Unveiling therapeutic targets and preventive components for kidney insufficiency and blood stasis-type BPH: bridging metabolomics, network pharmacology and reverse screening

Benign prostatic hyperplasia (BPH) is a common disease affecting male urinary system function and quality of life, with its incidence increasing due to population ageing and unhealthy lifestyles. Modern medicine mainly adopts symptomatic treatments such as 5-alpha reductase inhibitors and alpha1 adr...

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Main Authors: Xiangpeng Kong, Haiqin Ren, Ke Pei, Yajun Yao, Zhigang Liang, Yunfeng Xue, Shuang Liang, Tongtong Li, Jing Zhang, Yuxia Guo, Miaorong Pei, Huifeng Li
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-06-01
Series:Frontiers in Pharmacology
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Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2025.1584766/full
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author Xiangpeng Kong
Xiangpeng Kong
Haiqin Ren
Ke Pei
Yajun Yao
Zhigang Liang
Yunfeng Xue
Shuang Liang
Tongtong Li
Jing Zhang
Yuxia Guo
Miaorong Pei
Huifeng Li
author_facet Xiangpeng Kong
Xiangpeng Kong
Haiqin Ren
Ke Pei
Yajun Yao
Zhigang Liang
Yunfeng Xue
Shuang Liang
Tongtong Li
Jing Zhang
Yuxia Guo
Miaorong Pei
Huifeng Li
author_sort Xiangpeng Kong
collection DOAJ
description Benign prostatic hyperplasia (BPH) is a common disease affecting male urinary system function and quality of life, with its incidence increasing due to population ageing and unhealthy lifestyles. Modern medicine mainly adopts symptomatic treatments such as 5-alpha reductase inhibitors and alpha1 adrenergic receptor blockers. However, due to the complex pathogenesis of BPH, these drugs can only partially alleviate symptoms and have shortcomings such as high treatment costs and significant side effects. BPH is similar to the descriptions of “Jīng Lóng” and “Lóng Bì” in traditional Chinese medicine (TCM), and its onset is closely related to liver and kidney dysfunction. Kidney insufficiency and blood stasis are common clinical syndromes of BPH. Compared with modern medicine, treatment based on syndrome differentiation of TCM can achieve good results in treating this subtype of BPH. Therefore, guided by the holistic view of TCM, adopting a holistic and systematic research approach to explore therapeutic targets and potential therapeutic components for BPH with a specific syndrome can provide new ideas for the clinical treatment of BPH. This study integrated clinical metabolomics and network pharmacology to identify therapeutic targets for kidney insufficiency and blood stasis-type BPH. Serum analysis of BPH patients and healthy controls for testosterone, estradiol, SRD5α2, NF-κB p65, and TGF-β levels, alongside metabolomics and network pharmacology, revealed hormonal imbalance, increased inflammatory/fibrotic markers, and 58 differential metabolites in BPH. Pathway enrichment analysis identified 6 key metabolic pathways, while network pharmacology constructed four compound-reaction-enzyme-gene networks and pinpointed 178 potential targets, including 23 core targets. Reverse screening against the Yaozh Database-Natural Product AI Engine Platform matched 11 druggable targets with 49 interacting components, and target-component fitting analysis confirmed the reliability of 8 core targets. This combined approach validated the findings of hormonal imbalance and significant metabolic pathway changes and provided valuable insights for BPH treatment and drug development.
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spelling doaj-art-dff119ee45e3450ea3f7a01b1781af512025-08-20T02:10:24ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-06-011610.3389/fphar.2025.15847661584766Unveiling therapeutic targets and preventive components for kidney insufficiency and blood stasis-type BPH: bridging metabolomics, network pharmacology and reverse screeningXiangpeng Kong0Xiangpeng Kong1Haiqin Ren2Ke Pei3Yajun Yao4Zhigang Liang5Yunfeng Xue6Shuang Liang7Tongtong Li8Jing Zhang9Yuxia Guo10Miaorong Pei11Huifeng Li12Institute of Pharmaceutical & Food Engineering, Chinese Medicine Master Studio of Wang Shimin, Shanxi University of Chinese Medicine, Jinzhong, ChinaShanxi Province Doctor Innovation Station (Shanxi Zhendong WuheTang Pharmaceutical Co., Ltd. Station), Changzhi, ChinaInstitute of Pharmaceutical & Food Engineering, Chinese Medicine Master Studio of Wang Shimin, Shanxi University of Chinese Medicine, Jinzhong, ChinaInstitute of Pharmaceutical & Food Engineering, Chinese Medicine Master Studio of Wang Shimin, Shanxi University of Chinese Medicine, Jinzhong, ChinaDepartment of Chinese Medicine, Shanxi Pharmaceutical Vocational College, Taiyuan, ChinaDepartment of Andrology, The Affiliated Hospital of Shanxi University of Chinese Medicine, Taiyuan, ChinaDepartment of Andrology, The Affiliated Hospital of Shanxi University of Chinese Medicine, Taiyuan, ChinaThe Third Clinical College, Shanxi University of Chinese