Gardenia jasminoides J. Ellis extract GJ-4 attenuates hyperlipidemic vascular dementia in rats via regulating PPAR-γ-mediated microglial polarization

作者：Hui Liu, Caixia Zang, Junmei Shang, Zihong Zhang, Lu Wang, Hanyu Yang, Chanjuan Sheng, Fang-Yu Yuan, Cheng Ju, Fangyuan Li, Yang Yu, Xin‐Sheng Yao, Xiuqi Bao, Dan Zhang · 发表于：Food & Nutrition Research · 年份：2022 · DOI：10.29219/fnr.v66.8101 · 被引用次数：11 · 研究领域：Saffron Plant Research Studies、Neurological Disease Mechanisms and Treatments、Regulation of Appetite and Obesity

Background: J. Ellis (Fructus Gardenia) with crocin composition and has been demonstrated to improve memory deficits in several dementia models in our previous studies. Objective: This study aimed to evaluate the effects of GJ-4 on hyperlipidemic vascular dementia (VD) and explore the underlying mechanisms. Design: 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. Results: 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. Conclusion: 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.