Organosulfur Compounds, S ‐Allyl‐L‐Cysteine and S ‐Ethyl‐L‐Cysteine, Target PCSK ‐9/ LDL ‐R‐Axis to Ameliorate Cardiovascular, Hepatic, and Metabolic Changes in High Carbohydrate and High Fat Diet‐Induced Metabolic Syndrome in Rats

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Autores principales: Parvej Ahmad, Arunim Shah, Mohd Waiz, Chandra P. Chaturvedi, Sahir Sultan Alvi, M. Salman Khan
Formato: Artículo Open Access
Publicado: Wiley 2024
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author Parvej Ahmad
Arunim Shah
Mohd Waiz
Chandra P. Chaturvedi
Sahir Sultan Alvi
M. Salman Khan
author_facet Parvej Ahmad
Arunim Shah
Mohd Waiz
Chandra P. Chaturvedi
Sahir Sultan Alvi
M. Salman Khan
Parvej Ahmad
Arunim Shah
Mohd Waiz
Chandra P. Chaturvedi
Sahir Sultan Alvi
M. Salman Khan
collection Wiley Open Access
contents Organosulfur Compounds, S ‐Allyl‐L‐Cysteine and S ‐Ethyl‐L‐Cysteine, Target PCSK ‐9/ LDL ‐R‐Axis to Ameliorate Cardiovascular, Hepatic, and Metabolic Changes in High Carbohydrate and High Fat Diet‐Induced Metabolic Syndrome in Rats Parvej Ahmad Arunim Shah Mohd Waiz Chandra P. Chaturvedi Sahir Sultan Alvi M. Salman Khan Phytotherapy Research ABSTRACT Metabolic syndrome (MetS) is an ever‐evolving set of diseases that poses a serious health risk in many countries worldwide. Existing evidence illustrates that individuals with MetS have a 30%–40% higher chance of acquiring type 2 diabetes mellitus (T2DM), cardiovascular disease (CVD), or both. This study was undertaken to uncover the regulatory role of natural organosulfur compounds (OSCs), S ‐allyl‐L‐cysteine (SAC), and S ‐ethyl‐L‐cysteine (SEC), in targeting high carbohydrate high fat (HCHF)‐diet‐induced MetS‐associated risk management. Our findings suggested that SAC and SEC ameliorated HCHF‐diet‐induced diabetic profiles, plasma lipid and lipoprotein level, liver function, oxidative‐stress, inflammatory cytokines, and chemokines including monocyte chemoattractant protein‐1 (MCP‐1), lipid peroxidation, plasma proprotein convertase subtilisin/kexin type‐9 (PCSK‐9), and high‐sensitivity C‐reactive protein (hs‐CRP). Moreover, the assessment of the hepatic mRNA expression of the key genes involved in cholesterol homeostasis depicted that SAC and SEC downregulated the PCSK‐9 mRNA expression via targeting the expression of HNF‐1α, a transcriptional activator of PCSK‐9. On the other hand, the LDL‐receptor (LDL‐R) expression was upregulated through the activation of its transcriptional regulator sterol regulatory element binding protein‐2 (SREBP‐2). In addition, the activity and the mRNA expression of 3‐hydroxy‐3‐methylglutaryl coenzyme‐A reductases (HMG‐R) and peroxisome proliferator‐activated receptors (PPARs) were also improved by the treatment of SAC and SEC. We concluded that SAC and SEC can protect against MetS via improving the lipid and lipoprotein content, glycemic indices, hepatic function, targeting the inflammatory cascades, and oxidative imbalance, regulation of the mRNA expression of PCSK‐9, LDL‐R, SREBP‐2, HNF‐1α, PPARs, and inflammatory biomarkers. 10.1002/ptr.8323 http://onlinelibrary.wiley.com/termsAndConditions#vor
doi_str_mv 10.1002/ptr.8323
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spellingShingle Organosulfur Compounds, S ‐Allyl‐L‐Cysteine and S ‐Ethyl‐L‐Cysteine, Target PCSK ‐9/ LDL ‐R‐Axis to Ameliorate Cardiovascular, Hepatic, and Metabolic Changes in High Carbohydrate and High Fat Diet‐Induced Metabolic Syndrome in Rats
Parvej Ahmad
Arunim Shah
Mohd Waiz
Chandra P. Chaturvedi
Sahir Sultan Alvi
M. Salman Khan
Phytotherapy Research
Organosulfur Compounds, S ‐Allyl‐L‐Cysteine and S ‐Ethyl‐L‐Cysteine, Target PCSK ‐9/ LDL ‐R‐Axis to Ameliorate Cardiovascular, Hepatic, and Metabolic Changes in High Carbohydrate and High Fat Diet‐Induced Metabolic Syndrome in Rats Parvej Ahmad Arunim Shah Mohd Waiz Chandra P. Chaturvedi Sahir Sultan Alvi M. Salman Khan Phytotherapy Research ABSTRACT Metabolic syndrome (MetS) is an ever‐evolving set of diseases that poses a serious health risk in many countries worldwide. Existing evidence illustrates that individuals with MetS have a 30%–40% higher chance of acquiring type 2 diabetes mellitus (T2DM), cardiovascular disease (CVD), or both. This study was undertaken to uncover the regulatory role of natural organosulfur compounds (OSCs), S ‐allyl‐L‐cysteine (SAC), and S ‐ethyl‐L‐cysteine (SEC), in targeting high carbohydrate high fat (HCHF)‐diet‐induced MetS‐associated risk management. Our findings suggested that SAC and SEC ameliorated HCHF‐diet‐induced diabetic profiles, plasma lipid and lipoprotein level, liver function, oxidative‐stress, inflammatory cytokines, and chemokines including monocyte chemoattractant protein‐1 (MCP‐1), lipid peroxidation, plasma proprotein convertase subtilisin/kexin type‐9 (PCSK‐9), and high‐sensitivity C‐reactive protein (hs‐CRP). Moreover, the assessment of the hepatic mRNA expression of the key genes involved in cholesterol homeostasis depicted that SAC and SEC downregulated the PCSK‐9 mRNA expression via targeting the expression of HNF‐1α, a transcriptional activator of PCSK‐9. On the other hand, the LDL‐receptor (LDL‐R) expression was upregulated through the activation of its transcriptional regulator sterol regulatory element binding protein‐2 (SREBP‐2). In addition, the activity and the mRNA expression of 3‐hydroxy‐3‐methylglutaryl coenzyme‐A reductases (HMG‐R) and peroxisome proliferator‐activated receptors (PPARs) were also improved by the treatment of SAC and SEC. We concluded that SAC and SEC can protect against MetS via improving the lipid and lipoprotein content, glycemic indices, hepatic function, targeting the inflammatory cascades, and oxidative imbalance, regulation of the mRNA expression of PCSK‐9, LDL‐R, SREBP‐2, HNF‐1α, PPARs, and inflammatory biomarkers. 10.1002/ptr.8323 http://onlinelibrary.wiley.com/termsAndConditions#vor
title Organosulfur Compounds, S ‐Allyl‐L‐Cysteine and S ‐Ethyl‐L‐Cysteine, Target PCSK ‐9/ LDL ‐R‐Axis to Ameliorate Cardiovascular, Hepatic, and Metabolic Changes in High Carbohydrate and High Fat Diet‐Induced Metabolic Syndrome in Rats
topic Phytotherapy Research
url https://onlinelibrary.wiley.com/doi/10.1002/ptr.8323