Mechanism of 3-arylcoumarin derivatives inhibiting vascular calcification

LI Yufei; CHU Haiping; LI Yan; WANG Xiaojing; MU Yanling; SUN Jie

doi:10.11665/j.issn.1000-5048.20220213

Journal of China Pharmaceutical University > 2022 > 53(2): 222-231. > DOI: 10.11665/j.issn.1000-5048.20220213

LI Yufei, CHU Haiping, LI Yan, WANG Xiaojing, MU Yanling, SUN Jie. Mechanism of 3-arylcoumarin derivatives inhibiting vascular calcification[J]. Journal of China Pharmaceutical University, 2022, 53(2): 222-231. DOI: 10.11665/j.issn.1000-5048.20220213

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Mechanism of 3-arylcoumarin derivatives inhibiting vascular calcification

1.
Institute of Materia Medica, Shandong First Medical University & Shandong Academy of Medical Sciences, Ji'nan 250014
2.
Department of Anesthesiology and Perioperative Medicine, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan 250014, China

Funds: This study was supported by the Natural Science Foundation of Shandong Province (No. ZR2020KH020)

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Received Date: January 31, 2021
Revised Date: March 14, 2022

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Abstract

Abstract

To reveal the pharmacological mechanism of 3-arylcoumarin derivative 3-(4′-hydroxyphenyl)-6-hydroxycoumarin (SJ-6) against vascular calcification, advanced glycation end products (AGEs) were used to induce the calcification of human aortic vascular smooth muscle cells (HCASMCs), and calcification was identified by alizarin red staining and quantification.The effects of SJ-6 on alkaline phosphatase (ALP) activity, cell proliferation rate, calcium content, and total reactive oxygen species (ROS), superoxide dismutase (SOD), AGEs, and tetra methylethlene diamine proteinase factor-α (TNF-α), interleukin-6 (1L-6), interleukin-β (1L-β), runt-related transcription factor 2 mRNA (Runx2 mRNA), the receptor of advanced glycation endproducts (RAGE), nuclear factor kappa-B (NF-κB), napdh oxidase-1 (NoX-1), protein kinase C(PKC), protein kinase b(AKT), p38 mitogen-activated protein kinase (p38 MAPK), and smooth muscle actin-α (SMA-α) protein expression were determined.According to our results, SJ-6 significantly decreased AGEs content, ALP activity, intracellular calcium content, ROS content, Runx2 mRNA and inflammatory factors TNF-α, 1L-6 and 1L-β (P < 0.05) and increased SOD content (P < 0.01), with similar to those of the positive control drug aminoguanidine hydrochloride (AGH).Therefore, we investigated the pharmacological mechanism of compound SJ-6, which was found to significantly inhibit the expression of RAGE, NF-κB, NoX-1, PKC, Akt, p-p38 and other essential signaling proteins in the calcified cell model (P < 0.01) and increas the expression of smooth actin SMA-α (P < 0.01).SJ-6 inhibits vascular calcification by inhibiting oxidative stress and the expression of AGEs/RAGE, Akt/PKC and NF-κB signaling pathways, suggesting that it may be a novel drug for the treatment of vascular calcification.
- 3-arylcoumarin derivatives,
- vascular calcification,
- advanced glycation end products

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