Cell Journal (May 2023)
Comparative Analysis of Apigenin-3 Acetate versus Apigenin and Methyl-Prednisolone in Inhibiting Proliferation and Gene Expression of Th1 Cells in Multiple Sclerosis
Abstract
Objective: In spite of the advances in therapeutic modalities, morbidity, due to multiple sclerosis (MS), still remains high.Therefore, a large body of research is endeavouring to discover or develop novel therapies with improved efficacy fortreating MS patients. In the present study, we examined the immunomodulatory effects of apigenin (Api) on peripheralblood mononuclear cells (PBMCs) isolated from MS patients. We also developed an acetylated form of Api (apigenin-3-acetate) to improve In its blood-brain barrier (BBB) permeability. Additionally, we compared its anti-inflammatoryproperties to original Api and methyl-prednisolone-acetate (a standard therapy), as a potential option in treating MSpatients.Materials and Methods: The current study was an experimental-interventional research. The half maximal inhibitoryconcentration (IC50) values for apigenin-3-acetate, apigenin, and methyl-prednisolone-acetate were determined inhealthy volunteers’ PBMCs (n=3). Gene expressions of T-box transcription factor (TBX21 or T-bet) and IFN-γ, as wellas proliferation of T cells isolated from MS patients’ PBMCs (n=5), were examined in co-cultures of apigenin-3-acetate,Api and methyl-prednisolone-acetate after 48 hours of treatment, using quantitative reverse transcription polymerasechain reaction (qRT-PCR).Results: Our findings showed that apigenin-3-acetate, apigenin, and methyl-prednisolone-acetate at concentrations of80, 80, and 2.5 M could inhibit Th1 cell proliferation after 48 hours (P=0.001, P=0.036, and P=0.047, respectively); theyalso inhibited T-bet (P=0.015, P=0.019, and P=0.022) and interferon-γ (IFN-γ) gene expressions (P=0.0001).Conclusion: Our findings suggested that Api may have anti-inflammatory properties, possibly by inhibiting proliferationof IFN-producing Th1 cells. Moreover, comparative immunomodulatory effects were found for the acetylated version ofapigenin-3-acetate versus Api and methyl-prednisolone-acetate.
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