Affiliation:
1. Integral Information & Research Center (IIRC‐5), Clinical Biochemistry & Natural Product Research Lab, Department of Biosciences Integral University Lucknow Uttar Pradesh India
2. Stem Cell Research Center, Department of Hematology Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS) Lucknow Uttar Pradesh India
3. Department of Medicine and Oncology ISU, School of Medicine University of Texas Rio Grande Valley McAllen Texas USA
4. South Texas Center of Excellence for Cancer Research, School of Medicine University of Texas Rio Grande Valley McAllen Texas USA
5. Department of Biotechnology Era University Lucknow Uttar Pradesh India
Abstract
ABSTRACTMetabolic 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.