Dipeptidyl peptidase IV inhibitory activity of Commiphora mukul monotherapy and combination therapy (with Metformin) attributes to its cardioprotective effects in experimental diabetes: In silico, in vitro and in vivo analysis
Keywords:
Keywords: DPP-IV inhibitor, Commiphora mukul, Combination Therapy, Diabetes, CardioprotectiveAbstract
Objectives: The marketed synthetic Dipeptidyl peptidase-IV (DPP-IV) inhibitors are expensive antidiabetic drugs and have been reported to cause unacceptable adverse effects. In this scenario research to develop novel DPP-IV inhibitors from alternative sources is the need of the hour. Commiphora mukul, a medicinal plant with antidiabetic and cardioprotective activities may represent a natural DPP-IV inhibitor, the DPP-IV inhibitory activity of which may translate into demonstrable therapeutic benefits in setting of diabetes with cardiovascular co-morbidities.
Materials and methods: The DPP-IV inhibitory, antidiabetic and cardioprotective effects of Commiphora mukul monotherapy and combination therapy (with Metformin) was evaluated in the experimental model of myocardial infarction co-existing with diabetes. To determine the active principle of Commiphora mukul responsible for DPP-IV inhibitory activity, the crystal structure of DPP-IV was considered as receptor which was docked against Gluggusterone E, Gluggusterone Z, Sitagliptin and Vildagliptin.
Results: Commiphora mukul monotherapy as well as in combination therapy (with Metformin) demonstrated significant DPP-IV inhibitory, antidiabetic and cardioprotective effects in the experimental model of myocardial infarction co-existing with diabetes. Cardioprotective effects of Commiphora mukul treatment may be attributed to several mechanisms (DPP-IV inhibition, hypolipidemic, reduced atherogenic potential, anti-thrombotic state, anti-inflammatory, antioxidant and anti-apoptotic activities. The Commiphora mukul possesses significant DPP-IV inhibitory activity as delineated, using in silico docking.
Conclusion: The present study will provide preliminary experimental evidence on the potential therapeutic benefits of using natural DPP-IV inhibitors in the setting of diabetes co-existing with cardiovascular diseases.
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