Plants Fagonia cretica L. and Hedera nepalensis K. Koch contain natural compounds with potent dipeptidyl peptidase-4 (DPP-4) inhibitory activity

<p>Ethnopharmacological relevance <br/>The two plants investigated here (Fagonia cretica L. and Hedera nepalensis K. Koch) have been previously reported as natural folk medicines for the treatment of diabetes but until now no scientific investigation of potential anti-diabetic effects has been reported. </p><p><br/>Materials and methods <br/>In vitro inhibitory effect of the two tested plants and their five isolated compounds on the dipeptidyl peptidase 4 (DPP-4) was studied for the assessment of anti-diabetic activity. </p><p>Results <br/>A crude extract of Fagonia cretica possessed good inhibitory activity (IC₅₀value: 38.1 μg/ml) which was also present in its n-hexane (FCN), ethyl acetate (FCE) or aqueous (FCA) fractions. A crude extract of Hedera nepalensis (HNC) possessed even higher inhibitory activity (IC₅₀value: 17.2 μg/ml) and this activity was largely retained when further fractionated in either ethyl acetate (HNE; IC₅₀: 34.4 μg/ml) or n-hexane (HNN; 34.2 μg/ml). Bioactivity guided isolation led to the identification of four known compounds (isolated for the first time) from Fagonia cretica: quinovic acid (1), quinovic acid-3β-O-β-d-glycopyranoside (2), quinovic acid-3β-O-β-d-glucopyranosyl-(28→1)-β-d-glucopyranosyl ester (3), and stigmasterol (4) all of which inhibited DPP-4 activity (IC₅₀: 30.7, 57.9, 23.5 and >100 μM, respectively). The fifth DPP-4 inhibitor, the triterpenoid lupeol (5) was identified in Hedera nepalensis (IC₅₀: 31.6 μM). </p><p>Conclusion <br/>The experimental study revealed that Fagonia cretica and Hedera nepalensis contain compounds with significant DPP-4 inhibitory activity which should be further investigated for their anti-diabetic potential.</p>