Effective Component Compatibility of Bufei Yishen Formula III Which Regulates the Mucus Hypersecretion of COPD Rats via the miR-146a-5p/EGFR/MEK/ERK Pathway

Jindi Ma; Xuefang Liu; Yumeng Wei; Ruilong Lu; Kexin Xu; Yange Tian; Jiansheng Li

doi:10.1155/2022/9423435

Effective Component Compatibility of Bufei Yishen Formula III Which Regulates the Mucus Hypersecretion of COPD Rats via the miR-146a-5p/EGFR/MEK/ERK Pathway

Evid Based Complement Alternat Med. 2022 Dec 28:2022:9423435. doi: 10.1155/2022/9423435. eCollection 2022.

Authors

Jindi Ma^{1

2}, Xuefang Liu^{1

3}, Yumeng Wei², Ruilong Lu^{1

3}, Kexin Xu^{1

3}, Yange Tian^{1

3}, Jiansheng Li^{1

3}

Affiliations

¹ Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases Co-Constructed By Henan Province & Education Ministry of China, Henan University of Chinese Medicine, Zhengzhou 450046, Henan, China.
² Traditional Chinese Medicine (Zhong Jing) School, Henan University of Chines Medicine, Zhengzhou 450046, Henan, China.
³ Henan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese Medicine, Zhengzhou 450046, Henan, China.

Abstract

Background: The effective-component compatibility of Bufei Yishen formula III (ECC-BYF III) with 5 ingredients (ginsenoside Rh1, astragaloside, icariin, nobiletin, and paeonol) has been shown to protect against chronic obstructive pulmonary disease (COPD). The present study aimed to observe the effects of ECC-BYF III in a COPD rat model and dissect its potential mechanisms in regulating mucus hypersecretion via the miR-146a-5p/epidermal growth factor receptor (EGFR)/MEK/ERK pathway.

Methods: COPD model rats were treated with normal saline, ECC-BYF III, or N-acetylcysteine (NAC). Pulmonary function, lung tissue histology with H & E and AB-PAS staining, expression levels of interleukin (IL)-4, IL-6, IL-1β, MUC5AC, MUC5B, and FOXA2 in lung tissues and the mRNA and proteins involved in the miR-146a-5p/EGFR/MEK/ERK pathway were evaluated.

Results: The COPD rats showed a significant decrease in the pulmonary function and serious pathological damage to the lung tissue. ECC-BYF III and NAC significantly improved the ventilation function and small airway pathological damage in the COPD rats. The goblet cells and the expression levels of IL-1β, IL-6, MUC5AC, and MUC5B were increased in the COPD rats and were significantly decreased after ECC-BYF III or NAC intervention. The expression levels of IL-4 and FOXA2 in the COPD rats were markedly decreased and were improved in the ECC-BYF III and NAC groups. ECC-BYF III appeared to have a potent effect in restoring the reduced expression of miR-146a-5p. The increased phosphorylation levels of EGFR, MEK, and ERK1/2 and the protein expression levels of SPDEF in the lungs of COPD rats could be significantly reduced by ECC-BYF III.

Conclusions: ECC-BYF III has a significant effect in improving the airway mucus hypersecretion in COPD model rats, as well as a protective effect against limited pulmonary function and injured lung histopathology. The protective effect of ECC-BYF III in reducing airway mucus hypersecretion in COPD may involve the miR-146a-5p/EGFR/MEK/ERK pathway.