Metabolite profiling, hypolipidemic, and anti-atherosclerosis activity of mixed vegetable fermentation extract

Although positive association between fermented vegetables intake with the risk of coronary heart disease (CHD) has increased attention nowadays, the metabolite profiling and the mechanism of action are still elusive. This study designed to investigate the secondary metabolites, hypolipidemic, and a...

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Main Authors: Ermin Rachmawati, Suharti Suharti, Djanggan Sargowo, Larasati Sekar Kinasih, Yudi Her Octaviano, Roihatul Mutiah, Mahrus Ismail, Ahmad Munjin Nasih
Format: Article
Language:English
Published: Elsevier 2023-05-01
Series:Saudi Pharmaceutical Journal
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S1319016423000543
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author Ermin Rachmawati
Suharti Suharti
Djanggan Sargowo
Larasati Sekar Kinasih
Yudi Her Octaviano
Roihatul Mutiah
Mahrus Ismail
Ahmad Munjin Nasih
author_facet Ermin Rachmawati
Suharti Suharti
Djanggan Sargowo
Larasati Sekar Kinasih
Yudi Her Octaviano
Roihatul Mutiah
Mahrus Ismail
Ahmad Munjin Nasih
author_sort Ermin Rachmawati
collection DOAJ
description Although positive association between fermented vegetables intake with the risk of coronary heart disease (CHD) has increased attention nowadays, the metabolite profiling and the mechanism of action are still elusive. This study designed to investigate the secondary metabolites, hypolipidemic, and anti-atherogenic effect of mixed vegetable fermentation extract (MVFE). The metabolite screening of the MVFE was assessed using the Liquid Chromatography Tandem Mass Spectrophotometer (LC-MS/MS) method. The result of LC-MS/MS was used as ligands to inhibit the binding of oxidized LDL (oxLDL) and Cluster Differentiation 36 (CD36), Scavenger Receptor A1 (SRA1), Lectin-type oxidized LDL receptor 1 (LOX1). This work was performed with molecular docking using Discovery Studio 2021, PyRx 0.9, and Autodock Vina 4.2 followed by analyzing Network Pharmacology, Protein Protein Interaction (PPI) using Cytoscape 3.9.1 and String 2.0.0. Finally, the clinical effect of MVFE was evaluated using in vivo study. Twenty rabbits were assigned to normal, negative control, and MVFE group that were fed with standard diet, high fat diet (HFD), HFD supplemented with MVFE 100, 200 mg/kg BW, respectively. The serum level of Total Cholesterol (TC) and Low-Density Lipoprotein (LDL-c) were detected at the end of week 4.The LC-MS/MS analysis identified 17 compounds categorized as peptides, fatty acids, polysaccharides, nucleoside, flavonoids, flavanols, and phenolic compounds. Based on the docking study, more negative binding affinity was observed in the interaction between metabolites with the scavenger receptors (SR) than simvastatin. The number of nodes and edges based on Network Pharmacology analysis were 268 and 482, respectively. The PPI network showed that MVFE metabolites exerts its athero-protective effect by modulating various cellular processes including inflammation, improvement of endothelial function, and modulation of lipid metabolism. Blood TC and LDL-c concentrations in the negative control (458.82 ± 82.03; 191.87 ± 92.16 mg/dL) were higher significantly compared to the normal group (87.03 ± 29.27; 43.33 ± 5.75 mg/dL). The MVFE administration decreased the TC (100, 200 mg/kg BW MVFE: 269.96 ± 85.34; 130.17 ± 45.02 mg/dL) and LDL-c level (100, 200 mg/kg BW MVFE = 87.24 ± 22.85; 41.82 ± 11.08 mg/dL) dose-dependently (p < 0,001).The secondary metabolites derived from fermented mixed vegetables extract might be developed as a potential strategy to prevent CHD by targeting the multiple pathways in atherosclerosis.
