Journal of Southern Medical University ›› 2025, Vol. 45 ›› Issue (9): 1889-1902.doi: 10.12122/j.issn.1673-4254.2025.09.09
Ziwei YANG1(), Chang LÜ2, Zhu DONG1, Shulei JI1, Shenghui BI1, Xuehua ZHANG1, Xiaowu WANG1(
)
Received:
2025-04-17
Online:
2025-09-20
Published:
2025-09-28
Contact:
Xiaowu WANG
E-mail:a_1779874531@smu.edu.cn;xzwkwxw@smu.edu.cn
Supported by:
Ziwei YANG, Chang LÜ, Zhu DONG, Shulei JI, Shenghui BI, Xuehua ZHANG, Xiaowu WANG. Rosa laevigata Michx. inhibits pulmonary arterial smooth muscle cell proliferation in hypertension by modulating the Src-AKT1 axis[J]. Journal of Southern Medical University, 2025, 45(9): 1889-1902.
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URL: https://www.j-smu.com/EN/10.12122/j.issn.1673-4254.2025.09.09
Fig.2 Target screening of RLM for treatment of pulmonary hypertension. A: Venn diagram of the intersecting targets of RLM and idiopathic pulmonary hypertension. B: Construction and screening process of the component-target network. The targets such as SRC and AKT1 show prominent network topological parameters (degree, betweenness centrality), indicating their core roles in regulating smooth muscle cell proliferation.
Fig.5 Molecular docking analysis of potential binding modes and reliability of interactions between the core compounds and the targets in RLM treatment of PAH. A: Calculation of the binding energy between 5 targets and 7 active components. The triangles indicate the top 5 binding energies. B: Schematic diagram of the three-dimensional structure of PPARγ-Beta-Sitosterol molecular docking result. C: EGFR-Kaempferol molecular docking result. D: EGFR-Beta-Sitosterol molecular docking result. E: EGFR-Kaempferol molecular docking result. F: SRC-Quercetin molecular docking result.
Fig.6 Inhibitory effect of RLM on proliferation of rat pulmonary arterial smooth muscle cells. A: Bar chart showing the effect of different concentrations of RLM on cell viability measured by CCK8 assay. B, C: Western blotting of PCNA in RLM-treated cells. D: Results of CCK-8 assay of RLM-treated rat pulmonary arterial smooth muscle cells under hypoxia condition. E: Quantitative analysis of PCNA expression by immunofluorescence after RLM treatment. F: Immunofluorescence assay of PCNA in RLM-treated cells (scale bar=10 μm). G:Representive image of EdU assay. H: Quantitative analysis bar graph of EdU. All data were analyzed by one-way ANOVA plus Dunnett multiple comparison test. *P<0.05, ***P<0.001.
Fig.7 RLM inhibits hypoxia-induced phosphorylation of AKT1 and Src. A: Western blotting of Src and p-Src in RLM-treated cells. B: Quantitative analysis of p-Src/Src expression. C: Western blotting of AKT1 and p-AKT1 in RLM-treated cells. D: Quantitative analysis of p-AKT1/AKT1 expression. E: Calcium ion concentration measurements show a decrease in intracellular calcium levels following RLM treatment. All data were analyzed by one-way ANOVA plus Dunnett multiple comparison test. **P<0.01, ***P<0.001.
Fig.8 RLM relieves pulmonary hypertension in MCT-induced PAH rat model. A: Schematic diagram and trace of animal experiments. B: Data analysis of RVSP, mRVP and Fulton Index [RV/(LV+S)] in the 5 groups of rats. All data were analyzed by one-way ANOVA plus Dunnett multiple comparison test. *P<0.05, **P<0.01, ***P<0.001.
Fig.10 RLM inhibits hypoxia-induced proliferation in MCT-induced PAH rat model. A: Representative images of PCNA and α-SMA immunofluorescence post‐RLM treatment. B: Representative images of HE staining. C. Quantitative analysis of PCNA immunofluorescence post‐RLM treatment.D: Quantitative analysis of α-SMA immunofluorescence post‐RLM treatment. E. Quantitative analysis of HE staining. All data were analyzed by one-way ANOVA plus Dunnett multiple comparison test. *P<0.05, **P<0.01, ***P<0.001.
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