Integrated Network Pharmacology Analysis and In Vitro Validation Revealed the Potential Active Components and Underlying Mechanistic Pathways of Herba Patriniae in Colorectal Cancer

Molecules. 2021 Oct 5;26(19):6032. doi: 10.3390/molecules26196032.

Abstract

Herba Patriniae (HP) are medicinal plants commonly used in colorectal cancer (CRC) patients. In this study, network pharmacology was used to predict the active components and key signaling pathways of HP in CRC. Patrinia heterophylla, one type of HP, was chosen for validation of the network pharmacology analysis. The phytochemical profile of Patrinia heterophylla water extract (PHW) was determined by UHPLC-MS. MTT, RT-PCR, and Western blot assays were performed to evaluate the bioactivities of PHW in colon cancer cells. Results showed that 15 potentially active components of HP interacted with 28 putative targets of CRC in the compound-target network, of which asperglaucide had the highest degree. Furthermore, the ErbB signaling pathway was identified as the pathway mediated by HP with the most potential against CRC. Both RT-PCR and Western blot results showed that PHW significantly downregulated the mRNA and protein levels of EGFR, PI3K, and AKT in HCT116 cells. Asperglaucide, present in PHW, exhibited an anti-migratory effect in HCT116 cells, suggesting that it could be an active component of PHW in CRC treatment. In conclusion, this study has provided the first scientific evidence to support the use of PHW in CRC and paved the way for further research into the underlying mechanisms of PHW against CRC.

Keywords: CRC; ErbB signaling pathway; FoxO signaling pathway; Herba Patriniae; Patrinia heterophylla; colorectal cancer; network pharmacology.

MeSH terms

  • Adenocarcinoma / drug therapy
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Cell Movement / drug effects
  • Colorectal Neoplasms / drug therapy*
  • Dipeptides / pharmacology
  • Drug Discovery / methods
  • Drugs, Chinese Herbal / chemistry*
  • Drugs, Chinese Herbal / pharmacology*
  • ErbB Receptors / metabolism
  • Forkhead Box Protein O1 / metabolism
  • Gene Expression Regulation, Neoplastic
  • HCT116 Cells
  • Humans
  • Medicine, Chinese Traditional
  • Patrinia / chemistry
  • Plant Extracts / chemistry*
  • Plant Extracts / pharmacology*
  • Plants, Medicinal / chemistry
  • Signal Transduction / drug effects*

Substances

  • Antineoplastic Agents
  • Dipeptides
  • Drugs, Chinese Herbal
  • FOXO1 protein, human
  • Forkhead Box Protein O1
  • Plant Extracts
  • N-benzoylphenylalanylphenylalinol acetate
  • EGFR protein, human
  • ErbB Receptors