Figure - available from: Molecular Neurobiology
This content is subject to copyright. Terms and conditions apply.
Source publication
The pentane extract of the Peruvian plant, Lepidium meyenii (Maca), has been demonstrated to possess neuroprotective activity in previous in vitro and in vivo studies (Pino-Figueroa et al. in Ann N Y Acad Sci 1199:77–85, 2010; Pino-Figueroa et al. in Am J Neuroprot Neuroregener 3:87–92, 2011). This extract contains a number of macamides that may ac...
Similar publications
Background: Fatty acid amide hydrolase (FAAH) is a membrane-bound homodimeric enzyme that gets in contact with a lipophilic substrate in the lipid bilayer, and then cleaves it into water soluble products. FAAH plays a critical role in modulating in vivo content and biological activity of endocannabinoids (eCBs), and its function is affected by memb...
Thirty years ago, the discovery of a cannabinoid (CB) receptor that interacts with the psychoactive compound in Cannabis led to the identification of anandamide, an endogenous receptor ligand or endocannabinoid. Research on endocannabinoids has since exploded, and additional receptors along with their lipid mediators and signaling pathways continue...
Citations
... Leading pharmaceutical companies spend billions of dollars researching and developing new drugs with these receptors as therapeutic targets. Among the promising novel medicines in treating neurological diseases are macamides [16][17][18][19]. Extracted from Maca (Lepidium meyenii), macamides are non-polar secondary metabolites with a structure composed of an N-benzyl ring linked to a long chain of fatty acids through an amide bond. ...
... However, they have one or more carbonyl groups (C=O), which introduces polar regions to the molecule that can be electron donors. Several authors have mentioned that this amphipathic character of macamides could be responsible for their antioxidant properties and ability to bind to other molecules, including cellular receptors, among them GPCRs [18,30,[37][38][39][40]. , where the 3D structure shows the electrostatic surface calculated at a B3LYP/3ZVP level of theory, with red, blue, and green indicating nucleophilic zones, electrophilic zones, and neutral zones, respectively; (b) structure of the fatty acid amide hydrolase 1 (FAAH) enzyme involved in the degradation of anandamide, a neurotransmitter related to the CB1 receptors of the nervous system and CB2 of the peripheral nervous system; (c) schematic representation of the Adenosine A2A, opioid, CB2, and CB1 receptors, which are involved in different neurological disorders. ...
... Currently, four GPCRs have been recognized in which macamides can directly affect the biological functions ( Figure 2b). Among thees, the best known are the CB1 and CB2 receptors, which belong to the endocannabinoid system and are responsible for intercellular communication, release of neurotransmitters, and regulation of pain perception, among several other functions [17,18,35]. A third receptor is adenosine A2A, one of the receptors responsible for regulating the cardiovascular and immune systems and neurotransmitter secretion of neurotransmitters [38,41]. ...
Therapeutic treatment of nervous system disorders has represented one of the significant challenges in medicine for the past several decades. Technological and medical advances have made it possible to recognize different neurological disorders, which has led to more precise identification of potential therapeutic targets, in turn leading to research into developing drugs aimed at these disorders. In this sense, recent years have seen an increase in exploration of the therapeutic effects of various metabolites extracted from Maca (Lepidium meyenii), a plant native to the central alpine region of Peru. Among the most important secondary metabolites contained in this plant are macamides, molecules derived from N-benzylamides of long-chain fatty acids. Macamides have been proposed as active drugs to treat some neurological disorders. Their excellent human tolerance and low toxicity along with neuroprotective, immune-enhancing, and and antioxidant properties make them ideal for exploration as therapeutic agents. In this review, we have compiled information from various studies on macamides, along with theories about the metabolic pathways on which they act.