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spelling doaj.art-216d2a575aa8458bb94c35669943c3712023-05-03T04:09:41ZengElsevierSaudi Pharmaceutical Journal1319-01642023-05-01315639654Metabolite profiling, hypolipidemic, and anti-atherosclerosis activity of mixed vegetable fermentation extractErmin Rachmawati0Suharti Suharti1Djanggan Sargowo2Larasati Sekar Kinasih3Yudi Her Octaviano4Roihatul Mutiah5Mahrus Ismail6Ahmad Munjin Nasih7Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universitas Islam Negeri Maulana Malik Ibrahim Malang, East Java, IndonesiaDepartment of Chemistry, Faculty of Mathematics and Natural Science, Universitas Negeri Malang, East Java, Indonesia; Corresponding author at: Jl. Semarang No.5, 65145 District, East Java City, Malang Country, Indonesia.Department of Cardiology and Vascular Medicine, Faculty of Medicine, Universitas Brawijaya, Malang, IndonesiaDepartment of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universitas Islam Negeri Maulana Malik Ibrahim Malang, East Java, IndonesiaDepartment of Cardiology and Vascular Medicine, Faculty of Medicine, Universitas Airlangga, Surabaya, IndonesiaDepartment of Pharmacy, Faculty of Medicine and Health Sciences, UIN Maulana Malik Ibrahim Malang, East Java, IndonesiaDepartment of Biology, Faculty of Science and Technology, UIN Maulana Malik Ibrahim Malang, East Java, IndonesiaDepartment of Arabic language, Faculty of Sastra, Universitas Negeri Malang, East Java, IndonesiaAlthough positive association between fermented vegetables intake with the risk of coronary heart disease (CHD) has increased attention nowadays, the metabolite profiling and the mechanism of action are still elusive. This study designed to investigate the secondary metabolites, hypolipidemic, and anti-atherogenic effect of mixed vegetable fermentation extract (MVFE). The metabolite screening of the MVFE was assessed using the Liquid Chromatography Tandem Mass Spectrophotometer (LC-MS/MS) method. The result of LC-MS/MS was used as ligands to inhibit the binding of oxidized LDL (oxLDL) and Cluster Differentiation 36 (CD36), Scavenger Receptor A1 (SRA1), Lectin-type oxidized LDL receptor 1 (LOX1). This work was performed with molecular docking using Discovery Studio 2021, PyRx 0.9, and Autodock Vina 4.2 followed by analyzing Network Pharmacology, Protein Protein Interaction (PPI) using Cytoscape 3.9.1 and String 2.0.0. Finally, the clinical effect of MVFE was evaluated using in vivo study. Twenty rabbits were assigned to normal, negative control, and MVFE group that were fed with standard diet, high fat diet (HFD), HFD supplemented with MVFE 100, 200 mg/kg BW, respectively. The serum level of Total Cholesterol (TC) and Low-Density Lipoprotein (LDL-c) were detected at the end of week 4.The LC-MS/MS analysis identified 17 compounds categorized as peptides, fatty acids, polysaccharides, nucleoside, flavonoids, flavanols, and phenolic compounds. Based on the docking study, more negative binding affinity was observed in the interaction between metabolites with the scavenger receptors (SR) than simvastatin. The number of nodes and edges based on Network Pharmacology analysis were 268 and 482, respectively. The PPI network showed that MVFE metabolites exerts its athero-protective effect by modulating various cellular processes including inflammation, improvement of endothelial function, and modulation of lipid metabolism. Blood TC and LDL-c concentrations in the negative control (458.82 ± 82.03; 191.87 ± 92.16 mg/dL) were higher significantly compared to the normal group (87.03 ± 29.27; 43.33 ± 5.75 mg/dL). The MVFE administration decreased the TC (100, 200 mg/kg BW MVFE: 269.96 ± 85.34; 130.17 ± 45.02 mg/dL) and LDL-c level (100, 200 mg/kg BW MVFE = 87.24 ± 22.85; 41.82 ± 11.08 mg/dL) dose-dependently (p < 0,001).The secondary metabolites derived from fermented mixed vegetables extract might be developed as a potential strategy to prevent CHD by targeting the multiple pathways in atherosclerosis.http://www.sciencedirect.com/science/article/pii/S1319016423000543Fermented vegetablesAtherosclerosisMolecular dockingLC-MS/MSNetwork pharmacology
spellingShingle Ermin Rachmawati
Suharti Suharti
Djanggan Sargowo
Larasati Sekar Kinasih
Yudi Her Octaviano
Roihatul Mutiah
Mahrus Ismail
Ahmad Munjin Nasih
Metabolite profiling, hypolipidemic, and anti-atherosclerosis activity of mixed vegetable fermentation extract
Saudi Pharmaceutical Journal
Fermented vegetables
Atherosclerosis
Molecular docking
LC-MS/MS
Network pharmacology
title Metabolite profiling, hypolipidemic, and anti-atherosclerosis activity of mixed vegetable fermentation extract
title_full Metabolite profiling, hypolipidemic, and anti-atherosclerosis activity of mixed vegetable fermentation extract
title_fullStr Metabolite profiling, hypolipidemic, and anti-atherosclerosis activity of mixed vegetable fermentation extract
title_full_unstemmed Metabolite profiling, hypolipidemic, and anti-atherosclerosis activity of mixed vegetable fermentation extract
title_short Metabolite profiling, hypolipidemic, and anti-atherosclerosis activity of mixed vegetable fermentation extract
title_sort metabolite profiling hypolipidemic and anti atherosclerosis activity of mixed vegetable fermentation extract
topic Fermented vegetables
Atherosclerosis
Molecular docking
LC-MS/MS
Network pharmacology
url http://www.sciencedirect.com/science/article/pii/S1319016423000543
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