In-vitro wound healing effect of 15-hydroxyprostaglandin dehydrogenase inhibitor from plant

Background: Prostaglandins (PGs) have short existence in vivo because they are rapidly metabolized by NAD⁺-dependent 15-hydroxyprostaglandin dehydrogenase (15-PGDH) to 15-ketoprostaglandins. Inhibition of 15-PGDH causes elevated level of PGE₂ in cellular system. It will be valuable for the therapeutic management of diseases requiring elevated PGE₂ levels, like wound healing. Objective: Ninety-eight plant samples were screened for the discovery of potent 15-PGDH inhibitor. Among them, top five plant extracts as potent 15-PGDH inhibitor were chosen to determine PGE₂ release from HaCaT (Keratinocyte cell line) cell line. Finally, top 15-PGDH inhibitor was selected to evaluate in vitro wound healing effect on HaCaT scratch model. Method: The inhibitory activity for 15-PGDH inhibitors was evaluated using fluorescence spectrophotometer by measuring the formation of NADH at 468 nm following excitation at 340 nm. Cell viability assay and PGE₂ release was evaluated in HaCaT cell line after treatment of 15-PGDH inhibitors. Scratches were made using sterile 200 μL on HaCaT cell and wound-healing effect was evaluated after treatment of 15-PGDH inhibitor. Results: 15-PGDH inhibitors elevated PGE₂ levels in concentration-dependent manner. Ethanol extract of Artocarpus heterophyllus (EEAH), the most potent 15-PGDH inhibitor (IC₅₀ = 0.62 µg/mL) with least cytotoxicity (IC₅₀ = 670 µg/ml), elevated both intracellular and extracellular PGE₂ levels. EEAH facilitated in-vitro wound healing in a HaCaT (Keratinocyte cell line) scratch model. Conclusion: EEAH might apply to treat dermal wounds by elevating PGE₂ levels via COX-1 induction and 15-PGDH inhibition.