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Int Immunopharmacol. 2012 Dec;14(4):375-83. doi: 10.1016/j.intimp.2012.08.011. Epub 2012 Aug 28.

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

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Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.


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-α (TNF-α). Investigation of the effects on nuclear factor κB (NF-κB) signaling showed that alantolactone inhibits the phosphorylation of inhibitory κB (IκB)-α and IκB kinase (IKK) and the subsequent translocation of the p65 and p50 NF-κB 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-κB activation and MAPKs phophorylation via downregulation of the MyD88 signaling pathway. Thus, alantolactone may provide a useful therapeutic approach for inflammation-associated diseases.

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