# The Preparation and Evaluation of Carvacrol-Added Hyaluronic Acid for Early Osteoarthritis Treatment

## TL;DR

This study explores a new treatment for early osteoarthritis by combining hyaluronic acid with carvacrol, a natural compound that reduces inflammation and protects cartilage.

## Contribution

The novel contribution is the development of a hyaluronic acid formulation with carvacrol that combats inflammation and preserves cartilage in early osteoarthritis.

## Key findings

- The HA-Carvacrol combination reduced inflammation and preserved extracellular matrix in chondrocytes.
- In a rat model, the treatment alleviated pain and preserved cartilage structure.
- The formulation shows dual functionality by combining lubrication and anti-inflammatory properties.

## Abstract

Osteoarthritis (OA) is a prevalent degenerative joint disease characterized by cartilage degradation, synovial inflammation, and subchondral bone remodeling, leading to chronic pain and reduced mobility. In early-stage OA, sustained oxidative stress and inflammation drive chondrocyte dysfunction and extracellular matrix (ECM) loss. Hyaluronic acid (HA), a key component of synovial fluid responsible for lubrication and viscoelasticity, is prone to enzymatic and oxidative degradation under inflammatory conditions, limiting its therapeutic effect. To address this, we developed an HA-based system incorporating the natural antioxidant and anti-inflammatory molecule carvacrol. The potential of this formulation was assessed in interleukin-1b-stimulated chondrocytes, which mimic the inflammatory environment of OA. The carvacrol-added HA combination upregulated antioxidant enzyme expression, attenuated pro-inflammatory signaling, and promoted ECM preservation by up regulating cartilage-specific markers and glycosaminoglycan production. In vivo efficacy was further evaluated in a rat model of monosodium iodoacetate-induced OA. HA-Carvacrol treatment alleviated pain-related behaviors and preserved cartilage structure, as confirmed by behavioral assessments and histological analyses. This dual-function formulation integrates the lubricating benefits of HA with the bioactivity of carvacrol, providing preclinical proof-of-concept evidence for its potential in early-stage OA.