In addition, shikonin also demonstrated nephroprotective properties in diabetic nephropathy and lethal endotoxemia animal models by activating the renal nuclear factor-erythroid factor 2-related factor 2 (Nrf2) cascade and the antioxidant defense system, as well as decreasing circulating pro-inflammatory cytokines (Interleukin (IL)-6 and tumor necrosis factor (TNF)-α), and HIF-1 expression, along with inhibiting apoptosis, PKM2, NLRP3/caspase-1/IL-1β inflammasome, and improving animal survival [13,14,15,16,17]. This evidence concerns the gene TNF and diabetic kidney disease.