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Lepidium meyenii inhibits MAGL and increases the expression of LRP1 in neuroblastoma SH‐SY5Y cells
Author(s) -
RondonOrtiz Alejandro,
Su Pei Ying,
Khan Rimmal,
Böhlke Mark,
Maher Timothy,
PinoFigueroa Alejandro
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1192.2
Subject(s) - monoacylglycerol lipase , fatty acid amide hydrolase , chemistry , endocannabinoid system , anandamide , neuroblastoma , neuroprotection , biochemistry , pharmacology , cannabinoid receptor , receptor , biology , cell culture , antagonist , genetics
Lepidium meyenii (Maca) is a Peruvian plant that has previously been implicated to have effects on the endocannabinoid system. N ‐Benzylamides, also known as macamides, are compounds present in the Maca pentane extract (MPE) with a demonstrated inhibitory effect on fatty acid amide hydrolase (FAAH), one of the enzymes that terminates endocannabinoid signaling. The purpose of this project was to evaluate the effect of MPE on monoacyl glycerol lipase (MAGL), another enzyme involved in the endocannabinoid system, and additionally to demonstrate the effect of MPE on the expression of the low density lipoprotein receptor‐related protein 1 (LRP1) in neuroblastoma SH‐SY5Y cells. LRP1 is a receptor involved in the transcellular transport of peptides and proteins, including β‐amyloid. Macamides were quantified by LC‐MS/MS, demonstrating that N ‐benzylpalmitamide, N ‐benzyloctadeca‐ 9Z, 12Z ‐dienamide and N ‐benzyloctadeca‐ 9Z, 12Z, 15Z ‐trienamide were the most predominant compounds in the MPE with concentrations of 27.0, 8.4 and 5.5 mg/g, respectively. The FAAH and MAGL inhibitory activity of MPE was demonstrated with IC 50 values of 9.15 and 7.12 μg/mL, respectively, supporting an action via the endocannabinoid system. SH‐SY5Y neuroblastoma cells were treated with MPE at three different concentrations between 0.1 and 10 μg/mL. Cells were lysed and LRP1 levels were analyzed by immunoblotting, demonstrating that Lepidium meyenii was able to significantly increase LRP1 expression. While MPE was previously demonstrated to have neuroprotective effects associated with the inhibition of FAAH, this investigation reports that MPE additionally inhibits MAGL. This dual inhibitory activity on FAAH and MAGL could be responsible for the upregulation of LRP1. It is well known that LRP1 reduction is associated with neurological disorders such as Alzheimer's disease. The increase of LRP1 levels by MPE supports a novel mechanism which might be responsible for some of the biological activity of this plant. Further studies are necessary to better elucidate the activation of transcription factors by Maca constituents.