Jiedu-Quyu-Ziyin Fang (JQZF) inhibits the proliferation and activation of B cells in MRL/lpr mice via modulating the AKT/mTOR/c-Myc signaling pathway

J Ethnopharmacol. 2023 Oct 28:315:116625. doi: 10.1016/j.jep.2023.116625. Epub 2023 May 24.

Abstract

Ethnopharmacological relevance: Jiedu-Quyu-Ziyin Fang (JQZF) is a new herbal formula improved based on "Sheng Ma Bie Jia Tang" in the Golden Chamber, has been proved to be effective in the treatment of SLE. The ability of JQZF to prevent lymphocyte growth and survival has been demonstrated in earlier investigations. However, the specific mechanism of JQZF on SLE has not been fully investigated.

Aim of the study: To reveal the potential mechanisms of JQZF inhibiting B cell proliferation and activation in MRL/lpr mice.

Materials and methods: MRL/lpr mice were treated with low-dose, high-dose JQZF and normal saline for 6 weeks. The effect of JQZF on disease improvement in MRL/lpr mice was studied using enzyme-linked immunosorbent assay (ELISA), histopathological staining, serum biochemical parameters and urinary protein levels. The changes of B lymphocyte subsets in the spleen were analyzed by flow cytometry. The contents of ATP and PA in B lymphocytes from the spleens of mice were determined by ATP content assay kit and PA assay kit. Raji cells (a B lymphocyte line) were selected as the cell model in vitro. The effects of JQZF on the proliferation and apoptosis of B cells were detected by flow cytometry and CCK8. The effect of JQZF on the AKT/mTOR/c-Myc signaling pathway in B cells were detected via western blot.

Results: JQZF, especially at high dose, significantly improved the disease development of MRL/lpr mice. Flow cytometry results showed that JQZF affected the proliferation and activation of B cells. In addition, JQZF inhibited the production of ATP and PA in B lymphocytes. In vitro cell experiments further confirmed that JQZF can inhibit Raji proliferation and promote cell apoptosis through AKT/mTOR/c-Myc signaling pathway.

Conclusion: JQZF may affect the proliferation and activation of B cells by inhibiting the AKT/mTOR/c-Myc signaling pathway.

Keywords: AKT; B cell; Jiedu-Quyu-Ziyin Fang; Systemic lupus erythematosus; c-Myc; mTOR.

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • B-Lymphocytes
  • Cell Proliferation
  • Lupus Erythematosus, Systemic*
  • Mice
  • Mice, Inbred MRL lpr
  • Proto-Oncogene Proteins c-akt / metabolism
  • Proto-Oncogene Proteins c-myc / metabolism
  • Proto-Oncogene Proteins c-myc / pharmacology
  • Signal Transduction*
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Proto-Oncogene Proteins c-akt
  • Proto-Oncogene Proteins c-myc
  • TOR Serine-Threonine Kinases
  • Adenosine Triphosphate