Inhibitory Effects of IL-6-Mediated Matrix Metalloproteinase-3 and -13 by Achyranthes japonica Nakai Root in Osteoarthritis and Rheumatoid Arthritis Mice Models

Xiangyu Zhao,Dahye Kim,Jiwon Yang,Godagama Gamaarachchige Dinesh Suminda,Yunhui Min,Mangeun Kim,Young-Ok Son,Mrinmoy Ghosh,Yaping Zhao

doi:10.3390/ph14080776

Abstract

Achyranthes japonica Nakai root (AJNR) is used to treat osteoarthritis (OA) and rheumatoid arthritis (RA) owing to its anti-inflammatory and antioxidant effects. This study investigated the inhibitory effects of AJNR on arthritis. AJNR was extracted using supercritical carbon dioxide (CO2), and its main compounds, pimaric and kaurenoic acid, were identified. ANJR’s inhibitory effects against arthritis were evaluated using primary cultures of articular chondrocytes and two in vivo arthritis models: destabilization of the medial meniscus (DMM) as an OA model, and collagenase-induced arthritis (CIA) as an RA model. AJNR did not affect pro-inflammatory cytokine (IL-1β, TNF-α, IL-6)-mediated cytotoxicity, but attenuated pro-inflammatory cytokine-mediated increases in catabolic factors, and recovered pro-inflammatory cytokine-mediated decreases in related anabolic factors related to in vitro. The effect of AJNR is particularly specific to IL-6-mediated catabolic or anabolic alteration. In a DMM model, AJNR decreased cartilage erosion, subchondral plate thickness, osteophyte size, and osteophyte maturity. In a CIA model, AJNR effectively inhibited cartilage degeneration and synovium inflammation in either the ankle or knee and reduced pannus formation in both the knee and ankle. Immunohistochemistry analysis revealed that AJNR mainly acted via the inhibitory effects of IL-6-mediated matrix metalloproteinase-3 and -13 in both arthritis models. Therefore, AJNR is a potential therapeutic agent for relieving arthritis symptoms.

Highlights

Because we used ethanol as a co-solvent during supercritical CO2 extraction and an ethanol soluble phase of Achyranthes japonica Nakai root (AJNR) extract, in our experiment, ethanol was used as a and an ethanol soluble phase of AJNR extract, in our experiment, ethanol was used as a solvent for gas chromatography-mass spectrometry (GC-MS) analysis
The results showed solvent for gas chromatography-mass spectrometry (GC-MS) analysis
The results showed that nus formation in the ankle and knee was not observed in the NI group; CIApannus formation in the ankle and knee was not observed in the NI group; induced pannus formation was significantly reduced by AJNR in both the ankles

Summary

Introduction

Licensee MDPI, Basel, Switzerland.Attribution (CC BY) license (https://creativecommons.org/licenses/by/ 4.0/).Osteoarthritis (OA) is a severe chronic degenerative disease of the joints that is common in middle aged and older people [1]. The main clinical manifestations of OA are degeneration of the articular cartilage and changes in the subchondral bone structure [2]. When joint cartilage is completely lost following disruption of cartilage homeostasis through the induction of catabolic factors as well as downregulation of anabolic factors, the bones and soft tissue structures around the joint are altered, resulting in joint pain, swelling, deformity, and disability [3,4]. Although several risk factors associated with OA have

Results

Discussion

Conclusion