Medicine, Jinzhong, ChinaInstitute of Pharmaceutical & Food Engineering, Chinese Medicine Master Studio of Wang Shimin, Shanxi University of Chinese Medicine, Jinzhong, ChinaInstitute of Pharmaceutical & Food Engineering, Chinese Medicine Master Studio of Wang Shimin, Shanxi University of Chinese Medicine, Jinzhong, ChinaInstitute of Pharmaceutical & Food Engineering, Chinese Medicine Master Studio of Wang Shimin, Shanxi University of Chinese Medicine, Jinzhong, ChinaInstitute of Pharmaceutical & Food Engineering, Chinese Medicine Master Studio of Wang Shimin, Shanxi University of Chinese Medicine, Jinzhong, ChinaInstitute of Pharmaceutical & Food Engineering, Chinese Medicine Master Studio of Wang Shimin, Shanxi University of Chinese Medicine, Jinzhong, ChinaBenign prostatic hyperplasia (BPH) is a common disease affecting male urinary system function and quality of life, with its incidence increasing due to population ageing and unhealthy lifestyles. Modern medicine mainly adopts symptomatic treatments such as 5-alpha reductase inhibitors and alpha1 adrenergic receptor blockers. However, due to the complex pathogenesis of BPH, these drugs can only partially alleviate symptoms and have shortcomings such as high treatment costs and significant side effects. BPH is similar to the descriptions of “Jīng Lóng” and “Lóng Bì” in traditional Chinese medicine (TCM), and its onset is closely related to liver and kidney dysfunction. Kidney insufficiency and blood stasis are common clinical syndromes of BPH. Compared with modern medicine, treatment based on syndrome differentiation of TCM can achieve good results in treating this subtype of BPH. Therefore, guided by the holistic view of TCM, adopting a holistic and systematic research approach to explore therapeutic targets and potential therapeutic components for BPH with a specific syndrome can provide new ideas for the clinical treatment of BPH. This study integrated clinical metabolomics and network pharmacology to identify therapeutic targets for kidney insufficiency and blood stasis-type BPH. Serum analysis of BPH patients and healthy controls for testosterone, estradiol, SRD5α2, NF-κB p65, and TGF-β levels, alongside metabolomics and network pharmacology, revealed hormonal imbalance, increased inflammatory/fibrotic markers, and 58 differential metabolites in BPH. Pathway enrichment analysis identified 6 key metabolic pathways, while network pharmacology constructed four compound-reaction-enzyme-gene networks and pinpointed 178 potential targets, including 23 core targets. Reverse screening against the Yaozh Database-Natural Product AI Engine Platform matched 11 druggable targets with 49 interacting components, and target-component fitting analysis confirmed the reliability of 8 core targets. This combined approach validated the findings of hormonal imbalance and significant metabolic pathway changes and provided valuable insights for BPH treatment and drug development.https://www.frontiersin.org/articles/10.3389/fphar.2025.1584766/fullbenign prostatic hyperplasia (BPH)kidney insufficiency and blood stasismetabolomicsnetwork pharmacologyintegrationtarget
spellingShingle Xiangpeng Kong
Xiangpeng Kong
Haiqin Ren
Ke Pei
Yajun Yao
Zhigang Liang
Yunfeng Xue
Shuang Liang
Tongtong Li
Jing Zhang
Yuxia Guo
Miaorong Pei
Huifeng Li
Unveiling therapeutic targets and preventive components for kidney insufficiency and blood stasis-type BPH: bridging metabolomics, network pharmacology and reverse screening
Frontiers in Pharmacology
benign prostatic hyperplasia (BPH)
kidney insufficiency and blood stasis
metabolomics
network pharmacology
integration
target
title Unveiling therapeutic targets and preventive components for kidney insufficiency and blood stasis-type BPH: bridging metabolomics, network pharmacology and reverse screening
title_full Unveiling therapeutic targets and preventive components for kidney insufficiency and blood stasis-type BPH: bridging metabolomics, network pharmacology and reverse screening
title_fullStr Unveiling therapeutic targets and preventive components for kidney insufficiency and blood stasis-type BPH: bridging metabolomics, network pharmacology and reverse screening
title_full_unstemmed Unveiling therapeutic targets and preventive components for kidney insufficiency and blood stasis-type BPH: bridging metabolomics, network pharmacology and reverse screening
title_short Unveiling therapeutic targets and preventive components for kidney insufficiency and blood stasis-type BPH: bridging metabolomics, network pharmacology and reverse screening
title_sort unveiling therapeutic targets and preventive components for kidney insufficiency and blood stasis type bph bridging metabolomics network pharmacology and reverse screening
topic benign prostatic hyperplasia (BPH)
kidney insufficiency and blood stasis
metabolomics
network pharmacology
integration
target
url https://www.frontiersin.org/articles/10.3389/fphar.2025.1584766/full
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