1. Academic Validation
  2. N-Benzyl-linoleamide, a Constituent of Lepidium meyenii (Maca), Is an Orally Bioavailable Soluble Epoxide Hydrolase Inhibitor That Alleviates Inflammatory Pain

N-Benzyl-linoleamide, a Constituent of Lepidium meyenii (Maca), Is an Orally Bioavailable Soluble Epoxide Hydrolase Inhibitor That Alleviates Inflammatory Pain

  • J Nat Prod. 2020 Dec 24;83(12):3689-3697. doi: 10.1021/acs.jnatprod.0c00938.
Nalin Singh 1 Bogdan Barnych 1 Christophe Morisseau 1 Karen M Wagner 1 Debin Wan 1 Ashley Takeshita 1 Hoang Pham 1 Ting Xu 2 Abhaya Dandekar 3 Jun-Yan Liu 4 Bruce D Hammock 1
Affiliations

Affiliations

  • 1 Department of Entomology and Nematology and UC Davis Comprehensive Cancer Center, University of California Davis, Davis, California 95616, United States.
  • 2 Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Resources and Environmental Sciences, China Agricultural University, Beijing, 100193, People's Republic of China.
  • 3 Department of Plant Sciences, University of California Davis, Davis, California 95616, United States.
  • 4 Institute of Life Sciences, Chongqing Medical University, Chongqing, 400016, People's Republic of China.
Abstract

Lepidium meyenii (maca), a plant indigenous to the Peruvian Andes, recently has been utilized globally for claimed health or recreational benefits. The search for Natural Products that inhibit soluble Epoxide Hydrolase (sEH), with therapeutically relevant potencies and concentrations, led to the present study on bioactive amide secondary metabolites found in L. meyenii, the macamides. Based on known and suspected macamides, 19 possible macamides were synthesized and characterized. The majority of these amides displayed excellent inhibitory potency (IC50 ≈ 20-300 nM) toward the recombinant mouse, rat, and human sEH. Quantitative analysis of commercial maca products revealed that certain products contain known macamides (1-5, 8-12) at therapeutically relevant total concentrations (≥3.29 mg/g of root), while the inhibitory potency of L. meyenii extracts directly correlates with the sum of concentration/IC50 ratios of macamides present. Considering both its in vitro efficacy and high abundance in commercial products, N-benzyl-linoleamide (4) was identified as a particularly relevant macamide that can be utilized for in vivo studies. Following oral administration in the rat, compound 4 not only displayed acceptable pharmacokinetic characteristics but effectively reduced lipopolysaccharide-induced inflammatory pain. Inhibition of sEH by macamides provides a plausible biological mechanism of action to account for several beneficial effects previously observed with L. meyenii treatments.

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