Nam Jiho, Seol Dong-Won, Lee Choong-Gu, Wee Gabbine, Yang Siyoung, Pan Cheol-Ho
Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon 16499, Korea.
Department of Pharmacology, Ajou University School of Medicine, Suwon 16499, Korea.
Pharmaceuticals (Basel). 2021 Mar 10;14(3):249. doi: 10.3390/ph14030249.
Osteoarthritis (OA) is an age-related degenerative disease that causes cartilage dysfunction and inflammation. Obtusifolin, an anthraquinone extracted from (L.) H.S.Irwin & Barneby seeds, has anti-inflammatory functions; it could be used as a drug component to relieve OA symptoms. In this study, we investigated the effects of obtusifolin on OA inflammation. In vitro, interleukin (IL)-1β (1 ng/mL)-treated mouse chondrocytes were co-treated with obtusifolin at different concentrations. The expression of matrix metalloproteinase (Mmp) 3, Mmp13, cyclooxygenase 2 (Cox2), and signaling proteins was measured by polymerase chain reaction and Western blotting; collagenase activity and the PGE level were also determined. In vivo, OA-induced C57BL/6 mice were administered obtusifolin, and their cartilage was stained with Safranin O to observe damage. Obtusifolin inhibited Mmp3, Mmp13, and Cox2 expression to levels similar to or more than those after treatment with celecoxib. Additionally, obtusifolin decreased collagenase activity and the PGE level. Furthermore, obtusifolin regulated OA via the NF-κB signaling pathway. In surgically induced OA mouse models, the cartilage destruction decreased when obtusifolin was administered orally. Taken together, our results show that obtusifolin effectively reduces cartilage damage via the regulation of MMPs and Cox2 expression. Hence, we suggest that obtusifolin could be a component of another OA symptom reliever.
骨关节炎（OA）是一种与年龄相关的退行性疾病，会导致软骨功能障碍和炎症。钝叶决明素是从钝叶决明（L.）H.S.欧文和巴尼比种子中提取的一种蒽醌，具有抗炎功能；它可以用作缓解OA症状的药物成分。在本研究中，我们研究了钝叶决明素对OA炎症的影响。在体外，将白细胞介素（IL）-1β（1 ng/mL）处理的小鼠软骨细胞与不同浓度的钝叶决明素共同处理。通过聚合酶链反应和蛋白质免疫印迹法测量基质金属蛋白酶（Mmp）3、Mmp13、环氧合酶2（Cox2）和信号蛋白的表达；还测定了胶原酶活性和前列腺素E（PGE）水平。在体内，给OA诱导的C57BL/6小鼠施用钝叶决明素，并用番红O对其软骨进行染色以观察损伤情况。钝叶决明素将Mmp3、Mmp13和Cox2的表达抑制到与塞来昔布治疗后相似或更高的水平。此外，钝叶决明素降低了胶原酶活性和PGE水平。此外，钝叶决明素通过核因子κB（NF-κB）信号通路调节OA。在手术诱导的OA小鼠模型中，口服钝叶决明素时软骨破坏减少。综上所述，我们的结果表明钝叶决明素通过调节基质金属蛋白酶（MMPs）和Cox2的表达有效减少软骨损伤。因此，我们认为钝叶决明素可能是另一种OA症状缓解剂的成分。
