The Efficient Synthesis and Anti-Fatigue Activity Evaluation of Macamides: The Unique Bioactive Compounds in Maca

Abstract

Macamides are a class of amide alkaloids that are only found in maca and are widely considered to be its bioactive marker compounds. More than thirty macamide monomers have been identified in recent years; however, it is difficult to obtain a single macamide monomer from the maca plant because of their similar structures and characteristics. We used the carbodiimide condensation method (CCM) to efficiently synthesize five typical macamides, including N-benzyl-hexadecanamide (NBH), N-benzyl-9Z,12Z,15Z-octadecenamide, N-(3-methoxybenzyl)-9Z,12Z-octadecenamide, N-benzyl-9Z,12Z-octadecenamide, and N-(3-methoxybenzyl)-9Z,12Z,15Z-octadecadienamide. All the synthesized macamides were purified by a one-step HPLC with a purity of more than 95%. NBH is the most abundant macamide monomer in natural maca, and it was selected to evaluate the anti-fatigue effects of macamides. The results indicated that NBH could enhance the endurance capacity of mice by increasing liver glycogen levels and decreasing blood urea nitrogen, lactate dehydrogenase, blood ammonia, and blood lactic acid levels. Macamides might be the active substances that give maca its anti-fatigue active function.

Not All Maca Is Created Equal: A Review of Colors, Nutrition, Phytochemicals, and Clinical Uses

“…Macamides and macaenes are benzylated alkamides, which are natural compounds often used to identify maca accurately [ 39 , 125 ]. However, macamides are considered unique to maca [ 47 ], whereas macaenes can be found in other plants such as tomatoes and eggplants [ 125 ]. A review of analytical research using liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS) for L. meyenii extracts reported three macaenes ( C -18 fatty acid derivatives) and twenty-three macamides (fatty acid amides) [ 19 ].…”

“…A slightly older study using different analytical methods (UHPLC-ESI-Orbitrap MS and UHPLC-ESI-QqQ MS) on a methanolic extract of maca cited only eleven macaenes [ 104 ]. Macamides are a unique class of maca phytochemicals, with more than thirty compounds identified and explored for their anti-fatigue effects [ 9 , 47 ]. There is a suggestion in the scientific literature that macaene and macamide compounds could be (partly) responsible for the bioactive effects of maca on sexual performance in male animals [ 17 , 126 ].…”

“…As of November 7, 2023, using the search terms “maca,” “maca” [in title], “maca” [in title/abstract], “Lepidium meyenii” [in title/abstract], and “Lepidium peruvianum” [in title/abstract], results in 843, 256, 528, 292, and 17 findings, respectively [ 21 ]. Beginning with the early 2000s until the present day (2023), preclinical and clinical research has provided data that would expand maca’s use into other areas of health such as menstrual cycle regulation [ 22 , 23 ], menopausal symptoms [ 24 , 25 , 26 , 27 ], osteoporosis [ 28 ], sperm quality [ 29 , 30 , 31 , 32 , 33 , 34 , 35 ], memory [ 36 , 37 , 38 , 39 ], mood [ 36 , 40 ], prostate health [ 41 , 42 , 43 , 44 , 45 , 46 ], and fitness optimization (e.g., reducing inflammation and increasing strength) [ 47 , 48 , 49 ]. Even though maca has broader applications, there has been historical research emphasis on its ability to modify the endocrine system, pioneered by the work of Gonzales et al on males [ 29 , 31 , 33 , 42 , 50 , 51 ] and Meissner et al on pre- and post-menopausal women [ 24 , 25 , 26 , 27 ].…”

Investigating the Combined Effects of Mechanical Stress and Nutrition on Muscle Hypertrophic Signals Using Contractile 3D-Engineered Muscle (3D-EM)

“…Among them, over the past 20 years, there has been a growing interest in and demand for Lepidium meyenii Walp, or maca, due to its health benefits [ 9 ]. Recent studies indicate that maca may improve endurance, help with autism, and have anti-inflammatory and anticancer properties [ 10 , 11 , 12 , 13 ]. Maca’s secondary metabolites provide neuroprotective and cytoprotective benefits [ 14 ] and improve energy metabolism [ 15 ].…”