Integrating bioinformatics with pharmacological evaluation for illustrating the action mechanism of herbal formula Jiao'e mixture in suppressing lung carcinoma

J Ethnopharmacol. 2021 Dec 5:281:114513. doi: 10.1016/j.jep.2021.114513. Epub 2021 Aug 13.

Abstract

Ethnopharmacological relevance: Lung carcinoma (LC) is not only a kind of disease that seriously threatens human life but also an intractable problem in modern medicine. Jiao'e Mixture (JEM) is an innovative Chinese medicine formula with Chinese patent, which is composed of two herbal extracts with a specific ratio-zedoary turmeric oil and medicinal Zanthoxylum bungeanum Maxim(Z. bungeanum Maxim) seeds oil (ZMSO). Zedoary turmeric oil is extracted from dried rhizomes of Curcuma wenyujin Y.H.Chen et C. Ling, which has been reported have an anti-cancer effects. Medicinal ZMSO is a by-product of Z. bungeanum Maxim, refined from kernel shell separation, modern cold soaking and refining technology; JEM is used to treat Lung carcinoma (LC) patients in folk for many years. However, its therapeutic mechanisms for treating LC have not been fully explored.

Aim of the study: The purpose of this study was to explore the therapeutic mechanisms of JEM for treating LC.

Materials and methods: The action mechanism of JEM in LC treatment was analysed by comprehensive network pharmacology approach combined with experimental validation (in vivo and in vitro).

Results: Seventeen active compounds and 457 related targets were collected from the HERB, TCMSP, and Swiss Target Prediction platforms. Nine hundred and thirty-eight LC related targets were obtained from Gene Cards and OMIM databases. Finally, 140 overlapping targets were obtained, which representing the target of JEM in LC treatment. The pathway analysis showed that PI3K-AKT could be a potential pathway for JEM in LC treatment. In vivo results presented that JEM had a good effect in inhibiting the growth of LC tumour cells with high efficacy and low toxicity. In vitro experiments validated that JEM had inhibited LC cells' proliferation, migration and invasion, and had induced cell apoptosis mainly via PI3K/Akt signalling pathways.

Conclusion: The anti-LC activity of JEM might via regulating the PI3K-AKT signalling pathways.This study may provide further evidence for the potential use of JEM in LC treatment.

Keywords: Apoptosis; Jiao'e mixture; Lung carcinoma; Network pharmacology; PI3K/AKT.

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Antineoplastic Agents, Phytogenic / therapeutic use*
  • Apoptosis / drug effects
  • Cell Line
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Computational Biology
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phytochemicals / pharmacology
  • Phytochemicals / therapeutic use
  • Proto-Oncogene Proteins c-akt / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Wound Healing / drug effects

Substances

  • Antineoplastic Agents, Phytogenic
  • Phytochemicals
  • Proto-Oncogene Proteins c-bcl-2
  • Proto-Oncogene Proteins c-akt