Effect of MCH1, a fatty-acid amide hydrolase inhibitor, on the depressive-like behavior and gene expression of endocannabinoid and dopaminergic-signaling system in the mouse nucleus accumbens

Abstract MCH1 is a synthetic macamide that has shown in vitro inhibitory activity on fatty acid amide hydrolase (FAAH), an enzyme responsible for endocannabinoid metabolism. This inhibition can modulate endocannabinoid and dopamine signaling in the nucleus accumbens (NAc), potentially having an antidepressant-like effect. The present study aimed to evaluate the effect of the in vivo administration of MCH1 (3, 10, and 30 mg/kg, ip) in 2-month-old BALB/c male mice (n=97) on forced swimming test (FST), light-dark box (LDB), and open field test (OFT) and on early gene expression changes 2 h after drug injection related to the endocannabinoid system (Cnr1 and Faah) and dopaminergic signaling (Drd1 and Drd2) in the NAc core. We found that the 10 mg/kg MCH1 dose reduced the immobility time compared to the vehicle group in the FST with no effect on anxiety-like behaviors measured in the LDB or OFT. However, a 10 mg/kg MCH1 dose increased locomotor activity in the OFT compared to the vehicle. Moreover, RT-qPCR results showed that the 30 mg/kg MCH1 dose increased Faah gene expression by 2.8-fold, and 10 mg/kg MCH1 increased the Cnr1 gene expression by 4.3-fold compared to the vehicle. No changes were observed in the expression of the Drd1 and Drd2 genes in the NAc at either MCH1 dose. These results indicated that MCH1 might have an antidepressant-like effect without an anxiogenic effect and induces significant changes in endocannabinoid-related genes but not in genes of the dopaminergic signaling system in the NAc of mice.

Simultaneous determination of macaenes and macamides in maca using an HPLC method and analysis using a chemometric method (HCA) to distinguish maca origin

ABSTRACT Macamides and Macaenes are the bioactive marker compounds in maca (Lepidium meyenii Walp., Brassicaceae) tuber. To simultaneously quantify these two types of compound, HPLC method was studied. To distinguish and group the growing regions of different maca samples, Hierarchical cluster analysis, a chemometric method, was applied to analyze the HPLC data. The calibration curves obtained using the HPLC method showed satisfactory linearity with determination coefficients >0.9998. The precision and repeatability relative standard deviation values were <4%, and the accuracy relative standard deviation value was <5%. The limits of detection was <0.1 µg/ml and the limit of quantification was <0.3 µg/ml. Our HPLC method was successfully used for the separation and determination of macamides and macaenes in Maca within 45 min, i.e., two macaenes (9-oxo-10E,12Z-octadecadienoic acid and 9-oxo-10E,12E-octadecadienoic acid) and five macamides (N-benzyl-9-oxo-10E,12Z-octadecadienamide, N-benzyl-9-oxo-10E,12E-octadecadienamide, N-benzyl-9Z,12Z,15Z-octadecatrienamide, N-benzyl-9Z,12Z-octadecadienamide and N-benzyl-hexadecanamide). The HPLC method was applied to analyze and quantify the seven compounds in thirty maca samples with different colors and origins. The origins of all the maca samples were distinguished and grouped using hierarchical cluster analysis of the HPLC data. Accordingly, the metabolism of macaenes and macamides in maca post-harvest processing has also been proposed. The HPLC method is efficient to simultaneously quantify the macamides and macaenes in maca. Analyzing the HPLC data using hierarchical cluster analysis can distinguish maca growing origins.

Analysis of Maceaene and Macamide Contents of Petroleum Ether Extract of Black, Yellow, and Purple Lepidium Meyenii (Maca) and Their Antioxidant Effect on Diabetes Mellitus Rat Model

ABSTRACT Maceaene and macamide contents as well as antioxidant effect of petroleum ether extract of black maca (BM), yellow maca (YM), and purple maca (PM) on diabetes mellitus (DM) rats were investigated. The results showed that seven, six, and five analogues of macamides were identified from the petroleum ether extracts of BM, YM, and PM, respectively. BM extract exhibited the highest contents of total macamides. Comparatively, the PM extract has the lowest macamide quantity. The maceaene contents in all the extracts showed no significant difference (p>0.05). Macamide contents in maca with the same color were not statistically different. Pharmacological results showed that 60-day oral administration of the petroleum ether extract of maca (100 mg/kg.d) can significantly decrease lipid oxidation as indicated by the decreased thiobarbituric acid reactive substances (TBARS) and carbonylated proteins (CP) concentrations on DM rat model (P<0.05). Among them, oral administration of PM extract showed the lowest TBRAS and CP concentrations. All maca extracts can enhance antioxidant enzyme (SOD, superoxide dismutase; CAT, catalase) activity of liver and red blood cells (RBC) of DM rat. However, only oral administration of PM extract can increase SOD and CAT activity of both RBC and liver. The glutathion (GSH) contents in plasma were significantly increased in DM rats treated with PM extract (p<0.05). But, oral administration of BM and YM extracts did not enhance GSH levels. Take together, the data suggested that PM extract exhibited the most potent antioxidant activity on DM rat model. And, maceaene and macamide in maca extract was not correlated with its antioxidant ability.