Upregulation of claudin‑4 by Chinese traditional medicine Shenfu attenuates lung tissue damage by acute lung injury aggravated by acute gastrointestinal injury

CONTEXT: Many studies have explored new methods to cure acute lung injury (ALI); however, none of those methods could significantly change the high mortality rate of ALI. Shenfu is a Chinese traditional medicine that might be effective against ALI. OBJECTIVE: Our study explores the therapeutic potential of Shenfu in ALI. MATERIALS AND METHODS: Male C57BL/6 mice were assigned to control, lipopolysaccharide (LPS) (500 µg/100 μL per mouse), and LPS + Shenfu (30 mL/kg) groups. Shenfu (10 µL/mL) was added to LPS (10 µg/mL) treated MLE-12 cells for 48 h in vitro. Male C57BL/6 mice were divided into four groups: LPS, LPS + 3% dextran sulphate sodium (DSS), 3% DSS + Shenfu, and LPS + 3% DSS + Shenfu. RESULTS: Compared with the ALI group, Shenfu reduced wet/dry weight ratio (19.8%, 36.2%), and reduced the IL-2 (40.9%, 61.6%), IFN-γ (43.5%, 53.3%) TNF-α (54.1%, 42.1%), IL-6 (54.8%,70%), and IL-1β (39.9%, 65.1%), reduced serum uric acid (18.8%, 48.7%) and creatinine (17.4%, 41.1%). Moreover, Shenfu enhanced cell viability (17.2%, 59.9%) and inhibited cell apoptosis (63.0%) and p38/ERK phosphorylation in in vitro cultured epithelial cells with LPS stimulation. Mechanistically, Shenfu mediated the protective effect by upregulating claudin-4 expression. In addition, Shenfu could protect against both lung and intestinal epithelial damage in acute gastrointestinal injury-exacerbated ALI. DISCUSSION AND CONCLUSIONS: Taken together, the results revealed the therapeutic effect and the underlying mechanism of Shenfu injection in an ALI in mouse model, indicating its clinical potential to treat patients with ALI.