1. Academic Validation
  2. Exploring Cistanche's therapeutic potential and molecular mechanisms in asthma treatment

Exploring Cistanche's therapeutic potential and molecular mechanisms in asthma treatment

  • Phytomedicine. 2024 Nov 15:136:156265. doi: 10.1016/j.phymed.2024.156265.
Jiliu Liu 1 Jie Gao 1 Anying Xiong 1 Guoping Li 1 Kai Zhong 2 Lingling Bai 1 Xiaolan Li 3 Qin Ran 1 Ying Xiong 4 Xiang He 5
Affiliations

Affiliations

  • 1 School of Medicine, Southwest Jiaotong University, Laboratory of Allergy and Precision Medicine, Chengdu Institute of Respiratory Health, Affiliated Hospital of Southwest Jiaotong University, the Third People's Hospital of Chengdu, Chengdu 610031, China; Department of Respiratory Medicine, Chengdu Third People's Hospital Branch of National Clinical Research Center for Respiratory Disease, Affiliated Hospital of ChongQing Medical University, Chengdu 610031, China.
  • 2 College of Biomass Science and Engineering, Sichuan University, Chengdu, China.
  • 3 School of Medicine, Southwest Jiaotong University, Laboratory of Allergy and Precision Medicine, Chengdu Institute of Respiratory Health, Affiliated Hospital of Southwest Jiaotong University, the Third People's Hospital of Chengdu, Chengdu 610031, China; Department of Respiratory Medicine, Chengdu Third People's Hospital Branch of National Clinical Research Center for Respiratory Disease, Affiliated Hospital of ChongQing Medical University, Chengdu 610031, China; National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Disease, State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510120, China.
  • 4 Department of Pulmonary and Critical Care Medicine, Sichuan Friendship Hospital, Chengdu 610000, China.
  • 5 School of Medicine, Southwest Jiaotong University, Laboratory of Allergy and Precision Medicine, Chengdu Institute of Respiratory Health, Affiliated Hospital of Southwest Jiaotong University, the Third People's Hospital of Chengdu, Chengdu 610031, China; Department of Respiratory Medicine, Chengdu Third People's Hospital Branch of National Clinical Research Center for Respiratory Disease, Affiliated Hospital of ChongQing Medical University, Chengdu 610031, China; National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Disease, State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510120, China. Electronic address: xiangge530@hotmail.com.
Abstract

Asthma, a prevalent chronic respiratory disease, is characterized by airway inflammation and hyperresponsiveness, significantly impacting global health. Current treatments, including corticosteroids, face limitations due to variable patient responses and side effects. This study explores the therapeutic potential of Cistanche, a traditional Chinese medicinal herb, in an asthmatic mouse model induced by house dust mites (HDM). We employed a multidisciplinary approach, including transcriptomics, mass spectrometry, Weighted Gene Co-expression Network Analysis (WGCNA), and experimental validation in animal and cellular models. Our findings demonstrate that Cistanche significantly attenuates airway hyperresponsiveness, cellular infiltration, and mucus hypersecretion in asthmatic mice. Transcriptomic analysis identified 643 differentially expressed genes (DEGs), with Cistanche treatment disrupting pathways associated with IL-4, IL-5, and eosinophils. Gene Set Enrichment Analysis (GSEA) revealed Cistanche's involvement in glucocorticoid processes, suggesting its potential as an alternative or complementary therapy to conventional glucocorticoids. Liquid Chromatography-High Resolution Mass Spectrometry (LCHRMS) analysis identified Pinoresinol 4-O-Beta-D-Glucopyranoside (PG) as a key active component of Cistanche, with targets predominantly associated with the PI3K-AKT pathway. WGCNA analysis of an asthma dataset identified the "skyblue" module as highly associated with asthma, with inducible nitric oxide synthase (iNOS) emerging as a core gene. Molecular docking confirmed a strong binding affinity between PG and iNOS, with Cistanche treatment down-regulating iNOS expression, suggesting a potential mechanism for its anti-inflammatory effects. In conclusion, Cistanche exhibits therapeutic effects in asthma by modulating immune responses and targeting key asthma-related genes and proteins. Our study provides novel insights into the treatment of asthma with Natural Products and highlights the potential of Cistanche as an alternative or complementary therapeutic agent. Further research is warranted to validate these findings and explore the integration of Cistanche into clinical asthma management.

Keywords

Asthma; Cistanche; Traditional Chinese medicine; Transcriptomics; WGCNA; iNOS.

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