AUTHOR=Sherif Asmaa E. , Alam Rabia , Asif Muhammad , Khan Kashif-ur-Rehman , Ur Rehman Muhammad Sajid 

TITLE=Evaluation of the anti-inflammatory, antinociceptive, and antipyretic potential of ethanolic extract of Aristida depressa Retz through in vitro, in vivo, and in silico models

JOURNAL=Frontiers in Pharmacology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1326482

DOI=10.3389/fphar.2024.1326482

ISSN=1663-9812

ABSTRACT=<p>Uncontrolled inflammation is a crucial factor in the development of many diseases. Anti-inflammatory molecules based on natural sources are being actively studied, among which <italic>Aristida depressa</italic> Retz (<italic>Ar.dp</italic>) has been traditionally used as a paste to heal inflammation. The present study aimed to evaluate the anti-inflammatory, analgesic, and antipyretic potential of an ethanolic extract of <italic>A. depressa</italic> through a battery of <italic>in vivo</italic> and <italic>in vitro</italic> models. The ethanolic extract of <italic>A. depressa</italic> was prepared by maceration and chemically characterized using high-performance liquid chromatography, which revealed the presence of quercetin, vanillic acid, chlorogenic acid, <italic>p</italic>-coumaric acid, <italic>m</italic>-coumaric acid, ferulic acid, cinnamic acid, and sinapic acid; its antioxidant capacity was then screened with the DPPH <italic>in vitro</italic> assay, which indicated moderate scavenging capacity. A protein denaturation assay was next performed to evaluate the <italic>in vitro</italic> anti-inflammatory potential of <italic>Ar.dp</italic>, which showed significant inhibition (44.44%) compared to the standard drug (diclofenac sodium), with 89.19% inhibition at a concentration of 1 mg/mL. The <italic>in vivo</italic> safety profile of <italic>Ar.dp</italic> was evaluated in accordance with the OECD-425 acute toxicity guidelines and found to be safe up to 5 g/kg. The <italic>in vivo</italic> anti-inflammatory potentials of <italic>Ar.dp</italic> were evaluated at three different doses (125, 250, and 500 mg/kg) in acute (carrageenan-induced edema: 84.60%, histamine-induced paw edema: 84%), sub-chronic (cotton-pellet-induced granuloma: 57.54%), and chronic (complete-Freund’s-adjuvant-induced arthritis: 82.2%) models. Our results showed that <italic>Ar.dp</italic> had significant (<italic>p</italic> &lt; 0.05) anti-inflammatory effects over diclofenac sodium in the acute and chronic models. Histopathology studies indicated reduced infiltration of paw tissues with inflammatory cells in <italic>Ar.dp</italic>-treated animals. Similarly, <italic>Ar.dp</italic> showed significant (<italic>p</italic> &lt; 0.05) analgesic (yeast-induced-pyrexia model: 23.53%) and antipyretic (acetic-acid-induced writhing model: 51%) effects in a time-dependent manner. <italic>In silico</italic> studies on the interactions of COX-1 and COX-2 with the eight ligands mentioned earlier confirmed the inhibition of enzymes responsible for inflammation and fever. Based on the findings of the present study, it is concluded that <italic>Ar.dp</italic> has anti-inflammatory, analgesic, and antipyretic properties that are likely linked to its pharmacologically active phenolic bioactive molecules.</p>