Ma Tianwen, Chen Hong, Ruan Hongri, Lv Liangyu, Yu Yue, Jia Lina, Zhao Jinghua, Li Xin, Zang Yuxin, Xu Xinyu, Zhang Jiantao, Gao Li
College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.
College of Animal Science and Technology, College of Veterinary Medicine, Zhejiang Agriculture and Forestry University, Hangzhou, China.
Front Vet Sci. 2022 Oct 20;9:1034623. doi: 10.3389/fvets.2022.1034623. eCollection 2022.
Osteoarthritis (OA) is a common chronic musculoskeletal disease reported in veterinary clinics that severely reduces the quality of life of animals. The natural product, bilobalide, has positive effects on chondroprotection but its exact mechanism of action is unclear. This study aimed to investigate the antioxidant and anti-matrix degradation activities of bilobalide in a rabbit model of OA and its protective effects on joints. We also investigated the possible mechanisms underlying these effects. The rabbit OA model was established by intra-articular injection of 4% papain. Thirty healthy male New Zealand rabbits were randomly divided into control, untreated OA, Cel (100 mg/kg celecoxib intervention as a positive control), BB-L and BB-H (40 mg /kg and 80 mg /kg bilobalide gavage treatment, respectively) groups. Two weeks after surgical induction, bilobalide or celecoxib was administered by gavage daily for 8 weeks. After 8 weeks of bilobalide intervention, cartilage macroscopic observation and histopathological images showed alleviation of cartilage damage after bilobalide treatment, and the Osteoarthritis Research Society International (OARSI) score was significantly lower than that in the OA group. Bilobalide reduced the expression of metalloproteinase 3 (MMP-3) and MMP-13 in cartilage tissue of OA rabbits and reversed the levels of serum C-telopeptides of type II collagen (CTX-II), cartilage oligomeric matrix protein (COMP), interleukin 1(IL-1), and tumor necrosis factor (TNF-α). Bilobalide (80 mg/kg) could improve the biomechanical properties and microstructural changes in subchondral bone in the early stage of OA in rabbits, thereby delaying subchondral bone damage. Mechanistically, bilobalide exerted antioxidant and anti-matrix degradation effects by upregulating the oxidative stress signaling Nrf2/HO-1 pathway and inhibiting cartilage degeneration in rabbit OA. We thus speculate that bilobalide supplements recovery from OA damage.
骨关节炎（OA）是兽医诊所中常见的慢性肌肉骨骼疾病，会严重降低动物的生活质量。天然产物白果内酯对软骨保护具有积极作用，但其确切作用机制尚不清楚。本研究旨在探讨白果内酯在兔骨关节炎模型中的抗氧化和抗基质降解活性及其对关节的保护作用。我们还研究了这些作用的潜在机制。通过关节内注射4%木瓜蛋白酶建立兔骨关节炎模型。将30只健康雄性新西兰兔随机分为对照组、未治疗的骨关节炎组、Cel（100mg/kg塞来昔布干预作为阳性对照）组、BB-L组和BB-H组（分别给予40mg/kg和80mg/kg白果内酯灌胃治疗）。手术诱导两周后，每天通过灌胃给予白果内酯或塞来昔布，持续8周。白果内酯干预8周后，软骨宏观观察和组织病理学图像显示，白果内酯治疗后软骨损伤有所减轻，国际骨关节炎研究学会（OARSI）评分显著低于骨关节炎组。白果内酯降低了骨关节炎兔软骨组织中金属蛋白酶3（MMP-3）和MMP-13的表达，并逆转了血清II型胶原C末端肽（CTX-II）、软骨寡聚基质蛋白（COMP）、白细胞介素1（IL-1）和肿瘤坏死因子（TNF-α）的水平。白果内酯（80mg/kg）可改善兔骨关节炎早期软骨下骨的生物力学性能和微观结构变化，从而延缓软骨下骨损伤。机制上，白果内酯通过上调氧化应激信号Nrf2/HO-1通路发挥抗氧化和抗基质降解作用，并抑制兔骨关节炎中的软骨退变。因此，我们推测白果内酯有助于从骨关节炎损伤中恢复。
