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. Since then, 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 (3,5-6). Preliminary cytotoxicity activity has been determined in some of these compounds in specific cell lines (6, 7) and potential anti-inflammatory, anti-allergic, and anti-thrombotic effects, depending on the extract used (3).

 

Geng et al. (8) and Zhou et al. (9) 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 (10,11). One study has suggested the use of lepidilines as an analytical marker to identify maca (6), as they, along with macamides are considered unique to maca (12,13), whereas macaenes can be found in other plants such as tomatoes and eggplants (11). 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 newer study states there are twenty-six macamides that provide therapeutic benefits (14). 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 (9).

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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 (15,16). Macaenes may play a role in lipid metabolism (11). Macamides are a unique class of maca phytochemicals, with more than thirty compounds identified and explored for their anti-fatigue effects (12,17). There are five major macamides present in maca root (18) however, Macamide B is the predominant compound that indicates the quality of maca (19). Macamide B content in fermented maca is approximately 93% higher compared to non-fermented maca (19).

 

Macamides are also important anti-inflammatory, antioxidant, and anti-cancer compounds (11), contributing to maca’s anti-fatigue, neuroprotection, and fertility-enhancing effects (9,14,18). Macamides have been reported to serve as potential therapy in the treatment of neurological diseases due to their ability to bind to other molecules, including various cellular receptors (14). (Image 1) Macamides may also provide neuroprotection by activating the Nrf2/HO-1 signaling pathway, resulting in improved synaptic plasticity and modulating the gut microbiota (13). Macamides from maca extracts have been found to provide superior neuroprotective activity against PC12 cell injury* as compared to a drug therapy (nimodipine), along with higher nitric oxide (NO) inhibition, resulting in a greater anti-inflammatory response (18).

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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 (20). Recent studies note that the macamides in maca exhibit nuclear factor erythroid 2-related factor (Nrf2) activation (21) and enhances muscle differentiation by activating the AKT pathway attenuating muscle-atrophy (22). Further, fermenting maca has demonstrated an increase of macamides B content by 93.2%, while also providing an increase in amino acid content, and enhancing the fruity, buttery and floral scent of maca (19).

 

*PC12 cells are used in neuroscience research to study neurotoxicity, neuroprotection, neuronal differentiation, neurosecretion, neuroinflammation, and synaptogenesis.

 

Newer research on the science of maca phytochemicals continues, with some recent publications looking at the immunomodulatory (23) and neuroprotective (24) 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 (25).

 

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 (26). Comparatively, this fatty acid amide is found in higher amounts in Peruvian maca than Chinese maca (27), suggesting that elevation or other factors could be responsible for its synthesis. Additionally, macamides found in maca reduce inflammatory markers (IL-1B, Il-6, and TNF-A), restore gut microflora connected to cognitive aging, and activated Nrf2 pathways (28). 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 (29,30). Recent research has reported that fermented maca provided high neuroprotective effects due to the increase of antioxidants status, flavonoid, saponin, and macamide B content (19).

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*PC12 cells are used in neuroscience research to study neurotoxicity, neuroprotection, neuronal differentiation, neurosecretion, neuroinflammation, and synaptogenesis.

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Author: Kim Ross, DCN

Reviewed by: Deanna Minich, PhD

Last Updated: December 17, 2024

 

References

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