... Macamides, a unique series of non-polar long-chain fatty acids N-benzamide isolated from Maca, are mainly alkaloids with neuroprotective properties, 223 of which N-Benzyloctadeca-9Z,12Z-dienamide exhibits the best FAAH inhibitory activity and attenuates ischaemic stroke injury, 224 but this inhibition is an irreversible inhibitor that exhibits time-dependent inhibition. 205 Lavender essential oil, an over-The-counter herbal medicine approved by the European Medicines Agency for the relief of anxiety, displayed ...
Over the past decade, the idea of targeting the endocannabinoid system to treat anxiety disorders has received increasing attention. Previous studies focused more on developing cannabinoid receptor agonists or supplementing exogenous cannabinoids, which are prone to various adverse effects due to their strong pharmacological activity and poor receptor selectivity, limiting their application in clinical research. Endocannabinoid hydrolase inhibitors are considered to be the most promising development strategies for the treatment of anxiety disorders. More recent efforts have emphasized that inhibition of two major endogenous cannabinoid hydrolases, monoacylglycerol lipase (MAGL) and fatty acid amide hydrolase (FAAH), indirectly activates cannabinoid receptors by increasing endogenous cannabinoid levels in the synaptic gap, circumventing receptor desensitization resulting from direct enhancement of endogenous cannabinoid signaling. In this review, we comprehensively summarize the anxiolytic effects of MAGL and FAAH inhibitors and their potential pharmacological mechanisms, highlight reported novel inhibitors or natural products, and provide an outlook on future directions in this field.
... It has been proposed that macamides may act on the nervous system through their inhibitory effect on the degradation of endocannabinoids, by disrupting the activity of the FAAH enzyme. One study evaluated this property showing that the effect on FAAH was dependent on macamide concentrations and suggesting its probable irreversibility (Alasmari et al., 2019). Macamides have shown antioxidant activity as one of their bestknown properties and great potential as therapeutic agents; however, studies investigating this activity in humans are limited (Todorova et al., 2021). ...
... Macamides have shown antioxidant activity as one of their bestknown properties and great potential as therapeutic agents; however, studies investigating this activity in humans are limited (Todorova et al., 2021). Its ability to bind to the endocannabinoid CB1 receptor has also been observed, acting as analogs of anandamide and exhibiting neuroprotective activity (Alasmari et al., 2019). ...
... However, administration of 1.2 g/kg/day of maca powder for 30 days 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). ...
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.
... The technology has resulted in the development of relatively new field effect transistors (FET) sensors. The integration of potentiometric ion selective electrodes with FET has been realized in the form of ion selective field effect transistors (ISFET) having potential difference as the output signal [167]. The magnitude of surface potential changes with change in the activity or concentration of analyte ion. ...
... This novel performance is due to the use of red-shifted chalcogenpyrylium-based Raman reporters, which offered significant promise for the translation of NPs into clinical applications for non-invasive disease diagnostics based on this new chemical principle of measurement. Later [167], the depth penetration capabilities of SESORS was utilized and reported multiplexed imaging and classification of three singleplex nanotags and a triplex of nanotags within breast cancer tumor models through depths of 10 mm using a handheld SORS instrument for the first time. Although simultaneous detection of multiple targets in vivo is a significant challenge, this novel work was a significant step forward in detecting and classifying multiple vibrational fingerprints in vivo. ...
... Alkaloids have many effects on the health of humans and animals due to the presence of natural organic nitrogen bases. It also has aphrodisiac properties because of the presence of fatty acids and macamides [159][160][161][162][163][164][165][166][167]. Even the pentane extract of maca is comprised of macamides which in turn act on the endocannabinoid system via inhibitory activity on fatty acid amide hydrolase [168]. ...
