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DC通过调节C57BL/6小鼠的铁死亡来减轻腺嘌呤诱导的慢性肾病。

DC. Alleviates adenine-induced chronic kidney disease by regulating ferroptosis in C57BL/6 mice.

作者信息

Kim Jong Min, Kim Yiseul, Na Hyun-Jin, Hur Haeng Jeon, Lee Sang-Hee, Sung Mi Jeong

机构信息

Aging and Metabolism Research Group, Korea Food Research Institute, Wanju-gun, Republic of Korea.

出版信息

Front Pharmacol. 2025 Apr 29;16:1548660. doi: 10.3389/fphar.2025.1548660. eCollection 2025.

Abstract

DC. (MO) is a medicinal plant that reportedly possesses various bioactive properties, including anti-hyperplastic, anti-inflammatory, and anti-cancer effects. Chronic kidney disease (CKD) is a progressive disorder characterized by inflammation, fibrosis, and oxidative stress, which leads to renal dysfunction. This study aimed to evaluate the renoprotective effects of MO against adenine-induced CKD in C57BL/6 mice. MO significantly attenuated renal injury by reducing blood urea nitrogen level and morphological change. Additionally, MO effectively reduced inflammation by inhibiting the expression of tumor necrosis factor-α, interleukin (IL)-1β, IL-6, monocyte chemoattractant protein-1, F4/80, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1. MO also considerably ameliorated adenine-induced renal fibrosis by regulating the suppressor of mothers against decapentaplegic/matrix metalloproteinase signaling. Furthermore, MO significantly protected against renal senescence by reducing the protein expression of p53, p16, and p21 induced by CKD. Additionally, MO supplementation suppressed CKD-induced ferroptosis and ferritinophagy by regulating the protein expression of SLC7A11 glutathione peroxidase 4, prostaglandin-endoperoxide synthase 2, human palmitoyl-CoA ligase, NADPH oxidase 4, 4-hydroxynonenal, transferrin receptor, heme oxygenase-1, nuclear receptor coactivator 4, beclin-1, microtubule-associated proteins 1A/1B light chain 3B, and kallikrein-related peptidase 4. In conclusion, this study suggests that MO may be a potential functional food, pharmaceutical, or medicinal plant that can help regulate mechanisms associated with renal health.

摘要

DC.(MO)是一种药用植物,据报道具有多种生物活性,包括抗增生、抗炎和抗癌作用。慢性肾脏病(CKD)是一种以炎症、纤维化和氧化应激为特征的进行性疾病,可导致肾功能障碍。本研究旨在评估MO对C57BL/6小鼠腺嘌呤诱导的CKD的肾脏保护作用。MO通过降低血尿素氮水平和形态学变化显著减轻了肾损伤。此外,MO通过抑制肿瘤坏死因子-α、白细胞介素(IL)-1β、IL-6、单核细胞趋化蛋白-1、F4/80、细胞间黏附分子-1和血管细胞黏附分子-1的表达有效减轻了炎症。MO还通过调节母亲针对果蝇节段极性蛋白/基质金属蛋白酶信号通路的抑制因子,显著改善了腺嘌呤诱导的肾纤维化。此外,MO通过降低CKD诱导的p53、p16和p21的蛋白表达,显著预防了肾衰老。此外,补充MO通过调节溶质载体家族7成员11、谷胱甘肽过氧化物酶4、前列腺素内过氧化物合酶2、人棕榈酰辅酶A连接酶、烟酰胺腺嘌呤二核苷酸磷酸氧化酶4、4-羟基壬烯醛、转铁蛋白受体、血红素加氧酶-1、核受体辅激活因子4、贝林蛋白-1、微管相关蛋白1A/1B轻链3B和激肽释放酶相关肽酶4的蛋白表达,抑制了CKD诱导的铁死亡和铁自噬。总之,本研究表明MO可能是一种潜在的功能性食品、药物或药用植物,有助于调节与肾脏健康相关的机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b568/12069063/c9902b9dcec8/fphar-16-1548660-g001.jpg

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