Chrysophanol is associated with reduced inflammation and oxidative stress in sepsis-associated acute kidney injury

Sepsis-associated acute kidney injury (SA-AKI) is a common and severe complication in critically ill patients with high mortality, characterized by a dysregulated inflammatory response and oxidative stress. Chrysophanol (CHR), a natural anthraquinone, has demonstrated anti-inflammatory properties in other septic conditions, but its role and mechanism in SA-AKI remain unclear. This study aimed to investigate the protective effects of CHR against SA-AKI and the underlying mechanisms. Cell viability, inflammatory cytokine expression (IL-6, IL-1β, TNF-α, MCP-1, IL-10), and intracellular reactive oxygen species (ROS) levels were assessed after CHR pretreatment. An in vivo model was established using LPS method. Renal injury was evaluated through histopathology (H&E, Masson's, TUNEL staining), renal function (serum creatinine and BUN), and systemic inflammation (serum IL-6, TNF-α, IL-10). In vitro, LPS significantly reduced HK-2 cell viability and increased the production of pro-inflammatory cytokines and ROS. CHR pretreatment restored cell viability, suppressed the mRNA levels of IL-6, IL-1β, TNF-α, and MCP-1, enhanced IL-10 expression, and reduced intracellular ROS levels. In vivo, LPS-induced mice exhibited severe renal pathological damage, apoptosis, collagen deposition, and elevated serum creatinine and BUN. CHR treatment attenuate these pathological changes, reduced renal injury scores and apoptosis, and improved renal function. Furthermore, CHR significantly decreased serum levels of pro-inflammatory IL-6 and TNF-α while increasing the anti-inflammatory cytokine IL-10 in LPS mice. Chrysophanol treatment is associated with improved cell survival, reduced inflammatory cytokine expression, and decreased oxidative stress in LPS-stimulated HK-2 cells and septic mice. These associations suggest a potential protective role of chrysophanol in SA-AKI, though the underlying molecular mechanisms require further investigation.