SIRT1 activation by Ligustrazine ameliorates migraine via the paracrine interaction of microglia and neurons
Abstract
BACKGROUND: Neuroinflammation with associated oxidative stress aggravates the pathogenesis and progression of migraine. Ligustrazine (LGZ) is a key component from traditional edible-medicinal herb Ligusticum chuanxiong Hort., and has the effects of anti-platelet aggregation, expanding small arteries, improving microcirculation and promoting blood circulation and removing blood stasis in clinic.
HYPOTHESIS/PURPOSE: This study aims to investigate the pharmacological effect and mechanism of LGZ in migraine.
STUDY DESIGN/METHODS: A mouse model of migraine was induced by nitroglycerin (NTG), and LPS/IFN-γ stimulated microglial cell model was conducted to investigate neuroinflammation, the paracrine interactions between microglia and neurons were determined by the co-culture system, and the effect of LGZ on stability of SIRT1 protein was measured by cellular thermal shift assay (CETSA). Whilst, the SIRT1 inhibitor EX527 was used alone or co-treatment with LGZ in vitro or in vivo.
RESULTS: LGZ significantly attenuated migraine-like behaviors in NTG-induced mice, and ameliorated neuroinflammation and related oxidative damage in brain tissue, but co-treatment with SIRT1 inhibitor EX527 abolished the protective effects of LGZ. Mechanistically, LGZ mitigated neuroinflammation by upregulating SIRT1 expression and subsequently inhibiting the activation of NF-κB pathway in microglia. CETSA indicated that LGZ significantly maintained the stability of SIRT1 protein in microglia. While, in…
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