Exploring the therapeutic potential of H1-antihistamines in endometriosis—A gene regulation-based perspective
IntroductionRecent studies emphasize the role of immune dysregulation and inflammation in endometriosis (ES). While hormonal therapy remains the primary treatment, emerging research is exploring synergistic approaches that target inflammation. In this study, we investigate the potential of H1-antihi...
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Frontiers Media S.A.
2025-07-01
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmed.2025.1538368/full |
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| author | Kameswara Bharadwaj Mantha Mohan Kumar Gajendran |
| author_facet | Kameswara Bharadwaj Mantha Mohan Kumar Gajendran |
| author_sort | Kameswara Bharadwaj Mantha |
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| description | IntroductionRecent studies emphasize the role of immune dysregulation and inflammation in endometriosis (ES). While hormonal therapy remains the primary treatment, emerging research is exploring synergistic approaches that target inflammation. In this study, we investigate the potential of H1-antihistamines (H1-As) in ES management from a gene-regulation viewpoint.MethodsWe perform differential gene expression analysis on two gene-sequencing datasets from ES patients, with a primar focus on inflammatory signaling [nuclear factor-kappa B (NF-κB), tumor necrosis factor (TNF), and cytokine–cytokine receptor] and histamine synthesis and metabolism (HSM) pathways, considering disease severity and hormonal therapy usage.Results & DiscussionConsistent with the literature, our findings highlight the dysregulation of several genes involved in pro-inflammatory pathways, including interleukins (ILs), cyclooxygenase-2 (COX-2), chemokine ligands, cellular adhesionmolecules, and neuroangiogenesis. We also note dysregulation of genes in the HSM pathway, indicative of a microenvironment that favors histamine availability and inflammatory persistence through enhanced histamine synthesis and reduced breakdown, as well as a reduced potential to clear reactive aldehyde species. We also find that hormonal therapy minimally affects the dysregulation of the majority of pro-inflammatory and histaminic pathway genes, and their amplified dysregulation is noted in early stage disease. By placing our findings in the context of existing evidence on histamine-mediated modulation of inflammatory pathways via the H1 histamine receptor (HRH1), we present a comprehensive discussion on the potential therapeutic value of H1-As in ES management due to their anti-inflammatory and mast-cellstabilizing properties. |
| format | Article |
| id | doaj-art-a6e64b6ac4b54a4cacf4a237c90e3ce2 |
| institution | Matheson Library |
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| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Medicine |
| spelling | doaj-art-a6e64b6ac4b54a4cacf4a237c90e3ce22025-07-17T15:50:27ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2025-07-011210.3389/fmed.2025.15383681538368Exploring the therapeutic potential of H1-antihistamines in endometriosis—A gene regulation-based perspectiveKameswara Bharadwaj Mantha0Mohan Kumar Gajendran1University of Minnesota, Twin Cities, Minneapolis, MN, United StatesSchool of Science and Engineering, University of Missouri-Kansas City, Kansas City, MO, United StatesIntroductionRecent studies emphasize the role of immune dysregulation and inflammation in endometriosis (ES). While hormonal therapy remains the primary treatment, emerging research is exploring synergistic approaches that target inflammation. In this study, we investigate the potential of H1-antihistamines (H1-As) in ES management from a gene-regulation viewpoint.MethodsWe perform differential gene expression analysis on two gene-sequencing datasets from ES patients, with a primar focus on inflammatory signaling [nuclear factor-kappa B (NF-κB), tumor necrosis factor (TNF), and cytokine–cytokine receptor] and histamine synthesis and metabolism (HSM) pathways, considering disease severity and hormonal therapy usage.Results & DiscussionConsistent with the literature, our findings highlight the dysregulation of several genes involved in pro-inflammatory pathways, including interleukins (ILs), cyclooxygenase-2 (COX-2), chemokine ligands, cellular adhesionmolecules, and neuroangiogenesis. We also note dysregulation of genes in the HSM pathway, indicative of a microenvironment that favors histamine availability and inflammatory persistence through enhanced histamine synthesis and reduced breakdown, as well as a reduced potential to clear reactive aldehyde species. We also find that hormonal therapy minimally affects the dysregulation of the majority of pro-inflammatory and histaminic pathway genes, and their amplified dysregulation is noted in early stage disease. By placing our findings in the context of existing evidence on histamine-mediated modulation of inflammatory pathways via the H1 histamine receptor (HRH1), we present a comprehensive discussion on the potential therapeutic value of H1-As in ES management due to their anti-inflammatory and mast-cellstabilizing properties.https://www.frontiersin.org/articles/10.3389/fmed.2025.1538368/fullendometriosisendometriumgene expressioninflammationH1-antihistamines |
| spellingShingle | Kameswara Bharadwaj Mantha Mohan Kumar Gajendran Exploring the therapeutic potential of H1-antihistamines in endometriosis—A gene regulation-based perspective Frontiers in Medicine endometriosis endometrium gene expression inflammation H1-antihistamines |
| title | Exploring the therapeutic potential of H1-antihistamines in endometriosis—A gene regulation-based perspective |
| title_full | Exploring the therapeutic potential of H1-antihistamines in endometriosis—A gene regulation-based perspective |
| title_fullStr | Exploring the therapeutic potential of H1-antihistamines in endometriosis—A gene regulation-based perspective |
| title_full_unstemmed | Exploring the therapeutic potential of H1-antihistamines in endometriosis—A gene regulation-based perspective |
| title_short | Exploring the therapeutic potential of H1-antihistamines in endometriosis—A gene regulation-based perspective |
| title_sort | exploring the therapeutic potential of h1 antihistamines in endometriosis a gene regulation based perspective |
| topic | endometriosis endometrium gene expression inflammation H1-antihistamines |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2025.1538368/full |
| work_keys_str_mv | AT kameswarabharadwajmantha exploringthetherapeuticpotentialofh1antihistaminesinendometriosisageneregulationbasedperspective AT mohankumargajendran exploringthetherapeuticpotentialofh1antihistaminesinendometriosisageneregulationbasedperspective |