences Institute, Ann Arbor, MI 48109-2216, United States.
Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, People's Republic of China.
出版信息
Phytomedicine. 2024 Sep;132:155877. doi: 10.1016/j.phymed.2024.155877. Epub 2024 Jul 14.
BACKGROUND
White matter lesions (WMLs) are increasingly linked to the pathological process of chronic vascular dementia (VaD). An effective crocins fraction extracted from Gardenia Fructus, GJ-4, has been shown to improve cognitive function in several Alzheimer's disease models and VaD models.
OBJECTIVES
To explore the potential mechanisms of GJ-4 on WMLs in a chronic VaD mouse model.
METHODS
The chronic VaD mouse model was established, and WMLs were characterized by cerebral blood flow (CBF), behavioral tests, LFB staining, and immunohistochemistry. The anti-oxidative effect of GJ-4 was validated by examining biochemical parameters (SOD, MDA, and GSH) and the Keap1-Nrf2/HO-1 pathway. The impact of GJ-4 on lipid metabolism in WM was further investigated through lipidomic analysis.
RESULTS
GJ-4 significantly attenuated cognitive impairments and improved the CBF of BCAS (bilateral common carotid artery stenosis)-induced mice. Mechanism research showed that GJ-4 could enhance cognition by promoting the repair of WMLs by inhibiting oxidative stress. Furthermore, GJ-4 treatment significantly reduced chronic cerebral hypoperfusion (CCH)-induced WMLs via improving lipid metabolism disorder in the WM.
CONCLUSION
This research has provided valuable insights into the significance of WMLs in CCH-induced VaD and underscored the potential of GJ-4 as a therapeutic agent for improving cognitive function by targeting WMLs. These findings suggest that GJ-4 is a promising candidate for the treatment of VaD.
背景
脑白质病变（WMLs）与慢性血管性痴呆（VaD）的病理过程越来越相关。已证实从栀子果中提取的有效西红花酸（GJ-4）可改善几种阿尔茨海默病模型和 VaD 模型的认知功能。
目的
探讨 GJ-4 对慢性 VaD 小鼠模型 WMLs 的潜在作用机制。
方法
建立慢性 VaD 小鼠模型，通过脑血流（CBF）、行为学测试、LFB 染色和免疫组织化学检测特征性 WMLs。通过检查生化参数（SOD、MDA 和 GSH）和 Keap1-Nrf2/HO-1 通路，验证 GJ-4 的抗氧化作用。通过脂质组学分析进一步研究 GJ-4 对 WM 中脂质代谢的影响。
结果
GJ-4 显著减轻了 BCAS（双侧颈总动脉狭窄）诱导的小鼠认知障碍，并改善了 CBF。机制研究表明，GJ-4 通过抑制氧化应激来促进 WML 修复，从而增强认知能力。此外，GJ-4 通过改善 WM 中脂质代谢紊乱，显著减少了慢性脑低灌注（CCH）诱导的 WMLs。
结论
本研究深入探讨了 WMLs 在 CCH 诱导的 VaD 中的意义，并强调了 GJ-4 通过靶向 WMLs 改善认知功能的治疗潜力。这些发现表明 GJ-4 是治疗 VaD 的有前途的候选药物。
Zotero 插件