Heilaohuacid G, a new triterpenoid from Kadsura coccinea inhibits proliferation, induces apoptosis, and ameliorates inflammation in RA-FLS and RAW 264.7 cells via suppressing NF-��B pathway.

Abstract

Heilaohu, the roots of Kadsura coccinea, has been used in Tujia ethnomedicine to treat rheumatic arthritis (RA). Heilaohuacid G (1), a new 3,4-seco-lanostane type triterpenoid isolated from the ethanol extract of Heilaohu, whose structure was determined using HR-ESI-MS data, NMR spectroscopic analyses, and ECD calculations. In this study, our purpose is to elucidate the mechanisms of Heilaohuacid G in the treatment of RA by inhibited proliferation of rheumatoid arthritis-fibroblastoid synovial (RA-FLS) cells and inhibited the inflammatory reactions in LPS-induced RA-FLS and RAW 264.7 cell lines via inhibiting NF-κB pathway. The biological activity screening experiments indicated that Heilaohuacid G significantly inhibited proliferation of RA-FLS cells with IC50 value of 8.16 ± 0.47 μM. CCK-8 assay, ELISA, flow cytometry assay, and Western blot were used to measure the changes of cell viability, apoptosis, and the release of inflammatory cytokines. Heilaohuacid G was found not only induced RA-FLS cell apoptosis, but also inhibited the inflammatory reactions in LPS-induced RA-FLS and RAW 264.7 cell lines via inhibiting NF-κB pathway. Furthermore, Heilaohuacid G (p.o.) at doses of 3.0, 6.0, and 12.0 mg/kg and the ethanol extracts of Heilaohu (p.o.) at doses of 200, 400, and 800 mg/kg both were confirmed antiinflammatory effects on xylene-induced ear mice edema model.

• Authors: Yu-Pei Yang, Yu-Qing Jian, Yong-Bei Liu, Qing-Ling Xie, Huang-He Yu, Bin Wang, Bin Li, Cai-Yun Peng, Wei Wang
• Journal: Phytotherapy research : PTR (Phytother Res) Vol. 36 Issue 10 Pg. 3900-3910 (Oct 2022) ISSN: 1099-1573 [Electronic] England
• PMID: 36104304 (Publication Type: Journal Article)
• Copyright: © 2022 John Wiley & Sons Ltd.

Chemical References

• Cytokines
• Lipopolysaccharides
• NF-kappa B
• Plant Extracts
• Triterpenes
• Xylenes
• Ethanol

Topics

• Animals
• Apoptosis
• Arthritis, Rheumatoid (drug therapy, metabolism)
• Cell Proliferation
• Cells, Cultured
• Cytokines (metabolism)
• Ethanol (pharmacology)
• Fibroblasts (metabolism)
• Inflammation (drug therapy, metabolism)
• Kadsura
• Lipopolysaccharides (pharmacology)
• Mice
• NF-kappa B (metabolism)
• Osteoarthritis
• Plant Extracts (therapeutic use)
• RAW 264.7 Cells
• Rheumatic Fever (metabolism)
• Synovial Membrane
• Triterpenes (pharmacology, therapeutic use)
• Xylenes (metabolism, pharmacology, therapeutic use)