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Cited by 139Mangiferin and Mango ExtractsNatural Antidiabetic Agents StudiesNatural Compound Pharmacology Studies

Mangiferin: An effective therapeutic agent against several disorders (Review)

Open access
Du, Suya, Liu, Huirong, Lei, Tiantian, Xie, Xiaofang, Wang, Hailian, He, Xia, Tong, Rongsheng, Wang, Yi·2018·Molecular Medicine Reports
DOI 10.3892/mmr.2018.9529
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Abstract

Mangiferin (1,3,6,7‑tetrahydroxyxanthone‑C2‑β‑D‑glucoside) is a bioactive ingredient predominantly isolated from the mango tree, with potent antioxidant activity and multifactorial pharmacological effects, including antidiabetic, antitumor, lipometabolism regulating, cardioprotective, anti‑hyperuricemic, neuroprotective, antioxidant, anti‑inflammatory, antipyretic, analgesic, antibacterial, antiviral and immunomodulatory effects. Therefore, it possesses several health‑endorsing properties and is a promising candidate for further research and development. However, low solubility, mucosal permeability and bioavailability restrict the development of mangiferin as a clinical therapeutic, and chemical and physical modification is required to expand its application. This review comprehensively analyzed and collectively summarized the primary pharmacological actions of mangiferin that have been demonstrated in the literature, to support the potential future development of mangiferin as a novel therapeutic drug.

AI snapshot

Written from the paper’s full text.

TL;DR

Mangiferin is a mango-derived bioactive xanthone with antioxidant and broad pharmacological effects, including antidiabetic, antitumor, neuroprotective, cardiovascular, anti-inflammatory, antimicrobial, and immunomodulatory activities. However, its clinical development is limited by low solubility (0.111 mg/ml), low oral bioavailability (1.2%), and the fact that most evidence comes from in vivo and in vitro studies rather than clinical trials.

Key findings

  • Mangiferin shows antidiabetic effects in animal models: oral 40 mg/kg for 30 days in STZ-induced diabetic mice significantly reduced blood glucose, glycosylated hemoglobin, AST, ALT, and ALP, and improved red and white blood cell levels; in diabetic nephropathy rats, 40 mg/kg/day for 30 days decreased plasma glucose, kidney-to-body-weight ratio, BUN, plasma creatinine, uric acid, and urinary albumin.
  • Antitumor mechanisms include G2/M cell cycle arrest via CDK1-cyclin B1 regulation, S phase delay in colorectal HT29 and cervical HeLa cells, and apoptosis induction through NF-κB, caspase, Bcl-2/Bax, PKC-NF-κB, and Notch3 pathways in various cancer cell lines.
  • Neuroprotective and cardiovascular findings include reduced LPS-induced IL-6 and increased HO-1 in mouse hippocampus after oral mangiferin 50 mg/kg, attenuated depressive/anxiety-like behaviors after 20 and 40 mg/kg for 14 days, and cardioprotection in isoproterenol-induced myocardial infarction rats after 100 mg/kg for 28 days via upregulated antioxidant enzymes.
  • In a 12-week double-blind randomized clinical trial in overweight patients with hyperlipidemia, mangiferin 150 mg/day substantially increased serum mangiferin, HDL cholesterol, L-carnitine, β-hydroxybutyrate, acetoacetate, and lipoprotein lipase activity, but did not effectively decrease total cholesterol, LDL cholesterol, serum glucose, or insulin.

Methods

  • Narrative review that comprehensively analyzed and summarized the primary pharmacological actions of mangiferin demonstrated in the literature, covering antidiabetic, antitumor, neuroprotective, cardiovascular, and other properties.
  • Evidence base includes in vivo and in vitro studies, animal models, cell lines, and one 12-week double-blind randomized clinical trial of mangiferin (150 mg/day) in overweight patients with hyperlipidemia.
  • No systematic search strategy, meta-analysis, or standardized quantitative synthesis is described.

Limitations

  • The paper states that the pharmacodynamics of mangiferin remain unclear, most effects have only been demonstrated in in vivo and in vitro experiments, and further clinical research into pharmacology and pharmacokinetics is required.
  • The paper states that researchers did not use a standardized therapeutic approach; pharmacodynamic indexes including dose, concentration, and IC50 were not compared and analyzed at the same baseline, so experimental results are not universal.
  • Evident from the text: this is a narrative review without systematic search or quality assessment, it relies on cited studies, and it mentions some unpublished data; clinical evidence is sparse, with only one clinical trial described.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.3892/mmr.2018.9529

Cites

112 of 113 references verified0 citation errors · 1 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

51 of 137 cited sources checked · 32 supported · 1 flagged · accuracy not yet measured

  • Premisecitation

    Mangiferin facilitates beta-cell proliferation and islet regeneration through regulation of crucial genes in cell cycle and islet regeneration.

