Amelioration of Type 2 Diabetes Mellitus by Plant-derived Natural
Dipeptidyl Peptidase-4 Inhibitors through Incretin Degradation Lowering
Effect: An Updated Review

Hari      Kishan; Manjusha      Choudhary; Sachin      Sharma; Prabhjeet      Kaur Bamrah; Nitesh      Choudhary
doi:10.2174/1573408019666230912123312
Abstract

Glucagon-like peptide-1 and Glucose-dependent insulinotropic polypeptides are the most investigated gut peptides concerned with the biological glucose milieu. Early and late metabolism of incretin governs glucose homeostasis in diabetes mellitus. Dipeptidyl Peptidase-4, present in pancreatic alpha cells, is responsible for incretin degradation. Emerging biotechnological and molecular approaches established the pathophysiological role of Dipeptidyl Peptidase-4 and incretin in type 2 diabetes mellitus. Thus, various conventional synthetic Dipeptidyl Peptidase-4 inhibitors have been formulated, but they have serious adverse effects such as cancer, pancreatitis, cardiovascular risks, hepatic dysfunctions, etc. So, the concoction of a Dipeptidyl Peptidase-4 inhibitor entity with less or no severe adverse event becomes a need for society and medical corridor. Over the last two decades, natural or conventional herbal remedies have emerged as an alternate therapy for diabetes and treating its complications. This review summarized various plants (Emblica officinalis, Adenia viridiflora, Cleome droserifolia, Lens culinaris, Hedera nepalensis Melicope glabra, etc.) Dipeptidyl Peptidase-4 inhibitors, which have been preclinically proven for hyperglycemia treatment.
Keywords: Diabetes, dipeptidyl peptidase-4, medicinal plants, phytochemicals, amelioration, hyperglycemia.
« Previous
Graphical Abstract

[1]
IDF Diabetes Atlas.  Available from: https://diabetesatlas.org/

[2]
Campbell JE, Drucker DJ. Pharmacology, physiology, and mechanisms of incretin hormone action. Cell Metab  2013; 17(6): 819-37.
 [http://dx.doi.org/10.1016/j.cmet.2013.04.008] [PMID: 23684623]

[3]
Zhang T, Tong X, Zhang S, et al. The roles of dipeptidyl peptidase 4 (DPP4) and DPP4 inhibitors in different lung diseases: New evidence. Front Pharmacol  2021; 12: 731453.
 [http://dx.doi.org/10.3389/fphar.2021.731453] [PMID: 34955820]

[4]
Kumar S, Mittal A, Mittal A. A review upon medicinal perspective and designing rationale of DPP-4 inhibitors. Bioorg Med Chem  2021; 46: 116354.
 [http://dx.doi.org/10.1016/j.bmc.2021.116354] [PMID: 34428715]

[5]
Sharko A, Samuel S, Jain N. Acute pancreatitis induced by linagliptin: A rare but dangerous side effect. Cureus  2021; 13(3): 3.
 [http://dx.doi.org/10.7759/cureus.14104]

[6]
Spinar J, Smahelová A. [SAVOR TIMI 53 - Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus]. Vnitr Lek  2013; 59(11): 1003-7.
 [PMID: 24279445]

[7]
Cohen D. Reports of pancreatitis are 20-30 times more likely with GLP-1 drugs, analysis finds. BMJ  2013; 346: f2607.
 [http://dx.doi.org/10.1136/bmj.f2607] [PMID: 23613543]

[8]
Turdu G, Gao H, Jiang Y, Kabas M. Plant dipeptidyl peptidase-IV inhibitors as antidiabetic agents: A brief review. Future Med Chem  2018; 10(10): 1229-39.
 [http://dx.doi.org/10.4155/fmc-2017-0235] [PMID: 29749760]

