Isolates from Eleusine indica (Poaceae) Aerial Shoot Fraction Dually Inhibits 5-LOX and COX Enzyme Systems

Abstract

Recent studies supported the use of Eleusine indica in inflammatory processes as evidenced by the reduction of lipopolysaccharide-induced inflammation in vitro and in vivo. The aim of this research was to evaluate the anti-inflammatory activity of E. indica in the context of dual inhibition of 5-lipoxygenase (5-LOX)/ cyclooxygenase (COX). Drugs able to block the two main arachidonic acid pathways are of pharmacological interest due to the wide range of anti- inflammatory activity with no ulcerogenic risk. In addition, cytotoxicity screening using the HepG2 and HK-2 cells and analysis of the most active subfraction via UPLC-QTOF-MSE were performed. Preliminary screening of the crude methanolic extract and its fractions revealed significant dual 5-LOX/COX inhibition, with no significant difference among the fractions (p < 0.05). Ethyl acetate fraction, the most active among the four fractions and found to be rich in phenolic compounds after TLC derivatization, was considered for further purification and screening at 50 μg mL–1. Among its nine subfractions, subfraction 6 was regarded as the most promising dual inhibitor with a moderately hepatotoxic and nephrotoxic profile. Its median inhibitory concentration (IC50) was found to be 16.47 μg mL–1 for 5-LOX, 19.64 μg mL–1 for COX-1, and 22.26 μg mL–1 for COX-2. Two putative compounds namely Naringenin-7-O-β-D- glucuronide and Tricin-7-O-β-D-glucopyranoside were identified after the mass spectral analysis of subfraction 6. These results confirm that E. indica elicits its anti-inflammatory activity by targeting the arachidonic acid metabolic pathways.