Wu Yifan, Wang Zhanghong, Fu Xin, Lin Zeng, Yu Kehe
Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; The Second School of Medicine, Wenzhou Medical University, 109, Xueyuanxi Road, Wenzhou, Zhejiang 325027, China; Bone Research Institute, The Key Orthopaedic Laboratory of Zhejiang Province, 109, Xueyuanxi Road, Wenzhou, Zhejiang 325027, China.
The Second School of Medicine, Wenzhou Medical University, 109, Xueyuanxi Road, Wenzhou, Zhejiang 325027, China; Department of Anesthesiology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China.
Int Immunopharmacol. 2020 Sep;86:106713. doi: 10.1016/j.intimp.2020.106713. Epub 2020 Jun 23.
Osteoarthritis (OA) is a degenerative disease that has received increasing attention among the elderly. Its clinical manifestation is primarily long-term joint pain. Evidence for the pharmacological effects of geraniol in various diseases is accumulating. However, whether geraniol has a therapeutic effect against OA remains to be determined. In this study, we discussed the anti-inflammatory effects of geraniol in IL-1β-induced chondrocytes and the anti-cartilage degradation effects in a mouse model of destabilization of the medial meniscus (DMM). In cell experiments, we found that the treatment of geraniol inhibited the expression of IL-1β-induced PGE2, NO, COX-2, iNOS, TNF-α and IL-6 by western blot, qRT-PCR and immunofluorescence staining. Besides, geraniol inhibited the expression of MMP-9 and ADAMTS-5, and reversed the degradation of aggrecan and type II collagen. Mechanistically, we revealed that geraniol suppressed IL-1β-stimulated PI3K/Akt/NF-κB and MAPK activation. Importantly, we have found in animal experiments that oral treatment of geraniol was beneficial in protecting articular cartilage from degradation. Overall, these data indicated that geraniol may have the potential to be developed as an effective treatment for OA.
骨关节炎(OA)是一种在老年人中受到越来越多关注的退行性疾病。其临床表现主要为长期关节疼痛。香叶醇在各种疾病中的药理作用证据正在不断积累。然而,香叶醇对OA是否具有治疗作用仍有待确定。在本研究中,我们探讨了香叶醇在白细胞介素-1β(IL-1β)诱导的软骨细胞中的抗炎作用以及在半月板不稳定(DMM)小鼠模型中的抗软骨降解作用。在细胞实验中,我们通过蛋白质免疫印迹法、定量逆转录聚合酶链反应(qRT-PCR)和免疫荧光染色发现,香叶醇处理可抑制IL-1β诱导的前列腺素E2(PGE2)、一氧化氮(NO)、环氧化酶-2(COX-2)、诱导型一氧化氮合酶(iNOS)、肿瘤坏死因子-α(TNF-α)和白细胞介素-6的表达。此外,香叶醇抑制基质金属蛋白酶-9(MMP-9)和含血小板反应蛋白基序的解聚蛋白样金属蛋白酶-5(ADAMTS-5)的表达,并逆转了蛋白聚糖和II型胶原的降解。从机制上讲,我们发现香叶醇可抑制IL-1β刺激的磷脂酰肌醇-3激酶(PI3K)/蛋白激酶B(Akt)/核因子κB(NF-κB)和丝裂原活化蛋白激酶(MAPK)的激活。重要的是,我们在动物实验中发现,口服香叶醇有助于保护关节软骨免于降解。总体而言,这些数据表明香叶醇可能有潜力被开发成为OA的有效治疗方法。