Investigations of Limeum Indicum Plant for Diabetes Mellitus and Alzheimer's Disease Dual Therapy: Phytochemical, GC‐MS Chemical Profiling, Enzyme Inhibition, Molecular Docking and In‐Vivo Studies

Author:

Shamim Tahira1,Asif Hafiz Muhammad1,Abida Ejaz Syeda2ORCID,Hussain Zahid34,Wani Tanveer A.5,Sumreen Laila1,Abdullah Muhammad6,Ahmed Zubair7,Iqbal Jamshed34,Kim Song Ja8,Shah Muhammad Kamal9

Affiliation:

1. University College of Conventional Medicine Faculty of Medicine & Allied Health Sciences The Islamia University of Bahawalpur 63100 Bahawalpur Pakistan

2. Department of Pharmaceutical Chemistry Faculty of Pharmacy The Islamia University of Bahawalpur 63100 Bahawalpur Pakistan

3. Department of Chemistry COMSATS University Islamabad Abbottabad Campus 22060 Abbottabad Pakistan

4. Center for Advance Drug Research COMSATS University Islamabad Abbottabad Campus 22060 Abbottabad Pakistan

5. Department of Pharmaceutical Chemistry College of Pharmacy King Saud University P.O.Box 2452 11451 Riyadh Saudi Arabia

6. Cholistan Institute of Desert Studies The Islamia University of Bahawalpur 63100 Bahawalpur Pakistan

7. Department of Pharmacy COMSATS University Islamabad Abbottabad Campus 22060 Abbottabad Pakistan

8. College of Natural Sciences Department of Biological Sciences Kongju National University 32588 Gongju South Korea

9. Faculty of Veterinary and Animal Sciences Gomal University 29220 Dera Ismail Khan Pakistan

Abstract

AbstractLimeum indicum has been widely utilized in traditional medicine but no experimental work has been done on this herb. The primary objective of this study was to conduct a phytochemical analysis and assess the multifunctional capabilities of aforementioned plant in dual therapy for Alzheimer′s disease (AD) and Type 2 diabetes (T2D). The phytochemical screening of ethanol, methanol extract, and their derived fractions of Limeum indicum was conducted using GC‐MS, HPLC, UV‐analysis and FTIR. The antioxidant capacity was evaluated by DPPH method. The inhibitory potential of the extracts/fractions against α‐, β‐glucosidase acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and monoaminine oxidases (MAO‐A & B) was evaluated. Results revealed that acetonitrile fraction has highest inhibitory potential against α‐glucosidase (IC50=68.47±0.05 μg/mL), methanol extract against β‐glucosidase (IC50=91.12±0.07 μg/mL), ethyl acetate fraction against AChE (IC50=59.0±0.02 μg/mL), ethanol extract against BChE (28.41±0.01 μg/mL), n‐hexane fraction against MAO‐A (IC50=150.5±0.31 μg/mL) and methanol extract for MAO‐B (IC50=75.95±0.13 μg/mL). The docking analysis of extracts\fractions suggested the best binding scores within the active pocket of the respective enzymes. During the in‐vivo investigation, ethanol extract produced hypoglycemic effect (134.52±2.79 and 119.38±1.40 mg/dl) after 21 days treatment at dose level of 250 and 500 mg/Kg. Histopathological findings further supported the in‐vivo studies.

Publisher

Wiley

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