Natural Products: Potential Source of DPP-IV Inhibitors

Author(s): Rajeev K. Singla*, Rishabh Kumar, Sameer Khan, Mohit, Kajal Kumari, Arun Garg

Journal Name: Current Protein & Peptide Science

Volume 20 , Issue 12 , 2019

Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


Out of multiple therapeutic targets, DPP-IV is the lead target for the treatment of type 2 diabetes. Natural products have always been available for the possible lead generation against various diseases and disorders. In the present review, we have covered various natural sources which have experimentally validated anti-diabetic activity for type 2 diabetic patients with specific focus on the DPP-IV inhibition. Out of all, the most potent DPP-IV inhibitors were found to be resveratrol, luteolin, apigenin and flavone having activity in nanomolar range. Standard drugs like sitagliptin, saxagliptin, and diprotin A have complex structures as compared to these phenolic compounds. Flavonoids and phenolic compounds have their added advantages in being present in a number of functional foods and carry antioxidant properties as well. So, the scientists working on the new chemical entity hunting for the type 2 diabetes treatment can also explore these natural sources for lead generation.

Keywords: Dipeptidyl-peptidase IV, antidiabetes, type 2 diabetes, natural medicines, phenolic compounds, sitagliptin.

Matteucci, E.; Giampietro, O. Dipeptidyl peptidase-4 (CD26): knowing the function before inhibiting the enzyme. Curr. Med. Chem., 2009, 16, 2943-2951.
MacDonald, P.E.; El-kholy, W.; Riedel, M.J.; Salapatek, A.M.F.; Light, P.E.; Wheeler, M.B. The multiple actions of GLP-1 on the process of glucose-stimulated insulin secretion. Diabetes, 2002, 51, S434-S442.
Lambeir, A-M.; Durinx, C.; Scharpe, S.; Meester, I.D. Dipeptidyl-peptidase IV from bench to bedside: An update on structural properties, functions, and clinical aspects of the enzyme DPP IV. Crit. Rev. Clin. Lab. Sci., 2003, 40, 209-294.
Fan, J.; Johnson, M.H.; Lila, M.A.; Yousef, G.; de Mejia, E.G. Berry and citrus phenolic compounds inhibit dipeptidyl peptidase IV: Implications in diabetes management. Evidence-Based Complementary In: Altern. Med.,; , 2013. 2013, Article ID 479505.
Pandey, N.; Tripathi, Y.B. Antioxidant activity of tuberosin isolated from Pueraria tuberosa Linn. J. Inflamm. (Lond.), 2010, 7, 47.
Pandey, N.; Yadav, D.; Pandey, V.; Tripathi, Y.B. Antiinflammatory effect of Pueraria tuberosa extracts through improvement in activity of red blood cell anti-oxidant enzymes. Ayu, 2013, 34, 297-301.
Tripathi, A.K.; Kohli, S. Anti-diabetic activity and phytochemical screening of crude extracts of Pueraria tuberosa DC. (Fabaceae) grown in india on STZ-induced diabetic rats. Asian J. Med. Pharm., 2013, 3, 66-73.
Maji, A.K.; Pandit, S.; Banerji, P.; Banerjee, D. Pueraria tuberosa: A review on its phytochemical and therapeutic potential. Nat. Prod. Res., 2014, 28, 2111-2127.
Srivastava, S.; Koley, T.K.; Singh, S.K.; Tripathi, Y.B. The tuber extract of Pueraria tuberosa linn. competitively inhibits DPP-IV activity in normoglycemic rats. Int. J. Pharm. Pharm. Sci., 2015, 7, 227-231.
Srivastava, S.; Shree, P.; Tripathi, Y.B. Active phytochemicals of Pueraria tuberosa for DPP-IV inhibition: in silico and experimental approach. J. Diabetes Metab. Disord., 2017, 16, 46.
Umezawa, H.; Aoyagi, H.; Ogawa, K. Diprotein A and B, inhibitors of dipeptidyl amino peptidase IV, produced by bacteria. J. Antibiot. (Tokyo), 1984, 26, 422-425.
Yogisha, S.; Raveesha, K.A. Dipeptidyl peptidase IV inhibitory activity of Magnifera indica. J. Nat. Prod., 2010, 3, 76-79.
