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http://dx.doi.org/10.4062/biomolther.2015.048

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

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)
Publication Information
Biomolecules & Therapeutics / v.23, no.6, 2015 , pp. 549-556 More about this Journal
Abstract
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.
Keywords
Dimethyl cardamonin; Inflammatory mediators; HMGB1; PI3K; PKC${\alpha}$;
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