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Journal of Traditional Chinese Medicine >

2025 , Vol. 45 >Issue 2: 376 - 384

DOI: https://doi.org/10.19852/j.cnki.jtcm.2025.02.012

Original articles

Network pharmacology approach to unveiling the mechanism of berberine in the amelioration of morphine tolerance

  • Shuai HAN ,
  • Zhikang Du ,
  • Zirui WANG ,
  • Tianfeng HUANG ,
  • Yali GE ,
  • Jianwen SHI ,
  • Ju GAO
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  • 1 Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou 225009, China
    2 Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou University, Yangzhou 225009, China
    3 Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou 225009, China
    4 Peking University People's Hospital, Qingdao 266111, China
    5 Women and Children's Hospital, Qingdao University, Qingdao 266034, China

Received date: 2023-12-15

  Accepted date: 2024-05-23

  Online published: 2025-03-10

Supported by

Natural Science Foundation-funded Project: Study on the Mechanism of Mechanical Stress Sensing Element Piezo Type Mechanosensitive Ion Channel Component 2 Interacting with Nuclear Receptor Subfamily 4 Group A Member 2 Mediating Traumatic Brain Injury(82172190)

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Abstract

OBJECTIVE: To investigate the mechanism underlying the effect of the Huanglian decoction (黄连汤, HLD) on morphine tolerance (MT), using network pharmacology, and to verify these mechanisms in vitro and in vivo.

METHODS: Available biological data on each drug in the HLD were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. The target proteins of MT were retrieved from the GeneCards, PharmGkb, Therapeutic Target Database, DrugBank, and Online Mendelian Inheritance in Man databases. Information regarding MT and the drug targets was compared to obtain overlapping elements. This information was imported into the Search Tool for the Retrieval of Interacting Genes/Proteins platform to obtain a protein-protein interaction network diagram. Then, a “component-target” network diagram was constructed using screened drug components and target information, viaCytoscape (Institute for Systems Biology, Seattle, WA, USA). The database for annotation, visualization, and integrated discovery was used for Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathways analyses. Pathway information predicted by network pharmacology was verified using animal studies and cell experiments.

RESULTS: Network pharmacology analysis identified 22 active compounds of HLD and revealed that HLD partially ameliorated MT by modulating inflammatory, apoptosis, and nuclear factor kappa B (NF-κB) signaling pathways. Berberine (BBR), one of the main components of HLD, inhibited the development of MT in mice. BBR reduced cell viability while increasing B-cell lymphoma 2 (Bcl-2) protein expression and decreasing CD86, NF-κB, Bax, and Caspase-3 protein expression in brain vascular 2 (BV2) mcroglia cells treated with morphine. Additionally, BBR contributed to a reduction in pro-inflammatory cytokine release and apoptotic cell number.

CONCLUSIONS: BBR, a key component of HLD, effectively suppressed microglial activation and neuro-inflammation by regulating the NF-κB and apoptosis signaling pathways, thereby delaying MT. This study offers a novel approach to enhance the clinical analgesic efficacy of morphine.

Key words： microglia; berberine; network pharmacology; NF-kappa B; morphine tolerance; Huanglian decoction

Cite this article

Shuai HAN , Zhikang Du , Zirui WANG , Tianfeng HUANG , Yali GE , Jianwen SHI , Ju GAO . Network pharmacology approach to unveiling the mechanism of berberine in the amelioration of morphine tolerance[J]. Journal of Traditional Chinese Medicine, 2025 , 45(2) : 376 -384 . DOI: 10.19852/j.cnki.jtcm.2025.02.012

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