Mengwei Song,1,2,* Mi Han,1,2,* Haoyu Zhang,1 Yifan Yang,1,2 Yange Tian,1,2 Jiansheng Li,2,3 Jie Zhao1,2 

1Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, 450046, People’s Republic of China; 2Henan Key Laboratory of Chinese Medicine for Respiratory Disease, 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, Zhengzhou, 450046, People’s Republic of China; 3Department of Respiratory Diseases, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, 450000, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Jie Zhao, Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, 156 Jinshui East Road, Zhengdong, Zhengzhou, Henan, 450046, People’s Republic of China, Tel +86-15100165967, Email Jiezhao1702@163.com

Purpose: The effective compound combination of Bufei Yishen formula III (ECC-BYF III) has shown protective effects against chronic obstructive pulmonary disease (COPD). However, its effect on mitochondrial dysfunction remains unclear. The current study aimed to investigate the effect of ECC-BYF III on mitochondrial dysfunction in COPD mice and elucidate its potential mechanisms.
Methods: Twenty-eight BALB/c mice were randomized into four groups: control, model, ECC-BYF III, and NAC (N-acetylcysteine) groups. A COPD model was established using cigarette smoke and Klebsiella pneumoniae for 8 weeks. The mice in the ECC-BYF III group were treated with ECC-BYF III (7.7 mg/kg/d), and the NAC group was treated with NAC (78 mg/kg/d) for eight weeks. Mice in the control and model groups were administered with 0.5% sodium carboxymethyl cellulose (25 mL/kg/d) for eight weeks. Then pulmonary function, histopathology, inflammatory factor levels, mitochondrial ultrastructure and function, and immunoblotting analyses were evaluated.
Results: Compared with the model, ECC-BYF III significantly improved the decline in pulmonary function and histopathological changes. Furthermore, ECC-BYF III ameliorated mitochondrial dysfunction by restoring the mitochondrial membrane potential, increasing mitochondrial complex I activity, and decreasing tumor necrosis factor-α (TNF-α) level and protein expressions of SH3BP5 (Sab), Phospho-JNK (P-JNK), and cleaved CASP3.
Conclusion: The results suggest that the potential therapeutic benefit of ECC-BYF III against mitochondrial dysfunction in COPD is due to the inhibition of the JNK/Sab pathway, which will help to further understand the potential mechanisms of ECC-BYF III in the treatment of COPD.

Keywords: chronic obstructive pulmonary disease, Chinese medicine, mitochondrion, apoptosis, JNK/Sab pathway