Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Soochow University, No. 899 Pinghai Road, Suzhou, 215006, Jiangsu, China.
Orthopaedic Institute, Medical College, Soochow University, No. 178 East Ganjiang Road, Suzhou, 215000, Jiangsu, China.
J Nanobiotechnology. 2022 Jun 27;20(1):303. doi: 10.1186/s12951-022-01505-7.
Loss of extracellular matrix (ECM) of cartilage due to oxidative stress injury is one of the main characteristics of osteoarthritis (OA). As a bioactive molecule derived from the traditional Chinese Burdock, arctiin exerts robust antioxidant properties to modulate redox balance. However, the potential therapeutic effects of arctiin on OA and the underlying mechanisms involved are still unknown. Based on the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) tool, Burdock-extracted small molecule arctiin was identified as a potential anti-arthritic component. In vitro, treatment using arctiin rescued the interleukin (IL)-1β-induced activation of proteinases and promoted the cartilage ECM synthesis in human chondrocytes. In vivo, intraperitoneal injection of arctiin ameliorated cartilage erosion and encountered subchondral bone sclerosis in the post-traumatic OA mice. Transcriptome sequencing uncovered that arctiin-enhanced cartilage matrix deposition was associated with restricted oxidative stress. Mechanistically, inhibition of nuclear factor erythroid 2-related factor 2 (NRF2) abolished arctiin-mediated anti-oxidative and anti-arthritic functions. To further broaden the application prospects, a gellan gum (GG)-based bioactive gel (GG-CD@ARC) encapsulated with arctiin was made to achieve long-term and sustained drug release. Intra-articular injection of GG-CD@ARC counteracted cartilage degeneration in the severe (12 weeks) OA mice model. These findings indicate that arctiin may be a promising anti-arthritic agent. Furthermore, GG-modified bioactive glue loaded with arctiin provides a unique strategy for treating moderate to severe OA.
由于氧化应激损伤导致的软骨细胞外基质（ECM）丧失是骨关节炎（OA）的主要特征之一。作为一种源自传统中药牛蒡的生物活性分子，牛蒡子苷具有强大的抗氧化特性，可调节氧化还原平衡。然而，牛蒡子苷治疗 OA 的潜在疗效及其涉及的潜在机制尚不清楚。基于中药系统药理学数据库和分析平台（TCMSP）工具，鉴定出牛蒡小分子牛蒡子苷是一种有潜力的抗关节炎成分。在体外，牛蒡子苷治疗可挽救白细胞介素（IL）-1β诱导的蛋白水解酶的激活，并促进人软骨细胞中软骨 ECM 的合成。在体内，腹腔内注射牛蒡子苷可改善创伤后 OA 小鼠的软骨侵蚀和软骨下骨硬化。转录组测序揭示，牛蒡子苷增强软骨基质沉积与限制氧化应激有关。从机制上讲，核因子红细胞 2 相关因子 2（NRF2）的抑制消除了牛蒡子苷介导的抗氧化和抗关节炎功能。为了进一步拓宽应用前景，用牛蒡子苷包封的凝胶多糖（GG）基生物活性凝胶（GG-CD@ARC）被制成，以实现长期和持续的药物释放。关节内注射 GG-CD@ARC 可对抗严重（12 周）OA 小鼠模型中的软骨退化。这些发现表明，牛蒡子苷可能是一种有前途的抗关节炎药物。此外，牛蒡子苷负载的 GG 改性生物活性胶为治疗中度至重度 OA 提供了独特的策略。