    “The results indicated that mangiferin facilitates β-cell proliferation and islet regeneration through the regulation of crucial genes in cell cycle and islet regeneration (Fig. 2C) (32).”
    Quote in the paperSubstantial claim1 of 1 sources checked
  • Premisecitation

    Mangiferin protects kidneys from diabetic nephropathy.

    “Surprisingly, Pal et al (34) demonstrated that mangiferin could protect kidneys from DN.”
    Quote in the paperSubstantial claim1 of 1 sources checked
  • Premisecitation

    Mangiferin treatment is beneficial in streptozotocin-induced diabetic mice.

    “It was recently reported that mangiferin treatment was beneficial in streptozotocin (STZ)-induced diabetic mice.”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [25]
    • cites [26] source

      The Materials and Methods passage describes mangiferin treatment in STZ-induced diabetic rats, not mice. The Discussion reports improved blood glucose and insulin measures in those rats, supporting a beneficial effect but not the claimed species. (LLM, conf=0.90)

      Experimental — accuracy not yet measured
  • Premisecitation

    Glomerular hypertrophy and hydropsy were attenuated following mangiferin treatment at an oral dose of 40 mg/kg body weight/day in water for 30 days in a STZ-induced DN rat model.

    “Additionally, glomerular hypertrophy and hydropsy was attenuated following mangiferin treatment at an oral dose of 40 mg/kg body weight/day in water for 30 days (34).”
    Quote in the paperSubstantial claim1 of 1 sources checked
  • Premisecitation

    Oral treatment with 40 mg/kg mangiferin for 30 days significantly reduced blood glucose, glycosylated hemoglobin, AST, ALT and ALP in STZ-induced diabetic mice compared with diabetic control mice.

    “Compared with diabetic control mice, the levels of blood glucose, glycosylated hemoglobin, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) were significantly reduced in mangiferin-treated diabetic mice.”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [25]
    • cites [26] source

      Materials and Methods describes oral mangiferin at 40 mg/kg daily for 30 days in STZ-induced diabetic rats, not mice. The Glucose Tolerance Test section reports reduced blood glucose and glycosylated hemoglobin in treated rats relative to diabetic controls. Our copy does not report reductions in AST, ALT, or ALP; its reported liver-enzyme outcomes concern carbohydrate metabolism. (LLM, conf=0.90)

      Experimental — accuracy not yet measured
  • May combine two claims. 43
  • The quote only partly states this claim. 4
  • Classified as probably not a substantial claim. 1

  • May combine two claims.

    Premisecitation

    Mangiferin exerts neuroprotective effects against EBI by promoting the Nrf2/HO-1 cascade in the mitochondrial apoptosis pathway, as well as through NLRP3 inflammasome activation and NF-κB inhibition.

    “Mechanism analysis of mangiferin demonstrated that it exerts its neuroprotective effects against EBI by promoting the nuclear factor erythroid 2-related factor 2 (Nrf2)/HO-1 cascade in the mitochondrial apoptosis pathway, as well as through NLRP3 inflammasome activation and NF-κB inhibition (74).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [74] source

      The Results (page not available) support mangiferin’s effects on mitochondrial apoptosis and NF-κB inhibition in rats with early brain injury after subarachnoid hemorrhage. But the NLRP3 Results state the opposite of the claim’s 'NLRP3 inflammasome activation': mangiferin inhibited its activation. (LLM, conf=0.92)

      Checked by a reasoning model — may be wrong.

      Experimental — accuracy not yet measured

  • The quote only partly states this claim.

    Premisecitation

    Oral treatment with 40 mg/kg mangiferin for 30 days notably improved red and white blood cell levels in STZ-induced diabetic mice.

    “Furthermore, the levels of red and white blood cells were notably improved (25,26).”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [25]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [26] source

      Materials and Methods describes oral treatment with 40 mg/kg mangiferin for 30 days in STZ-induced diabetic rats, not mice. The Glucose Tolerance Test section reports increased hemoglobin after treatment, but neither it nor the searched passages reports improved red or white blood cell counts; hemoglobin is not a cell count. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Mangiferin exerts significant antidiabetic, antihyperlipidemic and antiatherogenic effects in diabetic rat models.

    “Similarly, Muruganandan et al (28), Miura et al (29,30) and Suman et al (31) verified that mangiferin exerted significant antidiabetic, antihyperlipidemic and antiatherogenic effects in diabetic rat models.”
    Quote in the paperSubstantial claim2 of 4 sources checked
    • cites [28] source
    • cites [29] source

      The Discussion reports that mangiferin with exercise reduced cholesterol and triglycerides in diabetic KK-Ay mice and describes antidiabetic activity in a preliminary study. The Materials section identifies the animals as mice, not rats. This paper does not report an antiatherogenic effect, and its principal lipid finding concerns mangiferin combined with exercise, not mangiferin alone. (LLM, conf=0.90)

      Experimental — accuracy not yet measured
    • cites [30] source
    • cites [31] source

  • May combine two claims.

