The Effective Compound Combination of Bufei Yishen Formula III Improves the Mitochondrial Dysfunction via Inhibiting JNK/Sab Pathway in COPD Mice.

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.