Alcoholic Extracts of Eleusine indica as Alternative Diuretic Regimens: A Computational Based Investigation

Abstract

Diuretics are widely used in current clinical practice to increase urine production and excrete electrolytes, particularly sodium and chloride ions, without affecting the absorption of protein, vitamins, carbohydrates, or amino acids. From the time of mercury chloride and organomercurials in ancient times to now (with sulphonamides, thiazides, and furosemide), a lot has changed in the field of diuretics. However, long-term use of such synthetic diuretic agents in clinical practice produces several adverse effects, such as blurred vision, loss of appetite, stomach upset, carcinomas, headaches, phototoxic impact, weakness., etc., as has been observed from recent investigations. Natural regimens can serve as potential alternatives to using nontoxic diuretic agents. Based on long-term ethnomedicinal and biological activity records, we have explored the diuretic effects of the widely known perennial herb in Pacific Islands regions and a weed in agricultural fields, Eleusine indica (L) Gaertn phytoconstituents, on a computation platform. Therefore, we conducted a bio-assay-guided crude extraction using ethanol, followed by further gas chromatography-mass spectrometry (GC-MS) analyses of the extracted crude extracts. Further selected nine constituents (EI_1 to EI_9) carried out the diuretic potency against three putative target enzymes (ACE, KCNJ1, and SLC12A1) along with three standard drugs (VU590, TSM, and FSM) through molecular docking studies using AutoDock 4.2 software. We also predict physicochemical profiles, or Lipinski Rule of Five profiles, toxicity, and pharmacokinetics using various bioinformatics and cheminformatics tools. Based on the overall investigation, it was revealed that EI_6 [Z, Z-6,28-Heptatriacontadien-2-one] was the most potential, nontoxic, and drug-able candidate. In summary, advanced computational tools play a crucial role in selecting potential preclinical candidates within limited resources to accelerate the current drug discovery process.