Bupi Yishen formula improves chronic kidney disease by restoring renal energy metabolism and mitochondrial oxidative phosphorylation

IF 6.7 1区医学 Q1 CHEMISTRY, MEDICINAL

Phytomedicine Pub Date : 2025-07-03 DOI:10.1016/j.phymed.2025.157055

Bingran Liu , Guowei Chen , Haoyu Mo , Xiaolin Liang , Xiaoyan Su , Fuhua Lu , Qizhan Lin , Xusheng Liu , Jiankun Deng , Difei Zhang

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Abstract

Background

Bupi Yishen formula (BYF) is a traditional Chinese herbal mixture with proven efficacy in attenuating kidney function deterioration among patients with advanced chronic kidney disease (CKD), and improving renal fibrosis of CKD animal models. Previous studies have shown that BYF rehabilitates metabolic dysregulation under CKD condition, but its exact mechanism remains unclear.

Purpose

This study aimed to elucidate the therapeutic effect and its potential mechanism on regulating renal energy metabolism in CKD.

Methods

An adenine-induced CKD rat model was treated with two doses of BYF decoction (15 g/kg/day or 30 g/kg/day) and losartan (as the positive control) for 4 weeks. Lipidomic and transcriptomic analyses of kidney samples from CKD rats revealed the BYF-reversed different lipid species and gene expression profiles respectively, thereby identifying potential pharmacological mechanisms. Further in vivo and in vitro experiments, network analyses, and molecular docking was used to confirm the proposed mechanisms affected by BYF.

Results

BYF had a profound impact on alleviating renal impairment and profibrotic phenotypes in CKD rats. Lipid profiling of kidneys from CKD rats showed that the dysmetabolism of glycerophospholipids, sphingolipids, and glycerolipids was primarily influenced by BYF. Transcriptome analysis of CKD rats identified renal energy metabolism (including fatty acid oxidation [FAO], glucose metabolism) and mitochondrial oxidative phosphorylation (OXPHOS) as the key dysregulated pathways, which were reversed by BYF. Further experiments confirmed that BYF partially restored defective FAO, dysregulated glucose metabolism, and impaired mitochondrial OXPHOS in the kidneys of CKD rats and TGFβ1-induced human tubule HK-2 cells. Besides, network analyses combined with molecular docking demonstrated a strong binding effect of BYF’s core compounds on key targets related to energy metabolism.

Conclusions

These results suggest that BYF protects against CKD by restoring renal energy homeostasis and mitochondrial OXPHOS, offering potential as an alternative therapy for renal fibrosis inherent to CKD.

Abstract Image

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补脾益肾方通过恢复肾脏能量代谢和线粒体氧化磷酸化，改善慢性肾脏疾病

补脾益肾方（BYF）是一种传统的中草药合剂，具有减轻晚期慢性肾病（CKD）患者肾功能恶化和改善CKD动物模型肾纤维化的功效。先前的研究表明，BYF可以恢复CKD患者的代谢失调，但其确切机制尚不清楚。目的探讨慢性肾病的治疗效果及其调节肾脏能量代谢的可能机制。方法以三腺苷诱导的CKD大鼠模型为研究对象，分别给药15 g/kg/d和30 g/kg/d，并以氯沙坦为阳性对照，治疗4周。对CKD大鼠肾脏样本的脂质组学和转录组学分析显示，byf分别逆转了不同的脂质种类和基因表达谱，从而确定了潜在的药理机制。通过进一步的体内和体外实验、网络分析和分子对接来证实所提出的BYF影响机制。结果黄芪多糖对减轻CKD大鼠肾脏损害和纤维化表型有明显作用。CKD大鼠肾脏脂质分析显示，甘油磷脂、鞘脂和甘油脂代谢异常主要受BYF的影响。CKD大鼠的转录组分析发现肾脏能量代谢（包括脂肪酸氧化[FAO]、葡萄糖代谢）和线粒体氧化磷酸化（OXPHOS）是关键的失调途径，而BYF可以逆转这些途径。进一步的实验证实，BYF部分恢复了CKD大鼠肾脏和tgf β1诱导的人小管HK-2细胞中有缺陷的FAO、葡萄糖代谢失调和线粒体OXPHOS受损。此外，结合分子对接的网络分析表明，BYF的核心化合物对能量代谢相关的关键靶点具有很强的结合作用。这些结果表明，BYF通过恢复肾脏能量稳态和线粒体OXPHOS来保护CKD，为CKD固有肾纤维化的替代治疗提供了潜力。

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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.