Dimethyl Cardamonin Exhibits Anti-inflammatory Effects via Interfering with the PI3K-PDK1-PKCα Signaling Pathway

Yu, Wan-Guo; He, Hao; Yao, Jing-Yun; Zhu, Yi-Xiang; Lu, Yan-Hua

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자료유형: 학술저널

저자정보: Yu, Wan-Guo (State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology) He, Hao (State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology) Yao, Jing-Yun (State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology) Zhu, Yi-Xiang (State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology) Lu, Yan-Hua (State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology)

저널정보: 한국응용약물학회 Biomolecules & Therapeutics(구 응용약물학회지) Biomolecules & therapeutics 제23권 제6호

발행연도: 2015.1

수록면: 549 - 556 (8page)

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Consumption of herbal tea [flower buds of Cleistocalyx operculatus (Roxb.) Merr. et Perry (Myrtaceae)] is associated with health beneficial effects against multiple diseases including diabetes, asthma, and inflammatory bowel disease. Emerging evidences have reported that High mobility group box 1 (HMGB1) is considered as a key "late" proinflammatory factor by its unique secretion pattern in aforementioned diseases. Dimethyl cardamonin (2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone, DMC) is a major ingredient of C. operculatus flower buds. In this study, the anti-inflammatory effects of DMC and its underlying molecular mechanisms were investigated on lipopolysaccharide (LPS)-induced macrophages. DMC notably suppressed the mRNA expressions of TNF-${\alpha}$, IL-$1{\beta}$, IL-6, and HMGB1, and also markedly decreased their productions in a time- and dose-dependent manner. Intriguingly, DMC could notably reduce LPS-stimulated HMGB1 secretion and its nucleo-cytoplasmic translocation. Furthermore, DMC dose-dependently inhibited the activation of phosphatidylinositol 3-kinase (PI3K), phosphoinositide-dependent kinase 1 (PDK1), and protein kinase C alpha (PKC${\alpha}$). All these data demonstrated that DMC had anti-inflammatory effects through reducing both early (TNF-${\alpha}$, IL-$1{\beta}$, and IL-6) and late (HMGB1) cytokines expressions via interfering with the PI3K-PDK1-PKC${\alpha}$ signaling pathway.

#Dimethyl cardamonin #Inflammatory mediators #HMGB1 #PI3K #PKC ${alpha}$

참고문헌 (40)

참고문헌 신청

Abraham, E. / 1998 / Double-blind randomised controlled trial of monoclonal antibody to human tumour necrosis factor in treatment of septic shock / Lancet 351 351:929~933

Andersson, U. / 2000 / High mobility group 1 protein (HMG-1) stimulates proinflammatory cytokine synthesis in human monocytes / J. Exp. Med 192:565~570

Amor, E. C. / 2005 / Spasmolytic flavonoids from Syzygium samarangense (Blume) Merr. & L.M Perry / Z. Naturforsch 60:67~71

Bonaldi, T. / 2003 / Monocytic cells hyperacetylate chromatin protein HMGB1 to redirect it towards secretion / EMBO J 22:5551~5560

Cheng, C. / 2014 / SOCS1 hypermethylation mediated by DNMT1 is associated with lipopolysaccharide- induced inflammatory cytokines in macrophages / Toxicol. Lett 225:488~497

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