Lepidium meyenii L. and Isolated Macamides Reduces Lipopolysaccharide-Induced Inflammatory Response in THP-1 Cells

Inflammation is a vital component of the immune system response to injury and infection, and it is linked to autoinflammatory and autoimmune disorders. Toll‐like receptor 4 (TLR4) has been identified as a receptor for lipopolysaccharide (LPS), a bacterial endotoxin which can induce systemic inflammation and sepsis. The LPS/TLR4 pathway triggers downstream signaling cascades, producing proinflammatory cytokines and chemokines. Therefore, the search for novel compounds that can reduce inflammation at this level is of great interest. The plant Lepidium meyenii L., known as maca, has attracted attention in the past several years due to its traditional uses in folk medicine, which include treating anemia and gastritis, preventing cancer, high blood pressure and depression, as well as enhancing fertility and sexual performance. Macamides are secondary metabolites isolated from maca which cause pharmacological inhibition of fatty acid amide hydrolase (FAAH), and this inhibition has been found to lead to anxiolytic, anti‐inflammatory and analgesic effects. However, the anti‐inflammatory mechanisms by which these natural compounds act remain to be elucidated. The purpose of this study was to evaluate the anti‐inflammatory effects of the n‐pentane extract of Lepidium meyenii L. (PELM), N ‐(benzyl) linolenamide (compound 1) and N ‐(3‐methoxybenzyl) linolenamide (compound 2) utilizing THP‐1 cells. To assess these effects, THP‐1 cells were treated with either 10 μg/mL PELM, 10 μM Cmpd 1, 10 μM Cmpd 2 or 0.5 % DMSO (vehicle); then, inflammation was induced for 24 h with 30 ng/mL LPS. Media supernatants were used to evaluate protein levels of cytokines in a human protein array. From 36 cytokines, maca and macamides reduced IL‐1β and IL‐6 protein levels following a 24 h stimulation with LPS. In order to confirm these results, ELISA was utilized to determine IL‐1β and IL‐6 cytokine levels in LPS‐stimulated THP‐1 cells. After a 24 h treatment with either 10 μg/mL PELM, 10 μM Cmpd 1 or 10 μM Cmpd 2, these treatments reduced protein levels of both cytokines IL‐1β and IL‐6. The transcriptional levels of these cytokines were also monitored by RT‐qPCR; treatment with 10 μM Cmpd 1 and 10 μM Cmpd 2 significantly decreased mRNA levels of IL‐1β. But, interestingly with a 10 μg/mL treatment of PELM the reduction of IL‐1β mRNA levels was not significant. Furthermore, IL‐6 mRNA levels were significantly reduced by the n‐pentane extract and isolated macamides. Taken together, these results demonstrated that Lepidium meyenii L. and isolated macamides reduced LPS‐induced inflammatory response by decreasing pro‐inflammatory cytokine production in THP‐1 cells. Effect of PELM, Cmpd 1 and Cmpd 2 on IL‐1β production in THP‐1 cells. Figure 1 Effect of PELM, Cmpd 1 and Cmpd 2 on IL‐1β mRNA levels in THP‐1 cells. Figure 2