    Premisecitation

    Mangiferin has been demonstrated to possess numerous pharmacological activities, including antioxidative, antiaging, antitumor, antibacterial, antiviral, immunomodulatory, antidiabetic, hepatoprotective and analgesic effects.

    “It has been demonstrated to possess numerous pharmacological activities, including antioxidative, antiaging, antitumor, antibacterial, antiviral, immunomodulatory, antidiabetic, hepatoprotective and analgesic effects (1)(2)(3).”
    Quote in the paperSubstantial claim1 of 3 sources checked
    • cites [1] source

      The Abstract reports antioxidant, hepatoprotective and analgesic effects of mangiferin. Results and Discussion also describes a chemoprotective finding in a rat colon-carcinogenesis model, but reports that mangiferin was inactive in the paper’s cancer-cell and anti-HIV tests. The cited passages do not establish the claimed antiaging, antibacterial or antidiabetic effects; the macrophage finding is narrower than the broad claim of immunomodulatory activity. (LLM, conf=0.90)

      Experimental — accuracy not yet measured
    • cites [2] source
    • cites [3] source

  • May combine two claims.

    Premisecitation

    In a high-fat high fructose diet and STZ-induced diabetic insulin-resistant rat model, mangiferin alleviated insulin resistance, improved beta-cell function, reduced serum TG, TC and LDL-C, decreased atherogenic index, liver TG and liver TC content.

    “Additionally, in a high-fat high fructose diet and STZ-induced diabetic insulin-resistant rat model, mangiferin was demonstrated to concurrently alleviate insulin resistance, improve β-cell function, reduce serum levels of triglyceride (TG), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), as well decrease the atherogenic index, liver TG and liver TC content.”
    Quote in the paperSubstantial claim1 of 1 sources checked

  • May combine two claims.

    Premisecitation

    Mangiferin inhibits expression of RelA and RelB, activates IκB and suppresses phosphorylation of NF-κB kinase, thereby inhibiting transcriptional activity of NF-κB and inducing apoptosis in tumor cells.

    “It was demonstrated that mangiferin inhibits the expression of RelA and RelB, activates inhibitor of NF-κB (IκB) and suppresses the phosphorylation of NF-κB kinase, thereby inhibiting the transcriptional activity of NF-κB and inducing apoptosis tumor cells (54)(55)(56).”
    Quote in the paperSubstantial claim1 of 3 sources checked
    • cites [54] source
    • cites [55] source

      The Results section, “Mangiferin induces apoptosis in A549 cells via inhibition of the PKC-NF-κB pathway” (page not provided), reports reduced NF-κB protein expression after mangiferin treatment; the Discussion links suppression of that pathway to apoptosis in A549 cells. The paper does not report reduced RelA or RelB expression, IκB activation, NF-κB kinase phosphorylation, or a direct measurement of NF-κB transcriptional activity. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [56] source

  • May combine two claims.

    Premisecitation

    In human lung carcinoma A549 cells, mangiferin exhibits antineoplastic properties by inducing G2/M phase cell cycle arrest via downregulation of CDK1-cyclin B1 and inducing apoptotic cell death by inhibiting PKC-NF-κB.

    “Similarly, in human lung carcinoma A549 cells, mangiferin exhibits antineoplastic properties, by inducing G2/M phase cell cycle arrest via downregulation of the cyclin-dependent kinase 1-cyclin B1 signaling pathway and inducing apoptotic cell death by inhibiting the PKC-NF-κB pathway (55).”
    Quote in the paperSubstantial claim1 of 1 sources checked

  • May combine two claims.

    Premisecitation

    Through regulation of Bcl-2 and Bax expression, mangiferin potently inhibits tumor cell proliferation and induces apoptosis in nasopharyngeal carcinoma cells.

    “Pan et al (60) demonstrated that through regulation of Bcl-2, apoptosis regulator (Bcl-2) and Bcl-2 associated X, apoptosis regulator (Bax) expression, mangiferin potently inhibits tumor cell proliferation and induces apoptosis in nasopharyngeal carcinoma cells.”
    Quote in the paperSubstantial claim1 of 1 sources checked

  • May combine two claims.

    Premisecitation

    Caspase-dependent apoptosis and downregulated Notch3 expression occur in mangiferin-treated human ovarian adenocarcinoma OVCAR3 cells.

