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.
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.
Int Immunopharmacol. 2017 Nov;52:34-43. doi: 10.1016/j.intimp.2017.08.010. Epub 2017 Aug 31.
Osteoarthritis (OA) is a joint disease characterized by inflammation and cartilage degradation. α-Mangostin (α-MG), which can be isolated from the fruit of the tropical evergreen tree Garcinia mangostana-L, is known to have anti-inflammatory properties. The aim of the study was to investigate the use of α-MG in the treatment of OA, using both rat chondrocytes and an OA rat model induced by destabilization of the medial meniscus (DMM). Rat chondrocytes were pretreated with α-MG (0, 1.25, 2.5, and 5.0μg/ml for 24h) prior to stimulation with interleukin-1β (IL-1β) (10ng/ml for 24h). Nitric oxide (NO) production was determined using the Griess method and prostaglandin E (PGE) was assessed using an enzyme-linked immunosorbent assay (ELISA). The expression of inducible nitric oxide synthase (INOS), cyclooxygenase-2 (COX-2), matrix metalloproteinase-3, -9, and -13 (MMP-3, MMP-9, and MMP-13), Collagen II, and Aggrecan were detected by both quantitative real-time PCR (qRT-PCR) and a western blot analysis. Nuclear factor-κB (NF-κB) signaling molecules were detected by western blot analysis. Detection of p65 nuclear translocation of NF-κB was examined using immunofluorescence staining. The OA rats received intraperitoneal injections of α-MG (10mg/kg) or saline every other day. Hematoxylin and eosin and Safranin-O-Fast green staining were used to evaluate the severity of cartilage lesions up to 8weeks following surgery. α-MG inhibited the production of NO and PGE. The elevated expression of INOS, COX-2, MMP-3, MMP-9, and MMP-13, and the degradation of Collagen II and Aggrecan, were reversed by α-MG in IL-1β-stimulated chondrocytes. In addition, IL-1β induced considerable phosphorylation of the NF-kB signaling pathway, which was inhibited by α-MG. Furthermore, the immunofluorescence staining demonstrated that α-MG could suppress IL-1β-induced p65 nuclear translocation. In vivo, cartilage treated with α-MG showed attenuated degeneration and had low Osteoarthritis Research Society International (OARSI) scores compared with the control group. Taken together, these results show that α-MG has potential therapeutic value in the treatment of OA.
骨关节炎（OA）是一种以炎症和软骨降解为特征的关节疾病。α-倒捻子素（α-MG）可从热带常绿藤本植物藤黄果实中分离得到，已知具有抗炎作用。本研究旨在探讨α-MG 治疗骨关节炎的作用，采用大鼠软骨细胞和内侧半月板不稳定（DMM）诱导的 OA 大鼠模型。在使用白细胞介素-1β（IL-1β）（10ng/ml，24h）刺激之前，将大鼠软骨细胞用 α-MG（0、1.25、2.5 和 5.0μg/ml，24h）预处理。通过格里斯法测定一氧化氮（NO）的产生，用酶联免疫吸附测定法（ELISA）测定前列腺素 E（PGE）。通过定量实时 PCR（qRT-PCR）和 Western blot 分析检测诱导型一氧化氮合酶（INOS）、环氧化酶-2（COX-2）、基质金属蛋白酶-3、-9 和 -13（MMP-3、MMP-9 和 MMP-13）、Collagen II 和 Aggrecan 的表达。通过 Western blot 分析检测核因子-κB（NF-κB）信号分子。通过免疫荧光染色检测 NF-κB p65 核易位。OA 大鼠每隔一天接受腹腔注射 α-MG（10mg/kg）或生理盐水。手术 8 周后，采用苏木精和伊红及番红 O-快绿染色评估软骨损伤的严重程度。α-MG 抑制了 NO 和 PGE 的产生。在 IL-1β 刺激的软骨细胞中，α-MG 逆转了 INOS、COX-2、MMP-3、MMP-9 和 MMP-13 的高表达以及 Collagen II 和 Aggrecan 的降解。此外，IL-1β 诱导了 NF-κB 信号通路的显著磷酸化，而 α-MG 抑制了这一磷酸化。此外，免疫荧光染色表明，α-MG 可以抑制 IL-1β 诱导的 p65 核易位。在体内，与对照组相比，用 α-MG 处理的软骨显示出退变减轻，Osteoarthritis Research Society International（OARSI）评分较低。综上所述，这些结果表明 α-MG 在治疗 OA 方面具有潜在的治疗价值。
