School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
State Key Laboratory of Component-Based Chinese Medicine, Tianjin Key Laboratory of TCM Chemistry and Analysis, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
Front Endocrinol (Lausanne). 2023 Feb 14;14:1031895. doi: 10.3389/fendo.2023.1031895. eCollection 2023.
Kidney stone disease (KS) is a complicated disease with an increasing global incidence. It was shown that Bushen Huashi decoction (BSHS) is a classic Chinese medicine formula that has therapeutic benefits for patients with KS. However, its pharmacological profile and mechanism of action are yet to be elucidated.
The present study used a network pharmacology approach to characterize the mechanism by which BSHS affects KS. Compounds were retrieved from corresponding databases, and active compounds were selected based on their oral bioavailability (≥30) and drug-likeness index (≥0.18). BSHS potential proteins were obtained from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, whereas KS potential genes were obtained from GeneCards and OMIM, TTD, and DisGeNET. Gene ontology and pathway enrichment analysis were used to determine potential pathways associated with genes. The ingredients of BSHS extract were identified by the ultra-high-performance liquid chromatography coupled with quadrupole orbitrap mass spectrometry (UHPLC-Q/Orbitrap MS). The network pharmacology analyses predicted the potential underlying action mechanisms of BSHS on KS, which were further validated experimentally in the rat model of calcium oxalate kidney stones.
Our study found that BSHS reduced renal crystal deposition and improved renal function in ethylene glycol(EG)+ammonium chloride(AC)-induced rats, and also reversed oxidative stress levels and inhibited renal tubular epithelial cell apoptosis in rats. BSHS upregulated protein and mRNA expression of E2, ESR1, ESR2, BCL2, NRF2, and HO-1 in EG+AC-induced rat kidney while downregulating BAX protein and mRNA expression, consistent with the network pharmacology results.
This study provides evidence that BSHS plays a critical role in anti-KS regulation of E2/ESR1/2, NRF2/HO-1, and BCL2/BAX signaling pathways, indicating that BSHS is a candidate herbal drug for further investigation in treating KS.
肾结石病（KS）是一种复杂的疾病，其发病率在全球范围内呈上升趋势。研究表明，补肾化石汤（BSHS）是一种经典的中药方剂，对 KS 患者具有治疗作用。然而，其药理作用和作用机制尚不清楚。
本研究采用网络药理学方法来描述 BSHS 影响 KS 的作用机制。从相应的数据库中检索化合物，并根据口服生物利用度（≥30）和药物相似指数（≥0.18）选择活性化合物。从中药系统药理学（TCMSP）数据库中获得 BSHS 潜在蛋白，而 KS 潜在基因则从 GeneCards 和 OMIM、TTD 和 DisGeNET 中获得。进行基因本体论和途径富集分析，以确定与基因相关的潜在途径。通过超高效液相色谱与四极杆轨道阱质谱联用（UHPLC-Q/Orbitrap MS）鉴定 BSHS 提取物中的成分。网络药理学分析预测了 BSHS 对 KS 的潜在作用机制，并在乙二醇（EG）+氯化铵（AC）诱导的大鼠模型中进行了实验验证。
本研究发现，BSHS 可减少乙二醇（EG）+氯化铵（AC）诱导的大鼠肾结晶沉积，改善肾功能，还可逆转氧化应激水平，抑制大鼠肾小管上皮细胞凋亡。BSHS 上调 EG+AC 诱导的大鼠肾脏中 E2、ESR1、ESR2、BCL2、NRF2 和 HO-1 的蛋白和 mRNA 表达，同时下调 BAX 蛋白和 mRNA 表达，与网络药理学结果一致。
本研究为 BSHS 在 E2/ESR1/2、NRF2/HO-1 和 BCL2/BAX 信号通路中的抗-KS 调节作用提供了证据，表明 BSHS 是一种治疗 KS 的候选草药药物。
