Solubilized curcuminoid complex prevents extensive immunosuppression through immune restoration and antioxidant activity: Therapeutic potential against SARS-CoV-2 (COVID-19).

• CTX-treated animals had fewer activation of innate and adaptive immune cells. • C S/M restores suppressed innate cell activations observed in CTX-induced immunosuppression. • CTX-injected mice pre-exposed to C S/M encourages the immuno-enhancing effects for Th1, CTL, and multifunctional T cell responses. • CTX-injected mice pre-exposed to C S/M increased antioxidant enzymes. • C S/M significantly reduced viral loads in SARS-CoV-2-infected hamsters. The therapeutic benefits of curcuminoids in various diseases have been extensively reported. However, little is known regarding their preventive effects on extensive immunosuppression. We investigated the immunoregulatory effects of a curcuminoid complex (C S/M), solubilized with stevioside, using a microwave-assisted method in a cyclophosphamide (CTX)-induced immunosuppressive mouse model and identified its new pharmacological benefits. CTX-treated mice showed a decreased number of innate cells, such as dendritic cells (DCs), neutrophils, and natural killer (NK) cells, and adaptive immune cells (CD4 and CD8 T cells) in the spleen. In addition, CTX administration decreased T cell activation, especially that of Th1 and CD8 T cells, whereas it increased Th2 and regulatory T (Treg) cell activations. Pre-exposure of C S/M to CTX-induced immunosuppressed mice restored the number of innate cells (DCs, neutrophils, and NK cells) and increased their activity (including the activity of macrophages). Exposure to C S/M also led to the superior restoration of T cell numbers, including Th1, activated CD8 T cells, and multifunctional T cells, suppressed by CTX, along with a decrease in Th2 and Treg cells. Furthermore, CTX-injected mice pre-exposed to C S/M were accompanied by an increase in the levels of antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase), which play an essential role against oxidative stress. Importantly, C S/M treatment significantly reduced viral loads in severe acute respiratory syndrome coronavirus 2-infected hamsters and attenuated the gross pathology in the lungs. These results provide new insights into the immunological properties of C S/M in preventing extensive immunosuppression and offer new therapeutic opportunities against various cancers and infectious diseases caused by viruses and intracellular bacteria. [ABSTRACT FROM AUTHOR]