Guanghua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 200052, People's Republic of China.
Shanghai Guanghua Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai, 200052, People's Republic of China.
Drug Des Devel Ther. 2024 Feb 21;18:493-512. doi: 10.2147/DDDT.S451197. eCollection 2024.
Intervertebral disc degeneration (IVDD) is a pathophysiological process that leads to severe back pain or neurological deficits. The Bushen Huoxue Formula (BSHXF) is a traditional herbal remedy widely used to treat diseases related to IVDD. However, its pharmacological mechanism needs further exploration.
This study aimed to elucidate the mechanisms through which BSHXF treats IVDD-related diseases by integrating metabolomics with network pharmacology.
Network pharmacology was utilized to identify potential targets of BSHXF against IVDD. Additionally, an animal model of needle puncture-induced disc degeneration was established to assess the effect of BSHXF. Mice were randomly assigned to the sham group, model group, and BSHXF group. Various techniques, including PCR, CCK-8 assay, MRI, histological examinations, and immunohistochemical analyses, were employed to evaluate degenerative and oxidative stress conditions in mouse disc tissue and cultured nucleus pulposus (NP) cells. UHPLC-HRMS/MS was used to differential distinct metabolites in the disc tissue from different groups, and MetaboAnalyst 5.0 was employed to enrich the metabolic pathways.
Through network pharmacology, 15 core proteins were identified through protein-protein interaction (PPI) network construction. Functional enrichment analysis highlighted the critical role of BSHXF in addressing IVDD by influencing the response to oxidative stress. Furthermore, experimental evidence demonstrated that BSHXF significantly improved the pathological progression of IVDD and increased oxidative stress markers SOD-1 and GPX1, both in the disc degeneration model and cultured NP cells. Metabolomics identified differential metabolites among the three groups, revealing 15 metabolic pathways between the sham and model groups, and 13 metabolic pathways enriched between the model and BSHXF groups.
This study, integrating network pharmacology and metabolomics, suggests that BSHXF can alleviate IVDD progression by modulating oxidative stress. Key metabolic pathways associated with BSHXF-mediated reduction of oxidative stress include the citrate cycle, cysteine and methionine metabolism, alanine, aspartate and glutamate metabolism, glycine, serine and threonine metabolism, D-glutamine and D-glutamate metabolism, glutathione metabolism, and tryptophan metabolism. While this research demonstrates the therapeutic potential of BSHXF in reducing oxidative stress levels in IVDD, further research is needed to thoroughly understand its underlying mechanisms.
椎间盘退行性变（IVDD）是导致严重腰痛或神经功能缺损的病理生理过程。补肾活血方（BSHXF）是一种广泛用于治疗与 IVDD 相关疾病的传统草药方剂。然而，其药理机制仍需进一步探索。
本研究旨在通过整合代谢组学和网络药理学，阐明 BSHXF 治疗 IVDD 相关疾病的作用机制。
利用网络药理学方法鉴定 BSHXF 治疗 IVDD 的潜在靶点。此外，建立了针刺诱导椎间盘退变的动物模型，以评估 BSHXF 的作用。将小鼠随机分为假手术组、模型组和 BSHXF 组。采用 PCR、CCK-8 检测、MRI、组织学检查和免疫组织化学分析等方法，评估小鼠椎间盘组织和培养的髓核（NP）细胞的退变和氧化应激情况。采用 UHPLC-HRMS/MS 检测不同组别椎间盘组织中的差异代谢物，并利用 MetaboAnalyst 5.0 对代谢通路进行富集分析。
通过网络药理学，通过构建蛋白质-蛋白质相互作用（PPI）网络鉴定了 15 个核心蛋白。功能富集分析表明，BSHXF 通过影响氧化应激反应，在治疗 IVDD 中发挥关键作用。此外，实验结果表明，BSHXF 可显著改善 IVDD 的病理进展，增加 SOD-1 和 GPX1 等氧化应激标志物，无论是在椎间盘退变模型还是培养的 NP 细胞中。代谢组学分析发现三组之间存在差异代谢物，假手术组和模型组之间有 15 条代谢通路，模型组和 BSHXF 组之间有 13 条代谢通路富集。
本研究通过整合网络药理学和代谢组学，表明 BSHXF 可以通过调节氧化应激来缓解 IVDD 的进展。与 BSHXF 介导的氧化应激减轻相关的关键代谢途径包括柠檬酸循环、半胱氨酸和蛋氨酸代谢、丙氨酸、天冬氨酸和谷氨酸代谢、甘氨酸、丝氨酸和苏氨酸代谢、D-谷氨酰胺和 D-谷氨酸代谢、谷胱甘肽代谢和色氨酸代谢。虽然本研究表明 BSHXF 具有降低 IVDD 氧化应激水平的治疗潜力，但仍需要进一步研究以深入了解其潜在机制。
