S-烯丙半胱氨酸（SAC）通过调节转化生长因子-β1/Smad3 通路介导的慢性肾衰竭基质重塑发挥肾保护作用。
S-Allylcysteine (SAC) Exerts Renoprotective Effects via Regulation of TGF- β1/Smad3 Pathway Mediated Matrix Remodeling in Chronic Renal Failure.
机构信息
Department of Biotechnology, Sri Shakthi Institute of Engineering and Technology, Coimbatore 641062, Tamil Nadu, India.
Translational Research Platform for Veterinary Biologicals, Tamil Nadu Veterinary and Animal Sciences University, Madhavaram Milk Colony, Chennai 600051, Tamil Nadu, India.
出版信息
Curr Pharm Des. 2022;28(8):661-670. doi: 10.2174/1381612828666220401114301.
BACKGROUND
S-Allylcysteine (SAC), an organosulfur phytochemical sourced from aged garlic extract, is well known for its varied biomedical applications, such as anti-oxidant, anti-inflammatory, and detoxification mechanisms. Despite this, the scientific findings on the defensive impact of SAC against kidney failure (KF) are still unclear. Therefore, in the current investigation, the animal model of KF was induced by adenine in Wistar rats, and the animals were divided into four groups as control, KF induction using adenine, SAC treated KF rats for an experimental duration of 8 weeks.
METHODS
KF progression was assessed by various serum and tissue markers, and the results demonstrated that the renal functions' markers, KIM-1 (kidney injury molecule-1), cystatin, NGAL (neutrophil gelatinase-associated lipocalin), were found increased in adenine-treated rats compared to control. In addition, the inflammatory markers, matrix proteins, and fibrosis signatures explicated by RT-PCR, ELISA demonstrated a profound increase. On the other hand, rats received SAC mitigated KF considerably (p < 0.001) with restored cellular functions. Besides, SAC pre-treatment abrogated the cytokines and pro-inflammatory signals (COX-2 and PGE2) in a dose-dependent manner.
CONCLUSION
Furthermore, the fibrosis signaling markers mediators, such as SMAD-2,-3 were increased with associated matrix proteins. Thus, the present study substantiated that SAC possesses a significant renoprotective effect that might have been demonstrated by the inhibition of the TGF-β1/Smad3 signaling pathway.
背景
S-烯丙半胱氨酸（SAC）是一种从陈年大蒜提取物中提取的有机硫植物化学物质，因其具有多种生物医学应用而广为人知，如抗氧化、抗炎和解毒机制。尽管如此，关于 SAC 对肾衰竭（KF）的防御作用的科学发现仍然不清楚。因此，在目前的研究中，通过腺嘌呤在 Wistar 大鼠中诱导 KF 动物模型，并将动物分为四组：对照组、用腺嘌呤诱导的 KF、SAC 处理的 KF 大鼠，实验持续 8 周。
方法
通过各种血清和组织标志物评估 KF 的进展，结果表明，与对照组相比，腺嘌呤处理的大鼠的肾脏功能标志物 KIM-1（肾损伤分子-1）、胱抑素、NGAL（中性粒细胞明胶酶相关脂质运载蛋白）升高。此外，通过 RT-PCR、ELISA 表明炎症标志物、基质蛋白和纤维化特征显著增加。另一方面，SAC 处理的大鼠显著减轻了 KF（p < 0.001），恢复了细胞功能。此外，SAC 预处理以剂量依赖的方式阻断了细胞因子和促炎信号（COX-2 和 PGE2）。
结论
此外，纤维化信号标志物介质，如 SMAD-2、-3 与相关基质蛋白一起增加。因此，本研究证实 SAC 具有显著的肾保护作用，这可能是通过抑制 TGF-β1/Smad3 信号通路来实现的。
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