Decoding the key compounds and mechanism of Shashen Maidong decoction in the treatment of lung cancer

Jieqi Cai, Yupeng Chen, Kexin Wang, Yi Li, Jie Wu, Hailang Yu, Qingping Li, Qi Wu, Wei Meng, Handuo Wang, Aiping Lu, Mianbo Huang*, Genxia Wei*, Daogang Guan*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

2 Citations (Scopus)

Abstract

Background: Lung cancer is a malignant tumour with the fastest increase in morbidity and mortality around the world. The clinical treatments available have significant side effects, thus it is desirable to identify alternative modalities to treat lung cancer. Shashen Maidong decoction (SMD) is a commonly used traditional Chinese medicine (TCM) formula for treating lung cancer in the clinic. While the key functional components (KFC) and the underlying mechanisms of SMD treating lung cancer are still unclear. 

Methods: We propose a new integrated pharmacology model, which combines a novel node-importance calculation method and the contribution decision rate (CDR) model, to identify the KFC of SMD and to deduce their mechanisms in the treatment of lung cancer. 

Results: The enriched effective Gene Ontology (GO) terms selected from our proposed node importance detection method could cover 97.66% of enriched GO terms of reference targets. After calculating CDR of active components in key functional network, the first 82 components covered 90.25% of the network information, which were defined as KFC. 82 KFC were subjected to functional analysis and experimental validation. 5–40 μM protocatechuic acid, 100–400 μM paeonol or caffeic acid exerted significant inhibitory activity on the proliferation of A549 cells. The results show that KFC play an important therapeutic role in the treatment of lung cancer by targeting Ras, AKT, IKK, Raf1, MEK, and NF-κB in the PI3K-Akt, MAPK, SCLC, and NSCLC signaling pathways active in lung cancer. 

Conclusions: This study provides a methodological reference for the optimization and secondary development of TCM formulas. The strategy proposed in this study can be used to identify key compounds in the complex network and provides an operable test range for subsequent experimental verification, which greatly reduces the experimental workload.

Original languageEnglish
Article number158
Number of pages15
JournalBMC Complementary Medicine and Therapies
Volume23
DOIs
Publication statusPublished - 15 May 2023

Scopus Subject Areas

  • Complementary and alternative medicine

User-Defined Keywords

  • Shashen Maidong decoction
  • Lung cancer
  • Network analysis
  • Key functional networks
  • Contribution decision rate

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