Ahmad Parvej, Shah Arunim, Waiz Mohd, Chaturvedi Chandra P, Alvi Sahir Sultan, Khan M Salman
Integral Information & Research Center (IIRC-5), Clinical Biochemistry & Natural Product Research Lab, Department of Biosciences, Integral University, Lucknow, Uttar Pradesh, India.
Stem Cell Research Center, Department of Hematology, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Lucknow, Uttar Pradesh, India.
Phytother Res. 2024 Sep 3. doi: 10.1002/ptr.8323.
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.
代谢综合征（MetS）是一组不断演变的疾病，在全球许多国家构成严重的健康风险。现有证据表明，患有代谢综合征的个体患2型糖尿病（T2DM）、心血管疾病（CVD）或两者兼有的几率高出30%-40%。本研究旨在揭示天然有机硫化合物（OSC）、S-烯丙基-L-半胱氨酸（SAC）和S-乙基-L-半胱氨酸（SEC）在针对高碳水化合物高脂肪（HCHF）饮食诱导的与代谢综合征相关的风险管理中的调节作用。我们的研究结果表明，SAC和SEC改善了HCHF饮食诱导的糖尿病特征、血浆脂质和脂蛋白水平、肝功能、氧化应激、炎性细胞因子和趋化因子，包括单核细胞趋化蛋白-1（MCP-1）、脂质过氧化、血浆前蛋白转化酶枯草溶菌素/kexin 9型（PCSK-9）和高敏C反应蛋白（hs-CRP）。此外，对参与胆固醇稳态的关键基因的肝脏mRNA表达的评估表明，SAC和SEC通过靶向PCSK-9的转录激活因子HNF-1α的表达来下调PCSK-9 mRNA表达。另一方面，低密度脂蛋白受体（LDL-R）的表达通过其转录调节因子固醇调节元件结合蛋白-2（SREBP-2）的激活而上调。此外，SAC和SEC处理还改善了3-羟基-3-甲基戊二酰辅酶A还原酶（HMG-R）和过氧化物酶体增殖物激活受体（PPARs）的活性和mRNA表达。我们得出结论，SAC和SEC可以通过改善脂质和脂蛋白含量、血糖指数、肝功能、靶向炎症级联反应和氧化失衡、调节PCSK-9、LDL-R、SREBP-2、HNF-1α、PPARs的mRNA表达以及炎症生物标志物来预防代谢综合征。
