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Network pharmacology and experimental evaluation strategies to decipher the underlying pharmacological mechanism of Traditional Chinese Medicine CFF-1 against prostate cancer.

ABSTRACT: Prostate cancer (PCa) is a common malignancy in elderly men. We have applied Traditional Chinese Medicine CFF-1 in clinical treatments for PCa for several years. Here, we aimed to identify the underlying mechanism of CFF-1 on PCa using network pharmacology and experimental validation. Active ingredients, potential targets of CFF-1 were acquired from the public databases. Subsequently, protein-protein interaction (PPI) and the herbs-active ingredients-target network was constructed. A prognostic model for PCa was also constructed based on key targets. In vitro experiments using PCa cell lines CWR22Rv1 and PC-3 were carried out to validate the potential mechanism of CFF-1 on PCa. A total of 112 bioactive compounds and 359 key targets were screened from public databases. PPI and herbs-active ingredients-target network analysis determined 12 genes as the main targets of CFF-1 on PCa. Molecular docking studies indicated that the primary active ingredients of CFF-1 possess strong binding affinity to the top five hub targets. DNMT3B, RXRB and HPRT1 were found to be involved in immune regulation of PCa. In vitro, CFF-1 was found to inhibit PCa cell proliferation, migration, invasion and induce apoptosis via PI3K-Akt, HIF-1, TNF, EGFR-TKI resistance and PD-1 checkpoint signaling pathways. This study comprehensively elucidates the underlying molecular mechanism of CFF-1 against PCa, offering a strong rationale for clinical application of CFF-1 in PCa treatment.

SUBMITTER: Wei Y

PROVIDER: S-EPMC11006490 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature

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Network pharmacology and experimental evaluation strategies to decipher the underlying pharmacological mechanism of Traditional Chinese Medicine CFF-1 against prostate cancer.

Wei Yong Y Zhu Mingxia M Chen Ye Y Ji Qianying Q Wang Jun J Shen Luming L Yang Xin X Hu Haibin H Zhou Xin X Zhu Qingyi Q

Aging 20240313 6

Prostate cancer (PCa) is a common malignancy in elderly men. We have applied Traditional Chinese Medicine CFF-1 in clinical treatments for PCa for several years. Here, we aimed to identify the underlying mechanism of CFF-1 on PCa using network pharmacology and experimental validation. Active ingredients, potential targets of CFF-1 were acquired from the public databases. Subsequently, protein-protein interaction (PPI) and the herbs-active ingredients-target network was constructed. A prognostic ...[more]

PMID: 38484140

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Project description:Diabetes mellitus (DM) is a chronic metabolic disease that is highly susceptible to kidney injury. Di'ao XinXueKang capsules (DXXK) is a novel Chinese herbal medicine that has been used in clinical trials for the therapy of DM and kidney disease, but the underlying pharmacological mechanism remains unclear. This study aims to integrate network pharmacology, molecular docking and in vivo experiments to explore the potential mechanisms of DXXK in the treatment of diabetic kidney injury. The chemical constituents of DXXK were extracted from the ETCM and Batman-TCM databases, and then evaluated for their pharmacological activity via the Swiss ADME platform. Multiple disease databases were searched and integrated for DM-related targets. Overlapping targets were then collected to construct a protein-protein interaction (PPI) network. KEGG and GO enrichment analyses were performed based on the Metascape database, and molecular docking was performed using AutoDock Vina software. The main components in DXXK were analyzed by HPLC. The results of network pharmacology and molecular docking were validated in an animal model of DM induced by the combination of a high-fat diet (HFD) and streptozotocin (STZ). We screened and obtained 7 ingredients and identified dioscin, protodioscin, and pseudoprotodioscin as the major components of DXXK by HPLC. A total of 2,216 DM-related pathogenic genes were obtained from DrugBank, GeneCards, OMIM, and DisGeNET databases. KEGG and GO enrichment analyses indicated that the TGF-beta signaling pathway is a critical pathway associated with DM therapy. Molecular docking revealed that the ingredients in DXXK bind to the pivotal targets TGFβ1, Smad2, and Smad3. In diabetic mice, we found that DXXK alleviated diabetic symptoms, lowered blood glucose, improved insulin tolerance, and modulated lipid metabolism. Furthermore, DXXK attenuated renal lesions and fibrosis by downregulating TGFβ1, Smad2, and Smad3. Collectively, our results suggest that DXXK has the potential to regulate glucolipid metabolism in DM, and it may serve as a viable therapeutic option for renoprotection by inhibiting of the TGF-β1/Smad2/3 pathway.

Dataset Information

Network pharmacology and experimental evaluation strategies to decipher the underlying pharmacological mechanism of Traditional Chinese Medicine CFF-1 against prostate cancer.

Publications

Network pharmacology and experimental evaluation strategies to decipher the underlying pharmacological mechanism of Traditional Chinese Medicine CFF-1 against prostate cancer.

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