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

BackgroundGJ-4 is extracted from Gardenia jasminoides J. Ellis (Fructus Gardenia) with crocin composition and has been demonstrated to improve memory deficits in several dementia models in our previous studies. ObjectiveThis study aimed to evaluate the effects of GJ-4 on hyperlipidemic vascular deme...

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Published in:Food & nutrition research 2022-07, Vol.66, p.1-15
Main Authors: 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
Format: Article
Language:English
Subjects:
gj-4
hyperlipidemia
microglial polarization
Original
ppar-γ
vascular dementia
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Summary:BackgroundGJ-4 is extracted from Gardenia jasminoides J. Ellis (Fructus Gardenia) with crocin composition and has been demonstrated to improve memory deficits in several dementia models in our previous studies. ObjectiveThis study aimed to evaluate the effects of GJ-4 on hyperlipidemic vascular dementia (VD) and explore the underlying mechanisms. DesignIn 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. ResultsOur 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. ConclusionOur 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.
ISSN:1654-661X
1654-661X
DOI:10.29219/fnr.v66.8101