Department of Orthopedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China; Key Laboratory of Orthopedics of Zhejiang Province, Wenzhou, Zhejiang Province, China; The Second Clinical School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
Department of Orthopedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China; Key Laboratory of Orthopedics of Zhejiang Province, Wenzhou, Zhejiang Province, China; The Second Clinical School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
Int Immunopharmacol. 2024 Mar 30;130:111758. doi: 10.1016/j.intimp.2024.111758. Epub 2024 Feb 28.
Glucocorticoid-induced osteonecrosis of the femoral head (GIONFH) represents a predominant etiology of non-traumatic osteonecrosis, imposing substantial pain, restricting hip mobility, and diminishing overall quality of life for affected individuals. Centella asiatica (L.) Urb. (CA), an herbal remedy deeply rooted in traditional oriental medicine, has exhibited noteworthy therapeutic efficacy in addressing inflammation and facilitating wound healing. Drawing from CA's historical applications, its anti-inflammatory, anti-apoptotic, and antioxidant attributes may hold promise for managing GIONFH. Asiatic acid (AA), a primary constituent of CA, has been substantiated as a key contributor to its anti-apoptotic, antioxidant, and anti-inflammatory capabilities, showcasing a close association with orthopedic conditions. For the investigation of whether AA could alleviate GIONFH through suppressing oxidative stress, apoptosis, and to delve into its potential cellular and molecular mechanisms, the connection between AA and disease was analyzed through network pharmacology. DEX-induced apoptosis in rat osteoblasts and GIONFH in rat models, got utilized for the verification in vitro/vivo, on underlying mechanism of AA in GIONFH. Network pharmacology analysis reveals a robust correlation between AA and GIONFH in multiple target genes. AA has demonstrated the inhibition of DEX-induced osteoblast apoptosis by modulating apoptotic factors like BAX, BCL-2, Cleaved-caspase3, and cleaved-caspase9. Furthermore, it effectively diminishes the ROS overexpression and regulates oxidative stress through mitochondrial pathway. Mechanistic insights suggest that AA's therapeutic effects involve phosphatidylinositol 3-kinase/Protein kinase B (PI3K/AKT) pathway activation. Additionally, AA has exhibited its potential to ameliorate GIONFH progression in rat models. Our findings revealed that AA mitigated DEX-induced osteoblast apoptosis and oxidative stress through triggering PI3K/AKT pathway. Also, AA can effectively thwart GIONFH occurrence and development in rats.
糖皮质激素诱导的股骨头坏死（GIONFH）是一种主要的非创伤性骨坏死病因，会给患者带来严重的疼痛，限制髋关节活动，并降低整体生活质量。积雪草（Centella asiatica（L.）Urb.）是一种传统东方医学中常用的草药，具有显著的抗炎和促进伤口愈合的疗效。基于积雪草的历史应用，其抗炎、抗凋亡和抗氧化特性可能对治疗 GIONFH 具有一定的作用。积雪草酸（AA）是积雪草的主要成分之一，已被证实是其抗凋亡、抗氧化和抗炎作用的关键贡献者，与骨科疾病密切相关。为了研究 AA 是否可以通过抑制氧化应激、细胞凋亡来缓解 GIONFH，我们通过网络药理学分析了 AA 与疾病之间的关系，探讨其在 GIONFH 中的潜在细胞和分子机制。AA 在体外/体内通过抑制 DEX 诱导的大鼠成骨细胞凋亡和 GIONFH 来验证其在 GIONFH 中的作用机制。网络药理学分析显示 AA 与多种靶基因之间存在较强的相关性。AA 通过调节 BAX、BCL-2、Cleaved-caspase3 和 Cleaved-caspase9 等凋亡因子，抑制 DEX 诱导的成骨细胞凋亡。此外，AA 还通过调节线粒体途径有效减少 ROS 过度表达和氧化应激。机制研究表明 AA 的治疗作用涉及磷脂酰肌醇 3-激酶/蛋白激酶 B（PI3K/AKT）通路的激活。此外，AA 还在大鼠模型中表现出改善 GIONFH 进展的潜力。我们的研究结果表明，AA 通过触发 PI3K/AKT 通路减轻 DEX 诱导的成骨细胞凋亡和氧化应激。AA 还可以有效阻止大鼠 GIONFH 的发生和发展。
