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BMC Complementary Medicine and Therapies

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01-12-2020 | Research article

Buyang Huanwu Tang inhibits cellular epithelial-to-mesenchymal transition by inhibiting TGF-β1 activation of PI3K/Akt signaling pathway in pulmonary fibrosis model in vitro

Authors: Zi-fei Yin, Yang-lin Wei, Xuan Wang, Li-na Wang, Xia Li

Published in: BMC Complementary Medicine and Therapies | Issue 1/2020

Abstract

Background

Pulmonary fibrosis (PF) is a chronic and progressive interstitial lung disease. Buyang Huanwu Tang (BYHWT), a classical traditional Chinese medicine formula, has been widely utilized for the treatment of PF in China. This present study aimed to explore the mechanism of BYHWT in the treatment of PF in vitro.

Methods

TGF-β1 stimulated human alveolar epithelial A549 cells were used as in vitro model for PF. Post the treatment of BYHWT, cell viability was measured by MTT assay, and cell morphology was observed under microscope. The epithelial-to-mesenchymal transition (EMT) markers (E-cadherin, Vimentin) and collagen I (Col I) were detected by western blot, immunofluorescence staining and real-time quantitative polymerase chain reaction. With the co-administration of activators (IGF-1, SC79) and inhibitors (LY294002, MK2206), the effect of BYHWT on PI3K/Akt pathway was analyzed by western blot.

Results

BYHWT inhibited cell growth, and prevented cell morphology changed from epithelial to fibroblasts in TGF-β1 induced A549 cells. BYHWT decreased Vimentin and Col I, while increased E-cadherin at both protein and mRNA levels. Moreover, phosphorylation of PI3K (p-PI3K) and phosphorylation of Akt (p-Akt) were significantly down-regulated by BYHWT in TGF-β1 stimulated A549 cells.

Conclusion

These results indicate that BYHWT suppressed TGF-β1-induced collagen accumulation and EMT of A549 cells by inhibiting the PI3K/Akt signaling pathway. These findings suggest that BYHWT may have potential for the treatment of PF.

Zhou XM, Wen GY, Zhao Y, Liu YM, Li JX. Inhibitory effects of alkaline extract of citrus reticulata on pulmonary fibrosis. J Ethnopharmacol. 2013;146(1):372–8.CrossRef

Mojiri-Forushani H, Hemmati AA, Dehghani MA, Malayeri AR, Pour HH. Effects of herbal extracts and compounds and pharmacological agents on pulmonary fibrosis in animal models: a review. Chin J Integr Med. 2017;15(6):433–41.CrossRef

Hopkins RB, Burke N, Fell C, Dion G, Kolb M. Epidemiology and survival of idiopathic pulmonary fibrosis from national data in Canada. Eur Respir J. 2016;48(1):187–95.CrossRef

Li L, Huang W, Li K, Zhang K, Lin C, Han R, Lu C, Wang Y, Chen H, Sun F, et al. Metformin attenuates gefitinib-induced exacerbation of pulmonary fibrosis by inhibition of TGF-beta signaling pathway. Oncotarget. 2015;6(41):43605–19.PubMedPubMedCentral

Mojiri-Forushani H, Hemmati AA, Khodadadi A, Rashno M. Valsartan attenuates bleomycin-induced pulmonary fibrosis by inhibition of NF-kappaB expression and regulation of Th1/Th2 cytokines. Immunopharmacol Immunotoxicol. 2018;40(3):225–31.CrossRef

Wang P, Wang Y, Nie X, Braini C, Bai R, Chen C. Multiwall carbon nanotubes directly promote fibroblast-myofibroblast and epithelial-mesenchymal transitions through the activation of the TGF-beta/Smad signaling pathway. Small. 2015;11(4):446–55.CrossRef

Takata T, Motoo Y, Tomosugi N. Effect of Saikokeishito, a Kampo medicine, on hydrogen peroxide-induced premature senescence of normal human dermal fibroblasts. J Integr Med. 2014;12(6):495–503.CrossRef

Lofdahl A, Rydell-Tormanen K, Larsson-Callerfelt AK, Wenglen C, Westergren-Thorsson G. Pulmonary fibrosis in vivo displays increased p21 expression reduced by 5-HT2B receptor antagonists in vitro - a potential pathway affecting proliferation. Sci Rep. 2018;8(1):1927.CrossRef

Yi GZ, Liu YW, Xiang W, Wang H, Chen ZY, Xie SD, Qi ST. Akt and beta-catenin contribute to TMZ resistance and EMT of MGMT negative malignant glioma cell line. J Neurol Sci. 2016;367:101–6.CrossRef

10.

Zhao H, Wu QQ, Cao LF, Qing HY, Zhang C, Chen YH, Wang H, Liu RY, Xu DX. Melatonin inhibits endoplasmic reticulum stress and epithelial-mesenchymal transition during bleomycin-induced pulmonary fibrosis in mice. PLoS One. 2014;9(5):e97266.CrossRef

11.

Xu X, Dai H, Geng J, Wan X, Huang X, Li F, Jiang D, Wang C. Rapamycin increases CCN2 expression of lung fibroblasts via phosphoinositide 3-kinase. Lab Investig. 2015;95(8):846–59.CrossRef

12.

Liu Q, Chu H, Ma Y, Wu T, Qian F, Ren X, Tu W, Zhou X, Jin L, Wu W, et al. Salvianolic acid B attenuates experimental pulmonary fibrosis through inhibition of the TGF-beta signaling pathway. Sci Rep. 2016;6:27610.CrossRef

13.

