Abstract

Background Yeju Jiangya decoction (CIF) is an herbal formula from traditional Chinese medicine (TCM) for the treatment of hypertension. Materials and Methods Based on the analysis of network pharmacology, combined with in animal experiments, the network pharmacology was used to explore the potential proteins and mechanisms of CIF against hypertension. The bioactive compounds of CIF were screened by using the platform, and the targets of hypertension and CIF were collected. Then, the Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein-protein interaction network (PPI) core targets were carried out, and the useful proteins were found by molecular docking technology. Finally, we used N-nitro-L-arginine (L-NNA) induced hypertension model rats to confirm the effect and mechanism of CIF on hypertension. Results 14 bioactive compounds of CIF passed the virtual screening criteria, and 178 overlapping targets were identified as core targets of CIF against hypertension. The CIF-related target network with 178 nodes and 344 edges is constructed. The topological results show that quercetin and luteolin are the key components in the network. The key targets NOS3 (nitric oxide synthase 3) and NOS2 (nitric oxide synthase 2) were screened by the protein-protein interaction network. The analysis of target protein pathway enrichment showed that the accumulation pathway is related to the vascular structure of CIF regulation of hypertension. Further verification based on molecular docking results showed that NOS3 had the good binding ability with quercetin and luteolin. On the other hand, NOS3 has an important relationship with the composition of blood vessels. Furthermore, the animal experiment indicated that after the L-NNA-induced hypertension rat model was established, CIF intervention was given by gavage for 3 weeks, and it can decrease serum concentrations of endothelin-1 (ET-1) and thromboxane B2 (TXB2), increase the expression of nitric oxide (NO) and prostacyclin 2 (PGI2), and improve renal, cardiac, and aortic lesions. At the same time, it can reduce blood pressure and shorten vertigo time. Western blot (WB) and immunohistochemistry (IHC) analyses indicated that CIF may downregulate the expression of NOS3, guanylyl cyclase-alpha 1 (GC-α1), guanylyl cyclase-alpha 2 (GC-α2), and protein kinase CGMP-dependent 1 (PRKG1). These results suggest that CIF may play an antihypertensive role by inhibiting the activation of the NOS3/PRKG1 pathway. Conclusions The results of this study indicate that CIF has the ability to improve target organs, protect endothelial function, and reduce blood pressure and that CIF might be a potential therapeutic drug for the prevention of hypertension. It provides new insight into hypertension and the potential biological basis and mechanism for CIF clinical research.

Highlights

  • Hypertension is a common cardiovascular and cerebrovascular disease [1]

  • Compared with the model control group, after oral administration with Flos Chrysanthemi Indici extract, the results showed the level of serum ET-1 and thromboxane B2 (TXB2) in CIF-H was significantly reduced (P < 0.01, 0.05) and the level of serum nitric oxide (NO) and PGI2 was increased (P < 0.01, 0.05)

  • Results showed that protein kinase CGMP-dependent 1 (PRKG1) staining was brown granular, mainly distributed in the interstitium. e brown granular substances in aortic smooth muscle cells and endothelial cells of rats in the L-NNA model group were significantly reduced compared with the normal control group; compared with the model control group (MC) group, the expression of brown substances in each group of CIF groups was increased in varying degrees as shown in Figure 13. is result suggests that CIF might regulate nitric oxide elevation in the aorta through the inhibition of the NOS3/PRKG1 pathway

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Summary

Introduction

Hypertension is a common cardiovascular and cerebrovascular disease [1]. Based on the statistics, the prevalence of hypertension among adults in China was 5.1% in 1959, 19% in 2002, and 25.2% in 2012. E disease is mainly characterized by the deficiency of the upper and lower numbers of blood pressure, which is mixed with the deficiency and reality [7]. It is the hyperactivity of liver-fire and disturbance of wind-fire and wind-phlegm, while the deficiency of the liver and kidney leads to the deficiency of lower yuan in TCM. TCM has gradually become the main choice of new drugs for treating hypertension because of its various components, ways, and targets. Further verification based on molecular docking results showed that NOS3 had the good binding ability with quercetin and luteolin. Western blot (WB) and immunohistochemistry (IHC) analyses indicated that CIF may downregulate the expression of NOS3, guanylyl cyclase-alpha 1 (GC-α1), guanylyl cyclase-alpha 2 (GC-α2), and protein kinase CGMP-dependent 1 (PRKG1)

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