[9]
Majeed M, Majeed S, Mundkur L, et al. Standardized Emblica officinalis fruit extract inhibited the activities of α ‐amylas glucosidase, and dipeptidyl peptidase-4 and displayed antioxidant potential. J Sci Food Agric  2020; 100(2): 509-16.
 [http://dx.doi.org/10.1002/jsfa.10020] [PMID: 31487036]

[10]
Wannasaksri W, On-Nom N, Chupeerach C, Temviriyanukul P, Charoenkiatkul S, Suttisansanee U. In vitro phytotherapeutic properties of aqueous extracted adenia viridiflora Craib. towards civilization diseases. Molecules  2021; 26(4): 1082.
 [http://dx.doi.org/10.3390/molecules26041082] [PMID: 33670795]

[11]
Abdel Motaal A, Salem HH, Almaghaslah D, et al. Flavonol Glycosides: In vitro inhibition of dppiv, aldose reductase and combating oxidative stress are potential mechanisms for mediating the antidiabetic activity of cleome droserifolia. Molecules  2020; 25(24): 5864.
 [http://dx.doi.org/10.3390/molecules25245864] [PMID: 33322431]

[12]
Kim BR, Kim H, Choi I, Kim JB, Jin C, Han AR. DPP-IV inhibitory potentials of flavonol glycosides isolated from the seeds of lens culinaris: In vitro and molecular docking analyses. Molecules  2018; 23(8): 1998.
 [http://dx.doi.org/10.3390/molecules23081998] [PMID: 30103438]

[13]
Saleem S, Jafri L, Haq I, et al. 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.
 [http://dx.doi.org/10.1016/j.jep.2014.08.017] [PMID: 25169215]

[14]
Quek A, Kassim NK, Ismail A, et al. Identification of dipeptidyl peptidase-4 and α-amylase inhibitors from melicope glabra (blume) T. G. hartley (rutaceae) using liquid chromatography tandem mass spectrometry, in vitro and in silico Methods. Molecules  2020; 26(1): 1.
 [http://dx.doi.org/10.3390/molecules26010001] [PMID: 33374962]

[15]
Quek A, Kassim NK, Lim PC, et al. α-Amylase and dipeptidyl peptidase-4 (DPP-4) inhibitory effects of Melicope latifolia bark extracts and identification of bioactive constituents using in vitro and in silico approaches. Pharm Biol  2021; 59(1): 962-71.
 [http://dx.doi.org/10.1080/13880209.2021.1948065] [PMID: 34347568]

[16]
Ram H, Kumar P, Purohit A, et al. Improvements in HOMA indices and pancreatic endocrinal tissues in type 2-diabetic rats by DPP-4 inhibition and antioxidant potential of an ethanol fruit extract of Withania coagulans. Nutr Metab  2021; 18(1): 43.
 [http://dx.doi.org/10.1186/s12986-021-00547-2] [PMID: 33882957]

[17]
Yang Y, Shi CY, Xie J, Dai JH, He SL, Tian Y. Identification of potential dipeptidyl peptidase (DPP)-IV inhibitors among moringa oleifera phytochemicals by virtual screening, molecular docking analysis, ADME/T-Based prediction, and in vitro analyses. Molecules  2020; 25(1): 189.
 [http://dx.doi.org/10.3390/molecules25010189] [PMID: 31906524]

[18]
Deacon CF. Physiology and pharmacology of DPP-4 in glucose homeostasis and the treatment of type 2 diabetes. Front Endocrinol  2019; 10: 80.
 [http://dx.doi.org/10.3389/fendo.2019.00080] [PMID: 30828317]

[19]
Liu L, Omar B, Marchetti P, Ahrén B. Dipeptidyl peptidase-4 (DPP-4): Localization and activity in human and rodent islets. Biochem Biophys Res Commun  2014; 453(3): 398-404.
 [http://dx.doi.org/10.1016/j.bbrc.2014.09.096] [PMID: 25268763]

[20]
Deacon CF. Peptide degradation and the role of DPP-4 inhibitors in the treatment of type 2 diabetes. Peptides  2018; 100: 150-7.
 [http://dx.doi.org/10.1016/j.peptides.2017.10.011] [PMID: 29412814]