    “In addition, in-depth research into the underlying mechanisms of mangiferin successfully elucidated that caspase-dependent apoptosis and obviously downregulated Notch3 expression occurs in mangiferin-treated human ovarian adenocarcinoma OVCAR3 cells (63).”
    Quote in the paperNot a substantial claim1 of 1 sources checked

  • May combine two claims.

    Premisecitation

    Mangiferin decreases mortality of animals with SAH, ameliorates neurological deficits and brain edema, attenuates SAH-induced oxidative stress and decreases cortical cell apoptosis in a dose-dependent manner.

    “It was demonstrated that mangiferin decreases the mortality of animals with SAH, ameliorates neurological deficits and brain edema, attenuates SAH-induced oxidative stress and decreases cortical cell apoptosis in a dose-dependent manner.”
    Quote in the paperSubstantial claim1 of 1 sources checked

  • May combine two claims.

    Premisecitation

    Mangiferin increases the AMP/ATP ratio upstream of AMPK, decreases DGAT2 expression, and decreases ACC activity.

    “Mangiferin increases the AMP/ATP ratio upstream of AMPK, decreases acyl-CoA:diacyl gycerol acyltransferase 2 (DGAT2) expression, decreases acetyl-CoA carboxylase (ACC) activity.”
    Quote in the paperSubstantial claim1 of 1 sources checked

  • May combine two claims.

    Premisecitation

    Mangiferin (400 mg/kg) administered with a high fat diet to C57BL6/J mice for 16 weeks protects against HFD-induced weight gain, promotes aerobic mitochondrial capacity and increases thermogenesis.

    “Apontes et al (88) administered mangiferin (400 mg/kg) and a high fat diet (HFD) to C57BL6/J mice for 16 weeks, demonstrating that mangiferin protects against HFD-induced weight gain, promotes aerobic mitochondrial capacity and increases thermogenesis.”
    Quote in the paperSubstantial claim1 of 1 sources checked

  • May combine two claims.

    Premisecitation

    Mangiferin promotes AMPK phosphorylation and upregulates expression of CD36 and CPT-1.

    “Furthermore, mangiferin promotes AMPK phosphorylation, and upregulates the expression of CD36 and CPT-1 (86).”
    Quote in the paperSubstantial claim1 of 1 sources checked

  • The quote only partly states this claim.

    Premisecitation

    Out of 865 quantified proteins, 87 are differentially regulated by mangiferin in C57BL6/J mice fed mixed granules containing mangiferin and HFD for 18 weeks.

    “It was demonstrated that out of 865 quantified proteins, 87 of them are differentially regulated by mangiferin.”
    Quote in the paperSubstantial claim1 of 1 sources checked

  • May combine two claims.

    Premisecitation

    Treatment with mangiferin in overweight patients with hyperlipidemia stimulated carbohydrate oxidation and improved glucose and insulin profiles.

    “In addition, treatment with mangiferin in overweight patients with hyperlipidemia stimulated carbohydrate oxidation and improved glucose and insulin profiles (88).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [88] source

      The Abstract and Results (‘MGF Promotes Carbohydrate Utilization’) report improved glucose and insulin profiles and increased glucose oxidation with mangiferin, but these findings are from high-fat-diet-fed mice, not overweight patients with hyperlipidemia. The claim incorrectly presents the animal findings as a human treatment result. (LLM, conf=0.91)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    In the same trial, mangiferin did not effectively decrease serum levels of total cholesterol, LDL-C, serum glucose or insulin.

    “However, mangiferin did not effectively decrease serum levels of total cholesterol, low-density lipoprotein cholesterol, serum glucose or insulin (87).”
    Quote in the paperSubstantial claim1 of 1 sources checked

  • May combine two claims.

    Premisecitation

    In a 12-week double-blind randomized clinical trial, mangiferin (150 mg/day) supplementation substantially increases serum levels of mangiferin, HDL-C, L-carnitine, beta-hydroxybutyrate and acetoacetate, and increases lipoprotein lipase activity in overweight patients with hyperlipidemia.

    “Mangiferin supplementation substantially increases the serum levels of mangiferin, high-density lipoprotein cholesterol, L-carnitine, β-hydroxybutyrate and acetoacetate, and increases lipoprotein lipase activity.”
    Quote in the paperSubstantial claim1 of 1 sources checked

  • May combine two claims.

    Premisecitation

    Anemarrhena asphodeloides has antiviral and antibacterial activities.

    “Anemarrhena asphodeloides, a plant widely used in traditional Chinese medicine, has been reported to possess antiviral and antibacterial activities (109).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [109] source

      The Abstract and Discussion address traditional use and antidiabetic effects of Anemarrhena asphodeloides, but neither addresses antiviral or antibacterial activity. Searches of our copy for antiviral, antibacterial, virus, bacteria, and antimicrobial activity found no passage supporting the cited claim. No page numbers were available for these passages. (LLM, conf=0.75)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Mangiferin permeates the stratum corneum and passes into the epidermis and dermis.

