Sun Kyung Hoon, Karna Sandeep, Moon Young-Sook, Cho Hoon, Choi Cheol-Hee
Department of Emergency Medicine, Chosun University Medical School, Gwangju, 501-759, Republic of Korea.
Department of Pharmacology, Chosun University Medical School, Gwangju, 501-759, Republic of Korea.
Biotechnol Lett. 2017 Oct;39(10):1575-1582. doi: 10.1007/s10529-017-2386-2. Epub 2017 Jun 29.
To find an inhibitor of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) that rapidly metabolises Prostaglandin E (PGE) as a mediator of wound healing, we examined seven flavonoids for this role.
7,3',4'-Trimethoxyflavone (TMF) had the lowest IC value of 0.34 µM for 15-PGDH inhibition but >400 µM for cytotoxicity, indicating a high therapeutic index. TMF elevated PGE 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 PGE in its wound healing effect.
TMF with a high therapeutic index can facilitate wound healing through PGE elevation by 15-PGDH inhibition.
为了找到一种15-羟基前列腺素脱氢酶（15-PGDH）抑制剂，该酶可快速代谢前列腺素E（PGE）作为伤口愈合的介质，我们研究了七种黄酮类化合物在这方面的作用。
7,3',4'-三甲氧基黄酮（TMF）对15-PGDH抑制的最低IC值为0.34 μM，但细胞毒性大于400 μM，表明其治疗指数较高。TMF在A549肺癌细胞和HaCaT细胞中均以浓度依赖性方式提高PGE水平。在HaCaT细胞中，它还显著增加了多药耐药相关蛋白4（MRP4）的mRNA表达，并轻微增加了前列腺素转运体（PGT）的表达。此外，在HaCaT划痕模型中，TMF促进了体外伤口愈合，通过添加15-PGDH和NAD作为辅因子可完全抑制该作用，证实了PGE参与其伤口愈合效应。
具有高治疗指数的TMF可通过抑制15-PGDH提高PGE水平来促进伤口愈合。
