Investigating the multi-target therapeutic mechanism of Guihuang formula on Chronic Prostatitis

Liu, Shengjing; Zhao, Feng; Deng, Ying-Jun; Yin, Zhimin; Yan, Bin; Guo, Jun; Gao, Qing-He

doi:10.1016/j.jep.2022.115386

Cited by 15 publications

(13 citation statements)

References 33 publications

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“…The study was approved by the Ethics Committee of Xiyuan Hospital of China Academy of Chinese Medical Sciences (2020XLC005). The CP rat model was established by intraprostatic injection of a mixture of complete Freund's adjuvant and prostate extracts, according to our previous research (S. Liu, Zhao, et al, 2022), as shown in Figure 1b.…”

Section: Methodsmentioning

confidence: 99%

“…Recently, increasing evidence has shown that an imbalance caused by the release of proinflammatory cytokines is an important factor in the pathogenesis of CP, and the regulation of its production and release is regarded as an effective means of treatment (S. Liu, Zhao, et al, 2022; Zhou et al, 2022). NOD‐like receptor thermal protein domain associated protein 3 (NLRP3) is related to innate immunity and aberrant NLRP3 inflammasome activation contributes to a wide variety of inflammatory diseases (Mayes‐Hopfinger et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

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Ursolic acid alleviates chronic prostatitis via regulating NLRP3 inflammasome‐mediated Caspase‐1/GSDMD pyroptosis pathway

Liu,

Guo,

Gao

et al. 2023

Phytotherapy Research

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Ursolic acid (UA) is a naturally occurring pentacyclic triterpenoid widely found in fruits and vegetables. It has been reported that UA has anti‐inflammatory effects. However, its efficacy and mechanism of action in the treatment of chronic prostatitis (CP) remain unclear. This study aimed to investigate the efficacy of UA treatment in CP and further explore the underlying mechanism. CP rat and pyroptosis cell models were established in vivo and in vitro, respectively. The efficacy of UA in inhibiting CP was evaluated via haematoxylin‐eosin (HE) staining and measurement of inflammatory cytokines. RNA sequencing and molecular docking were used to predict the therapeutic targets of UA in CP. The expression of pyroptosis‐related proteins was examined using various techniques, including immunohistochemistry, immunofluorescence, and flow cytometry. UA significantly ameliorated pathological damage and reduced the levels of proinflammatory cytokines in the CP model rats. RNA sequencing analysis and molecular docking suggested that NLRP3, Caspase‐1, and GSDMD may be key targets. We also found that UA decreased ROS levels, alleviated oxidative stress, and inhibited p‐NF‐κB protein expression both in vivo and in vitro. UA improved pyroptosis morphology as indicated by electron microscope and inhibited the expression of the pyroptosis‐related proteins NLRP3, Caspase‐1, ASC, and GSDMD, reversed the levels of IL‐1β, IL‐18, and lactate dehydrogenase in vivo and in vitro. UA can mitigate CP by regulating the NLRP3 inflammasome‐mediated Caspase‐1/GSDMD pathway. Therefore, UA may be a potential for the treatment of CP.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Ursolic acid alleviates chronic prostatitis via regulating NLRP3 inflammasome‐mediated Caspase‐1/GSDMD pyroptosis pathway

Liu,

Guo,

Gao

et al. 2023

Phytotherapy Research

Self Cite

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“…The results of the PPI analysis were imported into Cytoscape software (Version 3.7.2), and topological analysis of the PPI network was performed using the CytoNCA plug-in to obtain comprehensive data of each node (Tang et al, 2015). According to the network analysis method (Liu et al, 2022), the hub targets of MLST for the treatment of varicocele-related male infertility were screened by setting the degree centrality greater than 2 times the median and the betweenness centrality and closeness centrality both greater than the median. The components-targets mapping relationships were imported into Cytoscape software to construct a "Drug-Components-Targets-Disease" network.…”

Section: Network Analysis Drug Targets and Disease Targets Screeningmentioning

confidence: 99%

Mailuoshutong pill for varicocele-associated male infertility—Phytochemical characterisation and multitarget mechanism

Ji²,

Zhang³

et al. 2022

Front. Pharmacol.

