Network pharmacology and experimental validation to elucidate the pharmacological mechanisms of Bushen Huashi decoction against kidney stones

被引：6

作者：

Liu, Haizhao ^{[1
]}

Cao, Min ^{[1
]}

Jin, Yutong ^{[1
]}

Jia, Beitian ^{[1
]}

Wang, Liming ^{[2
]}

Dong, Mengxue ^{[1
]}

Han, Lu ^{[1
]}

Abankwah, Joseph ^{[1
]}

Liu, Jianwei ^{[1
]}

Zhou, Tao ^{[1
]}

Chen, Baogui ^{[3
]}

Wang, Yiyang ^{[1
]}

Bian, Yuhong ^{[1
]}

机构：

[1] Tianjin Univ Tradit Chinese Med, Sch Integrat Med, Tianjin, Peoples R China

[2] Tianjin Univ Tradit Chinese Med, State Key Lab Component Based Chinese Med, Tianjin Key Lab TCM Chem & Anal, Tianjin, Peoples R China

[3] Tianjin Univ Tradit Chinese Med, Wuqing Hosp Tradit Chinese Med, Tianjin, Peoples R China

来源：

FRONTIERS IN ENDOCRINOLOGY | 2023年 / 14卷

基金：

国家重点研发计划;

关键词：

Bushen Huashi decoction; kidney stone; network pharmacology; Chinese medicine formula; crystal deposition; OXALATE MONOHYDRATE CRYSTALS; POSTMENOPAUSAL HORMONE USE; TRANSCRIPTION FACTOR NRF2; OXIDATIVE STRESS; BETA-SITOSTEROL; NEPHROLITHIASIS; RISK; CELLS; DISEASE; HYPERTENSION;

D O I：

10.3389/fendo.2023.1031895

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

IntroductionKidney 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. MethodsThe 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. ResultsOur 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. DiscussionThis study provides evidence that BSHS plays a critical role in anti-KS via 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.

引用

页数：14