[21]
Gupta S, Sen U. More than just an enzyme: Dipeptidyl peptidase-4 (DPP-4) and its association with diabetic kidney remodelling. Pharmacol Res  2019; 147: 104391.
 [http://dx.doi.org/10.1016/j.phrs.2019.104391] [PMID: 31401210]

[22]
Nauck MA, Meier JJ. The incretin effect in healthy individuals and those with type 2 diabetes: Physiology, pathophysiology, and response to therapeutic interventions. Lancet Diabetes Endocrinol  2016; 4(6): 525-36.
 [http://dx.doi.org/10.1016/S2213-8587(15)00482-9] [PMID: 26876794]

[23]
Nauck MA, Meier JJ. Incretin hormones: Their role in health and disease. Diabetes Obes Metab  2018; 20 (Suppl. 1): 5-21.
 [http://dx.doi.org/10.1111/dom.13129] [PMID: 29364588]

[24]
Omar BA, Liehua L, Yamada Y, Seino Y, Marchetti P, Ahrén B. Dipeptidyl peptidase 4 (DPP-4) is expressed in mouse and human islets and its activity is decreased in human islets from individuals with type 2 diabetes. Diabetologia  2014; 57(9): 1876-83.
 [http://dx.doi.org/10.1007/s00125-014-3299-4] [PMID: 24939431]

[25]
Bugliani M, Syed F, Paula FMM, et al. DPP-4 is expressed in human pancreatic beta cells and its direct inhibition improves beta cell function and survival in type 2 diabetes. Mol Cell Endocrinol  2018; 473: 186-93.
 [http://dx.doi.org/10.1016/j.mce.2018.01.019] [PMID: 29409957]

[26]
Cornell S. A review of GLP-1 receptor agonists in type 2 diabetes: A focus on the mechanism of action of once-weekly agents. J Clin Pharm Ther  2020; 45(S1): 17-27.
 [http://dx.doi.org/10.1111/jcpt.13230] [PMID: 32910490]

[27]
Hasan AA, von Websky K, Reichetzeder C, et al. Mechanisms of GLP-1 receptor-independent renoprotective effects of the dipeptidyl peptidase type 4 inhibitor linagliptin in GLP-1 receptor knockout mice with 5/6 nephrectomy. Kidney Int  2019; 95(6): 1373-88.
 [http://dx.doi.org/10.1016/j.kint.2019.01.010] [PMID: 30979564]

[28]
Li YS, Tseng WL, Lu CY. Sensitive detection of quinoline-derivatized sitagliptin in small volumes of human plasma by MALDI-TOF mass spectrometry. Talanta  2020; 218: 121143.
 [http://dx.doi.org/10.1016/j.talanta.2020.121143] [PMID: 32797900]

[29]
Liu R, Cheng J, Wu H. Discovery of food-derived dipeptidyl peptidase IV inhibitory peptides: A review. Int J Mol Sci  2019; 20(3): 463.
 [http://dx.doi.org/10.3390/ijms20030463] [PMID: 30678216]

[30]
Mohanty IR, Borde M, Kumar CS, Maheshwari U. Dipeptidyl peptidase IV Inhibitory activity of Terminalia arjuna attributes to its cardioprotective effects in experimental diabetes: In silico, in vitro and in vivo analyses. Phytomedicine  2019; 57: 158-65.
 [http://dx.doi.org/10.1016/j.phymed.2018.09.195] [PMID: 30668318]

[31]
Jao CL, Hung CC, Tung YS, Lin PY, Chen MC, Hsu KC. The development of bioactive peptides from dietary proteins as a dipeptidyl peptidase IV inhibitor for the management of type 2 diabetes. Biomedicine  2015; 5(3): 14.
 [http://dx.doi.org/10.7603/s40681-015-0014-9] [PMID: 26267061]

