A Toxicological Evaluation of Mango Leaf Extract (Mangifera indica) Containing 60% Mangiferin
Open accessAbstract
A battery of OECD- and GLP-compliant toxicological studies was performed on mango leaf extract (Mangifera indica) containing 60% mangiferin (MLE). No evidence of genotoxicity was found in a bacterial reverse mutation test (Ames). While evidence of clastogenic activity was noted in an in vitro chromosomal aberration test, an in vivo mammalian micronucleus test showed no findings up to the limit dose (2000 mg/kg bw). A 90-day repeated dose oral toxicity study was conducted in rats using doses of 0 (vehicle control), 500, 1000, and 2000 mg/kg bw/day. Based on the lack of mortality or toxic effects in the 90-day study, the NOAEL for MLE in Han:Wist male and female rats was determined to be 2000 mg/kg bw/day, the highest dose tested.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
There are limited chronic toxicity datasets for purified MGF.
“i) Limited chronic toxicity datasets for purified MGF (as opposed to plant extracts) (108)”
From Mangiferin in human disease: Multifaceted mechanisms and applications (Review) (2026) · cites this paper as [108]
The Discussion and Conclusions (page not available) describes acute-toxicity and genotoxicity studies of ≥95%-pure mangiferin, while its 90-day repeated-dose study concerns a mango leaf extract containing 60% mangiferin. This supports the distinction between purified mangiferin and extracts, but the paper does not explicitly assess how many chronic-toxicity datasets exist for purified mangiferin. (LLM, conf=0.75)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
No references could be resolved yet.
Research works printed but not linked: 21
- [1]Shah K. Patel M. Patel R. Parmar P. Mangifera indica (mango) Pharmacognosy Reviews 2010 4 7 42 48 10.4103/0973-7847.65325 2-s2.0-77955674385 22228940 PMC3249901 · DOI
- [2]Dimitrov M. Nikolova I. Benbasat N. Kitanov G. Danchev N. Acute toxicity, antidepressive and MAO inhibitory activity of mangiferin isolated from Hypericum aucheri Biotechnology & Biotechnological Equipment 2011 25 4 2668 2671 2-s2.0-84856503687 10.5504/BBEQ.2011.0099 · DOI
- [3]Govindaraj Y. Melanaphuru V. Agrahari V. Genotoxicity studies of mangiferin isolated from Salacia chinensis Linn Academic Journal of Plant Sciences 2009 2 3 199 204
- [4]Matsushima T. Araki A. Yagame O. Mutagenicities of xanthone derivatives in Salmonella typhimurium TA100, TA98, TA97, and TA2637 Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis 1985 150 1-2 141 146 10.1016/0027-5107(85)90111-3 3889613 · DOI
- [5]Bhatt L. Sebastian B. Joshi V. Mangiferin protects rat myocardial tissue against cyclophosphamide induced cardiotoxicity Journal of Ayurveda and Integrative Medicine 2017 8 2 62 67 10.1016/j.jaim.2017.04.006 28610894 PMC5496998 · DOI
- [6]Rodeiro I. Hernandez S. Morffi J. Evaluation of genotoxicity and DNA protective effects of mangiferin, a glucosylxanthone isolated from Mangifera indica L. stem bark extract Food and Chemical Toxicology 2012 50 9 3360 3366 10.1016/j.fct.2012.06.032 22749943 · DOI
- [7]Rodeiro I. Cancino L. González J. E. Evaluation of the genotoxic potential of Mangifera indica L. extract (Vimang), a new natural product with antioxidant activity Food and Chemical Toxicology 2006 44 10 1707 1713 10.1016/j.fct.2006.05.009 2-s2.0-33747224281 16857303 · DOI
- [8]Garrido G. Rodeiro I. Hernández I. In vivo acute toxicological studies of an antioxidant extract from Mangifera indica L. (Vimang) Drug and Chemical Toxicology 2009 32 1 53 58 10.1080/01480540802432551 19514939 · DOI
- [9]González J. Rodríguez M. Rodeiro I. Lack of in vivo embryotoxic and genotoxic activities of orally administered stem bark aqueous extract of Mangifera indica L. (Vimang®) Food and Chemical Toxicology 2007 45 12 2526 2532 10.1016/j.fct.2007.05.029 17686561 · DOI
- [10]Zhang Y. Li J. Wu Z. Acute and long-term toxicity of mango leaves extract in mice and rats Evidence-Based Complementary and Alternative Medicine 2014 2014 8 691574 10.1155/2014/691574 PMC4163298 25246938 · DOI
- [12]Reddeman R. A. Glávits R. Endres J. R. A Toxicological assessment of creatyl-l-leucine International Journal of Toxicology 2018 37 2 171 187 10.1177/1091581817751142 29357766 · DOI · Paper page
- [13]Marx T. K. Reddeman R. Clewell A. E. An Assessment of the genotoxicity and subchronic toxicity of a supercritical fluid extract of the aerial parts of hemp Journal of Toxicology 2018 2018 26 8143582 10.1155/2018/8143582 PMC6011091 29977291 · DOI
- [14]Clewell A. E. Béres E. Vértesi A. A Comprehensive toxicological safety assessment of an extract of olea europaea l. leaves (Bonolive) International Journal of Toxicology 2015 35 2 208 221 26658007
