Mangiferin alleviates lipopolysaccharide and D-galactosamine-induced acute liver injury by activating the Nrf2 pathway and inhibiting NLRP3 inflammasome activation
Abstract
Mangiferin, a glucosylxanthone from Mangifera indica, has been reported to have anti-inflammatory effects. However, the protective effects and mechanisms of mangiferin on liver injury remain unclear. This study aimed to determine the protective effects and mechanisms of mangiferin on lipopolysaccharide (LPS) and D-galactosamine (D-GalN)-induced acute liver injury. Mangiferin was given 1h after LPS and D-GalN treatment. The results showed that mangiferin inhibited the levels of serum ALT, AST, IL-1β, TNF-α, MCP-1, and RANTES, as well as hepatic malondialdehyde (MDA) and ROS levels. Moreover, mangiferin significantly inhibited IL-1β and TNF-α production in LPS-stimulated primary hepatocytes. Mangiferin was found to up-regulate the expression of Nrf2 and HO-1 in a dose-dependent manner. Furthermore, mangiferin inhibited LPS/d-GalN-induced hepatic NLRP3, ASC, caspase-1, IL-1β and TNF-α expression. In conclusion, mangiferin protected against LPS/GalN-induced liver injury by activating the Nrf2 pathway and inhibiting NLRP3 inflammasome activation.
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In LPS and D-galactosamine-induced acute liver injury, mangiferin upregulates Nrf2 and HO-1 expression in a dose-dependent manner.
“In addition, in LPS and D-galactosamine (D-GalN)-induced acute liver injury, mangiferin upregulates the expression of Nrf2 and HO-1 in a dose-dependent manner.”
From Mangiferin: An effective therapeutic agent against several disorders (Review) (2018) · cites this paper as [102]
Mangiferin markedly inhibits LPS/D-GalN-induced inflammatory factors including IL-1β, TNF-α, NLRP3, ASC and caspase-1.
“Furthermore, mangiferin markedly inhibits LPS/D-GalN-induced inflammatory factors, including IL-1β, TNF-α, NLRP3, apoptosis-associated speck-like protein containing a CARD and caspase-1 (102).”
From Mangiferin: An effective therapeutic agent against several disorders (Review) (2018) · cites this paper as [102]
Cites
Bhatia, H. S., Candelario-Jalil, E., de Oliveira, A. C. P., Olajide, O. A., Martínez-Sánchez, G., & Fiebich, B. L. (2008) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2008.06.017 · Cited by 95 · see citing works
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Mangiferin: A xanthonoid with multipotent anti‐inflammatory potential
Saha, S., Sadhukhan, P., & Sil, P. C. (2016) · BioFactors · doi:10.1002/biof.1292 · Cited by 159 · see citing works
Mangiferin: An effective therapeutic agent against several disorders (Review)
Du, S., Liu, H., Lei, T., Xie, X., Wang, H., He, X., Tong, R., & Wang, Y. (2018) · Molecular Medicine Reports · doi:10.3892/mmr.2018.9529 · Cited by 139 · see citing works
“Furthermore, mangiferin markedly inhibits LPS/D-GalN-induced inflammatory factors, including IL-1 β , TNF-α , NLRP3, apoptosis-associated speck-like protein containing a CARD and caspase-1 (102).”
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
Alsaedi, A. Q., Nader, M. A., El-Kashef, D. H., & Abdelmageed, M. E. (2025) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1572758 · Cited by 5 · see citing works
- Authors
- Pan, C.-W., Pan, Z.-Z., Hu, J.-J., Chen, W.-L., Zhou, G.-Y., Lin, W., Jin, L.-X., & Xu, C.-L.
- Affiliations
- Wenzhou City People's Hospital (CN)
- Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University (CN)
- Venue
- European Journal of Pharmacology
- Publisher
- Elsevier BV
- Published
- 2016-01
- Volume
- 770
- Pages
- 85-91
- ISSN
- 0014-2999 (ISSN-L)
- OpenAlex
- W2183120901
- Cited by
- 105
- References
- 1
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 6 · 2023: 12 · 2022: 10 · 2021: 15 · 2020: 15 · 2019: 11 · 2018: 12 · 2017: 8 · 2016: 8
- FWCI
- 18.32
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Standards and Technology
- Topics
- Health Sciences › Medicine › Complementary and alternative medicine › Mangiferin and Mango Extracts
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
- Health Sciences › Medicine › Complementary and alternative medicine › Medicinal plant effects and applications
- Keywords
- mangiferin, acute liver injury, lipopolysaccharide, D-galactosamine, Nrf2 signaling, NLRP3 inflammasome, hepatoprotection, oxidative stress, inflammatory cytokines, heme oxygenase-1, caspase-1, hepatocytes
- MeSH terms
- NLR Family, Pyrin Domain-Containing 3 Protein, Acute Disease, Alanine Transaminase, Animals, Aspartate Aminotransferases, Carrier Proteins, Galactosamine, Lipopolysaccharides, Liver, Male, Malondialdehyde, Mice, Inbred C57BL, Signal Transduction, Gene Expression Regulation, Enzymologic, Apoptosis, Reactive Oxygen Species, Cytoprotection, Xanthones, NF-E2-Related Factor 2, Mice, Chemical and Drug Induced Liver Injury, Inflammasomes
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