Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 May 10:2024:7967999.
doi: 10.1155/2024/7967999. eCollection 2024.

Preliminary Exploration of Potential Active Ingredients and Molecular Mechanisms of Yanggan Yishui Granules for Treating Hypertensive Nephropathy Using UPLC-Q-TOF/MS Coupled with Network Pharmacology and Molecular Docking Strategy

Fan Yang  1   2 , Kailun Zhang  3 , Xiaohua Dai  2 , Weimin Jiang  1
Affiliations

Preliminary Exploration of Potential Active Ingredients and Molecular Mechanisms of Yanggan Yishui Granules for Treating Hypertensive Nephropathy Using UPLC-Q-TOF/MS Coupled with Network Pharmacology and Molecular Docking Strategy

Fan Yang et al. J Anal Methods Chem. .

Abstract

Hypertensive nephropathy (HN) is a prevalent complication of hypertension and stands as the second primary reason for end-stage renal disease. Research in clinical settings has revealed that Yanggan Yishui Granule (YGYSG) has significant therapeutic effects on HN. However, the material basis and action mechanisms of YGYSG against HN remain unclear. Consequently, this study utilized a comprehensive method integrating ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS), network pharmacology, and molecular docking to delineate the active ingredients and potential therapeutic mechanisms of YGYSG for treating HN. Firstly, sixty distinct components were recognized in total as potential active ingredients in YGYSG by UPLC-Q-TOF/MS. Subsequently, the mechanisms of YGYSG against HN were revealed for the first time using network pharmacology. 23 ingredients played key roles in the complete network and were the key active ingredients, which could affect the renin-angiotensin system, fluid shear stress and atherosclerosis, HIF-1 signaling pathway, and AGE-RAGE signaling pathway in diabetic complications by regulating 29 key targets such as TNF, IL6, ALB, EGFR, ACE, and MMP2. YGYSG could treat HN through the suppression of inflammatory response and oxidative stress, attenuating the proliferation of renal vascular smooth muscle cells, lessening glomerular capillary systolic pressure, and ameliorating renal dysfunction and vascular damage through the aforementioned targets and pathways. Molecular docking results revealed that most key active ingredients exhibited a high affinity for binding to the key targets. This study pioneers in clarifying the bioactive compounds and molecular mechanisms of YGYSG against HN and offers scientific reference into the clinical application.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no conflicts of interest.

Figures

Figure 1
Figure 1
Flowchart of this current study.
Figure 2
Figure 2
Chemical structures of the 27 reference standards used in this study.
Figure 3
Figure 3
Representative total ion current chromatograms of the reference standards (a) and the samples of YGYSG (b) in the negative ion mode. The sequence of the reference standards (S1–S27) is consistent with Figure 2. The sequence of the identified ingredients (1–60) is in conformity with Table 2.
Figure 4
Figure 4
Venn diagram of the common targets of YGYSG and HN.
Figure 5
Figure 5
Network construction of the potential active ingredients-targets of YGYSG in the treatment of HN. Triangles represent the TCMs of YGYSG, parallelograms depict the exclusive active components of different TCMs, hexagons represent the common active compounds of these TCMs, diamonds symbolize the targets, and blue acronyms represent the gene name of the targets.
Figure 6
Figure 6
Key targets obtained from PPI network analysis. (a) Target interaction in the STRING database. (b) PPI network of YGYSG in the treatment of HN. (c) Key targets of YGYSG in the treatment of HN. Each node represents a target in the PPI network, and each edge indicates the interaction between adjacent nodes. The greater the number of adjacent nodes, the greater the probability of becoming a key target.
Figure 7
Figure 7
GO function analysis (a) and KEGG pathway analysis (b) of the key targets of the YGYSG in the treatment of HN.
Figure 8
Figure 8
Network construction of the YGYSG-key active ingredients-key targets-key pathways of YGYSG against HN. Green triangles represent the TCMs of YGYSG, purple parallelograms symbolize the unique key active ingredients of various TCMs, red hexagons denote the common key active ingredients of these TCMs, blue diamonds represent the key targets, orange V shapes represent the key pathways, and yellow circles represent HN.
Figure 9
Figure 9
Molecular docking results of top 10 key active ingredients and key targets of YGYSG against HN. (a) Heatmap of the docking scores of top 10 key active ingredients and key targets of YGYSG. Molecular docking diagram of (b) zingibroside R1 with ACE, (c) chikusetsusaponin IVa with IFNG, (d) soyasaponin I with ACE, (e) kaempferol with TNF, (f) quercetin with ALB, and (g) ferulic acid with EGFR.
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Zhou B., Perel P., Mensah G. A., Ezzati M. Global epidemiology, health burden and effective interventions for elevated blood pressure and hypertension. Nature Reviews Cardiology . 2021;18(11):785–802. doi: 10.1038/s41569-021-00559-8. - DOI - PMC - PubMed
    1. Unger T., Borghi C., Charchar F., et al. 2020 International Society of Hypertension global hypertension practice guidelines. Journal of Hypertension . 2020;38(6):982–1004. doi: 10.1097/hjh.0000000000002453. - DOI - PubMed
    1. Costantino V. V., Gil Lorenzo A. F., Bocanegra V., Vallés P. G. Molecular mechanisms of hypertensive nephropathy: renoprotective effect of losartan through Hsp70. Cells . 2021;10(11):p. 3146. doi: 10.3390/cells10113146. - DOI - PMC - PubMed
    1. Xie T., Bai Z. Y., Chen Z. D., et al. Inhibition of ferroptosis ameliorates hypertensive nephropathy through p53/Nrf2/p21 pathway by Taohongsiwu decoction: based on network pharmacology and experimental validation. Journal of Ethnopharmacology . 2023;312 doi: 10.1016/j.jep.2023.116506. - DOI - PubMed
    1. Mennuni S., Rubattu S., Pierelli G., Tocci G., Fofi C., Volpe M. Hypertension and kidneys: unraveling complex molecular mechanisms underlying hypertensive renal damage. Journal of Human Hypertension . 2013;28(2):74–79. doi: 10.1038/jhh.2013.55. - DOI - PubMed