Anti-inflammatory Mechanism of Morin Hydrate by Suppressing the NF-B/MAPKs Mediated Cell Migration and Modulating Src/FAK and -Catenin
NATURAL PRODUCT COMMUNICATIONS(2023)
摘要
Background: Macrophage migration plays a critical role in inflammation and the development of pathological processes. Thus, inhibiting macrophage migration is a potential approach for reducing inflammation. Besides, mitigation of inflammatory mediators also inhibits macrophage migration. Morin hydrate (MH), a bioflavonoid found in fruits, vegetables, and herbs, has demonstrated various pharmacological effects, including anti-inflammatory and immunosuppressive properties. However, the specific molecular mechanisms underlying MH's anti-inflammatory effects and its impact on macrophage migration remain unclear. This study focused on MH's anti-inflammatory molecular mechanism and also elucidated how it is associated with inhibiting macrophage migration. Methods: The anti-inflammatory and antimigration effects of MH were investigated in lipopolysaccharide (LPS)-stimulated RAW264.7 cells, a murine macrophage cell line. The production of nitric oxide (NO) and the expression of inducible nitric oxide synthase (iNOS) were assessed by various assays. Additionally, the expression of key signaling molecules, such as extracellular signal-regulated kinase (ERK), JNK, p65, pSrc, focal adhesion kinase (FAK), beta-catenin, COX-2, p-p38, and p-Akt, was analyzed in response to MH treatment. Results: MH treatment reduced LPS-induced NO production and downregulated the mRNA and protein expression of iNOS in RAW264.7 cells. It concentration dependently inhibited the expression of ERK and JNK. At a high concentration of 20 mu M, MH also suppressed the expression of p65, pSrc, and pFAK. Moreover, MH effectively attenuated LPS-induced beta-catenin expression, while it did not exhibit a significant effect on COX-2, p-p38, and p-Akt expressions in LPS-stimulated RAW264.7 cells. Furthermore, MH pretreatment inhibited the migration of LPS-induced macrophages. Conclusion: This study reveals that MH exerts its anti-inflammatory effects by inhibiting NO production, downregulating iNOS expression, and modulating ERK/JNK and p65 phosphorylation. Additionally, MH suppresses Src/FAK phosphorylation and downregulates beta-catenin expression induced by LPS. The findings demonstrate a complex interplay between the inflammatory response and MH's impact on macrophage migration being intertwined with its anti-inflammatory properties.
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关键词
morin hydrate, inflammatory, iNOS/COX-2, ERK/JNK, Src/FAK pathways, migration
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