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Apigenin exerts its inflammatory properties by mediating the inhibition of the proliferation of interferon gamma-secreting Th1 cells. The acetylated version of apigenin-3-acetate exhibits comparative immunomodulatory outcomes compared to methyl-prednisolone-acetate and apigenin.

Despite advancements in the treatment modalities for multiple sclerosis (MS), the associated morbidity remains high. A study published in Cell Journal evaluated the immunomodulatory role of apigenin (API) against peripheral blood mononuclear cells (PBMCs) derived from patients with MS and also compared the anti-inflammatory activity of apigenin 3-acetate with methyl-prednisolone-acetate and Api in the treatment of MS. It was concluded that Api, methyl-prednisolone-acetate, and apigenin-3-acetate significantly inhibited gene expressions of T-box transcription factor (T-bex) and interferon-γ (IFN- γ) and proliferation of Th1 cells. 

Study Participant Characteristics

This experiment isolated PBMCs from 5 MS patients and 3 healthy volunteers. The Expanded Disability Status Scale score of MS patients was estimated to be < 3. The half-maximal inhibitory concentration (IC50) of methyl-prednisolone-acetate and apigenin 3-acetate was found to be 2.5 µM and 80 µM, respectively.

Apoptotic Effects on Peripheral Blood Mononuclear Cells  

There were no significant differences in the outcomes related to necrosis and early and late apoptosis of PBMCs derived from MS patients when the cells were treated with methyl-prednisolone-acetate, apigenin-3-acetate, and apigenin when compared with dimethyl sulfoxide (DMSO).

Reduction in Th2 Cell Proliferation

The PBMCs derived from patients newly diagnosed with MS were treated with apigenin 3-acetate, apigenin, and methyl-prednisolone-acetate. Flow cytometric analysis demonstrated that apigenin 3-acetate, apigenin, and methyl-prednisolone-acetate reduced Th1 cell proliferation to approximately 41%, 26%, and 33%, respectively, when compared to the inhibition of Th1 cell proliferation by dimethyl sulphoxide (DMSO).

Gene Expressions of T-Bet and IFN-γ

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Apigenin 3-acetate, apigenin, and methyl-prednisolone-acetate significantly downregulated T-box transcription factor (T-bet) and IFN-γ gene expressions in the Th1 cells. The reduction in the expression of IFN-γ was more pronounced for apigenin-3-acetate. There were no significant differences across the three treatment options for the gene expression of T-bet.

The study concluded that Api inhibits the proliferation of Th1 cells and suppresses T-bet and IFN-γ gene expressions. These properties are comparable to the therapeutic potential of apigenin-3-acetate and the standard treatment with methyl-prednisolone-acetate.


Kasiri, N., Ghannadian, S. M., Hosseini, R., Ahmadi, L., Rahmati, M., Ashtari, F., Pourazar, A., & Eskandari, N. (2023). Comparative Analysis of Apigenin-3 Acetate versus Apigenin and Methyl-Prednisolone in Inhibiting Proliferation and Gene Expression of Th1 Cells in Multiple Sclerosis. Cell Journal (Yakhteh), 25(5), 307–316. https://doi.org/10.22074/cellj.2023.1971743.1154