Phyllanthus amarus Schumach. & Thonn. and Momordica charantia L extracts improve memory function, attenuate cholinergic and purinergic dysfunction, and suppress oxidative stress in the brain of doxorubicin–treated rats

Abstract

Background: Phyllanthus amarus (P.A) and Momordica charantia (M.C) are common herbs known for their various pharmacological importance. However, limited studies have been done regarding their neuroactive effect. This study investigates the role of Phyllanthus amarus (P.A) and Momordica charantia (M.C) extracts on cognitive behavior and some neurochemicals associated with memory function in rats administered with doxorubicin (DOX). Methodology: Normal rats were pre-treated with P.A and M.C (200 and 400 mg/kg bwt.) for 14 days, while on the last day, DOX (15 mg/kg bwt. i.p.) was administered in a single dose. The cognitive behavior was evaluated using Y-maze and Morris Water Maze Tests. Thereafter, the biochemical assays [acetylcholinesterase (AChE), butyrylcholinesterase (BChE), arginase, 5′- nucleotidase, adenosine deaminase (ADA), angiotensin-I converting enzyme (ACE), and catalase activities, thiobarbituric acid reactive species, and non-protein thiol levels] were determined in rats’ brains. The extracts were characterized using a high-performance liquid chromatography-diode array detector (HPLC-DAD). Result: P.A and M.C extract restored cognitive behavior, nootropic-related enzyme activities, and improved antioxidant biomarkers altered by DOX. Furthermore, phenolic characterization of the extracts revealed gallic, chlorogenic, caffeic, and ellagic acids, catechin, epicatechin, rutin, quercitrin, isoquercitrin, quercetin, and kaempferol. Molecular docking analysis revealed that all the phenolic compounds detected in the studied plants had binding affinities for ACE, AChE, 5′-nucleotidase, and ADA proteins as the target proteins. Conclusion: Extract from P.A and M.C effectively suppressed DOX-induced neurotoxicity by improving brain antioxidant status. Thus, they could play a significant role in restoring cognitive function altered by DOX treatment.

Keywords

• Doxorubicin, momordica charantia, phyllanthus amarus, memory dysfunction
• Oxidative stress
• Purinergic enzymes