基于脂质组学调节的当归补血汤治疗糖尿病肾病的药效学物质基础的发现

IF 6.7 1区医学 Q1 CHEMISTRY, MEDICINAL

Phytomedicine Pub Date : 2025-03-22 DOI:10.1016/j.phymed.2025.156643

Xu Wang , Jing Liu , Tingting Liu , Cheng Fang , Lin Ding , Qiyao Li , Kaidi Yang , Xiuhong Wu

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引用次数: 0

摘要

当归补血汤是治疗糖尿病肾病（DKD）的方剂。然而，DBD在DKD治疗中的药效学物质基础尚不清楚，阻碍了其产业化发展和药物配方的创新。目的脂质代谢紊乱是DKD进展的重要病理机制。本研究采用脂质组学方法阐明并验证了DBD治疗DKD的药效学物质基础。方法选用雄性SD大鼠48只，每组8只。DKD模型采用高脂高糖饮食，腹腔注射低剂量STZ，单侧肾切除。连续给药10周，观察其对DKD的治疗效果。通过脂质组学分析DKD模型中的脂质生物标志物，通过uplc - q - orbitrap ms对dbd治疗大鼠血液中的过渡成分进行表征，通过体内脂质生物标志物与有效成分的关联，确定潜在的药效学物质，然后进行分子对接和体外实验，验证关键药效学成分。结果dbd能显著改善DKD模型大鼠的血糖、血脂水平和肾功能。脂质组学在DKD模型中鉴定出37种脂质生物标志物，DBD对这些生物标志物有显著的纠正作用。在治疗有效状态下，鉴定出91种DBD血液过渡成分。相关分析显示44种与DKD治疗相关的药效学物质，其中阿魏酸、毛蕊花素、黄芪甲苷和藁本内酯是关键成分。这些物质通过增加脂质沉积足细胞中SIRT1、PPARG和ABCA1蛋白的水平而起作用。综上所述，本研究首次从脂质代谢平衡角度，从药效学评价、药效学物质基础和作用机制三个方面，用现代科学语言阐释了DKD治疗DBD的科学内涵，为中药方剂的现代应用提供了经验依据。

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Discovery of the pharmacodynamic material basis of Danggui Buxue Decoction in the treatment of diabetic kidney disease based on lipidomics regulation

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Discovery of the pharmacodynamic material basis of Danggui Buxue Decoction in the treatment of diabetic kidney disease based on lipidomics regulation

Background

Danggui Buxue Decoction (DBD) is a formula used for treating diabetic kidney disease (DKD). However, the pharmacodynamic material basis of DBD in DKD therapy remains unclear, hindering its industrial development and innovation in drug formulations.

Purpose

Lipid metabolism disorder is a key pathological mechanism in DKD progression. This study employs lipidomics to elucidate and validate the pharmacodynamic material basis of DBD in treating DKD.

Methods

Forty-eight male SD rats were used in the experiment, with 8 rats per group. The DKD model was constructed with a diet high in fat and sugar, together with intraperitoneal administration of low-dose STZ and unilateral nephrectomy. DBD was administered continuously for 10 weeks to assess its therapeutic efficacy on DKD. Lipid biomarkers in the DKD models were analyzed using lipidomics, while the transitional components in the blood of DBD-treated rats were characterized through UPLC-QE-Orbitrap MS. Potential pharmacodynamic substances were identified by correlating lipid biomarkers with active ingredients in vivo, followed by molecular docking and in vitro experiments to validate key pharmacodynamic components.

Results

DBD significantly improved blood glucose, blood lipid levels, and renal function in DKD model rats. Lipidomics identified 37 lipid biomarkers in the DKD models, and DBD demonstrated a marked corrective effect on these biomarkers. In the therapeutically effective state, 91 blood transitional components of DBD were identified. Correlation analysis revealed 44 pharmacodynamic substances associated with DKD treatment, with ferulic acid, calycosin, astragaloside IV, and ligustilide being the key components. These substances acted by increasing the levels of SIRT1, PPARG, and ABCA1 proteins in lipid-deposited podocytes.

Conclusion

In conclusion, this study explained the scientific connotation of DBD treatment of DKD with modern scientific language from three aspects: pharmacodynamic evaluation, pharmacodynamic material basis and mechanism of action from the perspective of lipid metabolism balance for the first time, and provided an empirical basis for the modern application of traditional Chinese medicinal prescriptions.

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来源期刊

Phytomedicine 医学-药学

CiteScore

10.30

自引率

5.10%

发文量

670

审稿时长

91 days

期刊介绍： Phytomedicine is a therapy-oriented journal that publishes innovative studies on the efficacy, safety, quality, and mechanisms of action of specified plant extracts, phytopharmaceuticals, and their isolated constituents. This includes clinical, pharmacological, pharmacokinetic, and toxicological studies of herbal medicinal products, preparations, and purified compounds with defined and consistent quality, ensuring reproducible pharmacological activity. Founded in 1994, Phytomedicine aims to focus and stimulate research in this field and establish internationally accepted scientific standards for pharmacological studies, proof of clinical efficacy, and safety of phytomedicines.