Alantolactone suppresses inducible nitric oxide synthase and cyclooxygenase-2 expression by down-regulating NF-kappa B, MAPK and AP-1 via the MyD88 signaling pathway in LPS-activated RAW 264.7 cells

作者：Chun Jaemoo; Choi Ran Joo; Khan Salman; Lee Dong Sung; Kim Youn Chul; Nam Young Joo; Lee Dong Ung; Kim Yeong Shik^*

来源：International Immunopharmacology, 2012, 14(4): 375-383.

DOI：10.1016/j.intimp.2012.08.011

• Alantolactone
• Inflammation
• NF-kappa B
• MAPK
• AP-1
• Macrophage

Several sesquiterpene lactones are the active components of several medicinal plants and have been demonstrated to perform various pharmacological functions. In this study, we investigated the anti-inflammatory effects of alantolactone, a sesquiterpene lactone isolated from the root of Aucklandia lappa, in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells and peritoneal macrophages. Alantolactone inhibited inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) protein and mRNA transcription, as well as the downstream products, nitric oxide (NO), prostaglandin E-2 (PGE(2)) and tumor necrosis factor-alpha (TNF-alpha). Investigation of the effects on nuclear factor kappa B (NF-kappa B) signaling showed that alantolactone inhibits the phosphorylation of inhibitory kappa B (I kappa B)-alpha and I kappa B kinase (IKK) and the subsequent translocation of the p65 and p50 NF-kappa B subunits to the nucleus. Moreover, inhibition of mitogen-activated protein kinases (MAPKs), including c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK) and p38 MAPK, and activator protein-1 (AP-1) was also observed. A further study indicated that alantolactone attenuated the phosphorylation of Akt and inhibited the expression of MyD88 and Toll-interleukin 1 receptor domain-containing adaptor protein (TIRAP), an upstream signaling molecule required for IKK and MAPKs activation. Taken together, these results suggest that alantolactone exerts its anti-inflammatory effect in LPS-stimulated RAW 264.7 cells by suppressing NF-kappa B activation and MAPKs phophorylation via downregulation of the MyD88 signaling pathway. Thus, alantolactone may provide a useful therapeutic approach for inflammation-associated diseases.

• 出版日期2012-12