# Pelubiprofen and Shinbaro: a therapeutic approach for osteoarthritis in a murine medial meniscus destabilization model

## TL;DR

Combining pelubiprofen and Shinbaro capsules may offer a safer and more effective treatment for osteoarthritis in mice.

## Contribution

The study introduces a novel combination therapy for osteoarthritis using pelubiprofen and Shinbaro capsules.

## Key findings

- Combination treatment improved cell viability and reduced inflammation more effectively than individual treatments.
- The combination significantly reduced cartilage degradation and improved joint function in mice.
- Key markers of healthy cartilage were upregulated, while matrix degradation markers were reduced.

## Abstract

Current osteoarthritis treatments can cause serious long-term side effects, and Shinbaro capsules have limited efficacy when used alone. We aimed to determine whether combining pelubiprofen and Shinbaro capsules could offer a more effective and safer treatment strategy for osteoarthritis.

Primary chondrocytes treated with interleukin-1β were assessed under different conditions: Shinbaro capsules (200 μg/mL), pelubiprofen (25/50 µM), and Shinbaro capsules + pelubiprofen (200 μg/mL and 25 μM, respectively). Male C57BL/6 mice underwent medial meniscus destabilization surgery to induce osteoarthritis and were treated five times a week for 8 weeks with either a vehicle control (saline), Shinbaro capsules alone (100 mg/kg), pelubiprofen alone (1.5/4.5 mg/kg), or Shinbaro capsules + pelubiprofen (100 mg/kg and 1.5 mg/kg, respectively).

Shinbaro capsules + pelubiprofen significantly improved cell viability, inhibited nitric oxide production and lactate dehydrogenase activity, and reduced pro-inflammatory cytokine production more effectively than the individual treatments. Alcian blue staining showed a notable increase in expression intensity with Shinbaro capsules + pelubiprofen. In treated mice, combination treatment significantly reduced the hyaline cartilage/calcified cartilage ratio and synovitis scores, improved the Osteoarthritis Research Society International scores and subchondral bone plate thickness, and enhanced collagen regeneration. Key markers of healthy cartilage and growth plate activity were significantly upregulated, whereas markers involved in cartilage matrix degradation were markedly reduced with Shinbaro capsules + pelubiprofen. Behavioral tests showed significant improvements in pain sensitivity and joint function with combination treatment.

Shinbaro capsules + pelubiprofen effectively preserve chondrocytes, reduce inflammation, and alleviate osteoarthritis symptoms through synergistic mechanisms, making it a promising therapeutic strategy for osteoarthritis management.

Illustration depicting the process of DMM-induced osteoarthritis in C57BL/6 mice and the effects of combination treatment (SBR + Pel). The top section shows cartilage degeneration, inflammation, and pain with increased iNOS, CD68, Adamts5, MMP3, MMP13, and collagen X, and decreased arginase 1, Sox9, Col2a1, and aggrecan. The bottom section, after treatment, indicates improved cartilage integrity, anti-inflammation, and pain relief.