Roles and mechanism of carnosol for mice with lipopolysaccharide-induced acute lung injury

  Objective  To explore the role of carnosol for mice with lipopolysaccharide (LPS)-induced murine acute lung injury (ALI) and its molecular mechanism.

  Methods  A total of 40 male C57BL/6 mice aged 10 to 12 weeks were randomly divided into control group (n=10), carnosol group (n=10), ALI group(n=10) and treatment group (ALI+ carnosol, n=10). The carnosol group and the treatment group were given intragastric administration of carnosol for 20 mg/(kg·d) 1 week before LPS injection. The ALI group and the treatment group were injected with a single intraperitoneal injection of LPS (10 mg/kg) to construct a murine ALI model, while the control group and the carnosol group were injected with the same dose of normal saline. After 12 hours of LPS injection, the mouse aortic blood and lung tissues were collected, and the partial pressure of oxygenp_a(O₂), carbon dioxidep_a(CO₂)in the arterial blood, and serum lactic dehydrogenase (LDH) were measured. Lung wet-to-dry weight ratio was recorded, and the tissue damage was detected by HE staining. Western blot was used to detect the protein expression levels of ferroptosis markers including prostaglandin intraperoxidase synthase 2 (PTGS2) protein and glutathione peroxidase 4 (GPX4) protein in lung tissues of mice in each group. Finally, the expression of nuclear transcription factor red 2 related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway related proteins in lung tissues of mice was detected.

  Results  Compared with the control group, the ALI group showed obvious damage such as pulmonary edema, inflammatory cells and red blood cells infiltration, the wet-to-dry weight ratio, the airway pressure and p_a(CO₂) were significantly decreased, p_a(O₂)was significantly increased, the expression of PTSG2 protein in lung tissue was increased, GPX4 proteinwas decreased, and the expression levels of NRF2 and HO-1 protein were significantly reduced (P < 0.05). Compared with the ALI group, the lung injury in the treatment group was significantly reduced, the wet-to-dry weight ratio was significantly reduced, p_a(O₂)was significantly increased, p_a(CO₂) was significantly decreased, the expression of PTSG2 protein in lung tissue was decreased, GPX4 protein was increased, the expression levels of NRF2 and HO-1 protein were significantly increased (P < 0.05).

  Conclusion  Carnosol has the potential to protect against ALI in mice, and plays the role in inhibiting ferroptosis by activating NRF2/HO-1 pathway.