# Corosolic acid alleviates rheumatoid arthritis by down regulation of the NF-κB/PI3K/AKT signaling pathway

## TL;DR

Corosolic acid may help treat rheumatoid arthritis by reducing inflammation through a specific signaling pathway.

## Contribution

This study reveals that corosolic acid alleviates rheumatoid arthritis by inhibiting the NF-κB/PI3K/AKT signaling pathway.

## Key findings

- Corosolic acid reduced secretion of inflammatory cytokines TNF-α, IL-1β, and IL-6 in synovial cells.
- CRA downregulated phosphorylation of NF-κB and PI3K/AKT pathways in vitro and in vivo.
- In CIA rats, CRA decreased arthritis scores, synovial hyperplasia, and bone erosion after 21 days.

## Abstract

Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovitis. Existing treatments for RA have serious side effects. Corosolic acid (CRA) is a natural pentacyclic triterpenoid compound with anti-inflammatory potential. However, the effect of CRA on inflammation, its possible mechanism of action, and potential therapeutic effect on RA are not well understood. This study explored the CRA mechanism of treatment action on RA by evaluating the NF-κB/PI3K/AKT signaling pathway in vitro and in vivo. In vitro, fibroblast like synovial cells (FLS) from collagen induced arthritis (CIA) rats were assessed. ELISA, western blot, and immunofluorescence techniques demonstrated CRA (6 µg/mL) to significantly inhibit FLS secretion of TNF-α, IL-1β, and IL-6, as well as downregulate the phosphorylation of NF-κB and PI3K/AKT pathways. Inhibition experiments demonstrated that NF-κB activation was upstream of PI3K/AKT activation. In vivo, after 21 days of oral administration of CRA (10 mg/kg) to CIA rats, the arthritis score, organ index, and serum inflammatory factor levels were significantly decreased. Histopathologic analysis and Micro-CT showed that CRA reduced synovial hyperplasia and bone erosion. These results indicated that CRA exerted anti-inflammatory effects by inhibition of the NF-κB/PI3K/AKT signaling pathway, providing a potential new treatment strategy for RA patients.

The online version contains supplementary material available at 10.1038/s41598-026-46070-3.