Ginsenoside Rg3 Improves Mitochondrial Dysfunction and Suppresses Sepsis-Induced Multiple Organ Dysfunction

Abstract

Background: Sepsis, a complex and potentially life-threatening condition resulting from a dysregulated host response to infection, claims numerous lives and carries a high mortality rate. The development of multiple organ dysfunction syndrome (MODS), a cascade of events leading to the failure of vital organ systems, worsens the clinical prognosis and represents a devastating consequence of sepsis. Ginsenoside Rg3 (Rg3), a natural compound, has been demonstrated its potential in regulating mitochondrial dysfunction, offering a potential treatment avenue for sepsis-related complications. Our research aimed to explore the mechanism by which Rg3 treats sepsis-induced MODS. Method: In vitro, we established a sepsis cell model by subjecting normal cells (H9C2 cardiac cells, L02 human liver cells, and HK2 renal tubular cells) to lipopolysaccharide (LPS) treatment, with untreated cells as the control group. We conducted investigations to assess the impact of Rg3 on mitochondrial metabolism, respiratory function, oxidative stress, and mitochondrial homeostasis in cardiac, hepatic, and renal cells. In vivo, we employed the cecal ligation and puncture (CLP) method to induce a sepsis model in rats and administered or withheld Rg3 treatment. We assessed the general well-being of the rats, quantified inflammatory factors, conducted histological examinations, and performed biochemical analyses of key markers within the liver, kidneys, heart, and lungs to evaluate the extent of multi-organ dysfunction in CLP rats. Results: In vitro, the Rg3-treated group exhibited a significant amelioration in mitochondrial dysfunction, including mitochondrial metabolism, mitochondrial respiratory function of cardiomyocytes, oxidative stress in liver cells, and mitochondrial homeostasis of renal cells, compared to the control group (p < 0.05). In vivo, following Rg3 administration, a significant improvement in the overall Severity Scores was observed in CLP rats (p < 0.05). Rg3 was discovered to have notable organ protective properties. It repaired histopathologic abnormalities induced by CLP in the liver, kidney, heart, and lungs in addition to lowering inflammatory cytokine levels (p <0.05). Conclusion: Rg3 improves mitochondrial metabolism, respiratory function, and mitochondria homeostasis, and suppresses oxidative stress. Furthermore, Rg3 exhibits significant organ-protective properties and capacity to reduce inflammatory cytokine levels, thereby suppressing sepsis-induced MODS.