Journal
ACTA PHARMACOLOGICA SINICA
Volume 39, Issue 5, Pages 669-682Publisher
ACTA PHARMACOLOGICA SINICA
DOI: 10.1038/aps.2018.27
Keywords
Ischemic stroke; caveolin-1; reactive nitrogen species (RNS); MMPs; natural compound
Funding
- Hong Kong General Research Fund (GRF) [17102915, 17118717]
- Research Grant Council, Hong Kong SAR
- Health and Medical Research Fund, Hong Kong SAR [13142901]
- Areas of Excellence Scheme, RGC, Hong Kong SAR, China [AoE/P-705/16]
- Shenzhen Basic Research Plan Project [SIRI/04/04/2015/06]
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Reactive nitrogen species (RNS) play important roles in mediating cerebral ischemia-reperfusion injury. RNS activate multiple signaling pathways and participate in different cellular events in cerebral ischemia-reperfusion injury. Recent studies have indicated that caveolin-1 and matrix metalloproteinase (MMP) are important signaling molecules in the pathological process of ischemic brain injury. During cerebral ischemia-reperfusion, the production of nitric oxide (NO) and peroxynitrite (ONOO-), two representative RNS, down-regulates the expression of caveolin-1 (Cav-1) and, in turn, further activates nitric oxide synthase (NOS) to promote RNS generation. The increased RNS further induce MMP activation and mediate disruption of the blood-brain barrier (BBB), aggravating the brain damage in cerebral ischemia-reperfusion injury. Therefore, the feedback interaction among RNS/Cav-1/MMPs provides an amplified mechanism for aggravating ischemic brain damage during cerebral ischemia-reperfusion injury. Targeting the RNS/Cav-1/MMP pathway could be a promising therapeutic strategy for protecting against cerebral ischemia-reperfusion injury. In this mini-review article, we highlight the important role of the RNS/Cav-1/MMP signaling cascades in ischemic stroke injury and review the current progress of studies seeking therapeutic compounds targeting the RNS/Cav-1/MMP signaling cascades to attenuate cerebral ischemiareperfusion injury. Several representative natural compounds, including calycosin-7-O-beta-D-glucoside, baicalin, Momordica charantia polysaccharide (MCP), chlorogenic acid, lutein and lycopene, have shown potential for targeting the RNS/Cav-1/MMP signaling pathway to protect the brain in ischemic stroke. Therefore, the RNS/Cav-1/MMP pathway is an important therapeutic target in ischemic stroke treatment.
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