Dimethyl Cardamonin Exhibits Anti-inflammatory Effects via Interfering with the PI3K-PDK1-PKCalpha Signaling Pathway.
10.4062/biomolther.2015.048
- Author:
Wan Guo YU
1
;
Hao HE
;
Jing Yun YAO
;
Yi Xiang ZHU
;
Yan Hua LU
Author Information
1. State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, People's Republic of China. luyanhua@ecust.edu.cn
- Publication Type:Original Article
- Keywords:
Dimethyl cardamonin;
Inflammatory mediators;
HMGB1;
PI3K;
PKCalpha
- MeSH:
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
- From:Biomolecules & Therapeutics
2015;23(6):549-556
- CountryRepublic of Korea
- Language:English
-
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.