    “Research has revealed the ability of mangiferin to reversibly inhibit elastase and collagenase activity, as well as to permeate the stratum corneum and pass into the epidermis and dermis (115).”
    Quote in the paperNot a substantial claim1 of 1 sources checked

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Mangiferin increases islet regeneration in young and old diabetic mice.

    “Furthermore, our upcoming report successfully confirmed that mangiferin increases islet regeneration in young and old diabetic mice (unpublished data).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites unpublished data

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • The quote only partly states this claim.

    Premisecitation

    In a STZ-induced DN rat model, oral mangiferin (15, 30 and 60 mg/kg) for 9 weeks decreased albuminuria, BUN, kidney weight index, PAS-positive mesangial matrix area, glomerular extracellular matrix expansion and accumulation and glomerular basement membrane thickness, via targeting glyoxalase 1.

    “Similarly, in animal experiments performed by Liu et al (35) in an STZ-induced DN rat model, evidential decreases in albuminuria, BUN, kidney weight index, periodic acid-Schiff stain positive mesangial matrix area, glomerular extracellular matrix expansion and accumulation and glomerular basement membrane thickness were observed following oral mangiferin treatment (15, 30 and 60 mg/kg) for 9 weeks”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [35] source

  • May combine two claims.

    Premisecitation

    In a STZ-induced DN rat model, mangiferin did not improve body weight or blood glucose levels.

    “These results validate the beneficial actions of mangiferin in DN, although body weight and blood glucose levels were not improved (35).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [35] source

  • May combine two claims.

    Interpretationcitation

    Mangiferin has low solubility, transmembrane permeability and bioavailability, which restricts its clinical development and application.

    “These experimental data collectively indicate that despite a wide range of pharmacological activities, mangiferin has low solubility, transmembrane permeability and bioavailability, which restricts the clinical development and application of mangiferin.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationcitation

    Mangiferin possesses anti-diabetic efficacy without toxicity in chemically induced diabetic mice.

    “Therefore, mangiferin was demonstrated to possess anti-diabetic efficacy without toxicity in chemically induced diabetic mice (Fig. 2A).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    In diabetic cardiomyopathy rats, mangiferin reduces AGE production and decreases mRNA and protein expression of RAGE.

    “In diabetic cardiomyopathy (DCM) rats, mangiferin reduces AGE production, and decreases the mRNA and protein expression of RAGE (42), suggesting that mangiferin treatment may be beneficial in DCM.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [42] source

  • May combine two claims.

    Premisecitation

    In a STZ-induced diabetic rat model, mangiferin (60 mg/kg; oral gavage for 12 weeks) reduces blood glucose and cardiomyocyte apoptosis, and downregulates inositol-requiring enzyme 1, apoptotic signal-regulating kinase and JNK.

    “In a diabetic rat model induced by STZ, mangiferin (60 mg/kg; oral gavage for 12 weeks) reduces blood glucose and cardiomyocyte apoptosis, downregulates inositol-requiring enzyme 1, apoptotic signal-regulating kinase and JNK (43).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [43] source

  • May combine two claims.

    Premisecitation

    Mangiferin administration (15, 30 and 60 mg/kg; oral gavage) prevents HPA stress axis dysregulation, neuroinflammation and oxidative damage.

    “It was demonstrated that mangiferin administration (15, 30 and 60 mg/kg; oral gavage) prevents hypothalamic/pituitary/adrenal (HPA) stress axis dysregulation, neuroinflammation and oxidative damage.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [73] source

  • May combine two claims.

    Interpretationreasoning

    Mangiferin effectively alleviates free radical release in the ischemic myocardium and delays membrane lipid oxidation.

    “Those results suggested that mangiferin effectively alleviates free radical release in the ischemic myocardium and delays membrane lipid oxidation.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    In human breast carcinoma MCF-7 cells, mangiferin downregulates CDK1-cyclin B1 signaling and induces G2/M phase cell-cycle arrest to inhibit tumor cell growth.

    “In human breast carcinoma MCF-7 cells, mangiferin down regulates the cyclin-dependent kinase 1-cyclin Bl signaling pathway and induces G2/M phase cell-cycle arrest to inhibit tumor cell growth (62).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [62]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation

    In endothelial cells cultured with mangiferin at 0.1, 1 and 10 microM, expression of TXNIP, NLRP3, IL-1beta and IL-6, and phosphorylation of AMPK, was attenuated, demonstrating inhibitory effects on TXNIP/NLRP3 inflammasome activation and ameliorative effects on endothelial dysfunction.

