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The Mechanism of Triacetyl Andrographolide in Inhibiting Proliferation of Pulmonary Artery Smooth Muscle Cells
  • Zhe Wang 1, †,   
  • Yi-Xuan Zhang  2, †,   
  • Jun-Zhuo Shi 1, †,   
  • Chen-Chen Wang 1,   
  • Meng-Qi Zhang 1,   
  • Yi Yan 3,   
  • Yan-Ran Wang 1,   
  • Lu-Ling Zhao 1,   
  • Jie-Jian Kou 4,   
  • Qing-Hui Zhao 5,   
  • Xin-Mei Xie 1,   
  • Yang-Yang He 1, 2,   
  • Jun-Ke Song 6, *,   
  • Guang Han 1, 7, *,   
  • Xiao-Bin Pang 1, 2, *

Received: 17 Apr 2023 | Accepted: 27 Jul 2023 | Published: 28 Sep 2023

Abstract

This study examines the impact of triacetyl-diacyllactone (ADA) on the proliferation and migration of pulmonary artery smooth muscle cells (PASMCs) and elucidates its underlying mechanism. PASMCs derived from SD rats were cultured in vitro and randomly divided into four groups: control group, administration group, model group, and model administration group. The appropriate concentration of ADA for intervention was determined using the MTT assay. The proliferation ability of PASMCs in each group was assessed using the EdU assay. The migration ability of PASMCs in each group was evaluated using the Scratch wound healing assay and Transwell assay. Western blot analysis was performed to determine the protein expression levels of BMPR2, PCNA, and TGF-β1, as well as the phosphorylation levels of SMAD1 and SMAD2/3 in PASMCs from each group. Results show that at a concentration of 5 µmol/L, ADA did not impact the cell activity of PASMCs and instead exerted inhibitory effects on both the proliferation and migration of PASMCs induced by PDGF-BB. PDGF-BB was found to upregulate the expression levels of PCNA and TGF-β1, while downregulating the expression of BMPR2. Furthermore, PDGF-BB led to enhanced protein phosphorylation of SMAD1 and SMAD2/3. However, following ADA intervention, the expression levels of PCNA and TGF-β1 decreased, while the expression of BMPR2 increased. Additionally, protein phosphorylation of SMAD1 and SMAD2/3 decreased. Therefore, ADA can hinder the proliferation and migration of PASMCs induced by PDGF-BB, as well as suppress the upregulation of PCNA and TGF-β1 caused by PDGF-BB. Furthermore, the downregulation of BMPR2 may be associated with the inhibition of SMAD1 and SMAD2/3 signaling pathways.

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DOI
10.53941/ijddp.2023.100009
Issue
Volume 2, Issue 3
How to Cite
Wang, Z.; Zhang, Y.-X.; Shi, J.-Z.; Wang, C.-C.; Zhang, M.-Q.; Yan, Y.; Wang, Y.-R.; Zhao, L.-L.; Kou, J.-J.; Zhao, Q.-H.; Xie, X.-M.; He, Y.-Y.; Song, J.-K.; Han, G.; Pang, X.-B. The Mechanism of Triacetyl Andrographolide in Inhibiting Proliferation of Pulmonary Artery Smooth Muscle Cells. International Journal of Drug Discovery and Pharmacology 2023, 2 (3), 105–116. https://doi.org/10.53941/ijddp.2023.100009.
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Zhe Wang, Yi-Xuan Zhang, Jun-Zhuo Shi, Chen-Chen Wang, Meng-Qi Zhang , Yan-Ran Wang, Lu-Ling Zhao, Jie-Jian Kou, Qing-Hui Zhao, Xin-Mei Xie, Yang-Yang He, Jun-Ke Song, Guang Han, Xiao-Bin Pang