Silymarin inhibits macrophage activation

Abstract

The present study showed that silymarin, a polyphenolic flavonoid isolated from milk thistle (Silybum marianum), inhibited lipopolysaccharide (LPS)-induced morphological changes in the mouse RAW264.7 macrophage cell line. Silymarin inhibited adhesion activity, nitric oxide (NO) production, and inducible nitric oxide synthase gene expression. We also showed that silymarin inhibited the nuclear translocation and transactivation activities of nuclear factor-kappa B (NF-B), which is important for macrophage activation-associated changes in cell morphology and gene expression of inflammatory cytokines. BAY-11-7085, an NF-B inhibitor, abrogated LPS-induced morphological changes and NO production, similar to silymarin. Treatment of RAW264.7 cells with silymarin also inhibited LPS-stimulated activation of mitogen-activated protein kinases (MAPKs). Collectively, these experiments demonstrated that silymarin inhibited LPS-induced morphological changes in the RAW264.7 mouse macrophage cell line. Our findings indicated that the most likely mechanism underlying this biological effect involved inhibition of the MAPK pathway and NF-B activity. Inhibition of these activities by silymarin is a potentially useful strategy for the treatment of inflammation because of the critical roles played by MAPK and NF-B in mediating inflammatory responses in macrophages.|Silymarin은 Silybum marianum에서 분리해낸 폴리페놀릭 플라보노이드로 대식세포의 활성화에 대한 영향을 분석하였다. Silymarin은 LPS에 의해 유도된 마우스 대식세포주인 RAW264.7세포의 형태학적 변화, 세포부착 활성, NO생성, iNOS유전자 발현을 저해하였다. Silymarin은 또한 염증성 사이토카인 발현에 중요한 NF-B의 전사촉진과 핵으로의 이동을 억제하였다. NF-B의 억제제인 BAY-11-7085는 silymarin과 비슷하게 RAW264.7세포의 형태학적 변화와 NO생성을 억제하였다. RAW264.7세포에 silymarin을 처리하면 MAPKs의 활성 또한 저해됨을 확인하였다. 결과적으로 이 연구에서는 대식세포에서 silymarin의 LPS에 의한 형태학적 변화의 억제를 증명했다. MAPK와 NF-B가 대식세포의 염증반응을 매개하는데 중요한 역할을 하기 때문에 silymarin을 염증 조절에 활용가능 할 것으로 판단된다.