[32]
Mosquera JE, Torres N, Restrepo J, Ruz-Pau C, Suryanarayanan S. Linagliptin-induced pancreatitis. AACE Clin Case Rep  2020; 6(1): e37-9.
 [http://dx.doi.org/10.4158/ACCR-2019-0307] [PMID: 33163625]

[33]
Singh S, Chang HY, Richards TM, Weiner JP, Clark JM, Segal JB. Glucagonlike peptide 1-based therapies and risk of hospitalization for acute pancreatitis in type 2 diabetes mellitus: A population-based matched case-control study. JAMA Intern Med  2013; 173(7): 534-9.
 [http://dx.doi.org/10.1001/jamainternmed.2013.2720] [PMID: 23440284]

[34]
Chou HC, Chen WW, Hsiao FY. Acute pancreatitis in patients with type 2 diabetes mellitus treated with dipeptidyl peptidase-4 inhibitors: A population-based nested case-control study. Drug Saf  2014; 37(7): 521-8.
 [http://dx.doi.org/10.1007/s40264-014-0171-x] [PMID: 24859164]

[35]
Faillie J-L, Babai S, Crépin S, et al. Pancreatitis associated with the use of GLP-1 analogs and DPP-4 inhibitors: A case/non-case study from the French Pharmacovigilance Database. Acta Diabetol  2014; 51(3): 491-7.
 [PMID: 24352344]

[36]
Sue M, Yoshihara A, Kuboki K, Hiroi N, Yoshino G. A case of severe acute necrotizing pancreatitis after administration of sitagliptin. Clin Med Insights Case Rep  2013; 6: 23-7.
 [http://dx.doi.org/10.4137/CCRep.S10856]

[37]
Nakata H, Sugitani S, Yamaji S, et al. Pancreatitis with pancreatic tail swelling associated with incretin-based therapies detected radiologically in two cases of diabetic patients with end-stage renal disease. Intern Med  2012; 51(21): 3045-9.
 [http://dx.doi.org/10.2169/internalmedicine.51.7876] [PMID: 23124148]

[38]
Kunjathaya P, Ramaswami PK, Krishnamurthy AN, Bhat N. Acute necrotizing pancreatitis associated with vildagliptin. JOP  2013; 14(1): 81-4.

[39]
Saraogi R, Mallik R, Ghosh S. Mild acute pancreatitis with vildagliptin use. Indian J Endocrinol Metab  2012; 16(8 (S2)): 480.
 [http://dx.doi.org/10.4103/2230-8210.104138] [PMID: 23565473]

[40]
Packer M. Do DPP-4 inhibitors cause heart failure events by promoting adrenergically mediated cardiotoxicity? Circ Res  2018; 122(7): 928-32.
 [http://dx.doi.org/10.1161/CIRCRESAHA.118.312673] [PMID: 29436388]

[41]
Monami M, Dicembrini I, Mannucci E. Dipeptidyl peptidase-4 inhibitors and heart failure: A meta-analysis of randomized clinical trials. Nutr Metab Cardiovasc Dis  2014; 24(7): 689-97.
 [http://dx.doi.org/10.1016/j.numecd.2014.01.017] [PMID: 24793580]

[42]
Ayaori M, Iwakami N, Uto-Kondo H, et al. Dipeptidyl peptidase-4 inhibitors attenuate endothelial function as evaluated by flow-mediated vasodilatation in type 2 diabetic patients. J Am Heart Assoc  2013; 2(1): e003277.
 [http://dx.doi.org/10.1161/JAHA.112.003277] [PMID: 23525426]

[43]
Yi H, Lee JH, Shin JY. Signal detection for cardiovascular adverse events of DPP-4 inhibitors using the korea adverse event reporting system database, 2008–2016. Yonsei Med J  2019; 60(2): 200-7.
 [http://dx.doi.org/10.3349/ymj.2019.60.2.200] [PMID: 30666842]

