Effective-Component Compatibility of Bufei Yishen Formula III Suppresses Mitochondrial Oxidative Damage in COPD: Via Pkm2/Nrf2 Pathway

Abstract

Yang Liu,1 Lanxi Zhang,2 Jie Zhao,1,3 Ruilong Lu,1 Xuejie Shao,1 Kexin Xu,1 Jiansheng Li,1,3,4,* Yange Tian1,3,* 1Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases Co-Constructed by Henan Province and Education Ministry of People’s Republic of China, Henan University of Chinese Medicine, Zhengzhou, People’s Republic of China; 2School of Basic Medicine (Zhongjing School), Henan University of Chinese Medicine, Zhengzhou, People’s Republic of China; 3Henan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese Medicine, Zhengzhou, People’s Republic of China; 4First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, 450000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jiansheng Li; Yange Tian, Email [email protected]; [email protected]: The main objective of this study was to explore the mechanism of effective component compatibility of Bufei Yishen formula III (ECC-BYF III) in inhibiting mitochondrial oxidative stress in a rat model of chronic obstructive pulmonary disease (COPD).Methods: A549 cells exposed to cigarette smoke extract (CSE) were used to establish a model of mitochondrial oxidative damage. The cells were treated with the plasmid encoding Pkm2 and the enzymes and proteins involved in oxidative stress and mitochondrial function were measured. A rat model of COPD was established using CS and bacteria. Two different treatments were established, ECC-BYF III (5.5 mg/kg/d) and N-acetylcysteine (54 mg/kg/day). Animals were tested for pulmonary function (Vt, PEF, FVC, FEV0.1s and Cdyn) after eight weeks of therapy and were sacrificed. Pulmonary H&E staining was performed, and the total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px), total antioxidant capacity (T-AOC), and malondialdehyde (MDA) content were measured. The mitochondrial function was also examined. Furthermore, the Pkm2/Nrf2 signaling pathway was evaluated.Results: Overexpression of Pkm2 dramatically ameliorated the CS-induced mitochondrial oxidative damage. Further studies indicated that ECC-BYF III significantly improved mitochondrial function and inhibited oxidative stress in the lung tissues of COPD rats. Moreover, it can upregulate mitochondrial respiratory chain enzyme activity. ECC-BYF III also decreased the MDA content and increased T-SOD, GSH-Px, and T-AOC expression to facilitate oxidative homeostasis. Finally, our results indicated that the Pkm2/Nrf2 pathway is regulated by ECC-BYF III in A549 cells and lung tissue.Conclusion: These results indicate that ECC-BYF III exerts a strong effective therapeutic effect against cigarette smoke combined with bacteria-induced COPD in rats by activating the Pkm2/Nrf2 signaling pathway and restoring mitochondrial oxidative stress. Although more in vivo animal model research is needed to confirm these findings, this study contributes new data to support the conventional usage of ECC-BYF III.Keywords: chronic obstructive pulmonary disease, oxidative stress, ECC-BYF III, Pkm2, Nrf2

Keywords

• chronic obstructive pulmonary disease
• oxidative stress
• ecc-byf iii
• pkm2
• nrf2