Naringenin regulates production of matrix metalloproteinases in the knee-joint and primary cultured articular chondrocytes and alleviates pain in rat osteoarthritis model

Abstract

Inflammation of cartilage is a primary symptom for knee-joint osteoarthritis. Matrix metalloproteinases (MMPs) are known to play an important role in the articular cartilage destruction related to osteoarthritis. Naringenin is a plant-derived flavonoid known for its anti-inflammatory properties. We studied the effect of naringenin on the transcriptional expression, secretion and enzymatic activity of MMP-3 in vivo in the murine monosodium iodoacetate (MIA) osteoarthritis model. The assessment of pain behavior was also performed in the MIA rats. The destruction of knee-joint tissues was analyzed microscopically. Moreover, the effect of naringenin was also studied in vitro in IL-1β activated articular chondrocytes. The transcriptional expression of MMP-3, MMP-1, MMP-13, thrombospondin motifs (ADAMTS-4) and ADAMTS-5 was also studied in primary cultured chondrocytes of rats. Naringenin caused significant reduction in pain behavior and showed marked improvement in the tissue morphology of MIA rats. Moreover, a significant inhibition of MMP-3 expression in MIA rats was observed upon treatment with naringenin. In the in vitro tests, naringenin caused a significant reduction in the transcriptional expression, secretion and enzymatic activity of the studied degradative enzymes. The NF-κB pathway was also found to be inhibited upon treatment with naringenin in vitro. Overall, the study suggests that naringenin alleviated pain and regulated the production of matrix-metalloproteinases via regulation of NF-κB pathway. Thus, naringenin could be a potent therapeutic option for the treatment of osteoarthritis.

Protective effects of quercetin against inflammation and oxidative stress in a rabbit model of knee osteoarthritis

“…worsen the degeneration and exfoliation of articular cartilage, leading to the development of OA (Akhtar, Khan, Ashruf, & Haqqi, 2017;Wang et al, 2017). The levels of MMP-1, MMP-3, MMP-9, and MMP-13 in serum, joint synovial fluid, and cartilage in OA joints were higher than those in healthy joints, and the increase amount was consistent with the degree of cartilage destruction (Akhtar et al, 2017;Chijimatsu et al, 2015).…”

“…Degeneration of articular cartilage is related to altered expression of MMPs. MMPs can degrade many cartilage extracellular matrix (Type II collagen fibers, proteoglycans, and other substances) and worsen the degeneration and exfoliation of articular cartilage, leading to the development of OA (Akhtar, Khan, Ashruf, & Haqqi, ; Wang et al, ). The levels of MMP‐1, MMP‐3, MMP‐9, and MMP‐13 in serum, joint synovial fluid, and cartilage in OA joints were higher than those in healthy joints, and the increase amount was consistent with the degree of cartilage destruction (Akhtar et al, ; Chijimatsu et al, ).…”

Guyanxiao formula antagonizes LPS-induced KOA chondrocyte injury by regulating the SDF-1 / CXCR4 signaling pathway1

“…Massive degradation breaks the steady-state between ECM synthesis and degradation, altering the metabolic microenvironment within the joint. This leads to the destruction of the structural and functional integrity of the articular cartilage; hence, the occurrence and development of KOA (32) . The results showed that the chondrocytes in the model group were induced by lipopolysaccharide, which aggravated the ECM damage, reducing greatly the positive coloration of type II collagen and proteoglycan.…”

Antinociceptive and anti-inflammatory effects of the citrus flavanone naringenin

“…Recently, it was also found to have potential for immunomodulatory efficacy, which could be associated with suppression of the activities of mast cells, macrophages, dendritic cells, and T cells [1617181920]. Therefore, naringenin has been proposed for potential pharmaceutical application in rheumatoid arthritis and osteoarthritis [192122].…”