Integrated experimental and immunoinformatic study of Th1/Th2 balance by Ferula hezarlalehzarica: Gata3/T-bet expression, IFN- γ/IL-10 cytokine modulation, and multiorgan safety assessment

Khademi Rostami, Mohammad; Saleki, Kiarash; Azadmehr, Abbas; Hajiaghaee, Reza; Maliji, Ghorban; Khademi Rostami, Maryam; S. Nateri, Abdolrahman; Saleki, Andia

doi:10.22038/ajp.2026.27839

Integrated experimental and immunoinformatic study of Th1/Th2 balance by Ferula hezarlalehzarica: Gata3/T-bet expression, IFN- γ/IL-10 cytokine modulation, and multiorgan safety assessment

Articles in Press

Document Type : Original Research Article

Authors

¹ Veterinary Faculty, Islamic Azad University- Babol Branch, Babol, Iran.

² Cancer Genetics & Stem Cell Group, The BioDiscovery Institute, School of Medicine, University of Nottingham, Nottingham, NG7 2RD, UK.

³ Cellular and Molecular Biology Research Center, Health Research Institute, Babol, Iran. Department of Immunology, Babol University of Medical Sciences, Babol, Iran.

⁴ Iranian Academic Center for Education, Culture and Research, Tehran, Iran.

⁵ Medical Student, Mazandaran University of Medical Sciences, Mazandaran, Iran

⁶ School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

10.22038/ajp.2026.27839

Abstract

Objective: Anti-inflammatory and anti-cancer activities of Ferula hezarlalehzarica (F. hezarlalehzarica) are confirmed in ancient and modern studies. We explored the immunomodulatory properties of this plant and its role in the Th1/Th2 balance response.
Materials and Methods: The impact of F. hezarlalehzarica aerial parts total extract at doses of 50, 250, and 500 mg/kg on interleukin (IL)-10 and interferon (IFN)-γ in rats was evaluated using ELISA, alongside C-IMMSIM simulations predicting immune responses to F. hezarlalehzarica proteins.
Results: Our findings indicated the plant extract significantly, and dose-dependently increased IL-10 and IFN-γ cytokines (p<0.05), with IFN-γ showing greater elevation. IFN-γ levels in groups treated with 50, 250, and 500 mg/kg of the extract were 60.47, 117.79, and 172.14 pg/ml, respectively, compared to 32.82 pg/ml in controls (p<0.001). IL-10 was increased significantly. Flow cytometry demonstrated Th1 polarization in F. hezarlalehzarica-treated samples, boosting T-bet over Gata3, and immune simulation analyses suggested Th1-biased response.
Conclusions: This study suggests increased Th1/Th2 cytokines with a stronger boost in IFN-γ indicating a Th1-biased immune response which is potentially favorable in treatment of cancers. F. hezarlalehzarica can be used as an immunomodulator various disorders. However, further studies are needed to optimize F. hezarlalehzarica dosage, helping reduce potential adverse effects.

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