UPLC-Q-TOF/MS, Network Pharmacology, and Experimental Validation Reveal the Mechanisms of Shuangbai Tablet Against Albuminuria.

IF 3.2 4区医学 Q2 PHARMACOLOGY & PHARMACY

Current pharmaceutical design Pub Date : 2026-10-08 DOI:10.2174/0113816128504944260930051855

Xiaoqin Ma, Chenxia Hao, Huiting Jiang, Weixia Zhang, Qin Xia, Wanhua Yang, Jingjing Huang

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引用次数: 0

Abstract

Introduction: Shuangbai Tablet (SBT), a traditional Chinese medicine, has demonstrated efficacy in reducing albuminuria. This study aimed to investigate the therapeutic mechanisms underlying its antialbuminuric effects.

Methods: The phytochemicals of SBT were analyzed by UPLC-Q-TOF/MS. Subsequently, we crossvalidated the identified phytochemicals and predicted the potential targets of SBT for albuminuria by network pharmacology and molecular docking analysis. Albuminuric male Wistar rats were induced by a single tailvein injection of Adriamycin (ADR, 5 mg/kg) and orally administered SBT for 8 weeks. Then, 24-hour Urine Protein (24 h-UTP) and serum albumin were assessed, along with changes in renal function, systemic lipid metabolism, and serum COX-2 levels. Renal histopathology was evaluated by H&E staining, while the renal expressions of VEGFR-1, VEGFA, HIF-1α, NF-κB p65, ACTN-4, and podocin were assessed by immunohistochemistry and western blotting.

Results: Nine core active phytochemicals of SBT targeting HIF-1α and VEGFA were identified for albuminuria treatment. Molecular docking predicted favorable binding affinities between these phytochemicals and both HIF-1α and VEGFA. In ADR-treated rats, SBT significantly reduced proteinuria (24 h-UTP: 245.1 (95% CI, 174.9 to 315.3) mg/24 h in the middle-dose SBT group vs. 585.2 (95% CI, 460.0 to 710.4) mg/24 h in the ADR group; p < 0.0001), reversed hypoalbuminemia (ALB: 24.44 (95% CI, 17.62 to 31.25) g/L vs. 9.70 (95% CI, 4.94 to 14.46) g/L; p < 0.05), ameliorated renal dysfunction and lipid metabolic disturbances, and suppressed serum COX-2 levels. Histopathological analysis showed ameliorated renal injury. SBT stabilized the decreased expressions of renal VEGFR-1, VEGFA, HIF-1α, ACTN-4, and podocin, while suppressing NF-κB p65expression.

Discussion: Further functional characterization studies are warranted to validate the pharmacological effects of SBT on albuminuria.

Conclusion: SBT can alleviate albuminuria, inflammation, and renal injury, associated with the stabilization of HIF-1α and VEGFA expressions.

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UPLC-Q-TOF/MS、网络药理学及实验验证揭示双百片抗蛋白尿作用机制

简介：双白片是一种中药，具有降低蛋白尿的作用。本研究旨在探讨其抗蛋白尿作用的治疗机制。方法：采用UPLC-Q-TOF/MS对SBT的植物化学成分进行分析。随后，我们交叉验证了鉴定的植物化学物质，并通过网络药理学和分子对接分析预测了SBT治疗蛋白尿的潜在靶点。采用单次尾静脉注射阿霉素（ADR, 5 mg/kg）和口服SBT诱导白蛋白尿雄性Wistar大鼠8周。然后评估24小时尿蛋白（24 h-UTP）和血清白蛋白，以及肾功能、全身脂质代谢和血清COX-2水平的变化。采用H&E染色检测肾组织病理学，免疫组织化学和western blot检测肾组织中VEGFR-1、VEGFA、HIF-1α、NF-κB p65、ACTN-4、podocin的表达。结果：鉴定出9种靶向HIF-1α和VEGFA的SBT核心活性植物化学物质用于治疗蛋白尿。分子对接预测了这些植物化学物质与HIF-1α和VEGFA之间良好的结合亲和力。在ADR处理大鼠中，SBT显著降低蛋白尿(24 h- utp：中剂量SBT组245.1 (95% CI, 174.9 ~ 315.3) mg/24 h， ADR组585.2 (95% CI, 460.0 ~ 710.4) mg/24 h；p < 0.0001)，逆转低白蛋白血症(ALB: 24.44 (95% CI, 17.62 ~ 31.25) g/L vs. 9.70 (95% CI, 4.94 ~ 14.46) g/L；p < 0.05)，改善肾功能和脂质代谢紊乱，抑制血清COX-2水平。组织病理学分析显示肾损伤改善。SBT稳定了肾脏VEGFR-1、VEGFA、HIF-1α、ACTN-4和podocin的表达，同时抑制了NF-κB p65的表达。讨论：需要进一步的功能表征研究来验证SBT对蛋白尿的药理作用。结论：SBT可减轻蛋白尿、炎症和肾损伤，其作用与稳定HIF-1α和VEGFA表达有关。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current pharmaceutical design 医学-药学

CiteScore

6.30

自引率

0.00%

发文量

302

审稿时长

2 months

期刊介绍： Current Pharmaceutical Design publishes timely in-depth reviews and research articles from leading pharmaceutical researchers in the field, covering all aspects of current research in rational drug design. Each issue is devoted to a single major therapeutic area guest edited by an acknowledged authority in the field. Each thematic issue of Current Pharmaceutical Design covers all subject areas of major importance to modern drug design including: medicinal chemistry, pharmacology, drug targets and disease mechanism.