Effect of matrine in MAC-T cells and their transcriptome analysis: A basic study

PLoS One. 2023 Jan 27;18(1):e0280905. doi: 10.1371/journal.pone.0280905. eCollection 2023.

Abstract

Matrine, an alkaloid derived from herbal medicine, has a wide range of biological activities, including antibacterial. Matrine was toxic to multiple cells at high concentrations. Bovine mammary epithelial cells (MAC-T) could be used as model cells for cow breast. Matrine was a feasible option to replace antibiotics in the prevention or treatment of mastitis against the background of prohibiting antibiotics, but the safe concentration of matrine on MAC-T cells and the mechanism of action for matrine at different concentrations were still unclear. In this study, different concentrations of matrine (0.5, 1, 1.5, 2, 2.5 and 3 mg/mL) were used to treat MAC-T cells for various time periods (4, 8, 12, 16 and 24 h) and measure their lactic dehydrogenase (LDH). And then the optimal doses (2 mg/mL) were chosen to detect the apoptosis at various time periods by flow cytometry and transcriptome analysis was performed between the control and 2 mg/mL matrine-treated MAC-T cells for 8 hours. The results showed that matrine was not cytotoxic at 0.5 mg/mL, but it was cytotoxic at 1~3 mg/mL. In addition, matrine induced apoptosis in MAC-T cells at 2 mg/mL and the proportion of apoptosis cells increases with time by flow cytometry. RNA-seq analysis identified 1645 DEGs, 676 of which were expressed up-regulated and 969 were expressed down-regulated. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated the following pathways were linked to matrine-induced toxicity and apoptosis, including cytokine-cytokine receptor interaction pathway, viral protein interaction with cytokine and cytokine receptor, P53 and PPAR pathway. We found 7 DEGs associated with matrine toxicity and apoptosis. This study would provide a basis for the safety of matrine in the prevention or treatment of mastitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents* / pharmacology
  • Apoptosis
  • Cattle
  • Cytokines / pharmacology
  • Female
  • Matrines
  • Quinolizines / pharmacology
  • Quinolizines / therapeutic use
  • T-Lymphocytes
  • Transcriptome*

Substances

  • Matrines
  • Antineoplastic Agents
  • Cytokines
  • Quinolizines

Grants and funding

This work was supported by the National Natural Science Foundation of China (Grant numbers No. 32060822 and No. 81960385), the Subject Construction Funding of Gansu Agricultural University, Gansu Province, China (Grant numbers GSAU-XKJS-2018-074) and Key Research and Development Project Plan of Gansu Provincial Science and Technology Department (Grant numbers 18YF1NA077). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.