有机硫化合物 S-烯丙基-L-半胱氨酸和 S-乙基-L-半胱氨酸靶向 PCSK-9/LDL-R-Axis,改善高碳水化合物和高脂肪饮食诱发的大鼠代谢综合征的心血管、肝脏和代谢变化。

IF 6.1 2区 医学 Q1 CHEMISTRY, MEDICINAL
Parvej Ahmad, Arunim Shah, Mohd Waiz, Chandra P Chaturvedi, Sahir Sultan Alvi, M Salman Khan
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引用次数: 0

摘要

代谢综合征(MetS)是一组不断演变的疾病,在全球许多国家都构成了严重的健康风险。现有证据表明,患有 MetS 的人罹患 2 型糖尿病(T2DM)、心血管疾病(CVD)或同时罹患这两种疾病的几率要高出 30%-40% 。本研究旨在揭示天然有机硫化合物(OSCs)、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)饮食诱发的 MetS 相关风险管理中的调节作用。我们的研究结果表明,SAC和SEC能改善高碳水化合物高脂肪饮食诱发的糖尿病特征、血浆脂质和脂蛋白水平、肝功能、氧化应激、炎症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、血浆丙蛋白转换酶-9型(PCSK-9)和高敏C反应蛋白(hs-CRP)。此外,对参与胆固醇平衡的关键基因的肝脏 mRNA 表达进行的评估表明,SAC 和 SEC 通过靶向表达 HNF-1α(PCSK-9 的转录激活因子),下调了 PCSK-9 mRNA 的表达。另一方面,低密度脂蛋白受体(LDL-R)的表达则通过激活其转录调节因子固醇调节元件结合蛋白-2(SREBP-2)而上调。此外,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激活受体(PPARs)的活性和 mRNA 表达也因 SAC 和 SEC 的处理而得到改善。我们的结论是,SAC 和 SEC 可通过改善脂质和脂蛋白含量、血糖指数、肝功能、靶向炎症级联和氧化失衡、调节 PCSK-9、LDL-R、SREBP-2、HNF-1α、PPARs 和炎症生物标志物的 mRNA 表达来预防 MetS。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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.

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.

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来源期刊
Phytotherapy Research
Phytotherapy Research 医学-药学
CiteScore
12.80
自引率
5.60%
发文量
325
审稿时长
2.6 months
期刊介绍: Phytotherapy Research is an internationally recognized pharmacological journal that serves as a trailblazing resource for biochemists, pharmacologists, and toxicologists. We strive to disseminate groundbreaking research on medicinal plants, pushing the boundaries of knowledge and understanding in this field. Our primary focus areas encompass pharmacology, toxicology, and the clinical applications of herbs and natural products in medicine. We actively encourage submissions on the effects of commonly consumed food ingredients and standardized plant extracts. We welcome a range of contributions including original research papers, review articles, and letters. By providing a platform for the latest developments and discoveries in phytotherapy, we aim to support the advancement of scientific knowledge and contribute to the improvement of modern medicine.
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