Biomol Ther.  2015 Nov;23(6):549-556. 10.4062/biomolther.2015.048.

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

Affiliations
  • 1State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, People's Republic of China. luyanhua@ecust.edu.cn
  • 2Shanghai Collaborative Innovation Center for Biomanufacturing Technology, Shanghai 200237, People's Republic of China.

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-1beta, 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 (PKCalpha). All these data demonstrated that DMC had anti-inflammatory effects through reducing both early (TNF-alpha, IL-1beta, and IL-6) and late (HMGB1) cytokines expressions via interfering with the PI3K-PDK1-PKCalpha signaling pathway.

Keyword

Dimethyl cardamonin; Inflammatory mediators; HMGB1; PI3K; PKCalpha

MeSH Terms

Asthma
Teas, Herbal
Cytokines
Flowers
HMGB1 Protein
Inflammatory Bowel Diseases
Interleukin-6
Macrophages
Phosphatidylinositol 3-Kinase
Phosphotransferases
Protein Kinase C-alpha
RNA, Messenger
Tumor Necrosis Factor-alpha
Cytokines
HMGB1 Protein
Interleukin-6
Phosphatidylinositol 3-Kinase
Phosphotransferases
Protein Kinase C-alpha
RNA, Messenger
Tumor Necrosis Factor-alpha
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