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Abstract Hypertension has become a major contributor to the morbidity and mortality of cardiovascular diseases worldwide. Despite the evidence of the anti‐hypertensive effect of gastrodia‐uncaria granules (GUG) in hypertensive patients, little is known about its potential therapeutic targets as well as the underlying mechanism. GUG components were sourced from TCMSP and HERB, with bioactive ingredients screened. Hypertension‐related targets were gathered from DisGeNET, OMIM, GeneCards, CTD, and GEO. The STRING database constructed a protein–protein interaction network, visualized by Cytoscape 3.7.1. Core targets were analyzed via GO and KEGG using R package ClusterProfiler. Molecular docking with AutodockVina 1.2.2 revealed favorable binding affinities. In vivo studies on hypertensive mice and rats validated network pharmacology findings. GUG yielded 228 active ingredients and 1190 targets, intersecting with 373 hypertension‐related genes. PPI network analysis identified five core genes: AKT1, TNF‐α, GAPDH, IL‐6, and ALB. Top enriched GO terms and KEGG pathways associated with the anti‐hypertensive properties of GUG were documented. Molecular docking indicated stable binding of core components to targets. In vivo study showed that GUG could improve vascular relaxation, alleviate vascular remodeling, and lower blood pressure in hypertensive animal models possibly through inhibiting inflammatory factors such as AKT1, mTOR, and CCND1. Integrated network pharmacology and in vivo experiment showed that GUG may exert anti‐hypertensive effects by inhibiting inflammation response, which provides some clues for understanding the effect and mechanisms of GUG in the treatment of hypertension.

Objective: To analyze the expression of protein kinase C delta (PKCẟ, PRKCD) in Liver hepatocellular carcinoma and its clinical significance based on bioinformatics, in order to provide a new direction for the study of therapeutic targets for Liver hepatocellular carcinoma. Methods: The PRKCD gene expression data and patient clinical information data in Liver hepatocellular carcinoma tissues and adjacent tissues were downloaded from The TCGA (The Cancer Genome Atlas) and UCSC Xena databases. The mRNA expression of PRKCD in Liver hepatocellular carcinoma was analyzed, and the protein expression of PRKCD in Liver hepatocellular carcinoma was analyzed by Human Protein Atlas (HPA) databases. Furthermore, its relationship with clinicopathological features and prognosis in patients with Liver hepatocellular carcinoma was analyzed. GSEA enrichment analysis were carried out for PRKCD in Liver hepatocellular carcinoma. Finally, the causes of changes in PRKCD expression were analyzed from the perspective of genetic and epigenetics based on collated liver hepatocellular carcinoma data. Results: Both the mRNA and protein expression level of PRKCD gene in Liver hepatocellular carcinoma tissues was significantly higher than that in adjacent tissues. Its expression level was correlated with TNM stage, Histologic grade,Alpha fetoprotein (AFP) and Living status in clinicopathological features, and its expression level has certain clinical diagnostic accuracy. Kaplan-Meier analysis showed that the prognosis of patients with low PRKCD expression was significantly better than that with high PRKCD expression. Univariate and multivariate Cox regression analysis showed that PRKCD was an independent prognostic factor in patients with Liver hepatocellular carcinoma, and it was also found that the risk ratio of TNM stage III and stage IV survival curve (HR) was significantly greater than that of stage I and stage II. GSEA analysis showed that it was enriched in cell cycles and DNA replication, and was positively correlated with PRKCD. Enrichment analysis found that PRKCD is mainly involved in the chemokine signaling pathway, NOD-like receptor signaling pathway, PPAR signaling pathway, adipocytokine signaling pathway and T-cell receptor signaling pathway. Finally, through genetic and epigenetic analysis, it is found that the increase in the number of copies of genes will increase the expression level of PRKCD, and the methylation level is negatively correlated with the expression level of PRKCD. Conclusion: PRKCD gene is upregulated in Liver hepatocellular carcinoma tissues, and its overexpression level is closely related to patient poor prognosis. [ABSTRACT FROM AUTHOR]