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Current Alzheimer Research

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ISSN (Print): 1567-2050
ISSN (Online): 1875-5828

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General Research Article

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

Author(s): Heera Ram*, Noopur Jaipal, Pramod Kumar, Purbajyoti Deka, Shivani Kumar, Priya Kashyap, Suresh Kumar, Bhim P. Singh, Abdulaziz A. Alqarawi, Abeer Hashem, Baby Tabassum and Elsayed Fathi Abd_Allah

Volume 16, Issue 13, 2019

Page: [1230 - 1244] Pages: 15

DOI: 10.2174/1567205016666191203161509

Price: $65

Abstract

Background: Insulin resistance causes decreased uptake of glucose which promotes the susceptibility of type 2 associated neurological impairments.

Methods: The study was aimed to evaluate the inhibition potential of the ethanolic extract of Prosopis cineraria (EPC) pods against DPP-4 and cholinesterase enzymes by in-vitro, in-vivo and in-silico assessments. The present study consists of in vivo studies on a diabetes-induced rat model by HOMA (Homeostasis model assessment) and related parameters, in vitro studies through the DPP-4 enzyme assay and cholinesterase assays using Ellman’s reaction. The in-silico studies were conducted by the molecular docking of Cinerin C with targeted enzymes. The phytochemical characterization of the extract was demonstrated through LCMS studies. The antioxidant studies on the extract were performed by FRAP and TEAC assays.

Results: The extract showed 64.8% maximum inhibition of DPP-4, 34.91% inhibition of AChE and 74.35% inhibition of BuChE. The antioxidant capacity of the extract was observed to be 847.81±16.25μM Fe2+ equivalent in the FRAP assay and 0.40 ± 0.08 mmol/l of Trolox equivalent in the TEAC assay. The in vivo study showed competent glycaemic control against significant HOMA IR (1.5), HOMA % β (26.5) and HOMA % S (68.8) as well as pancreatic cell mass proliferation. The insilico analysis also revealed positive interactions of Cinerin C with targeted enzymes (DPP4 and cholinesterase).

Conclusion: It can be concluded that the phytoconstituents of Prosopis cineraria pod extract can be significantly considered in neuropharmacology to resolve insulin resistance-induced neurological complications as it showed inhibition against DPP-4, AChE and BuChE target enzymes.

Keywords: Prosopis cineraria, diabetes mellitus, Alzheimer’s disease, DPP-4, acetylcholinesterase (AChE), butyrylcholinesterase (BuChE).

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