title: Dimethyl Cardamonin Exhibits Anti-inflammatory Effects via Interfering with the PI3K-PDK1-PKCα Signaling Pathway.
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-α, IL-1β, 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 (PKCα). All these data demonstrated that DMC had anti-inflammatory effects through reducing both early (TNF-α, IL-1β, and IL-6) and late (HMGB1) cytokines expressions via interfering with the PI3K-PDK1-PKCα signaling pathway.
authors.affiliation: State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, People's Republic of China ; Shanghai Collaborative Innovation Center for Biomanufacturing Technology, Shanghai 200237, People's Republic of China.
authors.forename: Wan-Guo
authors.initials: WG
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, People's Republic of China ; Shanghai Collaborative Innovation Center for Biomanufacturing Technology, Shanghai 200237, People's Republic of China.
authors.forename: Hao
authors.initials: H
authors.lastname: He
authors.affiliation: State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, People's Republic of China ; Shanghai Collaborative Innovation Center for Biomanufacturing Technology, Shanghai 200237, People's Republic of China.
authors.forename: Jing-Yun
authors.initials: JY
authors.lastname: Yao
authors.affiliation: State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, People's Republic of China ; Shanghai Collaborative Innovation Center for Biomanufacturing Technology, Shanghai 200237, People's Republic of China.
authors.forename: Yi-Xiang
authors.initials: YX
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, People's Republic of China ; Shanghai Collaborative Innovation Center for Biomanufacturing Technology, Shanghai 200237, People's Republic of China.
authors.forename: Yan-Hua
authors.initials: YH
authors.lastname: Lu
keywords: Dimethyl cardamonin; HMGB1; Inflammatory mediators; PI3K; PKCα