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

AbstractCONTEXT:
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.
AuthorsXiaoyan Wang, Fang Xie, Xiaofeng Zhou, Ting Chen, Ye Xue, Wei Wang
JournalPharmaceutical biology (Pharm Biol) Vol. 59 Issue 1 Pg. 1098-1105 (Dec 2021) ISSN: 1744-5116 [Electronic] England
PMID34411493 (Publication Type: Journal Article, Retracted Publication)
Chemical References
  • Antiviral Agents
  • Fas Ligand Protein
  • RNA, Messenger
  • fas Receptor
  • 18alpha-glycyrrhetinic acid
  • Glycyrrhetinic Acid
Topics
  • Animals
  • Antiviral Agents (administration & dosage, pharmacology)
  • Apoptosis (drug effects)
  • Cell Cycle (drug effects)
  • Cell Line
  • Dose-Response Relationship, Drug
  • Fas Ligand Protein (metabolism)
  • Glycyrrhetinic Acid (administration & dosage, analogs & derivatives, pharmacology)
  • Haplorhini
  • RNA, Messenger (metabolism)
  • Rotavirus (drug effects)
  • Rotavirus Infections (drug therapy, virology)
  • fas Receptor (metabolism)

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