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

Haizhao Liu; Min Cao; Yutong Jin; Beitian Jia; Liming Wang; Mengxue Dong; Lu Han; Joseph Abankwah; Jianwei Liu; Tao Zhou; Baogui Chen; Yiyang Wang; Yuhong Bian

doi:10.3389/fendo.2023.1031895

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

Front Endocrinol (Lausanne). 2023 Feb 14:14:1031895. doi: 10.3389/fendo.2023.1031895. eCollection 2023.

Authors

Haizhao Liu¹, Min Cao¹, Yutong Jin¹, Beitian Jia¹, Liming Wang², Mengxue Dong¹, Lu Han¹, Joseph Abankwah¹, Jianwei Liu¹, Tao Zhou¹, Baogui Chen³, Yiyang Wang¹, Yuhong Bian¹

Affiliations

¹ School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
² State Key Laboratory of Component-Based Chinese Medicine, Tianjin Key Laboratory of TCM Chemistry and Analysis, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
³ Wuqing Hospital of Traditional Chinese Medicine Affiliated with Tianjin University of Traditional Chinese Medicine, Tianjin, China.

Abstract

Introduction: 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.

Methods: 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.

Results: 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.

Discussion: This 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.

Keywords: Bushen Huashi decoction; Chinese medicine formula; crystal deposition; kidney stone; network pharmacology.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Kidney Calculi* / drug therapy
NF-E2-Related Factor 2 / genetics
Network Pharmacology*
Proto-Oncogene Proteins c-bcl-2
RNA, Messenger
Rats

Substances

NF-E2-Related Factor 2
Proto-Oncogene Proteins c-bcl-2
RNA, Messenger

Grants and funding

This work was by supported by the National Key R&D Program of China (No. 2018YFC1706500), Postgraduate Science Research Fund of Tianjin (No. 2021YJSB293), and Postgraduate Science Research Fund of Tianjin University of Traditional Chinese Medicine (No. YJSKC-20211019).