- [16]European Commission Council Regulation (EC) No 440/2008 of 30 May 2008 laying down test methods pursuant to Regulation (EC) No 1907/2006 of the European Parliament and of the Council on the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) Official Journal of the European Union: Brussels 2008 L142/1 L142/739
- [18]International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH), et al., Guidance for Industry. S2(R1) Genotoxicity Testing and Data Interpretation for Pharmaceuticals Intended for Human Use. p. 31. 2012
- [22]Savage J. R. Classification and relationships of induced chromosomal structual changes. Journal of Medical Genetics 1976 13 2 103 122 10.1136/jmg.13.2.103 933108 PMC1013369 · DOI
- [28]Irwin S. Comprehensive observational assessment: Ia. A systematic, quantitative procedure for assessing the behavioral and physiologic state of the mouse Psychopharmacology 1968 13 3 222 257 10.1007/bf00401402 2-s2.0-0014424692 5679627 · DOI
- [29]Araújo M. C. P. Antunes L. M. G. Takahashi C. S. Protective effect of thiourea, a hydroxyl-radical scavenger, on curcumin-induced chromosomal aberrations in an in vitro mammalian cell system Teratogenesis, Carcinogenesis, and Mutagenesis 2001 21 2 175 180 2-s2.0-0035105943 10.1002/1520-6866(2001)21:2<175::AID-TCM6>3.0.CO;2-V 11223894 · DOI
- [30]Decker A. Phenolics: Prooxidants or Antioxidants? Nutrition Reviews 1997 55 11 396 398 10.1111/j.1753-4887.1997.tb01580.x 9420450 · DOI
- [31]Kunchandy E. Rao M. N. A. Oxygen radical scavenging activity of curcumin International Journal of Pharmaceutics 1990 58 3 237 240 10.1016/0378-5173(90)90201-E 2-s2.0-0025020674 · DOI
- [34]Vidal J. Mirsky M. L. Colman K. Whitney K. M. Chapter 18. Reproductive system and mammary gland Toxicologic Pathology. Nonclinical Safety Assessment 2013 Boca Raton, FL, USA CRC Press 717 830
Cited by
Sorted by citations
Klingel, T., Kremer, J. I., Gottstein, V., Rajcic de Rezende, T., Schwarz, S., & Lachenmeier, D. W. (2020) · Foods · doi:10.3390/foods9050665 · Cited by 264 · see citing works
Morozkina, S. N., Nhung Vu, T. H., Generalova, Y. E., Snetkov, P. P., & Uspenskaya, M. V. (2021) · Biomolecules · doi:10.3390/biom11010079 · Cited by 82 · see citing works
Recent Formulation Advances of Mangiferin
Barakat, S., Nasr, M., Ahmed, R. F., Badawy, S., & Mortada, N. (2022) · Revista Brasileira de Farmacognosia · doi:10.1007/s43450-022-00297-z · Cited by 28 · see citing works
Xia, J., Li, X., Yao, J., Song, D., Gu, Z., Zheng, G., & Tu, C. (2025) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2025.111520 · Cited by 5 · see citing works
Mangiferin in human disease: Multifaceted mechanisms and applications (Review)
Dai, Y., Huang, Q., Tan, M., Wang, Z., Jiang, C., Liu, Z., Zhang, S., & Song, S. (2026) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2026.5736 · Cited by 3 · see citing works
“However, several safety uncertainties remain: i) Limited chronic toxicity datasets for purified MGF (as opposed to plant extracts) (108); ii) sparse evaluation of drug‑drug interaction risks given pathway cross‑talk (for example, with PI3K/Akt, AMPK or NF‑ κ B modula‑ tors) (181‑183); and iii)…”
- Authors
- Reddeman, R. A., Glávits, R., Endres, J. R., Clewell, A. E., Hirka, G., Vértesi, A., Béres, E., & Szakonyiné, I. P.
- Affiliations
- AIBMR Life Sciences, Inc., 2800 E. Madison St., Suite 202, Seattle, WA 98373, USA
- TOXI-COOP Zrt., Magyar Jakobinusok Tere 4/B, H-1122 Budapest, Hungary
- Corresponding author
- Reddeman, Robin A.
- Venue
- Journal of Toxicology
- Publisher
- Wiley
- Published
- 2019-08-01
- Volume
- 2019
- Pages
- 1-14
- ISSN
- 1687-8191 (ISSN-L)
- 1687-8205
- PMC
- PMC6699309
- OpenAlex
- W2966027110
- Cited by
- 54
- References
- 0
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 6 · 2023: 11 · 2022: 7 · 2021: 7 · 2020: 9 · 2019: 1
- FWCI
- 7.73
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Journal of Toxicology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Nektium Pharma SL, Spain
- Topics
- Health Sciences › Medicine › Complementary and alternative medicine › Mangiferin and Mango Extracts
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Phytochemistry Medicinal Plant Applications
- Keywords
- mango leaf extract, mango, mangiferin, genotoxicity, clastogenicity, chromosomal abnormalities, micronucleus test, repeated dose oral toxicity, no-observed-adverse-effect level, safety assessment
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.
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.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
