Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, 109 Xue Yuan Xi Road, Wenzhou, Zhejiang, 325000, China.
Inflammation. 2017 Oct;40(5):1698-1706. doi: 10.1007/s10753-017-0611-8.
Paeonol, the main active component isolated from the root of Paeonia suffruticosa, has been reported to have anti-inflammatory properties. However, the effects of paeonol on osteoarthritis (OA) remain unclear. The aim of this study was to investigate the anti-inflammatory effects and mechanism of paeonol in IL-1β-induced human OA chondrocytes as well as mice OA models. Human OA chondrocytes were pretreated with different concentrations of paeonol 2 h prior to IL-1β (10 ng/mL) stimulation for 24 h. Nitric oxide (NO) production was determined by Griess method. The levels of prostaglandin E2 (PGE2), matrix metalloproteinase 1 (MMP-1), MMP-3, and MMP-13 were assessed by ELISA. Inducible nitric oxide synthase (INOS), COX-2, and PI3K/Akt/NF-κB-related signaling molecules production were measured by Western blot. In vivo, mice OA models were established by destabilization of the medial meniscus. One month after surgery, mice in paeonol-treated group were given intraperitoneal injection of paeonol in 30 mg/kg every day, while mice of vehicle-treated group were injected with DMSO under the same conditions. Hematoxylin and eosin as well as Safranin-O staining were applied to assess the severity of cartilage lesions. The results showed that pretreatment with paeonol could inhibit IL-1β-induced NO and PGE2 production. Meanwhile, the overproduction of INOS, COX-2, MMP-1, MMP-3, and MMP-13 were also reversed by paeonol. Moreover, paeonol was found to inhibit IL-1β-induced NF-κB activation, PI3K, and AKT phosphorylation. In vivo, treatment with paeonol exhibited less cartilage degradation and lower Osteoarthritis Research Society International scores in mice OA models. In conclusion, these results suggest that paeonol may be a potential therapeutic agent in the treatment of OA.
丹皮酚是从牡丹根中分离得到的主要活性成分，具有抗炎作用。然而，丹皮酚对骨关节炎（OA）的影响尚不清楚。本研究旨在探讨丹皮酚对 IL-1β诱导的人 OA 软骨细胞及小鼠 OA 模型的抗炎作用及其机制。将人 OA 软骨细胞用不同浓度的丹皮酚预处理 2 h，然后用 10 ng/mL 的 IL-1β刺激 24 h。用 Griess 法测定一氧化氮（NO）的产生。通过 ELISA 测定前列腺素 E2（PGE2）、基质金属蛋白酶 1（MMP-1）、MMP-3 和 MMP-13 的水平。通过 Western blot 测定诱导型一氧化氮合酶（INOS）、COX-2 和 PI3K/Akt/NF-κB 相关信号分子的产生。在体内，通过内侧半月板不稳定建立小鼠 OA 模型。手术后 1 个月，丹皮酚治疗组小鼠每天腹腔注射丹皮酚 30mg/kg，而溶媒处理组小鼠在相同条件下注射 DMSO。用苏木精和伊红以及番红 O 染色评估软骨损伤的严重程度。结果表明，丹皮酚预处理可抑制 IL-1β诱导的 NO 和 PGE2 的产生。同时，丹皮酚还逆转了 INOS、COX-2、MMP-1、MMP-3 和 MMP-13 的过度产生。此外，丹皮酚还抑制了 IL-1β诱导的 NF-κB 激活、PI3K 和 AKT 磷酸化。在体内，丹皮酚治疗可减少小鼠 OA 模型的软骨降解和降低骨关节炎研究协会国际评分。综上所述，这些结果表明丹皮酚可能是治疗 OA 的一种潜在治疗药物。