Zhang XL, Xing RG, Chen L, Liu CR, Miao ZG. PI3K/Akt signaling is involved in the pathogenesis of bleomycininduced pulmonary fibrosis via regulation of epithelialmesenchymal transition. Mol Med Rep. 2016;14(6):5699–706.CrossRef

14.

Shaw LH, Chen WM, Tsai TH. Identification of multiple ingredients for a Traditional Chinese Medicine preparation (bu-yang-huan-wu-tang) by liquid chromatography coupled with tandem mass spectrometry. Molecules. 2013;18(9):11281–98.CrossRef

15.

Yun Z, Liguo C, Mingzhi X, Zhen J, University J. Research progress of Buyang Huanwu decoction in the treatment of pulmonary fibrosis. Clin J Tradit Chin Med. 2019;31(03):18–21.

16.

Aiello M, Bertorelli G, Bocchino M, Chetta A, Fiore-Donati A, Fois A, Marinari S, Oggionni T, Polla B, Rosi E, et al. The earlier, the better: impact of early diagnosis on clinical outcome in idiopathic pulmonary fibrosis. Pulm Pharmacol Ther. 2017;44:7–15.CrossRef

17.

Jones MG, Richeldi L. Recent advances and future needs in interstitial lung diseases. Semin Respir Crit Care Med. 2016;37(3):477–84.CrossRef

18.

Li LC, Kan LD. Traditional Chinese medicine for pulmonary fibrosis therapy: Progress and future prospects. J Ethnopharmacol. 2017;198:45–63.CrossRef

19.

Xu JN, Que HF, Tang HJ. Effects and action mechanisms of Buyang Huanwu decoction in wound healing of chronic skin ulcers of rats. J Chin Integr Med. 2009;7(12):1145–9.CrossRef

20.

Ebina M. Pathognomonic remodeling of blood and lymphatic capillaries in idiopathic pulmonary fibrosis. Respir Investig. 2017;55(1):2–9.CrossRef

21.

Wang X, Li X, Wang LN, Pan JJ, Yang X, Wei YL. Buyang Huanwu decoction ameliorates bleomycin-induced pulmonary fibrosis in rats via downregulation of related protein and gene expression. Evid Based Complement Alternat Med. 2018;2018:9185485.PubMedPubMedCentral

22.

Baek SH, Ko JH, Lee JH, Kim C, Lee H, Nam D, Lee J, Lee SG, Yang WM, Um JY, et al. Ginkgolic acid inhibits invasion and migration and TGF-beta-induced EMT of lung cancer cells through PI3K/Akt/mTOR inactivation. J Cell Physiol. 2017;232(2):346–54.CrossRef

23.

Yan W, Xiaoli L, Guoliang A, Zhonghui Z, Di L, Ximeng L, Piye N, Li C, Lin T. SB203580 inhibits epithelial-mesenchymal transition and pulmonary fibrosis in a rat silicosis model. Toxicol Lett. 2016;259:28–34.CrossRef

24.

Conte E, Fruciano M, Fagone E, Gili E, Caraci F, Iemmolo M, Crimi N, Vancheri C. Inhibition of PI3K prevents the proliferation and differentiation of human lung fibroblasts into myofibroblasts: the role of class I P110 isoforms. PLoS One. 2011;6(10):e24663.CrossRef

25.

Zheng K, Zhang Q, Lin G, Li Y, Sheng Z, Wang J, Chen L, Lu HH. Activation of Akt by SC79 protects myocardiocytes from oxygen and glucose deprivation (OGD)/re-oxygenation. Oncotarget. 2017;8(9):14978–87.CrossRef

26.

Xiang RF, Wang Y, Zhang N, Xu WB, Cao Y, Tong J, Li JM, Wu YL, Yan H. MK2206 enhances the cytocidal effects of bufalin in multiple myeloma by inhibiting the AKT/mTOR pathway. Cell Death Dis. 2017;8(5):e2776.CrossRef

27.

Le Cras TD, Korfhagen TR, Davidson C, Schmidt S, Fenchel M, Ikegami M, Whitsett JA, Hardie WD. Inhibition of PI3K by PX-866 prevents transforming growth factor-alpha-induced pulmonary fibrosis. Am J Pathol. 2010;176(2):679–86.CrossRef

28.

He LF, Xu HW, Chen M, Xian ZR, Wen XF, Chen MN, Du CW, Huang WH, Wu JD, Zhang GJ. Activated-PAK4 predicts worse prognosis in breast cancer and promotes tumorigenesis through activation of PI3K/AKT signaling. Oncotarget. 2017;8(11):17573–85.PubMed

29.

Xu L, He S, Yin P, Li D, Mei C, Yu X, Shi Y, Jiang L, Liu F. Punicalagin induces Nrf2 translocation and HO-1 expression via PI3K/Akt, protecting rat intestinal epithelial cells from oxidative stress. Int J Hyperth. 2016;32(5):465–73.CrossRef

Title: Buyang Huanwu Tang inhibits cellular epithelial-to-mesenchymal transition by inhibiting TGF-β1 activation of PI3K/Akt signaling pathway in pulmonary fibrosis model in vitro
Authors: Zi-fei Yin
Yang-lin Wei
Xuan Wang
Li-na Wang
Xia Li
Publication date: 01-12-2020
Publisher: BioMed Central
Published in: BMC Complementary Medicine and Therapies / Issue 1/2020
Electronic ISSN: 2662-7671
DOI: https://doi.org/10.1186/s12906-019-2807-y

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Buyang Huanwu Tang inhibits cellular epithelial-to-mesenchymal transition by inhibiting TGF-β1 activation of PI3K/Akt signaling pathway in pulmonary fibrosis model in vitro

Abstract

Background

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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