Upwar, N.; Patel, R.; Waseem, N.; Mahobia, N.K. Hypoglycemic effect of methanolic extract of Berberis aristata DC stem on normal and streptozotocin induced diabetic rats. Int. J. Pharm. Pharm. Sci., 2011, 3, 222-224.
Chakrabarti, R.; Bhavtaran, S.; Narendra, P.; Varghese, N.; Vanchhawng, L.; Shihabudeen, H. M.S.; Thirumurgan, K. Dipeptidyl peptidase-IV inhibitory activity of Berberis aristata. J. Nat. Prod., 2011, 4, 158-163.
Okyar, A.C.; Akev, A.; Baktir, N. N.; Sutlupinar, T. Effect of Aloe vera leaves on blood glucose level in type I and type II diabetic rat models. Phytother. Res., 2001, 15, 157-161.
Prasanna, R.C.; Venkataraman, K. Aloe vera phytochemicals inhibits dipeptidyl peptidase IV (DPP-IV), an anti-diabetic agent. Int. J. Pharma Bio Sci., 2016, 7, 120-128.
Bisht, R.; Bhattacharya, S.; Jaliwala, Y.A. Evaluating the use of Desmodium gangeticum as alpha Glucosidase and DPPIV inhibitor for type-II diabetes. Am. J. Phytomed. Clin. Ther., 2014, 2, 530-539.
Kirtikar, K.R.; Basu, B.D. Indian Medicinal Plants, 2nd ed Vol. I.; International Book Distributors: Dehradun, India, 1987.
Rathi, A.; Rao, C.V.; Ravishankar, B.; Deb, S.; Mehrotra, S. Anti-inflammatory and antinociceptive activity of the water decoction Desmodium gangeticum. J. Ethnopharmacol., 2004, 95, 259-263.
Bisht, R.; Bhattacharya, S. Effect of various extracts of Desmodium gangeticum on streptozotocin-nicotinamide induced type-2 diabetes. Asian J. Plant Sci. Res., 2013, 3, 28-34.
Bharti, S.K.; Krishnan, S.; Kumar, A.; Rajak, K.K.; Murari, K.; Bharti, B.K.; Gupta, A.K. Antihyperglycemic activity with DPP-IV inhibition of alkaloids from seed extract of Castanospermum australe: Investigation by experimental validation and molecular docking. Phytomedicine, 2012, 20, 24-31.
Atique, A.; Iqbal, M.; Ghouse, A.K.M. Use of Annona squamosa and Piper nigrum against diabetes. Fitoterapia, 1985, 56, 190-192.
Topno, K.K. Plants used by tribals of Chotanagpur against diabetes. Botanica, 1997, 47, 99-101.
Gupta, R.K.; Kesari, A.N.; Murthy, P.S.; Chandra, R.; Tandon, V.; Watal, G. Hypoglycemic and antidiabetic effect of ethanolic extract of leaves of Annona squamosa L. in experimental animals. J. Ethnopharmacol., 2005, 99, 75-81.
Kato, E.; Uenishi, Y.; Inagaki, Y.; Kurokawa, M.; Kawabata, J. Isolation of rugosin A, B and related compounds as dipeptidyl peptidase-IV inhibitors from rose bud extract powder. Biosci. Biotechnol. Biochem., 2016, 80(11), 2087-2092.
Kim, B.R.; Kim, H.Y.; Choi, I.; Kim, J.B.; Jin, C.H.; Han, A.R. DPP-IV inhibitory potentials of flavonol glycosides isolated from the seeds of Lens culinaris: In vitro and molecular docking analyses. Molecules, 2018, 23, 1998.
Nongonierma, A.B.; Le Maux, S.; Dubrulle, C.; Barre, C.; FitzGerald, R.J. Quinoa (Chenopodium quinoa Willd.) protein hydrolysates with in vitro dipeptidyl peptidase IV (DPP-IV) inhibitory and antioxidant properties. J. Cereal Sci., 2015, 65, 112-118.
Ekayanti, M.; Sauriasari, R.; Elya, B. Dipeptidyl peptidase IV inhibitory activity of fraction from white tea ethanolic extract (Camellia sinensis (L.) Kuntze) ex vivo. Pharmacogn. J., 2018, 10, 190-193.
Ahmad, M.; Khan, M.A.; Arshad, M.; Zafar, M. Ethnophytotherapical approaches for the treatment of diabetes by the local inhabitants of district Attock (Pakistan). Ethnobotanical Leaflet, 2004. 2004, Article 7.
Aneel Gilani, S.; Qureshi, R.A.; Javaria Gilani, S. Indigenous uses of some important ethnomedicinal herbs of Ayubia National Park, Abbottabad, Pakistan. Ethnobotanical Leaflet, 2006, 10, 285-293.
Saleem, S.; Jafri, L. ul Haq, I.; Chang, L.C.; Calderwood, D.; Green, B.D.; Mirza, B. Plants Fagonia cretica L. and Hedera nepalensis K. Koch contain natural compounds with potent dipeptidyl peptidase-4 (DPP-4) inhibitory activity. J. Ethnopharmacol., 2014, 156, 26-32.
