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Alkaloids

In the 1960s, Dr. Gloria Chacón identified four alkaloids responsible for the fertility-enhancing effects of L. peruvianum (1). The bitter-tasting, nitrogen-containing, and potentially toxic alkaloids are part of the plant defense system. Several types of alkaloids have been identified in L. meyenii extracts, including, but not limited to, alkaloid amides (macamides), hydantoin derivatives (macahydantoins, meyeniihydantoins, and macathiohydantoins), hexahydroimidazothiazole derivatives (meyeniins), imidazole alkaloids known as lepidiline A, B, C, and D (2–4), and pyrrole alkaloids referred to as macapyrrolins (3,5). Preliminary cytotoxicity activity has been determined in some of these compounds in specific cell lines (6) and potential anti-inflammatory, anti-allergic, and anti-thrombotic effects, depending on the extract used (3).

 

Geng et al. (7) and Zhou et al. (8) reported that Peruvian maca (L. peruvianum) had higher alkaloid concentrations than maca cultivated in China.

 

Macamides and Macaenes

 

Macamides and macaenes are benzylated alkamides, which are natural compounds often used to identify maca accurately (9,10). However, macamides are considered unique to maca (11), whereas macaenes can be found in other plants such as tomatoes and eggplants (10). 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) (5). 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 (8).

 

Macamides are a unique class of maca phytochemicals, with more than thirty compounds identified and explored for their anti-fatigue effects (11,12). 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 (13,14). Macamides are also important anti-inflammatory, antioxidant, and anti-cancer compounds (10), contributing to maca’s anti-fatigue, neuroprotection, and fertility-enhancing effects (8). In mice, macamide administration helped reduce pro-inflammatory factors and reactive oxygen species after a swim test, improving markers of grip strength and extending time spent in activity (15). A recent study notes that the macamides in maca exhibit nuclear factor erythroid 2-related factor (Nrf2) activation (16). Macaenes may play a role in lipid metabolism (10).

 

Newer research on the science of maca phytochemicals continues, with some recent publications looking at the immunomodulatory (17) and neuroprotective (18) aspects of polysaccharides from maca, along with testing isolated compounds like a natural fatty amide known as N-benzylhexadecanamide for its ability to enhance testosterone production (19). Using proteomics and lipomics methods, the neuroprotective effects imparted by N-benzylhexadecanamide may be attributed to its effects on sphingolipid metabolism and mitochondrial function, suggesting that it could continue to be investigated for neurodegenerative diseases (20). Comparatively, this fatty acid amide is found in higher amounts in Peruvian maca than Chinese maca (21), suggesting that elevation or other factors could be responsible for its synthesis. Macamides are thought to influence mood states by modulating the endocannabinoid system and reducing the degradation of anandamide, which acts on the cannabinoid 1 (CB1) receptor (22,23).

 

Credit: Minich DM, Ross K, Frame J, Fahoum M, Warner W, Meissner HO. Not All Maca Is Created Equal: A Review of Colors, Nutrition, Phytochemicals, and Clinical Uses. Nutrients. 2024 Feb 14;16(4):530. doi: 10.3390/nu16040530. PMID: 38398854; PMCID: PMC10892513.  https://creativecommons.org/licenses/by/4.0/.

 

References

1. Meissner HO, Kedzia B, Mrozikiewicz PM, Mscisz A. Short and long-term physiological responses of male and female rats to two dietary levels of pre-gelatinized maca (lepidium peruvianum chacon). Int J Biomed Sci. 2006;

2. Cui B, Zheng BL, He K, Zheng QY. Imidazole alkaloids from Lepidium meyenii. J Nat Prod. 2003;66(8).

3. Purnomo KA, Korinek M, Tsai YH, Hu HC, Wang YH, Backlund A, et al. Decoding Multiple Biofunctions of Maca on Its Anti-allergic, Anti-inflammatory, Anti-thrombotic, and Pro-angiogenic Activities. J Agric Food Chem. 2021;69(40).

4. Mlostoń G, Kowalczyk M, Celeda M, Gach-Janczak K, Janecka A, Jasiński M. Synthesis and Cytotoxic Activity of Lepidilines A–D: Comparison with Some 4,5-Diphenyl Analogues and Related Imidazole-2-thiones. Vol. 84, Journal of Natural Products. 2021.

5. Carvalho F V., Ribeiro PR. Structural diversity, biosynthetic aspects, and LC-HRMS data compilation for the identification of bioactive compounds of Lepidium meyenii. Vol. 125, Food Research International. 2019.

6. Mlostoń G, Kowalczyk M, Celeda M, Jasiński M, Denel-Bobrowska M, Olejniczak AB. Fluorinated Analogues of Lepidilines A and C: Synthesis and Screening of Their Anticancer and Antiviral Activity. Molecules. 2022;27(11).

