⮚ Immunosuppressant at high concentration and immunomodulator at low/normal concentration ✓Negatively regulates IL-2 and IFNγ by lymphocytes and TNF-α and IL-12 by macrophages ✓Reduced immune-inflammatory responses ✓Activates Sirt1 which negatively interferes with the TLR4/NF-κB/STAT signal, with reduced cytokines secretion from inactivated immune cells and macrophage/mast cell-derived pro-inflammatory factors. ✓Activates macrophages, T cells, and NK cells ✓Regulates CD4+CD25+ regulatory T cell suppressive functions ✓Activates Sirt1 which deacetylates STAT3 interfering with th17 lymphocyte differentiation ✓Restores T-cell function targeting the immune-checkpoint signaling PD-1/PD-L1 ✓Activates NK cells through AKT- and mTORC2-mediated c-Myb upregulation ⮚ Mostly immunosuppressant but immunomodulator in the elderly ✓Provides general inhibitory effects on the immune system ✓Ameliorates some immune functions in the elderly, response to vaccination and improved outcomes from infections ✓Inactivates T and B lymphocytes ✓Impairs lipid to glucose metabolism and immune suppression in long-term use ✓Extends lifespan and delay aging in model organisms ✓Reduces p16INK4A protein expression and increases collagen VII protein levels in the skin ✓Reduces the negative effects on the immune system in COVID-19 patients ⮚ ostly immunomodulator ✓Exerts direct immunomodulatory effect on immune cells by AMPK induction and mTORC1 inhibition ✓Promotes health immunity via an H3K4 methyltransferase/demethylase complex, downregulating some targets, including mTOR and S6 kinase ✓Increases the differentiation of naïve T cells into both regulatory and memory T cells, while decreasing the ability of neutrophils to initiate in NETosis. ✓Exerts immunomodulatory effects and contributes to the reduction of lung metastases of melanoma cell ✓Increases the number and function of tumor-infiltrating lymphocytes (TILs) and inhibits oxidative phosphorylation in B cells ✓Reduces the stability and localization of PD-L1 ✓Contributes to the improvement of CTLs against cancer cells ✓Reduces the burden of autoimmune diseases in several animal models and some human studies