Syringic acid improves cyclophosphamide-induced immunosuppression in a mouse model

Abstract

Syringic acid (SA), a naturally occurring phenolic substance present in many edible plants and fruits, has been shown to have potential in immunoenhancement applications. In this study, we investigated the immunomodulatory effects of SA in mitigating cyclophosphamide (CYP)-induced immunosuppression in BALB/c mice using doxycycline as a positive control. SA administration prevented immune organ atrophy and morphological changes in the thymus, spleen, and bone marrow induced by CYP treatment in mice while also showing a dose-dependent enhancement of thymus and spleen indices compared to mice treated with CYP alone. Furthermore, SA improved thymocyte and splenocyte proliferation and exhibited significant antioxidant activity by reducing the elevated levels of malondialdehyde induced by CYP treatment. SA treatment effectively restored white blood cell (WBC) and lymphocyte counts to normal levels in CYP-treated animals, and the protective effects of CYP on immunological tissues were confirmed through histopathological examination. Moreover, SA treatment upregulated the expression of IL-6, IL-7, IL-15, and FoxN1. Finally, molecular docking studies revealed that binding energy values predicted minor inhibition potential toward IL-6, IL-7, FoxN1, IL-15, STAT3, STAT5, and JAK3. Overall, our findings suggest that SA treatment has the potential to reduce CYP-induced immunosuppression and may have applications as an immunologic adjuvant or functional food additive in chemotherapy.

Keywords: Cyclophosphamide; Cytokines; Docking; Immunoenhancement effect; Syringic acid; Thymus.