Sepsis-led mitochondrial dysfunction has become a critical pathophysiological procedure in sepsis. Since ginsenosides have been applied in the treatment of mitochondrial dysfunction, ginsenoside Rg3 was employed to study its effects on the mitochondrial dysfunction induced by sepsis. The apoptosis rate, oxygen consumption rate (OCR), reactive oxygen species (ROS), antioxidant glutathione (GSH) pools, and mitochondrial transmembrane potential (MTP) were determined in LPS-induced sepsis hepatocytes treated with different concentrations of Rg3. Then, the protein expression levels of mitochondrial biogenesis related transcription factors, autophagy-related proteins, and AMP-activated protein kinase (AMPK) signal pathway related proteins were determined by Western blotting in both in vitro and in vivo sepsis models. Rg3 shows functions of promotion of OCR, attenuation of ROS, and maintenance of GSH pools, and its conjugating activity in the in vitro sepsis models. Rg3-treated cells were observed to have a higher MTP value compared with the LPS only induced cells. Moreover, Rg3 treatment can inhibit mitochondrial dysfunction via increasing the protein expression levels of mitochondrial biogenesis related transcription factors. Rg3 treatment has the function of inhibitor of apoptosis of human primary hepatocytes, and Rg3 can up-regulate the autophagy-related proteins and activate AMPK signal pathway in sepsis models. Meanwhile, the mitochondrial protective function exerted by Rg3 decreased after the autophagy inhibitors or AMPK inhibitor treatment in LPS-induced human primary hepatocytes. Rg3 can improve mitochondrial dysfunction by regulating autophagy in mitochondria via activating the AMPK signal pathway, thus protecting cell and organ injuries caused by sepsis.

Objectives. To investigate the protective effect of ginsenoside Rg1 on relieving sepsis-induced lung inflammation and injury in vivo and in vitro. Methods. Cultured human pulmonary epithelial cell line A549 was challenged with LPS to induce cell injury, and CLP mouse model was generated to mimic clinical condition of systemic sepsis. Rg1 was applied to cells or animals at indicated dosage. Apoptosis of cultured cells was quantified by flow cytometry, along with ELISA for inflammatory cytokines in supernatant. For septic mice, lung tissue pathology was examined, plus ELISA assay for serum cytokines. Western blotting was used to examine the activation of inflammatory pathways and ER stress marker proteins in both cells and mouse lung tissues. Reactive oxygen species (ROS) level was quantified by DCFDA kit. Results. Ginsenoside Rg1 treatment remarkably suppressed apoptosis rate of LPS-induced A549 cells, relieved mouse lung tissue damage, and elevated survival rate. Rg1 treatment also rescued cells from LPS-induced intracellular ROS. In both A549 cells and mouse lung tissues, further study showed that Rg1 perfusion significantly suppressed the secretion of inflammatory cytokines including tumor necrosis factor- (TNF-) alpha and interleukin- (IL-) 6 and relieved cells from ER stress as supported by decreased expression of marker proteins via upregulating sirtuin 1 (SIRT1). Conclusion. Our results showed that ginsenoside Rg1 treatment effectively relieved sepsis-induced lung injury in vitro and in vivo, mainly via upregulating SIRT1 to relieve ER stress and inflammation. These findings provide new insights for unrevealing potential candidate for severe sepsis accompanied with lung injury.

Mesenchymal stem cells (MSCs) have been reported to regulate the systemic inflammatory response and sepsis-induced immunologic injury pre-clinically. However, whether MSCs from different sources elicit identical effects remains to be elucidated. The present study compared the effect of bone marrow‑derived MSCs (BMSCs) and adipose tissue-derived MSCs (ADMSCs) in a murine model of lipopolysaccharide (LPS)‑induced sepsis. SPF BALB/c mice were induced with an injection of LPS (10 mg/kg; 1 mg/ml) via the tail vein. To compare the effect of MSCs on the septic mice, either saline, BMSCs or ADMSCs were injected via the tail vein 5 min following the administration of LPS. The survival rates and body temperatures of the mice were observed regularly up to 48 h. The serum levels of pro‑inflammatory cytokines, including tumour necrosis factor‑α, interleukin (IL)‑6 and IL‑8, anti‑inflammatory cytokines, including IL‑2, IL‑4 and IL‑10, and biochemical markers, including lactate, creatinine, alanine aminotransferase and aspertate aminotransferase, were analyzed at 6 h. The BMSCs and ADMSCs significantly reduced mortality rates, body‑temperature fluctuations, serum levels of biochemical markers and the majority of cytokines. However, the levels of IL‑8 in the BMSC and ADMSC groups were increased and decreased, respectively. These findings suggested that BMSCs and ADMSCs ameliorated sepsis-associated organ injury and mortality, and had a similar regulatory effect on pro‑ and anti‑inflammatory cytokines despite the different MSC sources. Therefore, BMSCs and ADMSCs may serve as novel treatment modalities for sepsis.