Synthesis and biological activity of chalcone derivatives as potent activators of Nrf2 / 中国药科大学学报

@#To obtain ARE-Nrf2 potent activators through modifying the structure of the lead compound CPUY191001. 17 compounds were synthesized by aldol condensation, their cytotoxicity were tested using MTT assay, and ARE inductivity of these target compounds were analyzed by luciferase reporter gene assay. The biological evaluation results showed that most synthesized chalcone derivatives nearly had no cytotoxicity, and compounds 2, 3, 10 conducted better activity and in concentration-dependent manner. Compounds 2, 3, 10 are potential agents in the development of anti-inflammatory and chemoprevention, suggesting that compounds 2, 3, 10 are worth for further investigation.

Synergistic effect of PDGF and FGF2 for cell proliferation and hair inductive activity in murine vibrissal dermal papilla in vitro.

BACKGROUND: The dermal papilla is composed of a small clump of mesenchymal cells, called dermal papilla cells (DPCs). DPCs closely interact with epidermal cells to give rise to hair follicles and shafts during hair follicle development and the hair cycle. DPCs are promising cell sources for hair regeneration therapy for alopecia patients. However, once DPCs are put into conventional two-dimensional culture conditions, they quickly lose their capability to produce hair follicles. OBJECTIVE: We aimed to expand a sufficiently large population of DPCs that retain their hair inductive activity. METHODS: Murine DPCs were cultured in the presence of platelet-derived growth factor-AA (PDGF-AA) and fibroblast growth factor 2 (FGF2). Expressions of follicular-related genes were analyzed by real time PCR and hair inductive activity was determined by patch assay and chamber assay in vivo. RESULTS: FGF2 significantly increased the expression of platelet-derived growth factor receptor alpha (PDGFRα) in cultured vibrissal DPCs. PDGF-AA, a ligand of PDGFRα, promoted proliferation of DPCs synergistically when utilized with FGF2 and enhanced the expression of several follicular-related genes in DPCs. Hair reconstitution assays revealed that DPCs treated with both PDGF-AA and FGF-2 were able to maintain their hair inductive activity better than those treated with FGF2 alone. CONCLUSION: Both cell proliferation and hair inductive activity in murine DPCs are maintained by the synergistic effect of FGF2 and PDGF-AA.