What question did this study set out to answer?

To explore the immunomodulatory effects of Mangifera indica extract on innate immune mechanisms in Inflammatory Bowel Disease.

January 23, 2026

P0022Mango extract to treat Inflammatory Bowel Disease? - The effect of Mangifera indica L. extract on innate immunity: MyD88/NF-kB signalling, cytokine production and macrophage programming

Key Points

To explore the immunomodulatory effects of Mangifera indica extract on innate immune mechanisms in Inflammatory Bowel Disease.
Examined the effect of mango extract on primary human monocytes and macrophages.
Used a reverse translational approach.
Assessed monocyte transmigration across TNF-α-activated endothelial cells.
Conducted transcriptomic profiling via RNA sequencing in human macrophages.
Validated pathways in a murine model with toll-like receptor agonists.
Mango extract impaired monocyte adhesion and transmigration across activated endothelium.
It selectively decreased pro-inflammatory M1 macrophage phenotype, reducing TNF-α and IL-6 secretion.
Transcriptomic analysis revealed disruption of NF-κB and TLR inflammatory signaling.
Mango extract acted as an immunological regulator, downregulating MyD88 and inhibiting NF-κB translocation.

Abstract

Abstract Background Immune- mediated diseases require therapies that modulate and/or suppress the immune system on a broad basis with systemic reach associated with adverse effects. Mangifera indica L. extract (MIE) modulates adaptive immunity. 1,2 We aimed to investigate the specific mechanism on innate immune triggers, monocyte recruitment and macrophage polarization in a cohort of treatment- naïve patients with Inflammatory Bowel Disease (IBD), directly after diagnosis, and symptomatic controls with normal colonoscopy.3,4 Methods We investigated the effects of MIE on primary human monocytes and macrophages using a reverse translational approach. We examined MIE’s ability to inhibit monocyte transmigration across TNF-α-activated endothelial monolayers and to modulate macrophage polarization along the M1/M2 axis. Furthermore, using transcriptomic profiling via RNA sequencing we identified MIE-responsive pathways in human macrophages. We functionally validated these pathways by using a model of murine peritoneal macrophages stimulated with a panel of nine distinct toll-like receptor (TLR) agonists. Results Our research showed that MIE impaired monocyte adhesion and transmigration across activated endothelium. Secondly, MIE selectively decreased the pro-inflammatory M1 phenotype in macrophages, by suppressing TNF-α and IL-6 secretion in cells from both IBD and symptomatic controls. Simultaneously the effects on the M2 profile were minimal. Thirdly, the transcriptomic analysis revealed that MIE disrupts NF-κB and TLR inflammatory signalling networks. Mechanistically, MIE operated as a precise immunological regulator, selectively diminishing responses to TLR2, TLR4, and TLR6 agonists. This targeted modulation was mediated via downregulation of the adaptor protein MyD88 and inhibition of NF-κB nuclear translocation, resulting overall in a decreased pro-inflammatory cytokine production. Conclusion We identified a novel, multi-level immunomodulatory pathway for MIE. The working mechanism acts both by blocking monocyte recruitment and by operating as a selective antagonist of the pro-inflammatory TLR2/4/6 axis. This dual pathway, by comparison to broad-spectrum immunosuppressive agents, shows that MIE is a potential therapeutic candidate for restoring innate immune homeostasis in chronic immune-mediated diseases. References: 1.Saviano A, Schettino A, Iaccarino N, Mansour AA, Begum J, Marigliano N, et al. A reverse translational approach reveals the protective roles of Mangifera indica in inflammatory bowel disease. J Autoimmun. 2024 Apr;144:103181. doi: 10.1016/j.jaut.2024.103181. Epub 2024 Mar 23. PMID: 38522129. 2.Lucarini E, Schettino A, Marigliano N, Ciampi C, Smimmo M, Romano F, et al. Exploring the dual role of Mangifera indica L. in regulating immune response and pain persistence in inflammatory bowel disease. Pharmacol Res. 2025 Jul;217:107773. doi: 10.1016/j.phrs.2025.107773. Epub 2025 May 17. PMID: 40389041. 3.Wang Y, Smith W, Hao D, He B, Kong L. M1 and M2 macrophage polarization and potentially therapeutic naturally occurring compounds. Int Immunopharmacol. 2019 May;70:459-466. doi: 10.1016/j.intimp.2019.02.050. Epub 2019 Mar 9. PMID: 30861466. 4.Saviano A, Raucci F, Casillo GM, Mansour AA, Piccolo V, Montesano C, et al. Anti-inflammatory and immunomodulatory activity of Mangifera indica L. reveals the modulation of COX-2/mPGES-1 axis and Th17/Treg ratio. Pharmacol Res. 2022 Aug;182:106283. doi: 10.1016/j.phrs.2022.106283. Epub 2022 Jun 1. PMID: 35662629. Conflict of interest: Dr. Stoica, Rodica Viorelia: No conflict of interest Schettino, Anna: No conflict of interest Saviano, Anella: No conflict of interest Marigliano, Noemi: No conflict of interest Smimmo, Martina: No conflict of interest Esposito, Erika: No conflict of interest Begum, Jenefa: Funding from Hoffmann La Roche Areeba, Fatima: No conflict of interest Urbanowski, Alyssa: No conflict of interest Mahony, Christopher: No conflict of interest Khormi, Amnah: No conflict of interest Mansour, Adel Abo: No conflict of interest Rimmer, Peter: I have received research funding from F. Hoffman La Roche. I have received educational grants from Abbvie and Johnson & Johnson. I have received speaker fees from Abbvie, Ferring, Johnson & Johnson and Takeda. Iqbal, Tariq: Speaker fees from Pharmacosmos Mcgettrick, Helen: No conflict of interest Iqbal, Asif J: Funding from Hoffmann La Roche Maione, Francesco: No conflict of interest

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P0022Mango extract to treat Inflammatory Bowel Disease? - The effect of Mangifera indica L. extract on innate immunity: MyD88/NF-kB signalling, cytokine production and macrophage programming

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