Key Laboratory of Natural Medicines of Changbai Mountain, Ministry of Education, College of Pharmacy, Yanbian University, Gongyuan Street, Yanji, Jilin 133000, China.
College of Agriculture, Yanbian University, Gongyuan Street, Yanji, Jilin 133000, China.
Ecotoxicol Environ Saf. 2024 Oct 15;285:117093. doi: 10.1016/j.ecoenv.2024.117093. Epub 2024 Sep 23.
Taraxasterol is one of the bioactive ingredients from traditional Chinese herb Taraxacum, which exhibits multiple pharmacological activities and protective effects. However, the underlying influence and mechanism of its use against kidney damage caused from zearalenone (ZEA) remain unexplored. The ZEA-induced kidney damage model of mice was established by feeding diets containing ZEA (2 mg/kg), and taraxasterol (5 and 10 mg/kg) was administered by gavage for 28 days. Results demonstrated taraxasterol increased average daily gain (ADG) and average daily feed intake (ADFI), reduced feed-to-gain ratio (F/G) and kidney index of mice induced by ZEA. Taraxasterol alleviated histopathological changes of kidney, reduced ZEA residue and the levels of blood urea nitrogen (BUN), uric acid (UA), and creatinine (CRE). Concurrently, taraxasterol reduced the contents of oxidative stress indicator reactive oxygen species (ROS) and malondialdehyde (MDA), and increased the activities of antioxidant enzymes catalase (CAT), total superoxide dismutase (T-SOD), and glutathione peroxidase (GSH-Px). Further, taraxasterol up-regulated the mRNA and protein expression of nuclear factor erythroid-2-related factor 2 (Nrf2), GSH-Px, NAD(P)H quinone oxidoreductase 1 (NQO1), and heme oxygenase-1 (HO-1), and down-regulated the mRNA and protein expression of KELCH like ECH associated protein (Keap1) in Nrf2/Keap1 pathway. Taraxasterol down-regulated the mRNA and protein expression of immunoglobulin binding protein (Bip), C/EBP homologous protein (CHOP), Bcl-2 associated X (Bax), cysteine protease (Caspase)-12, and Caspase-3, and up-regulated B-cell lymphoma 2 (Bcl-2) expression in endoplasmic reticulum stress pathway. This study suggests that taraxasterol attenuates ZEA-induced mouse kidney damage through the modulation of Nrf2/Keapl pathway to play antioxidant role and endoplasmic reticulum stress pathway to enhance anti-apoptotic ability. It will provide a basis for taraxasterol as a potential drug to prevent and treat ZEA-induced kidney damage.
蒲公英甾醇是来自传统中药蒲公英的一种生物活性成分，具有多种药理活性和保护作用。然而，其用于对抗玉米赤霉烯酮（ZEA）引起的肾损伤的潜在影响和机制尚不清楚。通过喂食含有 ZEA（2mg/kg）的饮食建立了 ZEA 诱导的小鼠肾损伤模型，并通过灌胃给予蒲公英甾醇（5 和 10mg/kg）28 天。结果表明，蒲公英甾醇增加了 ZEA 诱导的小鼠的平均日增重（ADG）和平均日采食量（ADFI），降低了饲料与增重比（F/G）和肾指数。蒲公英甾醇减轻了肾的组织病理学变化，降低了 ZEA 残留量以及血尿素氮（BUN）、尿酸（UA）和肌酐（CRE）的水平。同时，蒲公英甾醇降低了氧化应激指标活性氧（ROS）和丙二醛（MDA）的含量，并增加了抗氧化酶过氧化氢酶（CAT）、总超氧化物歧化酶（T-SOD）和谷胱甘肽过氧化物酶（GSH-Px）的活性。此外，蒲公英甾醇上调了核因子红细胞 2 相关因子 2（Nrf2）、GSH-Px、NAD（P）H 醌氧化还原酶 1（NQO1）和血红素加氧酶-1（HO-1）的 mRNA 和蛋白表达，并下调了 Nrf2/Keap1 通路中 Kelch 样 ECH 相关蛋白（Keap1）的 mRNA 和蛋白表达。蒲公英甾醇下调了免疫球蛋白结合蛋白（Bip）、C/EBP 同源蛋白（CHOP）、Bcl-2 相关 X（Bax）、半胱氨酸蛋白酶（Caspase）-12 和 Caspase-3 的 mRNA 和蛋白表达，并上调了内质网应激通路中的 B 细胞淋巴瘤 2（Bcl-2）表达。本研究表明，蒲公英甾醇通过调节 Nrf2/Keap1 通路发挥抗氧化作用和内质网应激通路增强抗细胞凋亡能力，减轻 ZEA 诱导的小鼠肾损伤。这为蒲公英甾醇作为预防和治疗 ZEA 诱导的肾损伤的潜在药物提供了依据。
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