1. The wound-healing effect of 7,3′,4′-trimethoxyflavone through increased levels of prostaglandin E2 by 15-hydroxyprostaglandin dehydrogenase inhibition
- Author
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Cheol-Hee Choi, Young-Sook Moon, Hoon Cho, Sandeep Karna, and Kyung Hoon Sun
- Subjects
0301 basic medicine ,medicine.medical_specialty ,medicine.medical_treatment ,Bioengineering ,Pharmacology ,Applied Microbiology and Biotechnology ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,Therapeutic index ,Internal medicine ,medicine ,Prostaglandin E2 ,Cytotoxicity ,IC50 ,integumentary system ,PROSTAGLANDIN TRANSPORTER ,Chemistry ,General Medicine ,HaCaT ,030104 developmental biology ,Endocrinology ,Wound healing ,Biotechnology ,medicine.drug ,Prostaglandin E - Abstract
To find an inhibitor of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) that rapidly metabolises Prostaglandin E2 (PGE2) as a mediator of wound healing, we examined seven flavonoids for this role. 7,3′,4′-Trimethoxyflavone (TMF) had the lowest IC50 value of 0.34 µM for 15-PGDH inhibition but >400 µM for cytotoxicity, indicating a high therapeutic index. TMF elevated PGE2 levels in a concentration-dependent manner in both A549 lung cancer and HaCaT cells. It also significantly increased mRNA expression of multidrug resistance-associated protein 4 (MRP4) and of prostaglandin transporter (PGT) slightly in HaCaT cells. In addition, TMF facilitated in vitro wound healing in a HaCaT scratch model, which was completely inhibited by adding both 15-PGDH and NAD+ as cofactor, confirming the involvement of PGE2 in its wound healing effect. TMF with a high therapeutic index can facilitate wound healing through PGE2 elevation by 15-PGDH inhibition.
- Published
- 2017
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