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

Tahira Shamim; Hafiz Muhammad Asif; Syeda Abida Ejaz; Zahid Hussain; Tanveer A Wani; Laila Sumreen; Muhammad Abdullah; Zubair Ahmed; Jamshed Iqbal; Song Ja Kim; Muhammad Kamal Shah

doi:10.1002/cbdv.202301858

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

Chem Biodivers. 2024 Apr 12:e202301858. doi: 10.1002/cbdv.202301858. Online ahead of print.

Authors

Affiliations

¹ The Islamia University of Bahawalpur Pakistan, Eastern Medicine, University College of Conventional Medicine, the Islamia University of Bahawalpu, Bahawalpur, 6300, Bahawalpur, PAKISTAN.
² The Islamia University of Bahawalpur Pakistan, Department of Pharmaceutical Chemistry, Khawaja farred campus iub bahawalpur, 63100, bahawalpur, PAKISTAN.
³ COMSATS University Islamabad - Abbottabad Campus, Department of Chemistry, department of chemistry, Abbottabad, PAKISTAN.
⁴ King Saud University, Department of pharmaceutical Chemistry, College of Science, Riyadh, SAUDI ARABIA.
⁵ The Islamia University of Bahawalpur Pakistan, Homoeopathic medical system, University College of Conventional Medicine, the Islamia University of Bahawalpu, Bahawalpur, 6300, Bahawalpur, PAKISTAN.
⁶ The Islamia University of Bahawalpur Pakistan, Cholistan Institute of Desert Studies, Cholistan Institute of Desert Studies, Bahawalpur, 6300, Bahawalpur, PAKISTAN.
⁷ COMSATS University Islamabad - Abbottabad Campus, Department of Pharmacy, Department of Pharmacy, Abbottabad, PAKISTAN.
⁸ COMSATS University Islamabad - Abbottabad Campus, Center for Advance Drug Research, department of chemistry, Abbottabad, PAKISTAN.
⁹ Kongju National University, College of Natural Sciences,, Department of Biological Sciences,, gongju, KOREA, REPUBLIC OF.
¹⁰ Gomal University, veterinary and animal sciences, gomal university, D.I.Khan, PAKISTAN.

PMID: 38608202
DOI: 10.1002/cbdv.202301858

Abstract

Limeum 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±0.05µg/mL), methanol extract against β-glucosidase (IC50=91.12±0.07µg/mL), ethyl acetate fraction against AChE (IC50=59.0±0.02 µg/mL), ethanol extract against BChE (28.41±0.01µg/mL), n-hexane fraction against MAO-A (IC50=150.5±0.31µg/mL) and methanol extract for MAO-B (IC50=75.95±0.13µg/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.

Keywords: Limeum indicum, Type 2 Diabetes Mellitus (T2D), Alzheimer's Disease (AD), Medicinal plants.