ArticleInflammation research : official journal of the European Histamine Research Society ... [et al.]2025
Melatonin inhibits salivary gland epithelial cell ferroptosis via the NRF2/HO-1/GPX4 signaling pathway in primary Sjögren's syndrome.
Article in Inflammation research : official journal of the European Histamine Research Society ... [et al.], 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Agomelatine for Sjögren's syndrome: a study on its therapeutic effects and mechanisms.Inflammopharmacology · 2026Article
- Selenoproteins: Minute yet vital players governing cellular fate.Genes & diseases · 2026Review
- Molecular Insights into Oral Manifestations in Sjögren's Disease.International journal of molecular sciences · 2026Review
- Targeting the ferritinophagy axis: multi-target regulation of TFRC/FTH1/NCOA4 by artesunate ameliorates salivary gland dysfunction in Sjögren's Disease.Chinese medicine · 2026Article
- Ferroptosis in salivary gland disorders: mechanisms, biomarkers, and therapeutic perspectives.Apoptosis : an international journal on programmed cell death · 2026Review
- Targeting glutathione peroxidase 4 in ferroptosis: from immune regulation to pharmacological development and translational applications.Frontiers in pharmacology · 2026Review
- Artemisinin derivatives modulate KEAP1-NRF2-xCT pathway to alleviate Sjögren's disease: insights from scRNA-seq and systems biology.Frontiers in immunology · 2025Article
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5 authors.
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Abstract
backgroundPrimary Sjögren's syndrome (pSS) is an autoimmune disease characterized by xerostomia and autoimmune sialadenitis. Interferon-γ (IFN-γ) induces ferroptosis in salivary gland epithelial cells (SGECs), leading to salivary gland (SG) hypofunction. We previously demonstrated the beneficial effects of melatonin (MLT) in alleviating SG dysfunction and inflammation in a pSS animal model. However, the precise underlying mechanism remains unclear.
methodsFemale NOD/ltj and ICR mice were used as the pSS mouse model and control group, respectively. MLT was administered via intraperitoneal injection to NOD/ltj mice to detect its effect on ferroptosis in SGs. Primary human SGECs and A253 cells were treated with IFN-γand ferroptosis inducers, with or without MLT.
resultsExogenous MLT alleviated pathological SG alterations and promoted saliva production through inhibiting SGEC ferroptosis. MLT inhibited SGEC ferroptosis induced by IFN-γ and ferroptosis inducers via nuclear factor erythroid 2-related factor 2/heme oxygenase-1/glutathione peroxidase 4 (NRF2/HO-1/GPX4) pathway activation. Moreover, MLT suppressed the nuclear factor-kappa B (NF-κB) pathway, which is triggered by ferroptosis in SGECs. Nevertheless, ML385-mediated NRF2 inhibition abrogated the antiferroptotic protective effects of MLT on SGECs.
conclusionsMLT inhibits SGEC ferroptosis through NRF2/HO-1/GPX4 pathway activation and thus attenuates ferroptosis-triggered NF-κB activity. Melatonin represents a potential therapeutic approach for pSS owing to its capacity to regulate ferroptosis.
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