Journal
INTERNATIONAL IMMUNOPHARMACOLOGY
Volume 14, Issue 4, Pages 375-383Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.intimp.2012.08.011
Keywords
Alantolactone; Inflammation; NF-kappa B; MAPK; AP-1; Macrophage
Categories
Funding
- Korean Food and Drug Administration for Studies on the Identification of the Efficacy of Biologically Active Components from Oriental Herbal Medicines
- MRC grant
- Korean government (National Research Foundation of Korea) [20090083533]
- National Research Foundation of Korea [핵C6A3403, 과C6A2102, 2009-0062748] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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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. (c) 2012 Elsevier B.V. All rights reserved.
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