DOI: http://dx.doi.org/10.18203/2319-2003.ijbcp20190668

DPP-4 inhibitory activity and myocardial salvaging effects of Commiphora mukul in experimental diabetes

Manjusha K. Borde, Ipseeta Ray Mohanty, Ujwala Maheshwari, Rajesh Kumar Suman, Y. A. Deshmukh

Abstract


Background: Commiphora mukul (Burseraceae) is commonly known as Guggul in Ayurveda. Several studies have reported antidiabetic activity of Commiphora mukul but there are no studies to explore the DPP-4 inhibitory activity and myocardial salvaging effects of Commiphora mukul in setting of diabetes mellitus. The present study was designed to evaluate the cardioprotective efficacy as well as safety of the medicinal plant Commiphora mukul (Guggul) in the experimental model of myocardial infarction co-existing with diabetes.

Methods: Diabetes was induced with single dose of streptozotocin (STZ): 45mg/kg ip and myocardial infarction was produced by administering isoproterenol (ISP): (85mg/kg, sc) to rats 24 and 48 h prior to scarification (5th week). After the confirmation of diabetes on 7th day (glucose>200mg/dl), vildagliptin (10 mg/kg) and Commiphora mukul (200 mg/kg) were administered orally from 1st to 5th week (4 weeks). At the end of experimental period, normal control, diabetic-isoproterenol control, vildagliptin and Commiphora mukul group rats were sacrificed for further biochemical investigations as well as histopathological evaluation.

Results: Commiphora mukul treatment demonstrated significant antidiabetic as well as myocardial salvaging effects as indicated by restoration of blood glucose, HbA1c and CPK-MB serum DPP-4, hs-CRP levels as compared to diabetic ISP control group. In addition, Commiphora mukul showed significant cardioprotection as indicated by positive correlation between cardiac marker CPK-MB and serum DPP-4. The histopathological assessment of heart, pancreas and biochemical indices of injury confirmed the cardioprotective effects of Commiphora mukul. In addition, Commiphora mukul was found to be safe to the liver and kidney.

Conclusions: The natural DPP-4 inhibitor Commiphora mukul demonstrated significant cardioprotective effects in experimental model of myocardial infarction co-existing with diabetes.


Keywords


Commiphora mukul, DPP-4 inhibitor, Diabetes, Experimental model, Myocardial infarction

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References


Grundy SM, Benjamin IJ, Burke GL, Chait A, Eckel RH, Howard BV et al. Diabetes and cardiovascular disease: a statement for health professionals from the American Heart Association. Circulation. 1999;100:1134-46.

Sauvé M, Ban K, Momen MA, Zhou YQ, Henkelman RM, Husain M et al. Genetic deletion or pharmacological inhibition of dipeptidyl peptidase-4 improves cardiovascular outcomes after myocardial infarction in mice. Diabetes Epub. 2010;59(4):1063-73.

Stone PH, Muller JE, Hartwell T, York BJ, Rutherford JD, Parker CB, Turi ZG, et al. the MILIS Study Group. The effect ofdiabetes mellitus on prognosis and serial left ventricular function after acute myocardial infarction: contribution of both coronary disease and diastolic left ventricular dysfunction to the adverse prognosis. J Am Coll Cardiol. 1989;14:49-57.

Singer DE, Moulton AW, Nathan DM. Diabetic myocardial infarction: interaction of diabetes with other preinfarction risk factors. Diabetes.1989;38:350-57.

Smith JW, Marcus FI, Serokman R. Prognosis of patients with diabetes mellitus afteracute myocardial infarction. Am J Cardiol.1984;54:718-21.

Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS) UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998;352:837-55.

Kim W, Egan JM. The role of incretins in glucose homeostasis and diabetes treatment. Pharmacol Rev. 2008:60(4):470-12.

Avogaro A, Kreutzenberg SD, Fadini G. Dipeptidyl-peptidase 4 inhibition: linking metabolic control to cardiovascular protection. Current Pharm Design. 2014;20:2387-94.

Scheen AJ. Cardiovascular effects of dipeptidyl peptidase-4 inhibitors: from risk factors to clinical outcomes. Postgrad Med. 2013;125(3):7-20.

Fisman EZ and Tenenbaum A. treatment with gliptins: focus on cardiovascular effects and outcomes. Cardiovasc Diabetol. 2015;14(129):1-13.

Kalshetti P, Thakurdesai P, Alluri R. A Review on Bioactive Phytoconstituents and Pharmacological Uses of Commiphora mukul. J Curr Pharma Res. 2014;5(1):1392-405.

