Effective-Component Compatibility of Bufei Yishen Formula (ECC-BYF) III Inhibits Mucus Hypersecretion by BEAS-2B Cells via miR-146a-5p-Mediated Regulation of the EGFR/MEK/ERK Pathway

Yumeng Wei,1,* Jindi Ma1,2,* 1Traditional Chinese Medicine (Zhongjing) School, Henan University of Chinese Medicine, Zhengzhou, People’s Republic of China; 2Collaborative 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*These authors contributed equally to this workCorrespondence: Jindi Ma, Email [email protected]: To explore the role of the miR-146a-5p-mediated regulation of the EGFR/MEK/ERK pathway in the effect of effective-component compatibility of Bufei Yishen Formula III (ECC-BYF III) on ameliorating mucus hypersecretion by bronchial epithelial cells (BEAS-2B cells).Methods: BEAS-2B cells exposed to cigarette smoke extract (CSE) were used to establish a mucus hypersecretion model of BEAS-2B cells. The optimal intervention concentration of ECC-BYF III was screened by CCK-8, qRT-PCR and ELISA, the effects of ECC-BYF III on MUC5AC, MUC5B, IL-4, IL-8, TNF-α, IL-1α, miR-146a-5p and EGFR/MEK/ERK pathway expression were assessed. Furthermore, dual luciferase reporter gene was used to verify the relationship between miR-146a-5p and EGFR/MEK/ERK, and to observe the effect of down-regulating miR-146a-5p on ECC-BYF III ameliorating mucus hypersecretion and EGFR/MEK/ERK pathway.Results: ECC-BYF III reduced the expression of MUC5AC and MUC5B, decreased the mRNA expression of IL-1α, IL-8 and TNF-α, increased the mRNA expression of IL-4, and decreased the protein expression of TNF-α. Moreover, ECC-BYF III ameliorated CSE induced mucus hypersecretion in BEAS-2B cells through EGFR/MEK/ERK pathway. Finally, our results indicated that ECC-BYF III ameliorated the model by targeting miR-146a-5p and downregulating the EGFR/MEK/ERK pathway.Conclusion: ECC-BYF III can ameliorate CSE induced mucus hypersecretion by BEAS-2B cells and reduce the inflammatory response. The underlying mechanism may be related to the regulation of miR-146a-5p and the EGFR/MEK/ERK pathway. ECC-BYF III can inhibit activation of the EGFR/MEK/ERK pathway by upregulating the expression of miR-146a-5p, thereby ameliorating mucus hypersecretion by BEAS-2B cells.Keywords: mucus hypersecretion, COPD, effective-component compatibility of Bufei Yishen Formula III, traditional Chinese medicine, miR-146a-5p