Atractylodin Inhibits Interleukin-6 by Blocking NPM-ALK Activation and MAPKs in HMC-1.
Atractylodin is one of the major constituents of the rhizome of Atractylodes lancea, which is widely used in Korean traditional medicine as a remedy for the treatment of gastritis and gastric ulcers. Despite of a major constituent of widely used botanical to treat inflammatory responses little is known about anti-inflammatory effect of atractylodin in the human mast cell (HMC-1). Hence, we evaluated the effect of atractylodin on the release of IL-6, the involvement of nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) and mitogen-activated protein kinases (MAPKs) in phorbol-12-myristate-13-acetate and A23187-induced HMC-1. In addition, Janus kinase 2 (JAK2), signal transducer and activator of transcription 3 (STAT3), phospholipase C (PLC) gamma 1, and AKT phosphorylation relevant to NPM-ALK signal pathway were assessed. IL-6 levels in the HMC-1 stimulated by phorbol-12-myristate-13-acetate and A23187 were apparently decreased by the treatment of atractylodin. Concurrently, atractylodin not only inhibited the phosphorylation of NPM-ALK, but also suppressed the phosphorylation of JAK2, STAT3, PLC gamma 1, and AKT. Furthermore, the activated mitogen-activated protein kinases (MAPKs) by phorbol-12-myristate-13-acetate and A23187 were inhibited by atractylodin. These results suggested that atractylodin might have a potential regulatory effect on inflammatory mediator expression through blockade of both the phosphorylation of MAPKs and the NPM-ALK signaling pathway.
College of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University-Seoul, 32 Dongguk-lo, Ilsandong-gu, Goyang-si, Gyeonggi-do 10326, Korea. chaeheesung83@gmail.com.
Hee-Sung
HS
Chae
College of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University-Seoul, 32 Dongguk-lo, Ilsandong-gu, Goyang-si, Gyeonggi-do 10326, Korea. 0210121@hanmail.net.
Young-Mi
YM
Kim
College of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University-Seoul, 32 Dongguk-lo, Ilsandong-gu, Goyang-si, Gyeonggi-do 10326, Korea. f2744@dongguk.edu.
Young-Won
YW
Chin
D031174:Atractylodes / Q000737:chemistry; D000001:Calcimycin / Q000494:pharmacology; D002460:Cell Line; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005663:Furans / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008407:Mast Cells / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D027343:Rhizome / Q000737:chemistry; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D005663:Furans; C508600:IL6 protein, human; D015850:Interleukin-6; D000001:Calcimycin; C106914:atractylodin; C107023:p80(NPM-ALK) protein; D011505:Protein-Tyrosine Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D013755:Tetradecanoylphorbol Acetate
Atractylodes lancea; atractylodin; human mast cell-1; interleukin-6; nucleophosmin-anaplastic lymphoma kinase