Wang C C, Guo L, Tian F D, An N, Luo L, Hao R H, Wang B, Zhou Z H
Department II of Orthopedics, Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning, China.
Department of Respiratory Medicine, Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning, China.
Braz J Med Biol Res. 2017 Mar 23;50(4):e5714. doi: 10.1590/1414-431X20165714.
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.
软骨炎症是膝关节骨关节炎的主要症状。已知基质金属蛋白酶（MMPs）在与骨关节炎相关的关节软骨破坏中起重要作用。柚皮素是一种植物来源的黄酮类化合物，以其抗炎特性而闻名。我们在小鼠碘乙酸钠（MIA）骨关节炎模型中研究了柚皮素对MMP-3转录表达、分泌和酶活性的体内影响。还对MIA大鼠进行了疼痛行为评估。通过显微镜分析膝关节组织的破坏情况。此外，还在体外研究了柚皮素对IL-1β激活的关节软骨细胞的影响。在大鼠原代培养软骨细胞中也研究了MMP-3、MMP-1、MMP-13、含血小板反应蛋白基序的解聚素样金属蛋白酶（ADAMTS-4）和ADAMTS-5的转录表达。柚皮素可显著减轻疼痛行为，并使MIA大鼠的组织形态有明显改善。此外，在用柚皮素治疗后，观察到MIA大鼠中MMP-3表达受到显著抑制。在体外试验中，柚皮素可使所研究的降解酶的转录表达、分泌和酶活性显著降低。在体外，用柚皮素处理后还发现NF-κB通路受到抑制。总体而言，该研究表明柚皮素通过调节NF-κB通路减轻疼痛并调节基质金属蛋白酶的产生。因此，柚皮素可能是治疗骨关节炎的一种有效治疗选择。
