Network pharmacology and experimental validation to elucidate the pharmacological mechanisms of Bushen Huashi decoction against kidney stones
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...
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Frontiers Media S.A.
2023-02-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2023.1031895/full |
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| author | 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 |
| author_facet | 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 |
| author_sort | Haizhao Liu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-10T15:18:57Z |
| format | Article |
| id | doaj.art-01987ff571344af19af9492a24fafa87 |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-04-10T15:18:57Z |
| publishDate | 2023-02-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Endocrinology |
| spelling | doaj.art-01987ff571344af19af9492a24fafa872023-02-14T16:38:52ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922023-02-011410.3389/fendo.2023.10318951031895Network pharmacology and experimental validation to elucidate the pharmacological mechanisms of Bushen Huashi decoction against kidney stonesHaizhao Liu0Min Cao1Yutong Jin2Beitian Jia3Liming Wang4Mengxue Dong5Lu Han6Joseph Abankwah7Jianwei Liu8Tao Zhou9Baogui Chen10Yiyang Wang11Yuhong Bian12School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaSchool of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaSchool of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaSchool of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaState Key Laboratory of Component-Based Chinese Medicine, Tianjin Key Laboratory of TCM Chemistry and Analysis, Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaSchool of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaSchool of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaSchool of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaSchool of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaSchool of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaWuqing Hospital of Traditional Chinese Medicine Affiliated with Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaSchool of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaSchool of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaIntroductionKidney 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.https://www.frontiersin.org/articles/10.3389/fendo.2023.1031895/fullBushen Huashi decoctionkidney stonenetwork pharmacologyChinese medicine formulacrystal deposition |
| spellingShingle | 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 Network pharmacology and experimental validation to elucidate the pharmacological mechanisms of Bushen Huashi decoction against kidney stones Frontiers in Endocrinology Bushen Huashi decoction kidney stone network pharmacology Chinese medicine formula crystal deposition |
| title | Network pharmacology and experimental validation to elucidate the pharmacological mechanisms of Bushen Huashi decoction against kidney stones |
| title_full | Network pharmacology and experimental validation to elucidate the pharmacological mechanisms of Bushen Huashi decoction against kidney stones |
| title_fullStr | Network pharmacology and experimental validation to elucidate the pharmacological mechanisms of Bushen Huashi decoction against kidney stones |
| title_full_unstemmed | Network pharmacology and experimental validation to elucidate the pharmacological mechanisms of Bushen Huashi decoction against kidney stones |
| title_short | Network pharmacology and experimental validation to elucidate the pharmacological mechanisms of Bushen Huashi decoction against kidney stones |
| title_sort | network pharmacology and experimental validation to elucidate the pharmacological mechanisms of bushen huashi decoction against kidney stones |
| topic | Bushen Huashi decoction kidney stone network pharmacology Chinese medicine formula crystal deposition |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2023.1031895/full |
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