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

Overview

Journal Evid Based Complement Alternat Med

Specialty Rehabilitation Medicine

Date 2023 Jan 9

PMID 36619199

Authors

Jindi Ma

Xuefang Liu

Yumeng Wei

Ruilong Lu

Kexin Xu

Yange Tian

Jiansheng Li

Affiliations

Soon will be listed here.

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-1, 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-1, 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.

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References

Rabe K, Watz H . Chronic obstructive pulmonary disease. Lancet. 2017; 389(10082):1931-1940. DOI: 10.1016/S0140-6736(17)31222-9. View

Wang Y, Xu J, Meng Y, Adcock I, Yao X . Role of inflammatory cells in airway remodeling in COPD. Int J Chron Obstruct Pulmon Dis. 2018; 13:3341-3348. PMC: 6190811. DOI: 10.2147/COPD.S176122. View

Sandelowsky H, Weinreich U, Aarli B, Sundh J, Hoines K, Stratelis G . COPD - do the right thing. BMC Fam Pract. 2021; 22(1):244. PMC: 8666021. DOI: 10.1186/s12875-021-01583-w. View

Hicks-Berthet J, Ning B, Federico A, Tilston-Lunel A, Matschulat A, Ai X . Yap/Taz inhibit goblet cell fate to maintain lung epithelial homeostasis. Cell Rep. 2021; 36(2):109347. PMC: 8346236. DOI: 10.1016/j.celrep.2021.109347. View

Gordon A, Young M, Bihler E, Cheema T . COPD Maintenance Pharmacotherapy. Crit Care Nurs Q. 2020; 44(1):19-25. DOI: 10.1097/CNQ.0000000000000336. View

Li J, Ye Z . The Potential Role and Regulatory Mechanisms of MUC5AC in Chronic Obstructive Pulmonary Disease. Molecules. 2020; 25(19). PMC: 7582261. DOI: 10.3390/molecules25194437. View

Vogelmeier C, Roman-Rodriguez M, Singh D, Han M, Rodriguez-Roisin R, Ferguson G . Goals of COPD treatment: Focus on symptoms and exacerbations. Respir Med. 2020; 166:105938. DOI: 10.1016/j.rmed.2020.105938. View

Okuda K, Chen G, Subramani D, Wolf M, Gilmore R, Kato T . Localization of Secretory Mucins MUC5AC and MUC5B in Normal/Healthy Human Airways. Am J Respir Crit Care Med. 2018; 199(6):715-727. PMC: 6423099. DOI: 10.1164/rccm.201804-0734OC. View

Sheikh K, Coxson H, Parraga G . This is what COPD looks like. Respirology. 2015; 21(2):224-36. DOI: 10.1111/resp.12611. View

10.

Fu H, Zhang Y, Zhang P, Wu H, Sun X, Shen S . Tumor necrosis factor-α promotes airway mucus hypersecretion by repressing miR-146a-5p and miR-134-5p levels in human airway epithelial cells. Transl Cancer Res. 2022; 10(9):4047-4056. PMC: 8797934. DOI: 10.21037/tcr-20-3375. View

11.

Osei E, Florez-Sampedro L, Tasena H, Faiz A, Noordhoek J, Timens W . miR-146a-5p plays an essential role in the aberrant epithelial-fibroblast cross-talk in COPD. Eur Respir J. 2017; 49(5). DOI: 10.1183/13993003.02538-2016. View

12.

Cheng Z, Dai L, Wang X, Jia L, Jing X, Li P . MicroRNA-145 down-regulates mucin 5AC to alleviate airway remodeling and targets EGFR to inhibit cytokine expression. Oncotarget. 2017; 8(28):46312-46325. PMC: 5542269. DOI: 10.18632/oncotarget.17933. View

13.

Chan K, Tsoi Y, McCall M . The Effectiveness of Traditional Chinese Medicine (TCM) as an Adjunct Treatment on Stable COPD Patients: A Systematic Review and Meta-Analysis. Evid Based Complement Alternat Med. 2021; 2021:5550332. PMC: 8195656. DOI: 10.1155/2021/5550332. View

14.

Zhou M, Wang H, Zeng X, Yin P, Zhu J, Chen W . Mortality, morbidity, and risk factors in China and its provinces, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2019; 394(10204):1145-1158. PMC: 6891889. DOI: 10.1016/S0140-6736(19)30427-1. View

15.

Takahashi M, Fukuoka J, Nitta N, Takazakura R, Nagatani Y, Murakami Y . Imaging of pulmonary emphysema: a pictorial review. Int J Chron Obstruct Pulmon Dis. 2008; 3(2):193-204. PMC: 2629965. DOI: 10.2147/copd.s2639. View

16.

Feng F, Du J, Meng Y, Guo F, Feng C . Louqin Zhisou Decoction Inhibits Mucus Hypersecretion for Acute Exacerbation of Chronic Obstructive Pulmonary Disease Rats by Suppressing EGFR-PI3K-AKT Signaling Pathway and Restoring Th17/Treg Balance. Evid Based Complement Alternat Med. 2019; 2019:6471815. PMC: 6360623. DOI: 10.1155/2019/6471815. View

17.

Huang L, Pu J, He F, Liao B, Hao B, Hong W . Positive feedback of the amphiregulin-EGFR-ERK pathway mediates PM2.5 from wood smoke-induced MUC5AC expression in epithelial cells. Sci Rep. 2017; 7(1):11084. PMC: 5593934. DOI: 10.1038/s41598-017-11541-1. View

18.

Li Y, Li S, Li J, Deng L, Tian Y, Jiang S . A rat model for stable chronic obstructive pulmonary disease induced by cigarette smoke inhalation and repetitive bacterial infection. Biol Pharm Bull. 2012; 35(10):1752-60. DOI: 10.1248/bpb.b12-00407. View

19.

de Oliveira Rodrigues S, da Cunha C, Soares G, Silva P, Silva A, Goncalves-de-Albuquerque C . Mechanisms, Pathophysiology and Currently Proposed Treatments of Chronic Obstructive Pulmonary Disease. Pharmaceuticals (Basel). 2021; 14(10). PMC: 8539950. DOI: 10.3390/ph14100979. View

20.

Li W, Du X, Yang Y, Yuan L, Yang M, Qin L . miRNA-34b/c regulates mucus secretion in RSV-infected airway epithelial cells by targeting FGFR1. J Cell Mol Med. 2021; 25(22):10565-10574. PMC: 8581336. DOI: 10.1111/jcmm.16988. View