2. Academic Validation
  3. Licoricesaponin G2 ameliorates bleomycin-induced pulmonary fibrosis via targeting TNF-α signaling pathway and inhibiting the epithelial-mesenchymal transition

Licoricesaponin G2 ameliorates bleomycin-induced pulmonary fibrosis via targeting TNF-α signaling pathway and inhibiting the epithelial-mesenchymal transition

  • Front Pharmacol. 2024 Sep 5:15:1437231. doi: 10.3389/fphar.2024.1437231.
Jing Ma # 1,  Lu Ding # 2 3,  Xiaoyu Zang # 1,  Ruonan Wei 4,  Yingying Yang 5,  Wei Zhang 6,  Hang Su 2,  Xueyan Li 7,  Min Li 7,  Jun Sun 1,  Zepeng Zhang 2 3,  Zeyu Wang 2,  Daqing Zhao 2,  Xiangyan Li 2,  Linhua Zhao 8,  Xiaolin Tong 1 8
Affiliations

Affiliations

  • 1 College of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, China.
  • 2 Key Laboratory of Active Substances and Biological Mechanisms of Ginseng Efficacy, Jilin Provincial Key Laboratory of Bio-Macromolecules of Chinese Medicine, Ministry of Education, Northeast Asia Research Institute of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, China.
  • 3 Research Center of Traditional Chinese Medicine, College of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, China.
  • 4 Shiyan Hospital of Traditional Chinese Medicine, Shiyan, China.
  • 5 China-Japan Friendship Hospital, National Center for Integrated Traditional Chinese and Western Medicine, Beijing, China.
  • 6 School of Basic Medicine, Gansu University of Traditional Chinese Medicine, Lanzhou, China.
  • 7 College of Integrated Traditional Chinese and Western Medicine, Changchun University of Chinese Medicine, Changchun, China.
  • 8 Institute of Metabolic Diseases, Guang' Anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
  • # Contributed equally.
PMID: 39301567 DOI: 10.3389/fphar.2024.1437231
Abstract

Background: Pulmonary fibrosis (PF) emerges as a significant pulmonary sequelae in the convalescent phase of coronavirus disease 2019 (COVID-19), with current strategies neither specifically preventive nor therapeutic. Licoricesaponin G2 (LG2) displays a spectrum of natural activities, including Antibacterial, anti-inflammatory, and antioxidant properties, and has been effectively used in treating various respiratory conditions. However, the potential protective effects of LG2 against PF remain underexplored.

Methods: Network analysis and molecular docking were conducted in combination to identify the core targets and pathways through which LG2 acts against PF. In the model of bleomycin (BLM)-induced C57 mice and transforming growth factor-β1 (TGF-β1)-induced A549 and MRC5 cells, techniques such as western blot (WB), quantitative Real-Time PCR (qPCR), Immunohistochemistry (IHC), Immunofluorescence (IF), and Transwell migration assays were utilized to analyze the expression of Epithelial-mesenchymal transition (EMT) and inflammation proteins. Based on the analysis above, we identified targets and potential mechanisms underlying LG2's effects against PF.

Results: Network analysis has suggested that the mechanism by which LG2 combats PF may involve the TNF-α pathway. Molecular docking studies have demonstrated a high binding affinity of LG2 to TNF-α and MMP9. Observations from the study indicated that LG2 may mitigate PF by modulating EMT and extracellular matrix (ECM) remodeling. It is proposed that the therapeutic effect is likely arises from the inhibition of inflammatory expression through regulation of the TNF-α pathway.

Conclusion: LG2 mitigates PF by suppressing TNF-α signaling pathway activation, modulating EMT, and remodeling the ECM. These results provide compelling evidence supporting the use of LG2 as a potential natural therapeutic agent for PF in clinical trials.

Keywords

TNF-α signaling pathway; epithelial-mesenchymal transition; licoricesaponin G2; network analysis; pulmonary fibrosis.

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