Samreen Saleem1, Laila Jafri2, Ihsan ul Haq3, Leng Chee Chang4, Danielle Calderwood5, Brian D Green6, Bushra Mirza7. 1. Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad 45320, Pakistan. Electronic address: samreen.qau@gmail.com. 2. Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad 45320, Pakistan. Electronic address: lailashah9@gmail.com. 3. Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad 45320, Pakistan. Electronic address: ihaq@qau.edu.pk. 4. 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. 5. 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. 6. 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. 7. Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad 45320, Pakistan. Electronic address: bushramirza@qau.ed.pk.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: 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. MATERIALS AND 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). CONCLUSION: 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.
ETHNOPHARMACOLOGICAL RELEVANCE: 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. MATERIALS AND 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 triterpenoidlupeol (5) was identified in Hedera nepalensis (IC₅₀: 31.6 μM). CONCLUSION: 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: Kamran Saeed; Shahid Ali Shah; Rahat Ullah; Sayed Ibrar Alam; Jun Sung Park; Samreen Saleem; Myeung Hoon Jo; Min Woo Kim; Jong Ryeal Hahm; Myeong Ok Kim Journal: Oxid Med Cell Longev Date: 2020-11-20 Impact factor: 6.543