Nanotechnology is essential in the development of advanced technologies for medicine and healthcare. Advances depend on the ability to study these materials and nano-biotechnologies using advanced analytical techniques. Providing a comprehensive overview of analytical techniques for applications in biomedical nanotechnology at both the fundamental and applied level, this book provides a broad perspective of the development of analytical methods involved in materials science and electronics. It highlights the fundamentals and systematic developments of techniques to achieve better characterization, rapid diagnostics, cost-effective and user-friendly approaches, and state-of-the-art methodologies for personalized health management, and explains how this fundamental knowledge can be translated into applications in nano-enabled biomedical research. The multidisciplinary readership includes chemists, biologists, physicists, materials scientists, engineers and information technologists.Key features• Provides a comprehensive overview of analytical techniques for applications in biomedical nanotechnology at both the fundamental and applied level.• Explains how fundamental knowledge of the techniques can be translated to applications in nano-enabled biomedical research.• Covers state-of-art analytical techniques for biomedical nanotechnology.• Includes the prospects and challenges with each technique, including potential solutions.• Provides a multidisciplinary view of interest to chemists, biologists, physicists, materials scientists, engineers and information technologists.
... The technology has resulted in the development of relatively new field effect transistors (FET) sensors. The integration of potentiometric ion selective electrodes with FET has been realized in the form of ion selective field effect transistors (ISFET) having potential difference as the output signal [167]. The magnitude of surface potential changes with change in the activity or concentration of analyte ion. ...
... This novel performance is due to the use of red-shifted chalcogenpyrylium-based Raman reporters, which offered significant promise for the translation of NPs into clinical applications for non-invasive disease diagnostics based on this new chemical principle of measurement. Later [167], the depth penetration capabilities of SESORS was utilized and reported multiplexed imaging and classification of three singleplex nanotags and a triplex of nanotags within breast cancer tumor models through depths of 10 mm using a handheld SORS instrument for the first time. Although simultaneous detection of multiple targets in vivo is a significant challenge, this novel work was a significant step forward in detecting and classifying multiple vibrational fingerprints in vivo. ...
... Alkaloids have many effects on the health of humans and animals due to the presence of natural organic nitrogen bases. It also has aphrodisiac properties because of the presence of fatty acids and macamides [159][160][161][162][163][164][165][166][167]. Even the pentane extract of maca is comprised of macamides which in turn act on the endocannabinoid system via inhibitory activity on fatty acid amide hydrolase [168]. ...
Over the last few decades, magnetic nanostructures have been providing the platform to develop magnetically guided systems for biomedical nanotechnology and applications such as biosensors, nanomedicine, targeted drug delivery, etc. Magnetic nanoparticles especially super-paramagnetic iron oxide nanoparticles (SPIONs) have gained more importance in biomedical applications. This chapter discusses the biomedical uses of magnetic nanoparticles. The use of magnetic nanoparticles in hyperthermia, drug delivery, imaging tools, MRI, electrochemical sensors, cell and gene therapy for cancer treatment are discussed after reviewing some of the basic principles of magnetism. Finally, a summary of the magnetic nanostructure based biomedical nanotechnology is presented by examining current possibilities in this area, especially the huge hurdles faced when implementing laboratory-tested technologies.
... The underground root of this plant is rich in macamides, maca alkaloids, glucosinolates, volatile oils, sterols, polyphenols, and macaenes [2,3]. A wide array of maca extracts has been obtained by petroleum ether [4], pentane [5], methanolic [6], alcoholic [7,8], or aqueous [9] extraction and widely used in pharmacological studies. Macamides, secondary amides with variable hydrocarbon chain lengths and levels of unsaturation, are formed by combining benzylamine and a fatty acid moiety. ...
... The 1 H NMR spectrum (Figures 5d and S4) exhibited two or three cis-coupled olefinic protons at δ 5.37 (d, J = 4.0 Hz, H-9) and 5.36 (m, H-10), four other olefinic protons between δ 5.31 and 5.34 (m, H-12, H-13, H-15, and H- , as well as other protons between δ 1.30 and 1.33, assigned to the methylene group. Compared with macamide 1 (NBH), the other four compounds (2)(3)(4)(5) contain two or three unsaturated double bonds and a 6-substituted phenyl ring replacing the methoxy group, which is verified in IR, MS, 1 H, and 13 C NMR spectra (Supplementary data). The pure precipitates were analyzed by HPLC-DAD, ESI-MS, IR, and NMR ( 1 H and 13 C). ...
