2. Academic Validation
  3. Identification of key anti-pulmonary fibrosis components in Hyssopus cuspidatus Boriss. and its mechanism exploration

Identification of key anti-pulmonary fibrosis components in Hyssopus cuspidatus Boriss. and its mechanism exploration

  • Phytomedicine. 2025 Dec 5:150:157676. doi: 10.1016/j.phymed.2025.157676.
Yuan-Yuan Zhao 1,  Ze-Bin Weng 2,  Neng-Yu Chen 1,  Can Cui 1,  Da-Jun Jiang 3,  Gulixianayi Ainiwaer 3,  Bin-Yan Lin 4,  Zheng-Meng Jiang 5,  E-Hu Liu 6
Affiliations

Affiliations

  • 1 State Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture / School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China; Laboratory of Herbal Active Compound Omics and Target Identification / School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
  • 2 State Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture / School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China; Laboratory of Herbal Active Compound Omics and Target Identification / School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: [email protected].
  • 3 Xinjiang Uyghur Pharmaceutical Co., Ltd., Urumqi 830026, China.
  • 4 State Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture / School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China; Laboratory of Herbal Active Compound Omics and Target Identification / School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: [email protected].
  • 5 State Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture / School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China; Laboratory of Herbal Active Compound Omics and Target Identification / School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: [email protected].
  • 6 State Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture / School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China; Laboratory of Herbal Active Compound Omics and Target Identification / School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: [email protected].
PMID: 41389405 DOI: 10.1016/j.phymed.2025.157676
Abstract

Background: Hyssopus cuspidatus Boriss. (HC) is a renowned herbal medicine commonly used in treating respiratory diseases. However, its potential in alleviating pulmonary fibrosis (PF) remains unexplored.

Purpose: This study aims to investigate the anti-PF mechanisms of HC and identify activity-guided biomarkers to improve its quality standards.

Methods: The anti-fibrotic effects of HC were evaluated using TGF-β1-induced MRC-5 cell fibrosis and bleomycin-induced mouse PF models. In vitro, GSK-3β was silenced using shRNA or the inhibitor lithium chloride (LiCl), while active GSK-3β was overexpressed to validate the underlying mechanisms. Chemical profiling and spectrum-effect relationship analysis were conducted to identify key anti-fibrotic constituents.

Results: HC alleviates PF by ameliorating inflammatory injury, reducing extracellular matrix (ECM) deposition, and suppressing epithelial-mesenchymal transition (EMT). The underlying mechanism involves modulation of the GSK-3β/β-catenin pathway, specifically through decreased phosphorylation of p-GSK-3β at Ser9, which enhances phosphorylation of β-catenin at Ser33/37/Thr41, thereby promoting its ubiquitination and subsequent degradation. Chemical analysis tentatively identified 88 compounds, including 38 newly reported in HC, with rosmarinic acid (RA) identified as a key activity-guided quality marker for the first time.

Conclusions: The therapeutic potential of HC in pulmonary fibrosis is mainly attributed to its regulation of the GSK-3β/β-catenin pathway, with RA serving as a key bioactive component.

Keywords

GSK-3β/β-catenin signaling pathway; Hyssopus cuspidatus boriss.; Pulmonary fibrosis; Spectrum-effect relationship.

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