    “The expression of thioredoxin-interacting protein (TXNIP), NLR family pyrin domain containing 3 (NLRP3), IL-1β and IL-6, as well as the phosphorylation of AMP-activated protein kinase (AMPK), was attenuated in endothelial cells cultured with mangiferin at concentrations of 0.1, 1 and 10 µM, demonstrating its inhibitory effects on TXNIP/NLRP3 inflammasome activation and it ameliorative effects on”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [45] source

  • The quote only partly states this claim.

    Premisecitation

    Pretreatment with mangiferin (100 mg/kg) for 28 days regulates the tissue defense system against cardiac damage in ISPH-induced MI rats.

    “Prabhu et al (76) demonstrated that pretreatment with mangiferin (100 mg/kg) for 28 days regulates the tissues defense system against cardiac damage.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [76] source

  • May combine two claims.

    Premisecitation

    Mangiferin reduces LPS-induced IL-1beta expression and oxidative stress when used in depressive and anxiety disorders.

    “Furthermore, mangiferin reduces LPS-induced IL-1β expression and oxidative stress when used in depressive and anxiety disorders (71).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [71] source

  • May combine two claims.

    Premisecitation

    In myocardial cells under ISPH-induced MI, mangiferin protects structural integrity by reducing oxidative damage and increasing mitochondrial energy metabolism.

    “In addition, studies in myocardial cells under the condition of ISPH-induced MI demonstrated mangiferin protects the structural integrity of by reducing the effects of oxidative damage and increasing mitochondrial energy metabolism (78).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [78] source

  • May combine two claims.

    Premisecitation

    Mangiferin exerts beneficial effects due to its antioxidant potential, which reduces myocardial oxygen consumption and relieves angina pectoris.

    “It was concluded that mangiferin exerts its beneficial effects due to its antioxidant potential, which reduces myocardial oxygen consumption and relieves angina pectoris (76).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [76] source

  • May combine two claims.

    Premisecitation

    Mangiferin increases glutathione concentration, SOD and catalase activity in mice, and decreases lipid peroxidation and nitrite level in the hippocampus and prefrontal cortex.

    “Further research has ascertained that mangiferin increases glutathione concentration, superoxide dismutase (SOD) and catalase activity in mice; as well as decreasing lipid peroxidation and nitrite level in the hippocampus and prefrontal cortex (71).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [71] source

  • May combine two claims.

    Premisecitation

    Mangiferin modulates expression of proinflammatory signaling molecules, including TNF-alpha and COX-2, and regulates transcription factors NF-κB and Nrf-2.

    “Furthermore, mangiferin is capable of modulating the expression of proinflammatory signaling molecules, including the expression of TNF-α and COX-2, as well as regulating various transcription factors, such as NF-κB, and NF-E2-related factor 2 (Nrf-2) (64).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [64] source

  • May combine two claims.

    Interpretationcitation

    Mangiferin exhibits potent antioxidant and anti-inflammatory properties by decreasing PGE-2 production, free radical formation and COX-2 synthesis.

    “Taken together, these data demonstrated mangiferin exhibits potent antioxidant and anti-inflammatory properties, by decreasing PGE-2 production, free radical formation and COX-2 synthesis.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    In an allergic murine experimental model, mangiferin produces a remarkable reduction in airway inflammation around vessels and bronchi, decreases IgE levels and lymphocyte proliferation.

    “The results revealed that mangiferin produces a remarkable reduction in airway inflammation around vessels and bronchi, decreases immunoglobulin (Ig)E levels and lymphocyte proliferation.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [96] source

  • May combine two claims.

    Premisecitation

    Mangiferin prevents free radical-mediated lipid peroxidation and increases lysosomal instability, thus alleviating MI injury.

    “In addition, mangiferin has been reported to prevent free radical-mediated lipid peroxidation and increase lysosomal instability, thus alleviating MI injury (79).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [79] source

  • May combine two claims.

    Premisecitation

    Body weight, liver weight, visceral fat-pad weight, serum TG, FFA concentration, hepatic TG levels, hepatic FFA and muscle FFA contents are immensely decreased following mangiferin treatment.

    “Body weight, liver weight, visceral fat-pad weight, serum TG, FFA concentration, hepatic TG levels, hepatic FFA and muscle FFA contents are immensely decreased following mangiferin treatment (85).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [85] source

  • May combine two claims.

    Premisecitation

    Treatment prevents mitochondrial NADPH-linked substrate depletion and NADPH spontaneous oxidation, making them suitable antioxidants with potential use in atherosclerosis susceptible conditions.

    “In addition, treatment prevents mitochondrial nicotinamide-adenine dinucleotide phosphate hydrate (NADPH)-linked substrate depletion and NADPH spontaneous oxidation, making them suitable antioxidants with potential use in atherosclerosis susceptible conditions (84).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [84] source

  • May combine two claims.