Velarde-Salcedo, A.J.; Barrera-Pacheco, A.; Lara-Gonzalez, S.; Montero-Moran, G.M.; Diaz-Gois, A.; de Mejia, E.G.; Barba de la Rosa, A.P. In vitro inhibition of dipeptidyl peptidase IV by peptides derived from the hydrolysis of amaranth (Amaranthus hypochondriacus L.) proteins. Food Chem., 2013, 136, 758-764.
Dey, B.; Mitra, A.; Katakam, P.; Singla, R.K. Exploration of natural enzyme inhibitors with hypoglycemic potentials amongst Eucalyptus Spp. by in vitro assays. World J. Diabetes, 2014, 5, 209-218.
Borde, M.K.; Mohanty, I.R.; Maheshwari, U.; Suman, R.K.; Deshmukh, Y.A. Natural dipeptidyl peptidase-4 inhibitor Terminalia arjuna mitigates myocardial infarction co-existing with diabetes in experimental rats. J. Diabetes Metab. Disord. Control, 2018, 5, 48-56.
Matsabisa, M.G.; Chukwuma, C.I.; Chaudhary, S.K. South African traditional herbal formulation inhibits α-glucosidase, DPP-IV and glycation activities, and modulates glucose utilisation in Chang liver cells and 3T3-L1 adipocytes. S. Afr. J. Bot., 2019, 121, 121-127.
Gallego, M.; Aristoy, M.C.; Toldra, F. Dipeptidyl peptidase IV inhibitory peptides generated in Spanish dry-cured ham. Meat Sci., 2014, 96, 757-761.
Li-Chan, E.C.Y.; Hunag, S.L.; Jao, C.L.; Ho, K.P.; Hsu, K.C. Peptides derived from Atlantic salmon skin gelatin as dipeptidyl-peptidase IV inhibitors. J. Agric. Food Chem., 2012, 60, 973-978.
Huang, N.L. Fuscoporia obliqua-a mysterious folk medicinal mushroom in Russia. Edible Fungi of China, 2002, 4, 7-8.
Sun, J.E.; Ao, Z.H.; Lu, Z.M.; Xu, H.Y.; Zhang, X.M.; Dou, W.F.; Xu, Z.H. Antihyperglycemic and antilipidperoxidative effects of dry matter of culture broth of Inonotus obliquus in submerged culture on normal and alloxan-diabetes mice. J. Ethnopharmacol., 2008, 118, 7-13.
Geng, Y.; Lu, Z.M.; Huang, W.; Xu, H.Y.; Shi, J.S.; Xu, Z.H. Bioassay-guided isolation of DPP-4 inhibitory fractions from extracts of submerged cultured of Inonotus obliquus. Molecules, 2013, 18, 1150-1161.
Konrad, B.; Anna, D.; Marek, S.; Marta, P.; Aleksandra, Z.; Jozefa, C. The evaluation of dipeptidyl peptidase (DPP)-IV, α-glucosidase and angiotensin converting enzyme (ACE) inhibitory activities of whey proteins hydrolyzed with serine protease isolated from Asian pumpkin (Cucurbita ficifolia). Int. J. Pept. Res. Ther., 2014, 20, 483-491.
Lacroix, I.M.E.; Li-Chan, E.C.Y. Evaluation of the potential of dietary proteins as precursors of dipeptidyl peptidase (DPP)-IV inhibitors by an in silico approach. J. Funct. Foods, 2012, 4, 403-422.
Lacroix, I.M.E.; Li-Chan, E.C.Y. Dipeptidyl peptidase-IV inhibitory activity of dairy protein hydrolysates. Int. Dairy J., 2012, 25, 97-102.
Naseri, R.; Farzaei, F.; Haratipour, P.; Nabavi, S.F.; Habtemariam, S.; Farzaei, M.H.; Khodarahmi, R.; Tewari, D.; Momtaz, S. Anthocyanins in the management of metabolic syndrome: A pharmacological and biopharmaceutical review. Front. Pharmacol., 2018, 9, 1310.
Rasouli, H.; Farzaei, M.H.; Khodarahmi, R. Polyphenols and their benefits: A review. Int. J. Food Prop., 2017, 20, 1700-1741.
Das, R.; Gogoi, D.; Bhoumick, S.; Saikia, S.; Bezbaruah, R.L.; Bora, T.C.; Sarma, K.; Sahu, M.; Barooah, M. 3D- comparative modelling, structure comparison & docking studies for AVPR2 protein with some anti-diabetic plant compounds from North East India. Indo Global J. Pharm. Sci., 2014, 4, 8-17.
Bhattacharjee, R.; Mitra, A.; Dey, B.; Pal, A. Exploration of anti-diabetic potentials amongst marine species- a mini review. Indo Global J. Pharm. Sci., 2014, 4, 65-73.

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2019
Published on: 16 December, 2019
Page: [1218 - 1225]
Pages: 8
DOI: 10.2174/1389203720666190502154129
Price: $65

Article Metrics

PDF: 26