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

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.