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The wound-healing effect of 7,3′,4′-trimethoxyflavone through increased levels of prostaglandin E2 by 15-hydroxyprostaglandin dehydrogenase inhibition

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Abstract

Objective

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.

Results

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.

Conclusion

TMF with a high therapeutic index can facilitate wound healing through PGE2 elevation by 15-PGDH inhibition.

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Acknowledgements

This study was supported by research fund from Chosun University in 2016.

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Authors and Affiliations

  1. Department of Pharmacology, Chosun University Medical School, Gwangju, 501-759, Republic of Korea

    Sandeep Karna, Young-Sook Moon & Cheol-Hee Choi

  2. Department of Emergency Medicine, Chosun University Medical School, Gwangju, 501-759, Republic of Korea

    Kyung Hoon Sun

  3. Department of Polymer Science, Chosun University Medical School, Gwangju, 501-759, Republic of Korea

    Hoon Cho

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  1. Kyung Hoon Sun
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  2. Sandeep Karna
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  3. Young-Sook Moon
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  4. Hoon Cho
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  5. Cheol-Hee Choi
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Correspondence to Cheol-Hee Choi.

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Sun, K.H., Karna, S., Moon, YS. et al. The wound-healing effect of 7,3′,4′-trimethoxyflavone through increased levels of prostaglandin E2 by 15-hydroxyprostaglandin dehydrogenase inhibition. Biotechnol Lett 39, 1575–1582 (2017). https://doi.org/10.1007/s10529-017-2386-2

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  • DOI: https://doi.org/10.1007/s10529-017-2386-2

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