Effective-Component Compatibility of Bufei Yishen Formula III Protects Lung Air-Blood Barrier by Regulating the Oxidative Stress: via the Nuclear Factor-E2-Related Factor 2 Pathway

Kexin Xu,1,2 Xuejie Shao,1,2 Ruilong Lu,1,2 Yixi Liao,1,2 Yakun Zhao,1,2 Bo Wang,1,2 Zhiguang Qiu,1,2 Yange Tian1,2 1Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases Co-Constructed by Henan Province and Education Ministry of P.R. China, Henan University of Chinese Medicine, Zhengzhou, People’s Republic of China; 2Henan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese Medicine, Zhengzhou, People’s Republic of ChinaCorrespondence: Yange Tian, Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases Co-Constructed by Henan Province and Education Ministry of P.R. China, Henan University of Chinese Medicine, 156 East Jinshui Road, Jinshui District, Zhengzhou, Henan, People’s Republic of China, Email [email protected]: Bufei Yishen formula (BYF) is an effective treatment strategy for chronic obstructive pulmonary disease (COPD). Effective-component compatibility of BYF III (ECC-BYF III), composed of 5 active ingredients (ginsenoside Rh1, paeonol, astragaloside, icariin and nobiletin) from BYF, has similar effects to BYF in intervening COPD. The abnormal structure and hypofunction of lung air-blood barrier induces inefficiency gas exchange and promotes development of COPD. However, the role of ECC-BYF III in the air-blood barrier remains unknown. This study dedicated to exploring the effect and mechanism of ECC-BYF III improve structure and function of lung air-blood barrier in COPD.Methods: A COPD rat model was established to study the treatment of ECC-BYF III against COPD. The protective effect of ECC-BYF III on COPD was evaluated through pulmonary function and lung tissue pathology. The structure damage of the lung air-blood barrier was assessed using electron microscopy and immunofluorescence. Finally, we proved the regulating effect of ECC-BYF III in oxidative via the Nrf2 pathway.Results: The ECC-BYF III could significantly alleviate reduced pulmonary function, decrease damage of lung tissue and regulate oxidative stress in COPD rats. And ECC-BYF III reduced thickness of respiratory membrane, ameliorated damage of pulmonary capillary endothelial cells (PCECs) and alveolar epithelial cells (AECs) in COPD rats. Also, ECC-BYF III protected the function and normal cell morphology of type I alveolar epithelial cell (AT I) and type II alveolar epithelial cell (AT II) in COPD rats. Lastly, ECC-BYF III was indicated to adjust the Nrf2 pathway to improve oxidative stress and protect lung air-blood barrier in COPD rats.Conclusion: ECC-BYF III protects lung air-blood barrier in COPD by regulating oxidative stress via Nrf2 pathway. Keywords: effective-component compatibility of bufei yishen formula III, chronic obstructive pulmonary disease, lung air-blood barrier, oxidative stress, Nrf2 pathway