Anticancer and Neuroprotective Activities of Ethyl Acetate Fractions from Morus macroura Miq. Plant Organs with Ultraperformance Liquid Chromatography-Electrospray Ionization-Tandem Mass Spectrometry Profiling.

Abstract

Column chromatography afforded the isolation of seven secondary metabolites (1-(2,4,6-trihydroxy phenyl)-ethanone-4-O-β-d-glucopyranoside, naringenin-7-O-β-d-glucopyranoside, kaempferol-3-O-α-l-rhamnoside, kaempferol-3-O-β-d-glucopyranoside, quercetin-3-O-β-d-glucopyranoside, quercetin-3-O-β-d-galactopyranoside, rutin) from the ethyl acetate (ET) fractions of Morus macroura Miq. stems (S), leaves (L), and fruits (F). Their identification based on ultraviolet (UV), electron ionization (EI), electrospray ionization-mass spectrometry (ESI-MS), and 1D and 2D NMR data. In addition, profiling of ET fractions using ultraperformance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS) resulted in the identification of 82 compounds belonging to different classes, mainly polyphenolic constituents. Chemical profiling as well as molecular docking directed us to biological evaluation. Interestingly, the ET-L fraction exhibited a robust cytotoxic activity against HepG-2, MCF-7, and HELA cell lines. Also, it displayed a neuromodulatory activity against cisplatin neurotoxicity in rats by ameliorating the neurobehavioral dysfunction visualized in the open field and Y-maze test and modulating the neurochemical parameters such as brain amino acid levels (glutamate, aspartate, serine, and histidine), oxidative stress markers (GSH, MDA, and 8-hydroxy-2′-deoxyguanosine), and purinergic cell energy (adenosine triphosphate (ATP) and adenosine monophosphate (AMP)). In conclusion, the isolated compounds (kaempferol-3-O-β-glucoside and quercetin-3-O-β-glucoside) from the ET-L fraction could serve as potent anticancer agents due to their strong antioxidant, in vitro cytotoxicity, and in vivo neuroprotective activity.