Manjunath S, Kugali SN, Deodurg PM. Effect of clonidine on blood glucose levels in euglycemic and alloxan-induced diabetic rats and its interaction with glibenclamide. Indian J Pharmacol. 2009;41(5):218-20.

George GS, Uwakwe AA. Hypoglycemic properties of some local herbs extracts in streptozotocin-induced diabetic Wistar Albino rats. J Dental Med Sci. 2014;13(1):1-7.

Viswanatha SAH, Patel UM, Koti BC, Gadad PC, Patel NL, Thippeswamy AH. Cardioprotective effect of saraca indica against cyclophosphamide induced cardiotoxicity in rats: a biochemical, electrocardiographic and histopathological study. Indian J Pharmacol. 2013;45(1):44-8.

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 Inhibi. Medicinal Chemistry. 2009;24(50):1061-6.

Marcy EM, Hayes TE, Tracy RP. Variability in measurement of C-reactive protein in healthy subjects: implication reference interval and epidemiological applications. Clin Chem. 1997;43:52-8.

Imamura S, Hirayama T, Arai T, Takao K, Misaki H. An enzymatic method using 1, 2-diglyceride for pancreatic lipase test in serum. Clin Chem. 1989;35:1126-1132.

King EJ,2-4DNPH method of determination of serum GOT and GPT. Can Med Assoc J. 1934;31:326.

Jaffe M. On the precipitated which picric acid produces in normal urine and on a new reaction of creatinine. Z Physiol Chem. 1886;10:391-400.

Mohanty IR, Maheshwari U, Daniel J and Moghe V. Bacopa monniera augments endogenous antioxidants and attenuates myocardial injury. Int J Integrative Biol. 2009;7(2):73-9.

Srinivasan BT, Jarvis J, Khunti K, Davies MJ. Recent advances in the management of type 2 diabetes mellitus: a review. Postgrad Med J. 2008;84:524-31.

Matteucci E, Giampietro O. Dipeptidyl peptidase-4 inhibition: linking chemical properties to clinical safety. Curr Med Chem. 2011;18(31):4753-60.

Nicolau RJ, Masmiquel CL. The new antidiabetic Agents in firing line safety reason or witch hunt. Endocrinol Nutr. 2012;59(1):1-8.

Monami M, Dicembrini I, Mannucci E. Dipeptidyl peptidase-4 inhibitors and pancreatitis risk: a meta-analysis of randomized clinical trials. Diabetes, Obesity Meta. 2014;16:48-56.

Elashoff M, Matveyenko AV, Gier B, Elashoff R, Butler PC. Pancreatitis and thyroid cancer with glucagon like peptide-1-based therapies. Gasteroenterol. 2011;141:150-6.

Borde MK, Mohanty IR, Suman RK, Deshmukh YA. dipeptidyl peptidase-iv inhibitory activities of medicinal plants: terminalia arjuna, commiphora mukul, gymnema sylvestre, morinda citrifolia, emblica officinalis. Asian J Pharm Clin Res. 2016;9(3):180-2.

Ramesh B, Karuna R, Sreenivasa SR, Kasetti RB, Pasurla R, Chippada AR, et al. Antihyperglycemic and antioxidant activities of alcoholic extract of Commiphora mukul gum resin in streptozotocin induced diabetic rats. Pathophysiol. 2011;18:255-61.

Widad M. Al-Bishri and Omar S. Al-Attas. Guggul resin extract improve hyperglycemia and lipid profile in streptozotocin induced diabetes mellitus in rats. Life Sci J. 2013;10(1):2735-41.

Barve K, Bhonsle N. Commiphora mukul prevents myocardial dysfunction in streptozotocin induced diabetic rats. Pharmaceutical Crops. 2014;5(5):61-6.

Szapary PO, Wolfe ML, Bloedon LT, Cucchiara AJ, DerMarderosian AH, Cirigliano MD, et al. Guggulipid for the treatment of hypercholesterolemia: a randomized controlled trial. JAMA. 2003 Aug 13;290(6):765-72.

Taru P, Abhyankar M, Undale V, Bhosale A. Acute and subacute toxicity studies on shodhana processed guggul. IJPSR. 2013;4(2):796-9.

Read PA, Khan FZ, Dutka DP. Cardioprotection against ischaemia induced by dobutamine stress using glucagon-like peptide-1 in patients with coronary artery disease. Heart. 2012;98:408-13.

Connelly K, Zhang Y, Advani A Advani S, Thai K, Yuen D, Gilbert RE. DPP-4 Inhibition attenuates cardiac dysfunction and adverse remodeling following myocardial infarction in rats with experimental diabetes. Cardiovas Therap. 2013;31:259-67.