18β-Glycyrrhetinic acid inhibits the apoptosis of cells infected with rotavirus SA11 via the Fas/FasL pathway

Pharm Biol. 2021 Dec;59(1):1098-1105. doi: 10.1080/13880209.2021.1961821.

Abstract

Context: 18β-Glycyrrhetinic acid (18β-GA), a pentacyclic triterpenoid saponin metabolite of glycyrrhizin, exhibits several biological activities.

Objective: We investigated the effects of 18β-GA on MA104 cells infected with rotavirus (RV) and its potential mechanism of action.

Materials and methods: Cell Counting Kit-8 was used to assess tissue culture infective dose 50 (TCID50) and 50% cellular cytotoxicity (CC50) concentration. MA104 cells infected with RV SA11 were treated with 18β-GA (1, 2, 4, and 8 μg/mL, respectively). Cytopathic effects were observed. The virus inhibition rate, concentration for 50% of maximal effect (EC50), and selection index (SI) were calculated. Cell cycle, cell apoptosis, and mRNA and protein expression related to the Fas/FasL pathway were detected.

Results: TCID50 of RV SA11 was 10-4.47/100 µL; the CC50 of 18β-GA on MA104 cells was 86.92 µg/mL. 18β-GA showed significant antiviral activity; EC50 was 3.14 μg/mL, and SI was 27.68. The ratio of MA104 cells infected with RV SA11 in the G0/G1 phase and the G2/M phase decreased and increased, respectively, after 18β-GA treatment. 18β-GA significantly induced apoptosis in the infected cells. Furthermore, after 18β-GA treatment, the mRNA and protein expression levels of Fas, FasL, caspase 3, and Bcl-2 decreased, whereas the expression levels of Bax increased.

Discussion and conclusions: The study demonstrates that 18β-GA may be a promising candidate for the treatment of RV SA11 infection and provides theoretical support for the clinical development of glycyrrhizic acid compounds for the treatment of RV infection.

Keywords: MA104 cells; cell cycle; rotavirus infection.

Publication types

  • Retracted Publication

MeSH terms

  • Animals
  • Antiviral Agents / administration & dosage
  • Antiviral Agents / pharmacology*
  • Apoptosis / drug effects
  • Cell Cycle / drug effects
  • Cell Line
  • Dose-Response Relationship, Drug
  • Fas Ligand Protein / metabolism
  • Glycyrrhetinic Acid / administration & dosage
  • Glycyrrhetinic Acid / analogs & derivatives*
  • Glycyrrhetinic Acid / pharmacology
  • Haplorhini
  • RNA, Messenger / metabolism
  • Rotavirus / drug effects*
  • Rotavirus Infections / drug therapy*
  • Rotavirus Infections / virology
  • fas Receptor / metabolism

Substances

  • Antiviral Agents
  • Fas Ligand Protein
  • RNA, Messenger
  • fas Receptor
  • 18alpha-glycyrrhetinic acid
  • Glycyrrhetinic Acid

Grants and funding

Our study was supported by National Natural Science Foundation of China Youth Fund [No. 81704038, No. 81904128], and Shandong Post-doctoral Innovation Plan [No. 202003069].