In addition to an overall reduction in IR, silymarin treatment also reduced weight and epididymal fat mass, improved endothelial dysfunction, decreased oxidative stress indicators, such as nuclear factor kappa-light-chain-enhancer of activated B cell (NF-kB expression and tumor necrosis factor-alpha (TNF-α) levels, and restored, or prevented the inhibition of, the insulin receptor substrate 1(IRS-1)/phosphatidylinositol-3 kinase (P13K)/protein kinase B (Akt) pathway, and others [42,43,53,54,55,56,57,58,59,60,61]. The gene discussed is IRS1; the disease is endothelial dysfunction.