Ophiopogonin A alleviates acute lung inflammation via NF-κB/MAPK signaling pathway in a mouse model of Klebsiella pneumoniae

Abstract

Klebsiella pneumoniae (Kp) is a gram-negative bacterium present in the flora of the mouth, skin and intestines. Due to the emergence of antibiotic resistance, the outcome of Kp pneumonia is becoming worse. Exploring an effective treatment method is clinically important. Ophiopogon japonicus is a traditional Chinese herbal medicine for treating inflammation and oxidative stress damage, as ophiopogonin A (OP-A) is its main active ingredient. We investigated the impact of OP-A on Kp pneumonia and further elucidated the underlying mechanism. After the establishment of Kp mouse model, the animals were grouped and received intraperitoneal injection of OP-A, levofloxacin (Lvx) or PBS. After 12 hours, mice were dissected to detect the pathological changes of lung tissues, and the number of inflammatory proteins and inflammatory cells in the bronchoalveolar lavage fluid (BALF). Finally, Western blot and RT-qPCR analyses were carried out to detect MARK, JNK, ERK and NF-κB expression in mouse lung tissues upon treatments. Administration of OP-A attenuated the pathological damage of lung tissues of Kp pneumonia mice, as both Lvx and OP-A significantly controlled and inhibited the wet-to-dry ratio of the lung tissues. Increased protein content and inflammatory cells infiltration were visible in Kp pneumonia mice, while the advent of Lvx and OP-A dramatically diminished inflammatory cells infiltration in BALF of lung tissues with fewer contents of IL-1β, IL-6 and TNF-α. The protective effect of OP-A on Kp pneumonia correlated with the NF-κB/MAPK signaling. In conclusion, OP-A treatment may alleviate the pathological damage and reduce inflammation of Kp mice through inhibition of the NF-κB/MAPK signaling pathway. OP-A has a significant anti-inflammatory effect on Kp mice, and hence it is a promising alternative for treating Kp pneumonia.