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.
... The results of the Gas chromatography-mass spectrometric screening are presented in table 2 and figure 1. Table 2 showed the various phytocompounds identified their retention time, molecular formula, molecular weight, and peak area % (percentage abundance). Sixteen 19 . Inhibition of FAAH is crucial as it regulates endogenous concentrations of endocannabinoids 29 . ...
The methanolic fruit extract of Tetrapleura tetraptera was analyzed for the presence of
phytocompounds, their bioactivity, the functional groups involved in this activity, and its amino
acid profile using standard procedures. Phytochemicals such as tannins, phenols, flavonoids, and
alkaloids were identified as being highly present. Gas chromatographic-mass spectrometric (GCMS) analysis identified 16 bioactive compounds, with 2-thiopheneethanol (58.77%) being the
most abundant. Curcumin, with the most diverse pharmacological role, and other bioactive
compounds such as cedren-13-ol, 8 (1.56%), N-benzyl stearamide (4.46%), a prominent fatty acid
amide hydrolase (FAAH) inhibitor; pthalic acid, butyl undecyl ester (1.49%); and phenol, 2, 6
-bis
(1,1 dimethyl ethyl) (1.46%), were also present. Fourier transform infrared (FTIR) analysis
confirmed the presence of alkanes, esters, benzene rings, aliphatic, sulfonic acid, and methylene
chains. Also, the amino acid analysis of the T. tetraptera revealed that the fruit contains 18 amino
acids. Leucine (4.20%), phenylalanine (3.37%), and valine (3.25%) were the most abundant
essential amino acids identified, with glutamic (7.20%) and aspartic acid (5.61%) having the
highest concentrations as non-essential amino acids. This therefore indicates that T. tetraptera
fruit could be used as a pharmacological or therapeutic agent as well as a dietary condiment,
particularly at this time when there is a demand for novel protein sources.
... In addition to being safe for human consumption, macamides have been shown to possess multiple biological activities in previous years (1,2). For example, macamides have been shown to relieve exercise-induced fatigue and regulate lipid metabolism by inhibiting the activity of fatty acid amide hydrolase (3)(4)(5). Macamides also display anti-inflammatory effects by reducing the expression of proinflammatory factors and alleviating inflammatory-induced pain, such as in colitis (6,7). In addition, macamides can exert neuroprotective activity and attenuate hypoxic-ischemic brain damage through the regulation of apoptosis or autophagy (8,9). ...
Macamides are a class of bioactive natural products obtained from Lepidium meyenii (maca), which have been reported to exert inhibitory activity in cancer. However, their role in lung cancer is currently unknown. In the present study, macamide B was shown to inhibit the proliferation and invasion of lung cancer cells, as determined by Cell Counting Kit-8 and Transwell assays, respectively. By contrast, macamide B induced cell apoptosis, as determined by Annexin V-FITC assay. Moreover, combined treatment with macamide B and olaparib, an inhibitor of poly (ADP-ribose) polymerase, further suppressed the proliferation of lung cancer cells. At the molecular level, the expression of ataxia-telangiectasia mutated (ATM), RAD51, p53 and cleaved caspase-3 were significantly increased by macamide B, as determined by western blotting, whereas the expression levels of Bcl-2 were decreased. By contrast, when ATM expression was knocked down by small interfering RNA technology in A549 cells treated with macamide B, the expression levels of ATM, RAD51, p53 and cleaved caspase-3 were reduced, whereas those of Bcl-2 were increased. Consistently, cell proliferation and invasive ability were partially rescued by ATM knockdown. In conclusion, macamide B inhibits lung cancer progression by inhibiting cell proliferation and invasion, and inducing apoptosis. Furthermore, macamide B may participate in regulating the ATM signaling pathway. The present study provides a potential new natural drug for treating patients with lung cancer.
