Department of Entomology and Nematology and UC Davis Comprehensive Cancer Center, University of California Davis, Davis, California 95616, United States.
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.
J Nat Prod. 2020 Dec 24;83(12):3689-3697. doi: 10.1021/acs.jnatprod.0c00938. Epub 2020 Dec 15.
(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 , the macamides. Based on known and suspected macamides, 19 possible macamides were synthesized and characterized. The majority of these amides displayed excellent inhibitory potency (IC ≈ 20-300 nM) toward the recombinant mouse, rat, and human sEH. Quantitative analysis of commercial maca products revealed that certain products contain known macamides (-, -) at therapeutically relevant total concentrations (≥3.29 mg/g of root), while the inhibitory potency of extracts directly correlates with the sum of concentration/IC ratios of macamides present. Considering both its in vitro efficacy and high abundance in commercial products, -benzyl-linoleamide () was identified as a particularly relevant macamide that can be utilized for in vivo studies. Following oral administration in the rat, compound 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 treatments.
(maca)，一种原产于秘鲁安第斯山脉的植物，最近在全球范围内因其声称的健康或娱乐功效而被广泛使用。为了寻找具有治疗相关效力和浓度的抑制可溶性环氧化物水解酶 (sEH) 的天然产物，本研究对在 中发现的具有生物活性的酰胺类次生代谢产物 macamides 进行了研究。基于已知和疑似的 macamides，合成并表征了 19 种可能的 macamides。这些酰胺中的大多数对重组的小鼠、大鼠和人 sEH 显示出优异的抑制效力（IC ≈ 20-300 nM）。对商业 maca 产品的定量分析表明，某些产品以治疗相关的总浓度（≥3.29mg/g 根）含有已知的 macamides（-，-），而提取物的抑制效力与存在的 macamides 的浓度/IC 比值的总和直接相关。考虑到其体外功效和在商业产品中的高丰度，-苄基亚油酸酰胺（）被鉴定为一种特别相关的 macamide，可用于体内研究。在大鼠口服给药后，化合物 不仅表现出可接受的药代动力学特征，而且有效减轻脂多糖诱导的炎性疼痛。酰胺类对 sEH 的抑制作用提供了一种合理的生物学作用机制，可以解释以前用 治疗观察到的几种有益作用。
