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. 2024 May 9:15:1360829.
doi: 10.3389/fphar.2024.1360829. eCollection 2024.

Investigation of the molecular mechanism of Smilax glabra Roxb. in treating hypertension based on proteomics and bioinformatics

Xin Yang  1 , Haibing Qian  1 , Changfu Yang  1 , Zhiyuan Zhang  1
Affiliations

Investigation of the molecular mechanism of Smilax glabra Roxb. in treating hypertension based on proteomics and bioinformatics

Xin Yang et al. Front Pharmacol. .

Abstract

Background: Smilax glabra Roxb. (named tufuling in Chinese, SGR) has both medicinal and edible value. SGR has obvious pharmacological activity, especially in anti-inflammation and treating immune system diseases. This study investigated differential protein expression and its relationship with immune infiltration in hypertension treated with SGR using proteomics and bioinformatics.

Methods: N-Nitro L-arginine methyl ester (L-NAME) was used to replicate the hypertension model, with SGR administered by gavage for 4 weeks, and the systolic and diastolic blood pressure in each group of rats was measured using the tail-cuff method every 7 days. Furthermore, enzyme-linked immunosorbent assay (ELISA) was used to determine the serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) expressions in each group, followed by the detection of protein expression in rat liver samples using the tandem mass tag (TMT) technique. Additionally, hub targets were output using Cytoscape 3.9.1 software, and ALDH2 expression in the liver and serum in each group of rats was detected by ELISA. Moreover, R4.3.0 software was used to evaluate the relationship between acetaldehyde dehydrogenase 2 (ALDH2) and immune cells, and ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was performed to identify the components of SGR. Furthermore, the association between components of SGR and ALDH2 was analyzed with molecular docking and LigPlot1.4.5 software.

Results: Compared with the model group (L-NAME), SGR at high and medium doses reduced systolic and diastolic blood pressure while reducing TC, TG, and LDL-C levels and increasing HDL-C levels in hypertensive rats (p < 0.05). Moreover, 92 differentially expressed proteins (DEPs) were identified using TMT. These DEPs participated in peroxisome functioning, fatty acid degradation, and other signaling pathways, with ALDH2 being the core target and correlated with various immune cells. In addition, 18 components were determined in SGR, with 8 compounds binding to ALDH2. Molecular docking was performed to confirm that SGR played a role in hypertension based on the combined action of multiple components.

Conclusion: In conclusion, SGR has an antihypertensive effect on L-NAME-induced hypertension, with ALDH2 as its hub target. SGR may regulate neutrophil, regulatory T cell, and other cells' infiltration by targeting ALDH2, thereby contributing to the treatment of hypertension.

Keywords: ALDH2; Smilax glabra Roxb.; high blood pressure; immune cell infiltration; proteomics.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Changes in blood pressure (1 mmHg = 0. 133 kPa). Compared with the normal control group,*p < 0.05 and **p < 0.01; Compared with the model group (L-NAME), # p < 0.05 and ## p < 0.01.
FIGURE 2
FIGURE 2
Detection of the serum lipid index. Data are shown as mean ± SD. Compared with the normal control group,*p < 0.05 and **p < 0.05. Compared with the model group (L-NAME), # p < 0.05 and ## p < 0.01.
FIGURE 3
FIGURE 3
Liver pathology in rats. (A) Control. (B) Model group (L-NAME). (C) Captopril. (D) SGR-H. (E) SGR-M. (F) SGR-L.
FIGURE 4
FIGURE 4
Renal pathology in rats. (A) Control. (B) Model group (L-NAME). (C) Captopril. (D) SGR-H. (E) SGR-M. (F) SGR-L.
FIGURE 5
FIGURE 5
Result of DEP identification. (A) Differentially expressed genes in the model group compared with the control group. (B) Differentially expressed genes of SGR compared with the model group (L-NAME). (C) 92 different proteins in the model group and SGR.
FIGURE 6
FIGURE 6
DEPs were analyzed by GO and KEGG. (A) Biological process GO terms for DEPs. (B) Cellular component GO terms for DEPs. (C) Molecular function GO terms for DEPs. (D) KEGG pathways for DEPs.
FIGURE 7
FIGURE 7
Hub gene analyses. (A) EPC. (B) Stress. (C) Closeness. (D) Degree. (E) Four hub genes were obtained.
FIGURE 8
FIGURE 8
Representative correlation heatmap between the result of the ssGSEA algorithm and ALDH2. Data are shown as mean ± SD. *p < 0.05, **p < 0.01, and ***p < 0.001.
FIGURE 9
FIGURE 9
ALDH2 expression in serum and liver samples. (A) ALDH2 expression in liver samples. (B) ALDH2 expression in serum samples. Compared with the normal control group,*p < 0.05 and **p < 0.05. Compared with the model group (L-NAME), # p < 0.05 and ## p < 0.01.
FIGURE 10
FIGURE 10
Identification of compounds in water extract solutions of Smilax glabra Roxb. by UHPLC-MS/MS. (A) Total ion chromatography in positive ion modes for SGR samples as shown. (B) Total ion chromatography in negative ion modes for SGR samples as shown. (C) Positive and negative ion modes are congruent.
FIGURE 11
FIGURE 11
Analysis of the hydrogen bond and hydrophobic action. (A) Unoptimized rod model of compounds. (B) Optimized rod model of compounds. (C) PDB database-downloaded ALDH2 structure. (D) Location of the butt pocket.
FIGURE 12
FIGURE 12
Eight compounds with the ALDH2 docking pocket. (A) Cianidanol. (B) Taxifolin 7-rhamnoside. (C) Phloretin. (D) Naringin. (E) Hesperetin. (F) Naringenin. (G) Estriol. (H) Neobavaisoflavone.
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References

    1. Abaidullah M., La S., Liu M., Liu B., Cui Y., Wang Z., et al. (2023). Polysaccharide from Smilax glabra Roxb mitigates intestinal mucosal damage by therapeutically restoring the interactions between gut microbiota and innate immune functions. Nutrients 15, 4102. 10.3390/nu15194102 - DOI - PMC - PubMed
    1. Ajoolabady A., Pratico D., Vinciguerra M., Lip G. Y. H., Franceschi C., Ren J. (2023). Inflammaging: mechanisms and role in the cardiac and vasculature. Trends.Endocrinol. Metab. 34, 373–387. 10.1016/j.tem.2023.03.005 - DOI - PubMed
    1. Alexander M. R., Harrison D. G. (2024). Legumain regulates regulatory T cells in hypertension. Circ. Res. 134, 30–32. 10.1161/CIRCRESAHA.123.324010 - DOI - PMC - PubMed
    1. Chang S., Wu J., Jin J., Shi H., Gao R., Li X., et al. (2022). Aldehyde dehydrogenase 2 (ALDH2) elicits protection against pulmonary hypertension via inhibition of ERK1/2-mediated autophagy. Oxid. Med. Cell. Longev. 2022, 2555476. 10.1155/2022/2555476 - DOI - PMC - PubMed
    1. Chen X., Sun X., Ji S., Yu H., Wu P. (2024). TMT-based proteomics analysis identifies the interventional mechanisms of Qijia Rougan decoction in improving hepatic fibrosis. J. Ethnopharmacol. 319, 117334. 10.1016/j.jep.2023.117334 - DOI - PubMed