Integrated Evaluation of Medicinal Plants for Antidiabetic Potential: Bridging In Vivo and In Vitro Assessments with Advanced In Silico Analyses, including ADMET Prediction, Molecular Docking, and Molecular Dynamics Simulation

Abstract

The plant kingdom serves as an exceptional reservoir of bioactive compounds endowed with anti￾diabetic properties. This study aims to investigate the anti-diabetic effects of essential oils derived from Cotula cinerea and Origanum majorana L both in vivo and in vitro, as well as in silico. Initially, the essential oils were obtained through hydrodistillation, and their respective compounds were characterized using gas chromatography-mass spectrometry (GC/MS) analysis, with Cotula cinerea yielding 31 compounds and Origanum majorana L yielding 44 compounds. In vivo experiments using rats that had been given alloxan to induce diabetes were conducted during the study's first phase. Following a 15-day treatment period with 10 µl of the essential oils from Cotula cinerea and Origanum majorana L, the treatment's effectiveness was evaluated in comparison of control groups, including those using the Acarbose. The results demonstrated that alloxan caused a change in hematological parameters (LYM, GRA), glycemia and hepatic enzyme markers (AST, ALT), triglycerides and kidney function (urea, creatinine, UA).Additionally, alterations in the antioxidant defenses MDA and GSH. Histological examinations also revealed notable liver inflammation, atrophy of the Langerhans islet cells in the pancreas. Nonetheless, the administration of essential oils improved most of the adverse effects of alloxan especially, controlling blood sugar levels. In the laboratory setting, the inhibition of alpha-amylase activity was demonstrated through the preparation of a starch solution containing essential oils. Findings revealed a notable inhibitory effect of essential oils on alpha-amylase in plant sources, particularly in Cotula cinerea and Origanum majorana L (IC50=2.432, -ΔG =27.11) (IC50=3.68, -ΔG =25.83), as compared to Acarbose. Within the realm of computer science, an examination of Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) properties was conducted to predict the physicochemical, pharmaceutical, and toxicological characteristics of specific basic compounds present in each oil (more than 10%). This analysis utilized the SwissADME and Protox servers, with results indicating favorable medicinal attributes of all compounds in contrast to acarbose. In the docking, the basic compounds with a yield of (1%) were selected. For each plant oil, the obtained results confirm their occurrence in the laboratory, indicating negative ∆G values, which translates to a good interaction of the compounds with human amylase.In the domain of molecular dynamics simulation, the compound "trons_thujone" exhibited the most promising interaction with alpha-amylase in comparison to acarbose. Noteworthy results demonstrated minimal conformational changes throughout the simulation, affirming its potential efficacy in diabetes management and suggesting its viability as a prospective therapeutic agent for diabetes treatment.