Mangiferin: a Metabolic Nootropic ?

Mangiferin is one of the rising stars of the Nutraceutical industry.

Extracted from mango leaves, it has demonstrated Nootropic benefits and has recently shown promising potential for Metabolic regulation.

Could mangiferin become a staple ingredient in metabolism-related applications – both on its own or combined with other potent phytoactives ?


Mangiferin is a xanthonoid, more specifically a glycosylated form of norathyriol. As its name suggests, it is found in the mango tree (Mangifera indica) but also in the red kapok tree (Bombax ceiba) or even in the less exotic yellow gentian root (Gentiana lutea).

Xanthones and xanthonoids are a relatively unknown class of phytonutrients in the West. They are nonetheless well renowned in Asian medicine and can be extracted from the mango (mangiferin) and the mangosteen tree (mangostines), both of which are found in the traditional pharmacopoeias.

Given the available scientific data and the increasing incidence of metabolic imbalances in the Western world, it seems that this category of molecules with promising health effects is not to be neglected for this application. Therefore, this article aims at reviewing the available scientific data on mangiferin, while highlighting the interest of combining it with other phytonutrients for an effective nutraceutical approach or even in the context of a 2.0 clinical nutrition protocol.


2.1. Metabolic regulation


Although it has recently been put forward for its properties on the neurological sphere – and more specifically for its nootropic effects – mangiferin is mainly studied for its impact on metabolic regulation. Indeed, many studies have highlighted its ability to influence various aspects of metabolic balance, showing mangiferin acted on both glycaemic [1-6] and lipidemic metabolism [7-12].

The mechanisms involved in the regulatory action of mangiferin have not yet been entirely identified at this stage, however, the following effects have already been demonstrated:

  • Stimulation of the SIRT1/AMPK cascade [12-15].
  • Stimulation of Adiponectin [7; 16; 17] (which could be linked to the previous point).
  • Activation of alpha and gamma PPAR related pathways [3; 18-20].
  • inhibition of alpha-Glucosidase [21].

The underlying mechanisms behind these effects have also been related to autophagy [10; 22-25], as well as anti-inflammatory properties. The extended physiological impact of mangiferin therefore suggests its significant action on the intestine-microbiota-liver axis, through modulation of bile acids in particular (FXR, TGR5, SERBP, etc.).


2.2. Neurological effects


As far as scientific literature is concerned, mangiferin is essentially a metabolic regulator. However, several studies clearly highlight its neurological benefits [26], thus justifying its use in a nootropic context. Indeed, mangiferin shows neuroprotective effects [27-30], as well as a positive impact on various models of neurological pathologies, stemming – at least partially – from its neuroprotective effects [31-35]. In addition, a recent clinical study on ZYNAMITE, a mango leaf extract highly concentrated in mangiferin has shown significant nootropic effects [36].

It should be noted that the regulatory effects on the metabolic sphere are not necessarily to be dissociated from the neuroprotective and nootropic benefits. Indeed, many phytonutrients with demonstrated impact on the cognitive sphere do so through metabolic regulation – at least partially. For example, bile acids can act at the cerebral level and can thus influence the neurological sphere. Modulation of adipokines can also have a neurological impact.

Moreover, from a more practical point of view, the idea of ​​supporting cognitive functions while promoting metabolic performance is clearly fits well in the “active lifestyle” trends observed on the market, which can target several segments of the population – from “active senior” to the “young sports executive” and the “professional gamer”.


2.3. Other Health Perspectives


The health potential of mangiferin does not stop at the first and second brains. Its potential has been highlighted in various processes related to inflammation [37-50], cardiovascular health [51-57] or even oncology [58-70].



The concepts of “metabolic regulation”, “nootropic activity” and “vitality” in general are often associated with adaptogens. Indeed, these plants can deploy a true pleiotropic activity thanks to the diversity of their active compounds, which can intervene in a myriad of physiological mechanisms in aims to strengthen the overall resilience of the organism. Certain aspects of this pleiotropic activity can thus be optimized by combining adaptogens with more “targeted” active ingredients. Indeed, the diversity of the health benefits of an adaptogenic plant is reflected in the diversity of its molecular profile; the use of targeted active ingredients with a complementary mechanism of action could therefore be a promising strategy to reinforce and enhance their health properties.

