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Total glycosides of Yupingfeng protects against bleomycin-induced pulmonary fibrosis in rats associated with reduced high mobility group box 1 activation and epithelial–mesenchymal transition

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Abstract

Background

Pulmonary fibrosis (PF) is a fatal inflammatory disease with limited effective strategies. Epithelial–mesenchymal transition (EMT) is a pivotal origin of myofibroblasts that secrete extracellular matrix (ECM) in the development of PF. High mobility group box 1 (HMGB1), one of the mediators of inflammation, has been proved abnormal activation in the pathogenesis of PF.

Aim

The present study was aimed to investigate the potential effects of total glycoside of Yupingfeng (YPF-G), the natural compound extracted from Yupingfeng san, on HMGB1 activation and EMT in bleomycin-induced PF, which was a serious disease of respiratory system.

Methods

The Sprague–Dawley (SD) rat model of PF was duplicated by intratracheal instillation of bleomycin (5 mg kg−1). After that, YPF-G (5, 10 mg kg−1) and prednisone (5 mg kg−1) were separately administered intragastrically, and then the rats were killed at days 14 and 28, respectively. Hematoxylin and eosin and Masson’s trichrome staining were performed to assess the histopathologic level of lung tissues, western blotting and the common kits were utilized to investigate the hallmarks molecule expression of ECM and EMT, and the level of HMGB1 in lung tissues and serum.

Results

We found that both dose of YPF-G markedly reduced bleomycin-induced alveolitis and PF in rats. Besides, the levels of HMGB1, laminin, hyaluronic acid, and hydroxyproline were effectively reduced. Meanwhile, the increased protein expression of HMGB1 and the mesenchymal markers including vimentin and alpha-smooth muscle actin, and the decreased protein expression of epithelial marker E-cadherin were dramatically inhibited after YPF-G treatment.

Conclusion

Our results demonstrated that YPF-G could ameliorate bleomycin-induced PF by reducing HMGB1 activation and reversing EMT.

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Abbreviations

α-SMA:

Alpha-smooth muscle actin

E-cad:

E-cadherin

ECM:

Extracellular matrix

EMT:

Epithelial–mesenchymal transition

HA:

Hyaluronic acid

HMGB1:

High mobility group box 1

HYP:

Hydroxyproline

LN:

Laminin

PF:

Pulmonary fibrosis

Vim:

Vimentin

YPF-G:

Total glycosides of Yupingfeng

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Acknowledgments

This work was finally supported by the National Natural Science Foundation of China (No. 81274172, No. 81473267, and No. 30801535), the Open Project Program of State Key Laboratory of Natural Medicines, China Pharmaceutical University (No. SKLNMKF201206), and Traditional Chinese medicine research project of the health department of Anhui Province (No. 2012zy53).

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Authors and Affiliations

  1. School of Pharmacy, Anhui Medical University, 81 Meishan Road, Hefei, 230032, Anhui, China

    Wenhui Cui, Xiaoting Mo, Wencheng Zhou & Jian Gao

  2. The First Affiliated Hospital of Anhui Medical University, 218 Jixi Road, Hefei, 230022, Anhui, China

    Wenhui Cui, Xiaoting Mo, Wencheng Zhou, Zhihui Zhang & Jian Gao

  3. Department of Pharmacy, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, 3 East Qingchun Road, Hangzhou, 310016, Zhejiang, China

    Liucheng Li

  4. School of Pharmacy, Anhui University of Chinese Medicine, 103 Meishan Road, Hefei, 230038, Anhui, China

    Delin Li, Liang Xu & Ping Zhao

  5. State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjia Xiang, Jiangsu, 210009, Nanjing, China

    Lianwen Qi & Ping Li

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  1. Wenhui Cui
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Correspondence to Jian Gao.

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Responsible Editor: John Di Battista.

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Cui, W., Li, L., Li, D. et al. Total glycosides of Yupingfeng protects against bleomycin-induced pulmonary fibrosis in rats associated with reduced high mobility group box 1 activation and epithelial–mesenchymal transition. Inflamm. Res. 64, 953–961 (2015). https://doi.org/10.1007/s00011-015-0878-x

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  • DOI: https://doi.org/10.1007/s00011-015-0878-x

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