整合光谱效应关系、网络药理学和多组学，破译白屈菜抗慢性肾病的机制

摘要(中文译文)

※ 中文译文由 AI 辅助生成,仅供学术参考,请以英文原文为准。

中华鳖是一种传统的中药昆虫，传统上用于补肾，临床上用于治疗慢性肾病（CKD）。本研究致力于鉴定中药乙酸乙酯组分中的生物活性成分，并阐明其治疗慢性肾病的机制。分离化合物并用于建立指纹图谱。应用体外抗炎和抗损伤活性和灰色关联分析建立光谱效应关系。采用网络药理学与分子对接相结合的方法鉴定候选生物活性成分。通过Western blot、RT-PCR、转录组学和代谢组学，探讨了中药乙酸乙酯组分对阿霉素诱导的CKD大鼠模型的影响。分子动力学模拟用于评估生物活性成分的结合亲和力。细胞实验证实了这些成分对炎症、氧化应激和纤维化的影响。已确认C.chinensis的乙酸乙酯组分为活性组分。化合物6、10、22、23和27被筛选为潜在的活性成分。乙酸乙酯组分改善了CKD大鼠的病情，而多组学鉴定了一个对抗炎症、氧化应激和纤维化的三重功能网络，并验证了PI3K-AKT/MAPK/HIF-1通路。细胞实验和分子动力学模拟确定化合物6为关键活性成分，其调节作用通过PI3K-AKT/MAPK/HIF-1途径得到验证。中华猕猴桃乙酸乙酯组分及其活性成分通过调节PI3K-Akt、MAPK和HIF-1通路抑制CKD的炎症、氧化应激和纤维化，从而发挥肾脏保护作用。

Abstract

Cybister chinensis Motschulsky is a traditional Chinese medicinal insect traditionally used to tonify the kidney, and clinically applied for the management of chronic kidney disease (CKD). The present work was dedicated to identifying bioactive ingredients in the ethyl acetate fraction of C. chinensis and elucidating their mechanisms underlying the treatment of CKD. Compounds were isolated and used to establish fingerprints. Anti-inflammatory and anti-injury activities in vitro and grey relational analysis were applied to establish spectrum-effect relationships. Network pharmacology combined with molecular docking was employed to identify the candidate bioactive components. The effects of ethyl acetate fraction of C. chinensis were explored in doxorubicin-induced CKD rat model via Western blot, RT-PCR, transcriptomics, and metabolomics. Molecular dynamics simulation was applied to assess binding affinity of bioactive components. Cell experiments verified effects of components on inflammation, oxidative stress, and fibrosis. The ethyl acetate fraction of C. chinensis was confirmed as the active fraction. Compounds 6, 10, 22, 23 and 27 were screened as the potential active components. Ethyl acetate fraction improved the condition of CKD rats, while multi-omics identified a triple-functional network against inflammation, oxidative stress, and fibrosis, with PI3K-AKT/MAPK/HIF-1 pathways verified. Cell experiments and molecular dynamics simulation identified compound 6 as the key active component, with its regulatory effects validated through PI3K-AKT/MAPK/HIF-1 pathways. Ethyl acetate fraction of C. chinensis and its active component exerted renoprotective effects by suppressing inflammation, oxidative stress, and fibrosis in CKD via regulating PI3K-Akt, MAPK, and HIF-1 pathways.

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