In this context, the association between Korean ginseng (Panax ginseng) and mangiferin shows many advantages. Beyond the fact that ginseng is the most studied adaptogen in the world, its benefits are widely associated with mental performance, as well as resilience against fatigue. Moreover, ginseng’s effects on metabolic balance have been widely demonstrated and documented. Strengthening this metabolic dimension by adding mangiferin to ginseng could allow the nutraceutical industry to offer an effective active tandem in the short and long term and maximize the results.


When thinking of natural compounds used in metabolic regulation, berberine is probably the one that most often comes to mind for Western practitioners. It is an isoquinoline alkaloid found in the genus Berberis (Berberis aristata probably being the most common commercial source) but also in other medicinal plants such as Goldenseal (Hydrastis canadensis). Although health professionals may recommend it as an alternative to metformin, it should be remembered that berberine is marketed as a food supplement and not as a drug, and this despite it having significant pharmacological properties in high doses recognized by the ANSM.

However, berberine has a major drawback: its significant daily active dose must be divided into multiple doses to minimize the risk of intestinal disorders, a well-known side effect. But the idea of ​​having 5 daily intakes of a food supplement is not particularly pleasant and patient compliance may be affected. Furthermore, the health authorities consider that high doses of berberine also present a risk of drug interactions, which limits the possibilities of use in a clinical setting. This is an invitation to consider reducing the dose, however at the risk of diminishing the efficacy and potential interest of the substance.

The idea of ​​combining complementary phytonutrients with lower doses of berberine is therefore of great interest, whether in the context of dietary supplementation or in clinical nutrition. However, it should be noted that the “complementarity” of action is not integral since there are potential similarities in certain physiological mechanisms of action between Berberine and Mangiferin – in particular the mechanisms related to autophagy or PPARα, SIRT1 pathways.


Although still little known in Europe, mangiferin shows significant activity on the metabolic sphere and its resulting benefits (nootropic, ergogenic, etc.) make it a phytonutrient of choice for the future of clinical nutrition. Its association with adaptogenic plants such as Korean ginseng (Panax ginseng) and specific medicinal mushrooms such as Reishi (Ganoderma lucidum), or with other “metabolic phytoactives” such as berberine, could well make it a flagship in clinical nutrition. 2.0. Mangiferin’s future on the nutraceutical market on the other hand, appears to be all mapped out.


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[28] Xi JS, Wang YF, Long XX, Ma Y (2018) – “Mangiferin Potentiates Neuroprotection by Isoflurane in Neonatal Hypoxic Brain Injury by Reducing Oxidative Stress and Activation of Phosphatidylinositol-3-Kinase/Akt/Mammalian Target of Rapamycin (PI3K/Akt/mTOR) Signaling.” Med Sci Monit. 2018 Oct 19;24:7459-7468.

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[30] Wang Z, Guo S, Wang J, Shen Y, Zhang J, Wu Q (2017) – “Nrf2/HO-1 mediates the neuroprotective effect of mangiferin on early brain injury after subarachnoid hemorrhage by attenuating mitochondria-related apoptosis and neuroinflammation.” Sci Rep. 2017 Sep 19;7(1):11883.

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[38] Piao CH, Fan YJ, Nguyen TV, Song CH, Chai OH (2020) – “Mangiferin Alleviates Ovalbumin-Induced Allergic Rhinitis via Nrf2/HO-1/NF-κB Signaling Pathways.” Int J Mol Sci. 2020 May 12;21(10):3415.

[39] Li Y, Wu Y, Jiang K, Han W, Zhang J, Xie L, Liu Y, Xiao J, Wang X (2019) – “Mangiferin Prevents TBHP-Induced Apoptosis and ECM Degradation in Mouse Osteoarthritic Chondrocytes via Restoring Autophagy and Ameliorates Murine Osteoarthritis.” Oxid Med Cell Longev. 2019 Oct 15;2019:8783197.

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[41] Yun C, Chang M, Hou G, Lan T, Yuan H, Su Z, Zhu D, Liang W, Li Q, Zhu H, Zhang J, Lu Y, Deng J, Guo H (2019) – “Mangiferin suppresses allergic asthma symptoms by decreased Th9 and Th17 responses and increased Treg response.” Mol Immunol. 2019 Oct;114:233-242.

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[45] Liang CL, Lu W, Zhou JY, Chen Y, Zhang Q, Liu H, Qiu F, Dai Z (2018) – “Mangiferin Attenuates Murine Lupus Nephritis by Inducing CD4+Foxp3+ Regulatory T Cells via Suppression of mTOR Signaling.” Cell Physiol Biochem. 2018;50(4):1560-1573.

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