Exploring the chemical and pharmacological variability of Lepidium meyenii: a comprehensive review of the effects of maca

Abstract

Maca (Lepidium meyenii), a biennial herbaceous plant indigenous to the Andes Mountains, has a rich history of traditional use for its purported health benefits. Maca's chemical composition varies due to ecotypes, growth conditions, and post-harvest processing, contributing to its intricate phytochemical profile, including, macamides, macaenes, and glucosinolates, among other components. This review provides an in-depth revision and analysis of Maca's diverse bioactive metabolites, focusing on the pharmacological properties registered in pre-clinical and clinical studies. Maca is generally safe, with rare adverse effects, supported by preclinical studies revealing low toxicity and good human tolerance. Preclinical investigations highlight the benefits attributed to Maca compounds, including neuroprotection, anti-inflammatory properties, immunoregulation, and antioxidant effects. Maca has also shown potential for enhancing fertility, combating fatigue, and exhibiting potential antitumor properties. Maca's versatility extends to metabolic regulation, gastrointestinal health, cardio protection, antihypertensive activity, photoprotection, muscle growth, hepatoprotection, proangiogenic effects, antithrombotic properties, and antiallergic activity. Clinical studies, primarily focused on sexual health, indicate improved sexual desire, erectile function, and subjective wellbeing in men. Maca also shows promise in alleviating menopausal symptoms in women and enhancing physical performance. Further research is essential to uncover the mechanisms and clinical applications of Maca's unique bioactive metabolites, solidifying its place as a subject of growing scientific interest.

Keywords: Lepidium meyenii; clinical studies; glucosilonates; maca; macaenes; macamides; pharmacology; preclinical.

FIGURE 1

Chemical structure of macamides: (A) General structure; (B) N-benzyl-hexadecanamide; (C) N-benzyl-(9Z,12Z,15Z)-octadecatetraenamide; (D) N-benzyl-9Z,12Z-octadecadienamide; (E) N-benzyl-13-oxo-9E,11E,15E-octadecatrienamide.

FIGURE 2

Chemical structure of glucosinolates. (A) General chemical structure; (B) Structure of Glucotropaeolin; (C) Glucolepigramin (3-hydroxybenzylglucosinolate); (D) Sinalbin (4-hydroxybenzylglucosinolate); (E) Glucolimnanthin (m-methoxybenzyl glucosinolate).

FIGURE 3

Hypothetical biosynthetic pathway to exemplify macamides formation during natural air-drying process. (A) The biosynthesis of benzyl glucosinolate from phenylalanine comprised the formation of (E)-Phenylacetaldoxime as intermediate produced by CYP79A2. This later transform into thiohydroximate and is glycosylated and sulfated. The unstable sulfated compound leads to isothiocyanate formation by the Sulfotransferase (SOT) and Glucosyltransferasa (UGT74) (Blažević et al., 2020). (B) The enzymolysis of the benzylglucosinolate the generation of benzylamine is accomplished by (Zhang et al., 2023). (C) In this example Linoleic acid serves as the scaffold for the formation of 9-hydroperoxy-10E,12Z-octadecadienoic acid and 13-hydroperoxy-9Z,12E-octadecadienoic acid through lipoxygenase enzymes, and then transfers the fundamental skeleton of macaenes using 9 or 13-hydroperoxy-10E,12Z-octadecadienoic acid. Glutathione peroxidase and hydroxy-fatty acid dehydrogenase enzymes catalyze the conversion of 9 or 13-hydroxy-10E,12Z-octadecadienoic acid into 9 or 13-oxo-10E,12Z-octadecadienoic acid. Isomerization also produces more isomers of octadecadienoic acid, resulting in the known chemical variety of macamides (Xia, 2021). (D) Once the hydrolysis of lipids and glucosinolates release significant amounts of unsaturated free fatty acids and benzylamines. These are precursors are the core for macamide biosynthesis (Esparza, 2015). (E) Isomerization can also occur once the amide bond is formed with the unaltered linoleic acid (Xia, 2021).

FIGURE 4

Maca possible mechanism of action based on recent evidence. (A) L. meyenii macamides can modulate HPA axis via serotoninergic pathway via CBs Receptors (Alasmari et al., 2019), but also (B) induce 5-HT production by microbiota and gut–brain axis modulation by maca (Hong et al., 2023) (C) Activation of 5-HT in the neurosecretory serotoninergic cells in the Raphe nuclei located in the paraventricular nucleus (PVN) of the hypothalamus which in turn reduce the anterior pituitary gland releasing Antherocotropina (ACTH) and of (D) growth hormone, which in turn reduce expression and activity of Liver CYP450. (E) The reduction of ACTH consecuently modulate a reduction in cortisol production in the adrenal glands (Meissner et al., 2006b).