2. Academic Validation
  3. Fu-Zheng-Tong-Luo formula promotes autophagy and alleviates idiopathic pulmonary fibrosis by controlling the Janus kinase 2/signal transducer and activator of transcription 3 pathway

Fu-Zheng-Tong-Luo formula promotes autophagy and alleviates idiopathic pulmonary fibrosis by controlling the Janus kinase 2/signal transducer and activator of transcription 3 pathway

  • J Ethnopharmacol. 2023 Oct 5:314:116633. doi: 10.1016/j.jep.2023.116633.
Xing Zhang 1,  Jie Su 2,  Jiacheng Lin 3,  Lujiong Liu 4,  Jiamin Wu 5,  Wenli Yuan 6,  Yibao Zhang 7,  Qi Chen 8,  Zi Jian Su 9,  Guihua Xu 10,  Meng Sun 11,  Yile Zhang 12,  Xuan Chen 13,  Wei Zhang 14
Affiliations

Affiliations

  • 1 Department of Pulmonary Diseases, ShuGuang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China. Electronic address: zhangxing2012@shutcm.edu.cn.
  • 2 School of Life Sciences and Biotechnology and State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, National Research Center for Translational Medicine, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, Shanghai, China. Electronic address: su.jie@sjtu.edu.cn.
  • 3 Central Laboratory, ShuGuang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China. Electronic address: linjc_sh@shutcm.edu.cn.
  • 4 Department of Pulmonary Diseases, ShuGuang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China. Electronic address: shantapeace@163.com.
  • 5 Department of Pulmonary Diseases, ShuGuang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China. Electronic address: 769520635@qq.com.
  • 6 Department of Nephrology Diseases, YueYang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China. Electronic address: 2732847214@qq.com.
  • 7 Department of Pulmonary Diseases, ShuGuang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China. Electronic address: iamir@aliyun.com.
  • 8 Department of Pulmonary Diseases, ShuGuang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China. Electronic address: chenqiywl@126.com.
  • 9 Department of Pulmonary Diseases, ShuGuang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China. Electronic address: szj_ddm@163.com.
  • 10 Department of Pulmonary Diseases, ShuGuang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China. Electronic address: noan9602@163.com.
  • 11 Department of Pulmonary Diseases, ShuGuang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China. Electronic address: gulik002@aliyun.com.
  • 12 Department of Pulmonary Diseases, ShuGuang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China. Electronic address: realsondragon@sina.com.
  • 13 Department of Pulmonary Diseases, ShuGuang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China. Electronic address: chen77xuan@aliyun.com.
  • 14 Department of Pulmonary Diseases, ShuGuang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China. Electronic address: zhangw1190a@sina.com.
PMID: 37207878 DOI: 10.1016/j.jep.2023.116633
Abstract

Ethnopharmacological relevance: Fu-Zheng-Tong-Luo (FZTL) formula is a Chinese herbal prescription which is used to treat idiopathic pulmonary fibrosis (IPF). We previously reported that the FZTL formula could improve IPF injury in rats; however, the mechanism remains unelucidated.

Aim of the study: To elucidate the effects and mechanisms of the FZTL formula on IPF.

Materials and methods: The bleomycin-induced pulmonary fibrosis rat model and transforming growth factor-β-induced lung fibroblast model were used. Histological changes and fibrosis formation were detected in the rat model after treatment with the FZTL formula. Furthermore, the effects of the FZTL formula on Autophagy and lung fibroblast activation were determined. Moreover, the mechanism of FZTL was explored using transcriptomics analysis.

Results: We observed that FZTL alleviated IPF injury in rats and inhibited inflammatory responses and fibrosis formation in rats. Moreover, it promoted Autophagy and inhibited lung fibroblast activation in vitro. Transcriptomics analysis revealed that FZTL regulates the Janus kinase 2 (JAK)/signal transducer and activator of the transcription 3 (STAT) signaling pathway. The JAK2/STAT3 signaling activator interleukin 6 inhibited the anti-fibroblast activation effect of the FZTL formula. Combined treatment with the JAK2 Inhibitor (AZD1480) and Autophagy inhibitor (3-methyladenine) did not enhance the antifibrotic effect of FZTL.

Conclusions: The FZTL formula can inhibit IPF injury and lung fibroblast activation. Its effects are mediated via the JAK2/STAT3 signaling pathway. The FZTL formula may be a potential complementary therapy for pulmonary fibrosis.

Keywords

Fu-zheng-Tong-Luo formula; Idiopathic pulmonary fibrosis; Janus kinase 2/signal transducer and activator of transcription 3; Traditional Chinese medicine.

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