    Premisecitation

    Mangiferin administration (20 mg/kg for 4 weeks) restores cardiac ejection function, reduces accumulation of TNF-alpha and cleaved caspase-3, and upregulates Bcl-2.

    “Mangiferin administration (20 mg/kg for 4 weeks) restores the function of cardiac ejection, reduces the accumulation of TNF-α and cleaved caspase-3, and upregulates Bcl-2 (80).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [80] source

  • May combine two claims.

    Premisecitation

    Mangiferin administration (50 or 100 mg/kg for 5 weeks) protects against doxorubicin-induced mortality and electrocardiogram abnormality, and decreases expression of biochemical cardiac toxicity markers dehydrogenase and creatine phosphokinase isoenzyme.

    “Mangiferin administration (50 or 100 mg/kg for 5 weeks) also protects against doxorubicin-induced mortality and electrocardiogram abnormality, decreases the expression of biochemical cardiac toxicity markers, such as dehydrogenase and creatine phosphokinase isoenzyme (81).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [81] source

  • May combine two claims.

    Premisecitation

    Mangiferin has a therapeutic effect on post-MI left ventricular remodeling and improves cardiac function.

    “In addition, mangiferin has a therapeutic effect on post-MI left ventricular remodeling and improves cardiac function.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [80] source

  • May combine two claims.

    Premisecitation

    Mangiferin exerts antibacterial activity against Staphylococcus aureus and Salmonella typhi.

    “Mangiferin has been demonstrated to exert antibacterial activity against two bacterial species: Staphylococcus aureus (Gram positive) and Salmonella typhi (Gram negative) (111).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [111]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation

    Mangiferin has prominent antibacterial and antiviral effects.

    “In addition to its antioxidative, antidiabetic and antitumor properties, the antibacterial and antiviral effects of mangiferin are also prominent (110).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [110] source

  • May combine two claims.

    Interpretationnone given

    Mangiferin has been demonstrated to possess several beneficial properties, including antioxidant, antimicrobial, antidiabetic, antiallergic, neuroprotective, cardiovascular protective, anticancer, hypocholesterolemic and immunomodulatory effects.

    “Mangiferin has been demonstrated to possess several beneficial properties, including antioxidant, antimicrobial, antidiabetic, antiallergic, neuroprotective, cardiovascular protective, anticancer, hypocholesterolemic and immunomodulatory effects.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Mangiferin stimulates the immune system and increases resistance of Labeo rohita to Aeromonas hydrophila infection by promoting superoxide anion, serum protein, albumin production, lysozyme and serum bactericidal activity.

    “Similarly, mangiferin stimulates the immune systems and increases the resistance of Labeo rohita to Aeromonas hydrophila infection, by promoting superoxide anion, serum protein obtained from Labeo rohita and albumin production, as well as lysozyme and serum bactericidal activity (106).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [106] source
48 of 48

  • The paper relies on this without support.

    Pharmacological effects of mangiferin observed in animal and cell models are predictive of therapeutic effects in humans.

    “Taken together, these data provide evidence that mangiferin has promising application prospects in the treatment of diabetes.”
    “Taken together, these data suggest that mangiferin may be used in the treatment of metabolic disorders, by improving the protein expression profiles in mitochondrial synthesis and lipogenesis.”

  • The paper relies on this without support.

    Mangiferin is safe for human clinical use.

    “Therefore, mangiferin was demonstrated to possess anti-diabetic efficacy without toxicity in chemically induced diabetic mice (Fig. 2A).”

  • The paper relies on this without support.

    The main barrier for xenobiotic absorption through the skin is the stratum corneum.

    “The main barrier for xenobiotic absorption through the skin is the stratum corneum.”

  • The paper relies on this without support.

    Administration of mangiferin to animals or humans inevitably results in alterations in the body at the molecular, cellular, tissue and/or organ levels, along with its curative effects.

    “The administration of mangiferin to animals or humans will inevitably result in alterations in the body, at the molecular, cellular, tissue and/or organs level, along with its curative effects.”
4 of 4

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Several frequently cited mechanisms (NF-κB or MMP-9 modulation, G2/M arrest, AMPK activation) are highly context dependent and inconsistently replicated.

    “Notably, the results vary across cell lines and animal strains, and several mechanisms that are frequently cited (for example, NF-κB or MMP-9 modulation, G2/M arrest and AMPK activation) appear to be highly context dependent, with inconsistent replication under different stimuli or dosing conditions (4,13,117,124,186,187).”

