# Protective Effects of Lindera obtusiloba Leaf Extract on Osteoarthritis in Mouse Primary Chondrocytes and a Medial Meniscus Destabilization Model

## TL;DR

This study shows that Lindera obtusiloba leaf extract can reduce osteoarthritis symptoms in mice by lowering inflammation and cartilage damage.

## Contribution

The study demonstrates LO leaf extract's novel anti-osteoarthritic effects in both cell and animal models.

## Key findings

- LO leaf extract reduced OA-related catabolic factors and inflammation in chondrocytes.
- In mice, LO extract decreased cartilage degradation and subchondral bone changes.
- LO extract lowered systemic pro-inflammatory cytokine levels in OA models.

## Abstract

Osteoarthritis (OA) is a degenerative joint disorder characterized by progressive articular cartilage degradation, leading to pain, stiffness, and impaired mobility. This study investigated the anti-osteoarthritic effects of Lindera obtusiloba (LO) leaf extract in primary cultured chondrocytes and a mouse model of destabilization of the medial meniscus (DMM)-induced OA. Mouse primary chondrocytes were treated with IL-1β and various concentrations of LO leaf extract (50–150 μg/mL), and analyzed by RT-PCR, Western blotting, and ELISA. For the in vivo experiments, male C57BL/6 mice underwent DMM surgery and were administered LO leaf extract (50–200 mg/kg/day) for eight weeks, followed by micro-CT, histological, and immunohistochemical analyses. LO leaf extract exhibited no cytotoxicity in chondrocytes. In interleukin-1β-induced inflammatory chondrocytes, LO leaf extract significantly suppressed the expression of OA-associated catabolic factors, including cyclooxygenase-2 (Cox-2), matrix metalloproteinases (MMP3 and MMP13), and phosphorylated nuclear factor-kappa B (NF-κB). It also reduced the production of destructive mediators, such as prostaglandin E2 (PGE2) and collagenase, in a dose-dependent manner. In vivo, LO leaf extract-treated mice demonstrated significant reductions in articular cartilage degradation, subchondral bone sclerosis, and the expression of catabolic and inflammatory mediators. Additionally, LO leaf extract administration significantly decreased systemic pro-inflammatory cytokine levels in DMM-induced mice. Collectively, these findings indicate that LO leaf extract attenuates OA progression by suppressing both local and systemic inflammatory responses, supporting its potential as a natural therapeutic agent for the prevention and treatment of OA.