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Background: Varicocele (VC) is a relatively common and treatable cause of male infertility. Mailuoshutong pill (MLST), a traditional Chinese patent medicine, is widely used for treating varicose vein disease, but the underlying mechanism of MLST on varicocele-associated male infertility is unclear.Objective: To reveal the phytochemical characterisation and multitarget mechanism of MLST on varicocele-associated male infertility.Methods: The components in MLST were determined using UHPLC-MS/MS. Through network analysis, we constructed the “Drug-Components-Targets-Disease” network and predicted the potential biological functions and signaling pathways of MLST. Finally, the therapeutic effects and potential mechanisms of MLST were discovered by pharmacological experiments.Results: By network analysis, the “Drug-Components-Targets-Disease” network was constructed, 62 components such as apigenin, limonin, kaempferol, and obacunoic acid may be the main active components of MLST for varicocele-associated male infertility, 28 targets such as VEGFA, PIK3CA, AKT1, and MTOR are considered as hub targets, signaling pathways such as HIF-1, Estrogen, PI3K/Akt, and mTOR may be key pathways for MLST against varicocele-associated male infertility. Through pharmacological experiments, we found that MLST ameliorated VC-induced testicular atrophy. Further histomorphology showed that MLST reduced VC-induced damage to testicular spermatogonia and seminiferous tubule, while MLST reduced ROS and MDA levels and increased antioxidant enzymes (GSH, GSH-Px, SOD, and CAT) levels. TUNEL staining and immunofluorescence showed that MLST reduced VC-induced apoptosis in testicular tissue, decreased BAX, and increased BCL2. Western blot results showed that MLST decreased the phosphorylation of PI3K, AKT, and mTOR proteins, and decreased the expression of HIF1α.Conclusion: The phytochemical characterisation and multitarget mechanism of MLST on varicocele-associated male infertility were discovered using network analysis and pharmacological experiments. We verified that MLST can inhibit the activation of the PI3K/Akt/mTOR signaling pathway, reduce the expression of HIF1α, and further attenuate VC-induced oxidative stress and apoptosis in the testis. These findings provide evidence for the therapeutic role of MLST in varicocele-associated male infertility.

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“…In particular, network pharmacology can create a relationship prediction model between drugs and disease targets, integrate an interaction network to analyze drug interactions with specific nodes in each network module, and investigate the interaction relationship between drugs and potential targets from a systematic perspective [ 12 , 13 ]. Network pharmacology is highly suited for evaluating the numerous components, targets, and pathways of TCM due to its complex composition and multitarget therapeutic characteristics [ 14 , 15 ]. Computer simulation technology is used in molecular docking [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Network Pharmacology and Molecular Docking on the Molecular Mechanism of Jiawei-Huang Lian-Gan Jiang Decoction in the Treatment of Colorectal Adenomas

Long

Yang

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Purpose. Jiawei-Huang Lian-Gan Jiang decoction (JWHLGJD) was developed to treat and prevent the patients with colorectal adenomas (CRA) in China. This study is aimed to discover JWHLGJD’s active compounds and demonstrate mechanisms of JWHLGJD against CRA through network pharmacology and molecular docking techniques. Methods. All the components of JWHLGJD were retrieved from the pharmacology database of Traditional Chinese Medicine Systems Pharmacology (TCMSP). The GeneCards database, the Online Mendelian Inheritance in Man database (OMIM), the DrugBank database, and PharmGKB were used to obtain the genes matching the targets. Cytoscape created the compound-target network. The network of target protein-protein interactions (PPI) was constructed using the STRING database. Gene Ontology (GO) functional and the Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathways involved in the targets were analyzed by using the DAVID database. Cytoscape created the component-target-pathway (C-T-P) network. AutoDock Vina software was used to verify the molecular docking of JWHLGJD components and key targets. Core genes linked with survival and tumor microenvironment were analyzed through the Kaplan–Meier plotter and TIMER 2.0 databases, respectively. Results. Compound-target network mainly contained 38 compounds and 130 targets of the JWHLGJD associated with CRA. TP53, MAPK1, JUN, HSP90AA1, and AKT1 were identified as core targets by the PPI network. KEGG pathway shows that the pathways in cancer, lipids, and atherosclerosis, PI3K-Akt signaling pathway and MAPK signaling pathway, are the most relevant pathways to CRA. The C-T-P network suggests that the active component in JWHLGJD is capable of regulating target genes of these related pathways. The results of molecular docking showed that berberine and stigmasterol were the top two compounds of JWHLGJD, which had high affinity with TP53 and MAPK1, respectively. And, MAPK1 exerted a more significant effect on the prognosis of adenocarcinoma, for it was highly associated with various immune cells. Conclusion. Findings in this study provided light on JWHLGJD’s active components, prospective targets, and molecular mechanism. It also gave a potential way to uncovering the scientific underpinning and therapeutic mechanism of traditional Chinese medicine (TCM) formulas.

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Investigating the multi-target therapeutic mechanism of Guihuang formula on Chronic Prostatitis

Cited by 15 publications

References 33 publications

Ursolic acid alleviates chronic prostatitis via regulating NLRP3 inflammasome‐mediated Caspase‐1/GSDMD pyroptosis pathway

Ursolic acid alleviates chronic prostatitis via regulating NLRP3 inflammasome‐mediated Caspase‐1/GSDMD pyroptosis pathway

Mailuoshutong pill for varicocele-associated male infertility—Phytochemical characterisation and multitarget mechanism

Network Pharmacology and Molecular Docking on the Molecular Mechanism of Jiawei-Huang Lian-Gan Jiang Decoction in the Treatment of Colorectal Adenomas

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