Liu Hui, Zang Caixia, Shang Junmei, Zhang Zihong, Wang Lu, Yang Hanyu, Sheng Chanjuan, Yuan Fangyu, Ju Cheng, Li Fangyuan, Yu Yang, Yao Xinsheng, Bao Xiuqi, Zhang Dan
State Key Laboratory of Bioactive Substrate and Function of Natural Medicine, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Institute of TCM & Natural Products College of Pharmacy, Jinan University, Guangzhou, China.
Food Nutr Res. 2022 Jul 19;66. doi: 10.29219/fnr.v66.8101. eCollection 2022.
GJ-4 is extracted from J. Ellis (Fructus Gardenia) with crocin composition and has been demonstrated to improve memory deficits in several dementia models in our previous studies.
This study aimed to evaluate the effects of GJ-4 on hyperlipidemic vascular dementia (VD) and explore the underlying mechanisms.
In the current study, we employed a chronic hyperlipidemic VD rat model by permanent bilateral common carotid arteries occlusion (2-VO) based on high-fat diet (HFD), which is an ideal model to mimic the clinical pathogenesis of human VD.
Our results showed that GJ-4 could significantly reduce serum lipids level and improve cerebral blood flow in hyperlipidemic VD rats. Additionally, treatment with GJ-4 remarkedly ameliorated memory impairment and alleviated neuronal injury. Mechanistic investigation revealed that the neuroprotective effects of GJ-4 might be attributed to the inhibition of microglia-mediated neuro-inflammation via regulating the M1/M2 polarization. Our data further illustrated that GJ-4 could regulate the phenotype of microglia through activating the peroxisome proliferator-activated receptor-γ (PPAR-γ) and subsequently inhibited nuclear factor-κB (NF-κB) nuclear translocation and increased CCAAT/enhancer-binding protein β (C/EBPβ) expression.
Our results implied that GJ-4 might be a promising drug to improve VD through the regulation of microglial M1/M2 polarization and the subsequent inhibition of neuro-inflammation.
GJ-4是从栀子中提取的含有西红花苷成分的提取物，在我们之前的研究中已证明其可改善多种痴呆模型中的记忆缺陷。
本研究旨在评估GJ-4对高脂血症性血管性痴呆（VD）的影响并探索其潜在机制。
在本研究中，我们基于高脂饮食（HFD）通过永久性双侧颈总动脉闭塞（2-VO）建立了慢性高脂血症性VD大鼠模型，这是一种模拟人类VD临床发病机制的理想模型。
我们的结果表明，GJ-4可显著降低高脂血症性VD大鼠的血脂水平并改善脑血流量。此外，GJ-4治疗可显著改善记忆障碍并减轻神经元损伤。机制研究表明，GJ-4的神经保护作用可能归因于通过调节M1/M2极化抑制小胶质细胞介导的神经炎症。我们的数据进一步表明，GJ-4可通过激活过氧化物酶体增殖物激活受体-γ（PPAR-γ）来调节小胶质细胞的表型，随后抑制核因子-κB（NF-κB）核转位并增加CCAAT/增强子结合蛋白β（C/EBPβ）的表达。
我们的结果表明，GJ-4可能是一种通过调节小胶质细胞M1/M2极化及随后抑制神经炎症来改善VD的有前景的药物。
