Amorfrutin A ameliorates cerebral ischemia/reperfsion injury in vivo and in vitro via modulating Nrf2/HO-1 signaling pathway

• 발행기관: 대한생리학회-대한약리학회
• 저자명: Youxi Yang Liying Shi Xiaoting Xu Bilan Luo Xing Cui Lei Tang Jianta Wang
• 간행물 정보: 『The Korean Journal of Physiology & Pharmacology』제29권 제5호, 547~557쪽, 전체 11쪽
• 주제분류: 의약학 > 의학일반
• 파일형태: PDF
• 발행일자: 2025.09.01

국문 초록

Ischemic stroke is a leading cause of death and disability worldwide. Amorfrutin A (AA), a small molecule compound found in Amorpha fruticosa L. (bastard indigo), possesses various activities, including blood glucose regulation, antiinflammatory, analgesic, and tumor suppression. In this study, we used the middle cerebral artery occlusion/reperfusion (MCAO/R) model and the oxygen glucose deprivation/ reoxygenation (OGD/R) model to mimic the ischemia/reperfusion process in vivo and in vitro, respectively. The role of AA in ischemic stroke was evaluated by CCK-8 assay, ELISA, TTC staining, hematoxylin-eosin staining and Western blot assay. AA increased the survival of BV2 or PC12 cells following OGD/R injury. Meanwhile, AA effectively suppressed the release of reactive oxygen species, nitric oxide, and tumor necrosis factor-α (TNF-α) in BV2 or PC12 cells subjected to OGD/R. After 24 h of MCAO/R surgery, AA significantly reduced the neurological deficit score, diminished the cerebral infarct volume, and attenuated brain pathological injury in rats. AA administration significantly increased superoxide dismutase and glutathione peroxidase levels, reduced malondialdehyde production, and inhibited the release of inflammatory cytokines interleukin-1β and TNF-α in the ischemic brain tissue of MCAO/R rats. In addition, AA suppressed Kelch-like ECH-associated protein 1 expression and promoted nuclear factor erythroid 2-related factor 2 (Nrf2), NAD(P)H quinone oxidoreductase 1, and heme oxygenase 1 (HO-1) expression in rat ischemic brain. AA may be a potential drug for the treatment of ischemic stroke. Its antioxidant and anti-inflammatory effects in cerebral ischemia-reperfusion injury may be related to Nrf2/HO-1 signaling pathway.

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INTRODUCTION

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키워드

Anti-Inflammatory agents Brain ischemia Neuroprotection Oxidative stress