[44]
Toyoda-Akui M, Yokomori H, Kaneko F, et al. A case of drug-induced hepatic injury associated with sitagliptin. Intern Med  2011; 50(9): 1015-20.
 [http://dx.doi.org/10.2169/internalmedicine.50.5057] [PMID: 21532224]

[45]
Gross BN, Cross LB, Foard J, Wood Y. Elevated hepatic enzymes potentially associated with sitagliptin. Ann Pharmacother  2010; 44(2): 394-5.
 [http://dx.doi.org/10.1345/aph.1M323] [PMID: 20103614]

[46]
Kutoh E. Probable linagliptin-induced liver toxicity: A case report. Diabetes Metab  2014; 40(1): 82-4.
 [http://dx.doi.org/10.1016/j.diabet.2013.09.009] [PMID: 24378344]

[47]
Seino Y, Hiroi S, Hirayama M, Kaku K. Efficacy and safety of alogliptin added to sulfonylurea in Japanese patients with type 2 diabetes: A randomized, double-blind, placebo-controlled trial with an open-label, long-term extension study. J Diabetes Investig  2012; 3(6): 517-25.
 [http://dx.doi.org/10.1111/j.2040-1124.2012.00226.x] [PMID: 24843617]

[48]
Aschner P, Chan J, Owens DR, et al. Insulin glargine versus sitagliptin in insulin-naive patients with type 2 diabetes mellitus uncontrolled on metformin (EASIE): A multicentre, randomised open-label trial. Lancet  2012; 379(9833): 2262-9.
 [http://dx.doi.org/10.1016/S0140-6736(12)60439-5] [PMID: 22683131]

[49]
Li R, Zeng X, Yang M, et al. Antidiabetic DPP-4 inhibitors reprogram tumor microenvironment that facilitates murine breast cancer metastasis through interaction with cancer cells via a ROS–NF-кB–NLRP3 axis. Front Oncol  2021; 11: 728047.
 [http://dx.doi.org/10.3389/fonc.2021.728047] [PMID: 34631556]

[50]
Bajaj M, Gilman R, Patel S, Kempthorne-Rawson J, Lewis-D’Agostino D, Woerle HJ. Linagliptin improved glycaemic control without weight gain or hypoglycaemia in patients with Type 2 diabetes inadequately controlled by a combination of metformin and pioglitazone: A 24-week randomized, double-blind study. Diabet Med  2014; 31(12): 1505-14.
 [http://dx.doi.org/10.1111/dme.12495] [PMID: 24824197]

[51]
Kumar S, Mittal A, Babu D, Mittal A. Herbal medicines for diabetes management and its secondary complications. Curr Diabetes Rev  2021; 17(4): 437-56.
 [http://dx.doi.org/10.2174/18756417MTExfMTQ1z] [PMID: 33143632]

[52]
Ansari P, Hannon-Fletcher MP, Flatt PR, Abdel-Wahab YHA. Effects of 22 traditional anti-diabetic medicinal plants on DPP-IV enzyme activity and glucose homeostasis in high-fat fed obese diabetic rats. Biosci Rep  2021; 41(1): BSR20203824.
 [http://dx.doi.org/10.1042/BSR20203824] [PMID: 33416077]

[53]
Geng Y, Lu ZM, Huang W, Xu HY, Shi JS, Xu ZH. Bioassay-guided isolation of DPP-4 inhibitory fractions from extracts of submerged cultured of Inonotus obliquus. Molecules  2013; 18(1): 1150-61.
 [http://dx.doi.org/10.3390/molecules18011150] [PMID: 23325103]

[54]
Ram H, Jaipal N, Kumar P, et al. Dual inhibition of dpp-4 and cholinesterase enzymes by the phytoconstituents of the ethanolic extract of prosopis cineraria pods: Therapeutic implications for the treatment of diabetes-associated neurological impairments. Curr Alzheimer Res  2020; 16(13): 1230-44.
 [http://dx.doi.org/10.2174/1567205016666191203161509] [PMID: 31797759]

