A compound called obakulactone eased swelling and tissue damage in a rat model of rheumatoid arthritis and appeared to work by triggering the breakdown of a metabolic enzyme, ACOT1, researchers reported in the journal Engineering.
A natural compound called obakulactone (OL) reduced swelling and other signs of rheumatoid arthritis (RA) in rats, according to a report from Higher Education Press summarizing a study published in Engineering. (sciencedaily.com)
Researchers tested OL—a tetracyclic triterpenoid isolated from Phellodendri cortex—in rats with arthritis induced using complete Freund’s adjuvant (CFA). Animals received daily doses described as low (50 mg/kg/day), medium (100 mg/kg/day), or high (200 mg/kg/day) for 21 days. The treatment reduced joint swelling and helped restore the structure of cartilage and the synovium, the tissue lining the inside of joints, the report said. It also improved abnormal changes in immune organs including the thymus and spleen. (sciencedaily.com)
In joint tissue, OL was reported to reduce elevated levels of CD3+ T cells and CD68+ macrophages. The researchers also found evidence that OL shifted macrophages away from a pro-inflammatory “M1” profile (CD86) and toward an anti-inflammatory “M2” profile (CD206), and limited the development of CD4+ T cells into Th17 cells. (sciencedaily.com)
Blood tests in the animal model showed dose-dependent reductions in inflammatory molecules including IL‑1β, IL‑6, IL‑17 and TNF‑α, along with decreases in several RA-related markers, including rheumatoid factor (RF), CCP-Ab, C-reactive protein (CRP) and MMP‑3. (sciencedaily.com)
To probe mechanism, the researchers used “multiomics” approaches—described as metabolomics, MALDI mass spectrometry imaging, and proteomics—to assess changes linked to fatty-acid metabolism. They reported that RA disrupted the production and metabolism of multiple unsaturated fatty acids, and that OL helped correct abnormalities involving arachidonic acid, linoleic acid and α‑linolenic acid. (sciencedaily.com)
The report said several laboratory assays indicated OL binds directly to acyl coenzyme A thioesterase 1 (ACOT1). OL was also reported to promote ubiquitination-mediated proteasomal degradation of ACOT1, reducing levels of a downstream protein, stearoyl‑CoA desaturase‑1 (SCD1), and limiting activation of the JAK‑STAT and PI3K‑AKT signaling pathways in synovial fibroblasts. (sciencedaily.com)
The researchers described the findings as preclinical evidence that OL—or targeting ACOT1 and disturbed unsaturated fatty-acid metabolism—could represent a potential strategy for RA treatment. They cautioned that because the work was conducted in rats and isolated cells, further studies are needed to determine whether OL is safe and effective in humans. The report also described RA as a chronic systemic autoimmune disease affecting about 1% of people worldwide. (sciencedaily.com)
