■椎间盘退变(IVDD)是一种导致严重背痛或神经功能缺损的病理生理过程。补肾活血方(BSHXF)是一种传统的草药,广泛用于治疗与IVDD相关的疾病。然而,其药理机制有待进一步探索。
■本研究旨在阐明BSHXF通过整合代谢组学与网络药理学治疗IVDD相关疾病的机制。
■网络药理学用于确定BSHXF针对IVDD的潜在靶标。此外,建立针刺诱导椎间盘退变的动物模型,以评估BSHXF的疗效.将小鼠随机分配到假手术组,模型组,和BSHXF集团。各种技术,包括PCR,CCK-8测定,MRI,组织学检查,和免疫组织化学分析,用于评估小鼠椎间盘组织和培养的髓核(NP)细胞中的退行性和氧化应激条件。UHPLC-HRMS/MS用于区分不同组的椎间盘组织中的不同代谢物。和MetaboAnalyst5.0用于富集代谢途径。
■通过网络药理学,通过蛋白-蛋白相互作用(PPI)网络构建鉴定出15个核心蛋白。功能富集分析强调了BSHXF通过影响对氧化应激的反应来解决IVDD的关键作用。此外,实验证据表明,BSHXF显着改善了椎间盘退变模型和培养的NP细胞中IVDD的病理进展,并增加了氧化应激标志物SOD-1和GPX1。代谢组学鉴定了三组之间的差异代谢物,揭示了假手术组和模型组之间的15条代谢途径,模型组和BSHXF组之间富集了13条代谢途径。
■这项研究,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进展。与BSHXF介导的氧化应激减少相关的关键代谢途径包括柠檬酸盐循环,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.虽然这项研究证明了BSHXF在降低IVDD氧化应激水平方面的治疗潜力,需要进一步研究以彻底了解其潜在机制。
UNASSIGNED: 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.
UNASSIGNED: This
study aimed to elucidate the mechanisms through which BSHXF treats IVDD-related diseases by integrating metabolomics with network pharmacology.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.