[55]
Kalhotra P, Chittepu VCSR, Osorio-Revilla G, Gallardo-Velazquez T. Phytochemicals in garlic extract inhibit therapeutic enzyme DPP-4 and induce skeletal muscle cell proliferation: A possible mechanism of action to benefit the treatment of diabetes mellitus. Biomolecules  2020; 10(2): 305.
 [http://dx.doi.org/10.3390/biom10020305] [PMID: 32075130]

[56]
Perumal N, Nallappan M, Shohaimi S, Kassim NK, Tee TT, Cheah YH. Synergistic antidiabetic activity of Taraxacum officinale (L.) Weber ex F.H.Wigg and Momordica charantia L. polyherbal combination. Biomed Pharmacother  2022; 145: 112401.
 [http://dx.doi.org/10.1016/j.biopha.2021.112401] [PMID: 34785415]

[57]
Amin MS, Saputri FC, Munim A. Inhibition of dipeptidyl peptidase 4 (DPP IV) activity by some indonesia edible plants. Pharmacogn J  2019; 11(2): 231-6.
 [http://dx.doi.org/10.5530/pj.2019.11.36]

[58]
Shivanna Y, Raveesha KA. Dipeptidyl peptidase IV inhibitory activity of Mangifera indica. J Natural Prod  2010; 3: 76-9.

[59]
Yuliet, Sukandar EY, Adnyana IK. Active subfractions, phytochemical constituents, dipeptidyl peptidase-IV inhibitory activity and antioxidant of leaf extract from hibiscus surattensis L. Nat Prod J  2020; 10(4): 400-10.
 [http://dx.doi.org/10.2174/2210315509666190626125330]

[60]
Mahmood R, Kayani WK, Ahmed T, Malik F, Hussain S, Ashfaq M, et al. Assessment of antidiabetic potential and phytochemical profiling of Rhazya stricta root extracts. BMC Complement Med Ther  2020; 20(1): 296.
 [http://dx.doi.org/10.1186/s12906-020-03035-x]

[61]
Lim WXJ, Gammon CS, von Hurst P, Chepulis L, Page RA. The inhibitory effects of new zealand pine bark (Enzogenol®) on α-amylase, α-glucosidase, and dipeptidyl peptidase-4 (DPP-4) enzymes. Nutrients  2022; 14(8): 1596.
 [http://dx.doi.org/10.3390/nu14081596] [PMID: 35458159]

[62]
Tarigan TJE, Purwaningsih EH. Effects of sambiloto (Andrographis paniculata) on GLP-1 and DPP-4 concentrations between normal and prediabetic subjects: A crossover study. Evid Based Complement Alternat Med  2022; 2022: 1535703.

[63]
Lalitha N, Sadashivaiah B, Ramaprasad TR, Singh SA. Anti-hyperglycemic activity of myricetin, through inhibition of DPP-4 and enhanced GLP-1 levels, is attenuated by co-ingestion with lectin-rich protein. PLoS One  2020; 15(4): e0231543.
 [http://dx.doi.org/10.1371/journal.pone.0231543] [PMID: 32282828]

[64]
Wang X, Xiang J, Huang G, et al. Inhibition of podocytes DPP4 activity is a potential mechanism of lobeliae chinensis herba in treating diabetic kidney disease. Front Pharmacol  2021; 12: 779652.
 [http://dx.doi.org/10.3389/fphar.2021.779652] [PMID: 34950037]

[65]
Okechukwu P, Sharma M, Tan WH, et al. In-vitro anti-diabetic activity and in-silico studies of binding energies of palmatine with alpha-amylase, alpha-glucosidase and DPP-IV enzymes. Pharmacia  2020; 67(4): 363-71.
 [http://dx.doi.org/10.3897/pharmacia.67.e58392]

[66]
Hamden K, Bengara A, Amri Z, Elfeki A. Experimental diabetes treated with trigonelline: Effect on key enzymes related to diabetes and hypertension, β-cell and liver function. Mol Cell Biochem  2013; 381(1-2): 85-94.
 [http://dx.doi.org/10.1007/s11010-013-1690-y] [PMID: 23754616]

