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‐𝜅B 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.

Triterpenes as Potential Drug Candidates for Rheumatoid Arthritis Treatment

“…Heilaohuacid G ( 19) is a new 3,4-seco-lanostane type triterpenoid isolated from the roots of Kadsura coccinea, a medicinal plant distributed in South China and used in Tujia ethnomedicine to treat RA [100]. Biological activity screening tests revealed that 19 inhibited the proliferation of RA FLSs in a concentration-dependent manner, with IC 50 values of 8.16 ± 0.47 µM [100].…”

“…Heilaohuacid G ( 19) is a new 3,4-seco-lanostane type triterpenoid isolated from the roots of Kadsura coccinea, a medicinal plant distributed in South China and used in Tujia ethnomedicine to treat RA [100]. Biological activity screening tests revealed that 19 inhibited the proliferation of RA FLSs in a concentration-dependent manner, with IC 50 values of 8.16 ± 0.47 µM [100]. Further studies showed that 19 induced RA FLS apoptosis and suppressed inflammatory responses in LPS-induced RA FLSs and macrophages (RAW264.7 cells) by inhibiting NF-κB signaling [100].…”

“…Biological activity screening tests revealed that 19 inhibited the proliferation of RA FLSs in a concentration-dependent manner, with IC 50 values of 8.16 ± 0.47 µM [100]. Further studies showed that 19 induced RA FLS apoptosis and suppressed inflammatory responses in LPS-induced RA FLSs and macrophages (RAW264.7 cells) by inhibiting NF-κB signaling [100].…”

“…A double-blind, phase 2 study (NCT03755258) to evaluate the safety, efficacy and pharmacokinetics of ginsenoside CK (32) tablets in RA patients started in China in March 2017. RA patients (n = 128) were randomly assigned ginsenoside CK tablets (100,200 or 300 mg) or placebo once daily, orally, for 12 weeks. However, the study was suspended after two years due to the high cost associated with manufacturing of 32, essentially dependent on Panax plants, extraction and biotransformation of ginsenosides.…”

Songorine modulates macrophage polarization and metabolic reprogramming to alleviate inflammation in osteoarthritis

“…The immense potential of natural products in treating various diseases, including OA, has been a continuous exploration. Notably, key findings from current research underscore the promising role of natural products in mitigating OA symptoms, potentially influencing macrophage behavior and inflammatory responses within the joint microenvironment (7,8). Crucially, alkaloids, widespread in nature (9), play a key role in Traditional Chinese Medicine's therapeutic effects, exhibiting significant anti-cancer, anti-inflammatory, and antioxidant activities (10)(11)(12).…”