Insight into the blocking effects of curcumin on histamine H1 receptor as a natural anti-food allergic compound
Food Bioscience, cilt.83, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 83
- Basım Tarihi: 2026
- Doi Numarası: 10.1016/j.fbio.2026.109668
- Dergi Adı: Food Bioscience
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, INSPEC
- Anahtar Kelimeler: Anti-allergy, Curcumin, Histamine H1 receptor, Mast cell degranulation, Molecular dynamics simulation, SOCE pathway
- Çukurova Üniversitesi Adresli: Evet
Özet
Curcumin, a dietary polyphenol, exhibits anti-allergic activity, yet its direct interaction with the histamine H1 receptor (H1R) and underlying signaling modulation remain unclear. This investigation integrated molecular docking, molecular dynamics (MD) simulations, and cellular assays to systematically dissect curcumin's mechanism. Docking predicted stable binding within H1R orthosteric pocket (affinity: −9.4 kcal/mol), sustained by hydrogen bonds and π-π stacking with critical residues (Ser111, Asp178, Tyr431). MD simulations and MM/PBSA analysis (ΔG_bind = −26.47 kcal/mol) confirmed complex stability and hydrophobic-driven interaction. Functionally, curcumin (2-15 μg/mL) suppressed IgE/antigen-induced β-hexosaminidase release in RBL-2H3 cells and inhibited hyaluronidase with an IC50 of 9.4 μg/mL, without cytotoxicity. Notably, curcumin downregulated STIM1 and TRPC1 mRNA expression, implicating store-operated calcium entry (SOCE) pathway modulation in its anti-degranulation effect. These findings reveal a triple-tiered mechanism (Proposed direct H1R antagonism, putative SOCE-mediated Ca2+ signaling regulation, and proposed extracellular matrix stabilization) distinguishing curcumin from conventional single-target antihistamines. This study provides structural and mechanistic insights that support curcumin as a promising natural multi-target lead for anti-food allergic compound, bridging computational prediction with functional validation.