[67]
Akhtar N, Jafri L, Green BD, Kalsoom S, Mirza B. A multi-mode bioactive agent isolated from ficus microcarpa l. fill. with therapeutic potential for type 2 diabetes mellitus. Front Pharmacol  2018; 9: 1376.
 [http://dx.doi.org/10.3389/fphar.2018.01376] [PMID: 30542284]

[68]
Shaikh S, Ali S, Lim JH, et al. Dipeptidyl peptidase-4 inhibitory potentials of Glycyrrhiza uralensis and its bioactive compounds licochalcone A and licochalcone B: An in silico and in vitro study. Front Mol Biosci  2022; 9: 1024764.
 [http://dx.doi.org/10.3389/fmolb.2022.1024764] [PMID: 36250007]

[69]
Khan A, Khan I, Halim SA, et al. Anti-diabetic potential of β-boswellic acid and 11-keto-β-boswellic acid: Mechanistic insights from computational and biochemical approaches. Biomed Pharmacother  2022; 147: 112669.
 [http://dx.doi.org/10.1016/j.biopha.2022.112669] [PMID: 35121344]

[70]
Pan J, Zhang Q, Zhang C, et al. Inhibition of dipeptidyl peptidase-4 by flavonoids: Structure–activity relationship, kinetics and interaction mechanism. Front Nutr  2022; 9: 892426.
 [http://dx.doi.org/10.3389/fnut.2022.892426] [PMID: 35634373]

[71]
Imai C, Saito M, Mochizuki K, Fuchigami M, Goda T, Osonoi T. Cotreatment with the α-glucosidase inhibitor miglitol and DPP-4 inhibitor sitagliptin improves glycemic control and reduces the expressions of CVD risk factors in type 2 diabetic Japanese patients. Metabolism  2014; 63(6): 746-53.
 [http://dx.doi.org/10.1016/j.metabol.2013.12.014] [PMID: 24559582]

[72]
Ram H, Krishna A. Improvements in insulin resistance and β-Cells dysfunction by DDP-4 inhibition potential of Withania somnifera (L.) dunal root extract in type 2 diabetic rat. Biointerface Res Appl Chem  2020; 11(1): 8141-55.
 [http://dx.doi.org/10.33263/BRIAC111.81418155]

[73]
Purnomo Y, Soeatmadji DW, Sumitro SB, Widodo MA. Anti-diabetic potential of Urena lobata leaf extract through inhibition of dipeptidyl peptidase IV activity. Asian Pac J Trop Biomed  2015; 5(8): 645-9.
 [http://dx.doi.org/10.1016/j.apjtb.2015.05.014]

[74]
Zhao BT, Le DD, Nguyen PH, et al. PTP1B, α-glucosidase, and DPP-IV inhibitory effects for chromene derivatives from the leaves of Smilax china L. Chem Biol Interact  2016; 253: 27-37.
 [http://dx.doi.org/10.1016/j.cbi.2016.04.012] [PMID: 27060210]

[75]
Shukla A, Srinivasan BP. 16,17-Dihydro-17b-hydroxy isomitraphylline alkaloid as an inhibitor of DPP-IV, and its effect on incretin hormone and β-cell proliferation in diabetic rat. Eur J Pharm Sci  2012; 47(2): 512-9.

[76]
Nongonierma AB, Le Maux S, Dubrulle C, Barre C, FitzGerald RJ. Quinoa (Chenopodium quinoa Willd.) protein hydrolysates with in vitro dipeptidyl peptidase IV (DPP-IV) inhibitory and antioxidant properties. J Cereal Sci  2015; 65: 112-8.

