title: Plants Fagonia cretica L. and Hedera nepalensis K. Koch contain natural compounds with potent dipeptidyl peptidase-4 (DPP-4) inhibitory activity.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  A crude extract of Fagonia cretica possessed good inhibitory activity (IC₅₀ value: 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 (IC50 value: 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad 45320, Pakistan. Electronic address: samreen.qau@gmail.com.
authors.forename: Samreen
authors.initials: S
authors.lastname: Saleem
authors.affiliation: Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad 45320, Pakistan. Electronic address: lailashah9@gmail.com.
authors.forename: Laila
authors.initials: L
authors.lastname: Jafri
authors.affiliation: Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad 45320, Pakistan. Electronic address: ihaq@qau.edu.pk.
authors.forename: Ihsan
authors.initials: I
authors.lastname: ul Haq
authors.affiliation: Department of Pharmaceutical Sciences, Daniel K. Inouye College of Pharmacy, University of Hawaii at Hilo, Hilo, HI 96720, United States. Electronic address: lengchee@hawaii.edu.
authors.forename: Leng Chee
authors.initials: LC
authors.lastname: Chang
authors.affiliation: Advanced ASSET Centre, Institute for Global Food Security, School of Biological Sciences, Queens University Belfast, David Keir Building, Stranmillis Road, Belfast BT9 5AG, Northern Ireland, UK. Electronic address: dcalderwood01@qub.ac.uk.
authors.forename: Danielle
authors.initials: D
authors.lastname: Calderwood
authors.affiliation: Advanced ASSET Centre, Institute for Global Food Security, School of Biological Sciences, Queens University Belfast, David Keir Building, Stranmillis Road, Belfast BT9 5AG, Northern Ireland, UK. Electronic address: b.green@qub.ac.uk.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Green
authors.affiliation: Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad 45320, Pakistan. Electronic address: bushramirza@qau.ed.pk.
authors.forename: Bushra
authors.initials: B
authors.lastname: Mirza
mesh_terms: D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D035981:Hedera; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000494:pharmacology*; D008519:Medicine, Traditional / Q000379:methods; D010936:Plant Extracts / Q000737:chemistry* / Q000494:pharmacology*; D028461:Zygophyllaceae
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D010936:Plant Extracts
keywords: Diabetes; Dipeptidyl peptidase 4 (DPP-4) inhibition; Fagonia cretica; Hedera nepalensis; Incretin