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The Anti-atherosclerosis Mechanism of Ziziphora clinopodioides Lam. Based On Network Pharmacology

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Abstract

We investigated the mechanisms underlying the effects of Ziziphora clinopodioides Lam. (ZCL) on atherosclerosis (AS) using network pharmacology and in vitro validation.We collected the active components of ZCL and predicted their targets in AS. We constructed the protein-protein interaction, compound-target, and target-compound-pathway networks, and performed GO and KEGG analyses. Molecular docking of the active components and key targets was constructed with Autodock and Pymol software. Validation was performed with qRT-PCR, ELISA, and Western blot.We obtained 80 components of ZCL. The network analysis identified that 14 components and 37 genes were involved in AS. Then, 10 key nodes in the PPI network were identified as the key targets of ZCL because of their importance in network topology. The binding energy of 8 components (Cynaroside, α-Spinasterol, Linarin, Kaempferide, Acacetin, Genkwanin, Chrysin, and Apiin) to 4 targets (MMP9, TP53, AKT1, SRC) was strong and <−1 kJ/mol. In addition, 13 of the 14 components were flavonoids and thus total flavonoids of Ziziphora clinopodioides Lam. (ZCF) were used for in vitro validation. We found that ZCF reduced eNOS, P22phox, gp91phox, and PCSK9 at mRNA and protein levels, as well as the levels of IL-1β, TNF-α, and IL-6 proteins in vitro (P < 0.05).We successfully predicted the active components, targets, and mechanisms of ZCL in treating AS using network pharmacology. We confirmed that ZCF may play a role in AS by modulating oxidative stress, lipid metabolism, and inflammatory response via Cynaroside, Linarin, Kaempferide, Acacetin, Genkwanin, Chrysin, and Apiin.

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Data availability

The datasets generated and/or analyzed during the current study are not publicly available but are available from the corresponding author upon reasonable request.

Abbreviations

AS:

Atherosclerosis;

ZCL:

Ziziphora clinopodioides Lam.;

GO:

Gene Ontology;

PPI:

protein-protein interaction;

KEGG:

Kyoto Encyclopedia of Genes and Genomes;

ZCF:

flavonoids of Ziziphora clinopodioides Lam.;

HUVEC:

Human Umbilical Vein Endothelial Cells;

MDA:

Malondialdehyde;

SOD:

superoxide dismutase;

NO:

nitric oxide;

ADME:

absorption, distribution, metabolism, and excretion;

TCMSP:

Traditional Chinese Medicine Systems Pharmacology Database;

DL:

drug-likeness;

OB:

oral bioavailability;

VC:

Vitamin C

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Funding

This research was funded by Open Research Funding of the Key Laboratory of Xinjiang Uighur Autonomous Region [grant number 2016D03025].

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Authors and Affiliations

  1. School of Chinese Pharmacy, Beijing University of Chinese Medicine, 102488, Beijing, China

    Hongbing Liu, Xuehua Yan & Haimin Lei

  2. College of Traditional Chinese Medicine, Xinjiang Medical University, 830011, Urumqi, China

    Hongbing Liu, Jianxin Zhang, Xuehua Yan & Dongqing An

  3. Xinjiang Key Laboratory of Famous Prescription and Science of Formulas, 830011, Urumqi, China

    Hongbing Liu, Jianxin Zhang, Xuehua Yan & Dongqing An

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  1. Hongbing Liu
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Contributions

D.A. and H.L. designed the research study and revised the paper. H.L., J.Z., and X.Y. performed the research and analyzed the data. H.L. and J.Z. wrote the paper. All authors contributed to editorial changes in the paper. All authors read and approved the final paper.

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Correspondence to Dongqing An or Haimin Lei.

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Liu, H., Zhang, J., Yan, X. et al. The Anti-atherosclerosis Mechanism of Ziziphora clinopodioides Lam. Based On Network Pharmacology. Cell Biochem Biophys 81, 515–532 (2023). https://doi.org/10.1007/s12013-023-01151-2

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