[77]
Al-masri IM, Mohammad MK, Tahaa MO. Inhibition of dipeptidyl peptidase IV (DPP IV) is one of the mechanisms explaining the hypoglycemic effect of berberine. J Enzyme Inhib Med Chem  2009; 24(5): 1061-6.
 [http://dx.doi.org/10.1080/14756360802610761] [PMID: 19640223]

[78]
Mohanty IR, Kumar CS, Borde M. Antidiabetic activity of Commiphora mukul and Phyllanthus emblica and Computational analysis for the identification of active principles with dipeptidyl peptidase IV inhibitory activity. Indian J Pharmacol  2021; 53(5): 384-7.
 [PMID: 34854407]

[79]
Peng CH, Lin HC, Lin CL, Wang CJ, Huang CN. Abelmoschus esculentus subfractions improved nephropathy with regulating dipeptidyl peptidase-4 and type 1 glucagon-like peptide receptor in type 2 diabetic rats. Yao Wu Shi Pin Fen Xi  2019; 27(1): 135-44.
 [PMID: 30648566]

[80]
Abubakar A, Nazifi AB, Maje IM, Tanko Y, Anuka JA, Abdurahman EM. Antihyperglycaemic activity of ethylacetate extract of Chlorophytum alismifolium in type 2 diabetes: The involvement of peroxisome proliferator-activated receptor-γ and dipeptidyl peptidase-4. J Integr Med  2021; 19(1): 78-84.
 [http://dx.doi.org/10.1016/j.joim.2020.10.008] [PMID: 33223488]

[81]
Srivastava S, Shree P, Tripathi YB. Active phytochemicals of Pueraria tuberosa for DPP-IV inhibition: In silico and experimental approach. J Diabetes Metab Disord  2017; 16(1): 46.
 [http://dx.doi.org/10.1186/s40200-017-0328-0] [PMID: 29201861]

[82]
Kumar S, Krishnan S, Kumar A, Kishore K, Murari K, Kumar B, et al. Phytomedicine Antihyperglycemic activity with DPP-IV inhibition of alkaloids from seed extract of Castanospermum australe: Investigation by experimental validation and molecular docking. Eur J Integr Med  2012; 20(1): 24-31.

[83]
Andleeb S, Nadia A, Waqar H, Nouman R. In silico discovery of potential inhibitors against Dipeptidyl Peptidase-4: A major biological target of Type-2 diabetes mellitus. Int J Clin Microbiol Biochem Technol 2020; 01: pp. (3)01-10.

[84]
Mohanty I, Kumar S, Rajesh S. Dipeptidyl peptidase IV inhibitory activity of berberine and mangiferin An in silico approach.  J Clin Endocrinol Metab 2017; 01: pp. (3)18-22.

[85]
Shill MC, Bepari AK, Khan M, et al. Therapeutic potentials of colocasia affinis leaf extract for the alleviation of streptozotocin-induced diabetes and diabetic complications: In vivo and in silico-based studies. J Inflamm Res  2021; 14: 443-59.
 [http://dx.doi.org/10.2147/JIR.S297348] [PMID: 33642871]

[86]
Nisha J. Molecular docking analysis of potential dipeptidyl peptidase - 4 (DPP-4) inhibitors from siddha formulation pungampoo chooranam for treating diabetes mellitus. Int J Adv Res Biol Sci  2017; 4(10): 78-85.
 [http://dx.doi.org/10.22192/ijarbs.2017.04.10.011]
Rights & Permissions Print Cite
Article Metrics
24
2
Journal Information
For Authors
For Editors
For Reviewers
Explore Articles
Open Access
Open Access Articles
For Visitors
DOI https://dx.doi.org/10.2174/1573408019666230912123312	Print ISSN 1573-4080
Publisher Name Bentham Science Publisher	Online ISSN 1875-6662
Current Enzyme Inhibition

Amelioration of Type 2 Diabetes Mellitus by Plant-derived Natural Dipeptidyl Peptidase-4 Inhibitors through Incretin Degradation Lowering Effect: An Updated Review

Abstract

Graphical Abstract

Related Journals

Related Books

Related Articles