... The positive effects of alpine plants on exercise capacity declination via neuroprotection/stimulation during long-time exercise has been observed. Macamides demonstrated similar medicinal properties to cannabinoids via CB 1 receptor activation in the central nervous system [32]. Rhodiola and salidroside are also well-known for their neuroprotective and antidepressant activity [33]. ...
... High-altitude plants with anti-inflammatory activities, such as ethanoic extract from Maca [60], significantly inhibited the activities of TNF-α, IL-6, and IL-1β, and alleviated exercise-induced fatigue. In addition, macamides could also interacted the expression of analog of exogenous anandamide (AEA) and receptor (CB 1 ) [32], so that it might reduce exercise-induced inflammatory nociception mediated by endocannabinoid [61,62]. IL-10 is an anti-inflammatory cytokine that can reduce antigen presentation, negatively regulating the activity of pro-inflammatory cytokines. ...
Natural plants from plateaus have been the richest source of secondary metabolites extensively used in traditional and modern health care systems. They were submitted to years of natural selection, co-evolved within that habitat, and show significant anti-fatigue-related pharmacological effects. However, currently, no review on high-altitude plants with anti-fatigue related properties has been published yet. This study summarized several Chinese traditional high-altitude plants, including Rhodiola rosea L., Crocus sativus L., Lepidium meyenii W., Hippophaerhamnoides L., which are widely used in the Qinghai–Tibet Plateau and surrounding mountains, as well as herbal markets in the plains. Based on phytopharmacology studies, deeper questions can be further revealed regarding how these plants regulate fatigue and related mental or physical disease conditions. Many active derivatives in high-altitude medical plants show therapeutic potential for the management of fatigue and related disorders. Therefore, high-altitude plants significantly relieve central or peripheral fatigue by acting as neuroprotective agents, energy supplements, metabolism regulators, antioxidant, and inflammatory response inhibitors. Their applications on the highland or flatland and prospects in natural medicine are further forecast, which may open treatments to reduce or prevent fatigue-related disorders in populations with sub-optimal health.
... A database search and literature review identified 156 bioactive components in maca water extra, and a literature review identified 26 types of maca amides (Alasmari, Bhlke, Kelley, Maher, & Pino-Figueroa, 2019;Almukadi et al., 2013;McCollom, Villinski, McPhail, Craker, & Gafner, 2005;Muhammad, Zhao, Dunbar, & Khan, 2002;Zhao, Muhammad, Dunbar, Mustafa, & Khan, 2005; B. L.; Zheng et al., 2000;Zhu et al., 2020), as shown in Table 1. Twenty-six bioactive ingredients and targets were used to generate a "water extract-bioactive ingredient-target" network (Fig. 1A). ...
Lepidium meyenii Walp. is a type of food used to fight fatigue, and macamides is the key anti-fatigue component in Lepidium meyenii Walp. water extract (Maca). The mechanisms of action of several foods with anti-fatigue properties lie in the oxidative balance of tissues; however, little attention has been given to the microbiome. The gut microbial community is closely related to dietary choices, as well as exercise-induced skeletal muscle fatigue. As such, this study used a foodomics approach to analyze the anti-fatigue properties of maca amide, a key component in maca, on the gut microbiome. The key components in maca were identified, and after validation in a mouse model, an analysis of the gut microbiome was performed. The results of database searches and network analyses showed that the key anti-fatigue component of maca was N-benzyl-9Z, 12Z-octadecadienamide (Mm). Further analyses revealed that the key microbes metabolizing Mm belonged to Alistipes, Alloprevotella, Parabacteroides, and Butyricimonas genera and the Prevotellaceae in mice. The results of microbial analysis showed that Mm could improve exercise-induced skeletal muscle fatigue in mice by modulating the L-glutamate–ornithine–proline axis through the breakdown of histidine, arginine, and proline. Therefore, from foodomics and gut microbial genomics perspectives, this study demonstrates that macamide is the key anti-fatigue component in maca, and these findings provide new insights for the development of foods that fight fatigue.
