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Since 15-hydroxyprostaglandin dehydrogenase (15-PGDH) is the key metabolic enzyme of prostaglandin E2 (PGE2), inhibition of 15-PGDH is supposed to facilitate various physiological functions by increasing PGE2. Methanol extract of Artemisia argyi (AAME) inhibited 15-PGDH (IC50: 13.13 mg/mL) with relatively low cytotoxicity (IC50: 415.00 mg/mL) and elevated extracellular PGE2 levels in HaCaT cells. Real-time PCR analysis showed that AAME decreased significantly mRNA expression of PG transporter (PGT) in HaCaT cells. These results indicate that AAME could be applicable to functional materials as a 15-PGDH inhibitor and PGT expression inhibitor for the upregulation of extracellular PGE2 level.