Disclaimer: This summary is provided for informational purposes only and is based on a press release issued by Higher Education Press summarizing a scientific article published in the journal “Engineering” under https://doi.org/10.1016/j.eng.2025.10.029.

Summary

Researchers have investigated obakulactone (OL), a naturally occurring compound derived from Phellodendri cortex, as a potential therapeutic approach for rheumatoid arthritis (RA). The preclinical study found that OL reduced joint inflammation and tissue damage in an animal model while also influencing immune responses and fatty acid metabolism.

The researchers identified acyl-CoA thioesterase 1 (ACOT1) as a direct molecular target of obakulactone. OL promoted the degradation of ACOT1 through the ubiquitin–proteasome system, which affected downstream metabolic and inflammatory processes. In particular, the treatment helped normalize disturbances in unsaturated fatty acids, including pathways involving arachidonic, linoleic and α-linolenic acids.

Experiments also indicated that OL can suppress abnormal activity of rheumatoid arthritis synovial fibroblasts and reduce inflammatory signaling. The proposed mechanism involves regulation of the ACOT1/SCD1 axis and downstream JAK–STAT and PI3K–AKT signaling pathways. These findings point to ACOT1 and altered fatty acid metabolism as potential targets for future rheumatoid arthritis therapies.

The results are preclinical, based on experiments in rats and isolated cells. Further research will therefore be required to establish whether obakulactone is safe and effective in humans.