Kaempferol and ginsenoside Rg1 ameliorate acute hypobaric hypoxia induced lung injury based on network pharmacology analysis

Acute hypobaric hypoxia at high altitude can cause fatal non-cardiogenic high altitude pulmonary edema. Antiinflammatory and anti-oxidant treatments appear to be a prospective way to alleviate acute hypoxia lung injury. Kaempferol (KA) and ginsenoside Rg1 (GRg1) can be isolated and purified from ginseng with anti-inflammatory, antioxidant, anti-carcinogenic, neuroprotective, and antiaging effects. However, their effects and pharmacological mechanisms on lung injury remains unclear. Network pharmacology analyses were used to explore potential targets of KA and GRg1 against acute hypobaric hypoxia induced lung injury. Rat lung tissues were further used for animal experiment verification. Among the putative targets of KA and GRg1 for inhibition of acute hypobaric hypoxia induced lung injury, AKT1, PIK3R1, PTK2, STAT3, HSP90AA1 and AKT2 were recognized as higher interrelated targets. And PI3K-AKT signaling pathway is considered to be the most important and relevant pathway. The rat experimental results showed that KA and GRg1 significantly improved histopathological changes and decreased pulmonary edema in rats with lung injury caused by acute hypobaric hypoxia. The concentrations of IL-6, TNF-alpha, MDA, SOD and CAT in rats treated with KA and GRg1 were significantly ameliorated. Protein and mRNA levels of PI3K and AKTI were significantly inhibited after KA administration. KA and GRg1 can lower lung water content, improve lung tissue damage, reduce the production of pro-inflammatory cytokines and the oxidative stress level.