Neuroprotective activity of macamides on manganese-induced mitochondrial disruption in U-87 MG glioblastoma cells

Toxicology and Applied Pharmacology
Kuljeet S GugnaniAlejandro Pino-Figueroa

Abstract

Macamides are a distinct class of secondary metabolites, benzylamides of long chain fatty acids, which were isolated from the Peruvian plant Lepidium meyenii (Maca). As structural analogues of the endocannabinoid anandamide (AEA), they have demonstrated neuroprotective effects in vitro and in vivo. The purpose of this study was to demonstrate the neuroprotective activity of the macamides: N-(3-methoxybenzyl)oleamide (MAC 18:1), N-(3-methoxybenzyl)linoleamide (MAC 18:2) and N-(3-methoxybenzyl)linolenamide (MAC 18:3) in a neurotoxic environment caused by exposure of U-87 MG glioblastoma cells to manganese chloride (MnCl2). The neuroprotective effects of these macamides were reversed by the CB1 antagonist AM251. The mechanism by which manganese (Mn) induces cell damage was investigated by studying its effects on mitochondria. Reactive oxygen species (ROS) increase intracellular calcium and enhance the opening of mitochondrial permeability transition pores (MPTP), which leads to decreased mitochondrial membrane potential (MMP), to disruption of mitochondria and to neuron death in neurodegenerative disorders. In this study, MnCl2 at 50μM was responsible for mitochondrial disruption, which was attenuated by all three of the macamides...Continue Reading

Citations

Sep 13, 2018·Reviews in the Neurosciences·Xiao Juan SuDezhi Mu
Sep 5, 2019·Basic & Clinical Pharmacology & Toxicology·Kuan LiuBin Xu
Nov 15, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Yanyan ZhouBaolin Bian
May 1, 2021·International Journal of Molecular Sciences·Alexey A TinkovMichael Aschner
Jun 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Mengya JiaoHui Yin
Mar 1, 2019·Journal of Natural Products·Christopher W Cunningham
Dec 9, 2020·Food Research International·Hongkang ZhuHe Qian

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