    From Mangiferin in human disease: Multifaceted mechanisms and applications (Review) (2026) · cites this paper as [13]

    The Conclusions (page unavailable) say that studies did not use a standardized therapeutic approach and that results are not universal because dose, concentration and IC50 were not compared on the same baseline. The anti-tumor section (page unavailable) describes NF-κB modulation and G2/M arrest in particular cell lines, but the review does not establish that these mechanisms, MMP-9 modulation or AMPK activation were inconsistently replicated under different stimuli or dosing conditions. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

  • Results vary across cell lines and animal strains.

    “Notably, the results vary across cell lines and animal strains, and several mechanisms that are frequently cited (for example, NF-κB or MMP-9 modulation, G2/M arrest and AMPK activation) appear to be highly context dependent, with inconsistent replication under different stimuli or dosing conditions (4,13,117,124,186,187).”

    From Mangiferin in human disease: Multifaceted mechanisms and applications (Review) (2026) · cites this paper as [13]

    The Conclusions (section 7; page unavailable) say that studies used nonstandardized approaches and that their experimental results are not universal. The review discusses findings in several cell lines (section 3), but does not establish that results vary across cell lines or animal strains, or document inconsistent replication of the named mechanisms. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Diabetes experiment described as involving both mice and rats

    Minor

    The text describes the streptozotocin-induced diabetes experiment as involving mice, while Figure 2A describes the corresponding results as being observed in rats.

  • Opposite claims about lysosomal instability

    Minor

    The text says mangiferin increases lysosomal instability to alleviate myocardial injury, but the cited reference describes suppression of lysosomal instability as part of its protective action.

2 of 2

Cited works that were retracted

Works this paper cites that were later retracted, from the retraction notices publishers deposit. Major when the notice came out before this paper was published.

  • Cites a retracted work: 10.3892/mmr.2016.4947

    Info

    The cited work was retracted; the date of the notice is not on record.

    Cited work 10.3892/mmr.2016.4947 · retraction date not known · this paper published 2018-10-02

1 of 1

Cites

1 retracted

Flagged first, then by citations

4 of the 117 references couldn’t be matched to a known paper.

Research works printed but not linked: 6

  1. Wang, 2008, Improvement in the solubility of mangiferin by HP-β-CD inclusion, Chin Tradit Patent Med
  2. du Plessis-Stoman, 2011, Combination treatment with oxaliplatin and mangiferin causes increased apoptosis and downregulation of NFκB in cancer cell lines, Afr J Tradit Complement Altern Med, 8, 177
  3. Lv, 2013, Mangiferin induces apoptosis and cell cycle arrest in MCF-7 cells both in vitro and in vivo, J Anim Vet Adv, 12, 352
  4. Guo, 2016, Research progress of pharmacological action and clinical application in tibetan medicine ‘Zangyinchen’, Asia Pac Tradit Med
  5. Tan, 2017, Simultaneous determination of three iridoid glycosides and three flavonoids in Swertia mussotii Franch. from Qinghai by UPLC, Chin J Pharm Anal
  6. He, 2014, Choleretic action and spasmolysis of gallbladder smooth muscle of mangiferin, China Pharmacist

Cited by

Sorted by citations

Related

Authors
Du, S., Liu, H., Lei, T., Xie, X., Wang, H., He, X., Tong, R., & Wang, Y.
Affiliations
  • Chengdu Military General Hospital (CN)
  • Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital (CN)
  • University of Electronic Science and Technology of China (CN)
ORCID
Venue
Molecular Medicine Reports
Publisher
Spandidos Publications
Published
2018-10-02
Volume
18
Issue
6
Pages
4775-4786
ISSN
  • 1791-2997 (ISSN-L)
  • 1791-3004
DOI
10.3892/mmr.2018.9529
OpenAlex
W2895425690
Semantic Scholar
c0952a2f82f440cc8164211bdb78c7da29c63ae1
Cited by
139
References
117
Citations by year
2026: 7 · 2025: 18 · 2024: 22 · 2023: 24 · 2022: 21 · 2021: 28 · 2020: 13 · 2019: 4
FWCI
13.68
Type
journal article
Language
en
Open access
Licence
cc-by-nc-nd
Locations
  • Molecular Medicine Reports (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
National Natural Science Foundation of China (2018JY0645, 81802504, 30305030698, 16ZD0253)
Topics
  • Health Sciences › Medicine › Complementary and alternative medicine › Mangiferin and Mango Extracts
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Natural Antidiabetic Agents Studies
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Natural Compound Pharmacology Studies
Keywords
mangiferin, mango, xanthone glycosides, antioxidant activity, antidiabetic effect, anticancer activity, cardioprotection, neuroprotection, anti-inflammatory activity, antibacterial and antiviral activity, immunomodulation, bioavailability
MeSH terms
Animals, Antineoplastic Agents, Cardiotonic Agents, Humans, Hypoglycemic Agents, Xanthones

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-12.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-12.

Cited sources are checked by gpt-6-sol.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

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