Natural products in treating sepsis-associated lung and liver injuries by mediating ferroptosis, current progress, and future perspective.

Sepsis is a life-threatening disorder triggered by an unregulated host reaction to infection, and it represents a worldwide health dilemma given the scarcity of effective treatment strategies. Sepsis usually leads to lethal multiorgan dysfunctions, including acute liver failure (ALF) and acute lung injury (ALI). Recent studies have found that altered programmed cell death (PCD) processes, including apoptosis, autophagy, ferroptosis, and pyroptosis, belong to key mechanisms that trigger sepsis-associated multiorgan disorders. Among them, ferroptosis is a unique mode of PCD characterized by the accumulation of iron-dependent reactive oxygen species (ROS) and lipid peroxidation. Mediating ferroptosis is a promising strategy against sepsis. Recently, studies have identified multiple natural products for treating sepsis-associated lung and liver injuries by targeting ferroptosis. Here, we provide an overview of the mechanisms and potential therapeutic targets underlying ferroptosis in sepsis. The natural products with ferroptosis targeting will be summarized. Notably, most current evidence supporting the therapeutic potential of natural products is derived from preclinical investigations, and high-quality clinical data remain scarce, requiring further validation for clinical translation. We hope this study provides new perspectives for the future treatment of sepsis-induced ALI and ALF.