7. Geng P, Sun J, Chen P, Brand E, Frame J, Meissner H, et al. Characterization of Maca (Lepidium meyenii/Lepidium peruvianum) Using a Mass Spectral Fingerprinting, Metabolomic Analysis, and Genetic Sequencing Approach. Planta Med. 2020 Jul 20;86(10):674–85.

8. Zhou Y, Li P, Brantner A, Wang H, Shu X, Yang J, et al. Chemical profiling analysis of Maca using UHPLC-ESI-Orbitrap MS coupled with UHPLC-ESI-QqQ MS and the neuroprotective study on its active ingredients. Sci Rep. 2017;7.

9. Tarabasz D, Szczeblewski P, Laskowski T, Płaziński W, Baranowska-Wójcik E, Szwajgier D, et al. The Distribution of Glucosinolates in Different Phenotypes of Lepidium peruvianum and Their Role as Acetyl- and Butyrylcholinesterase Inhibitors—In Silico and In Vitro Studies. Int J Mol Sci. 2022 Apr 27;23(9):4858.

10. Xia C, Deng J, Chen J, Zhu Y, Song Y, Zhang Y, et al. Simultaneous determination of macaenes and macamides in maca using an HPLC method and analysis using a chemometric method (HCA) to distinguish maca origin. Revista Brasileira de Farmacognosia. 2019;29(6).

11.  Liu T, Peng Z, Lai W, Shao Y, Gao Q, He M, et al. The Efficient Synthesis and Anti-Fatigue Activity Evaluation of Macamides: The Unique Bioactive Compounds in Maca. Molecules. 2023;28(9).

12. Sun Y, Dai C, Shi S, Zheng Y, Wei W, Cai D. Composition analysis and antioxidant activity of essential oils, lipids and polysaccharides in different phenotypes of Lepidium meyenii. J Chromatogr B Analyt Technol Biomed Life Sci. 2018;1099.

13. Wang Y, Wang Y, McNeil B, Harvey LM. Maca: An Andean crop with multi-pharmacological functions. Vol. 40, Food Research International. 2007.

14.  Zheng BL, He K, Kim CH, Rogers L, Shao Y, Huang ZY, et al. Effect of a lipidic extract from Lepidium meyenii on sexual behavior in mice and rats. Urology. 2000;55(4).

15.  Zhu H, Wang R, Hua H, Cheng Y, Guo Y, Qian H, et al. The macamide relieves fatigue by acting as inhibitor of inflammatory response in exercising mice: From central to peripheral. Eur J Pharmacol. 2022;917.

16.  Hahn D, Lee T, Lee S, Bae JS, Na M, Kim M. Discovery and Quantitative Analysis of Nuclear Factor Erythroid 2-Related Factor (Nrf2) Activators in Maca (Lepidium meyenii) Using the Synthetic Macamides. Curr Dev Nutr. 2020;4.

17. Cao F, Zhang H, Yan Y, Chang Y, Ma J. Extraction of polysaccharides from Maca enhances the treatment effect of 5-FU by regulating CD4+T cells. Heliyon. 2023;9(6).

18.  Zhou Y, Zhu L, Li H, Xie W, Liu J, Zhang Y, et al. In vivo and in vitro neuroprotective effects of maca polysaccharide. Frontiers in Bioscience - Landmark. 2022;27(1).

19.  Zhang KY, Li CN, Zhang NX, Gao XC, Shen JM, Cheng DD, et al. UPLC-QE-Orbitrap-Based Cell Metabolomics and Network Pharmacology to Reveal the Mechanism of N-Benzylhexadecanamide Isolated from Maca (Lepidium meyenii Walp.) against Testicular Dysfunction. Molecules. 2023;28(10).

20. Zhou Y, Wang H, Guo F, Si N, Brantner A, Yang J, et al. Integrated proteomics and lipidomics investigation of the mechanism underlying the neuroprotective effect of N-benzylhexadecanamide. Molecules. 2018;23(11).

21. Huang YJ, Peng XR, Qiu MH. Progress on the Chemical Constituents Derived from Glucosinolates in Maca (Lepidium meyenii). Vol. 8, Natural Products and Bioprospecting. 2018.

22. Gonzales-Arimborgo C, Yupanqui I, Montero E, Alarcón-Yaquetto DE, Zevallos-Concha A, Caballero L, et al. Acceptability, Safety, and Efficacy of Oral Administration of Extracts of Black or Red Maca (Lepidium meyenii) in Adult Human Subjects: A Randomized, Double-Blind, Placebo-Controlled Study. Pharmaceuticals (Basel). 2016 Aug 18;9(3).

23. Hajdu Z, Nicolussi S, Rau M, Lorántfy L, Forgo P, Hohmann J, et al. Identification of endocannabinoid system-modulating N-alkylamides from Heliopsis helianthoides var. scabra and Lepidium meyenii. J Nat Prod. 2014;77(7).

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