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Novel mechanistic insight on the neuroprotective effect of berberine: The role of PPARδ for antioxidant action.
Shou, Jia-Wen; Li, Xiao-Xiao; Tang, Yun-Sang; Lim-Ho Kong, Bobby; Wu, Hoi-Yan; Xiao, Meng-Jie; Cheung, Chun-Kai; Shaw, Pang-Chui.
Affiliation
  • Shou JW; School of Life Sciences, The Chinese University of Hong Kong, Hong Kong, China.
  • Li XX; Li Dak Sum Yip Yio Chin R&D Centre for Chinese Medicine, The Chinese University of Hong Kong, Hong Kong, China.
  • Tang YS; School of Life Sciences, The Chinese University of Hong Kong, Hong Kong, China.
  • Lim-Ho Kong B; School of Life Sciences, The Chinese University of Hong Kong, Hong Kong, China.
  • Wu HY; Li Dak Sum Yip Yio Chin R&D Centre for Chinese Medicine, The Chinese University of Hong Kong, Hong Kong, China.
  • Xiao MJ; School of Life Sciences, The Chinese University of Hong Kong, Hong Kong, China.
  • Cheung CK; School of Life Sciences, The Chinese University of Hong Kong, Hong Kong, China.
  • Shaw PC; School of Life Sciences, The Chinese University of Hong Kong, Hong Kong, China; Li Dak Sum Yip Yio Chin R&D Centre for Chinese Medicine, The Chinese University of Hong Kong, Hong Kong, China; State Key Laboratory of Research on Bioactivities and Clinical Applications of Medicinal Plants and Inst
Free Radic Biol Med ; 181: 62-71, 2022 03.
Article in En | MEDLINE | ID: mdl-35093536
Cerebral ischemic stroke ranks the second leading cause of death and the third leading cause of disability in lifetime all around the world, urgently necessitating effective therapeutic interventions. Reactive oxygen species (ROS) have been implicated in stroke pathogenesis and peroxisome proliferator-activated receptors (PPARs) are prominent targets for ROS management. Although recent research has shown antioxidant effect of berberine (BBR), little is known regarding its effect upon ROS-PPARs signaling in stroke. The aim of this study is to explore whether BBR could target on ROS-PPARs pathway to ameliorate middle cerebral artery occlusion (MCAO)-induced stroke. Herein, we report that BBR is able to scavenge ROS in oxidation-damaged C17.2 neural stem cells and stroked mice. PPARδ, rather than PPARα or PPARγ, is involved in the anti-ROS effect of BBR, as evidenced by the siRNA transfection and specific antagonist treatment data. Further, we have found BBR could upregulate NF-E2 related factor-1/2 (NRF1/2) and NAD(P)H:quinone oxidoreductase 1 (NQO1) following a PPARδ-dependent manner. Mechanistic study has revealed that BBR acts as a potent ligand (Kd = 290 ± 92 nM) to activate PPARδ and initiates the transcriptional regulation functions, thus promoting the expression of PPARδ, NRF1, NRF2 and NQO1. Collectively, our results indicate that BBR confers neuroprotective effects by activating PPARδ to scavenge ROS, providing a novel mechanistic insight for the antioxidant action of BBR.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Berberine / Neuroprotective Agents / PPAR delta Limits: Animals Language: En Journal: Free Radic Biol Med Journal subject: BIOQUIMICA / MEDICINA Year: 2022 Document type: Article Affiliation country: Country of publication:

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Berberine / Neuroprotective Agents / PPAR delta Limits: Animals Language: En Journal: Free Radic Biol Med Journal subject: BIOQUIMICA / MEDICINA Year: 2022 Document type: Article Affiliation country: Country of publication: