巴西林通过调节炎症、氧化应激和线粒体功能障碍减轻肾缺血再灌注损伤。

IF 2 4区 生物学 Q3 CELL BIOLOGY
Jinyi Zhao, Lulu Zhang, Fei Mu, Ying Yu, Chen Cui, Meng Tang, Kexin Sun, Yanping Yin, Jingwen Wang, Rui Gong
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引用次数: 0

摘要

巴西黄酮是一种天然的同型异黄酮,是一种主要的生物活性成分,从巴西杉树的树皮和心材中提取,已被证明在慢性退行性疾病、纤维化疾病、炎症性疾病和癌症中表现出多种生物活性和治疗潜力。然而,它是否参与调节急性肾损伤(AKI)的病理过程尚不完全清楚。本研究旨在阐明巴西巴西林在AKI中的作用及其关键药理分子机制。我们的数据表明,巴西林预处理可以显著降低缺血/再灌注(I/R)小鼠血清肌酐(Scr)、血尿素氮(BUN)和脂载素-2 (LCN2)的高表达,减轻肾脏组织病理学损伤。同时,巴西林预处理可通过部分抑制toll样受体4 (TLR4)/核因子κB (NF-κB)/ nod样受体家族pyrin domain containing 3 (NLRP3)炎症通路或激活核因子红系2相关因子2 (Nrf2)/血红素加氧酶-1 (HO-1)抗氧化通路,减轻肾组织细胞的凋亡、炎症和氧化应激损伤。在体外实验中,巴西黄酮预处理显著下调人肾近端小管细胞(HK-2)中促凋亡的Bax和抗凋亡的Bcl-2的表达。此外,它还通过促进线粒体生物发生和恢复线粒体膜电位来改善线粒体功能障碍。这些作用共同抑制氧化应激损伤和NLRP3炎性小体信号通路的激活。综上所述,巴西豆素通过减轻炎症、氧化应激、细胞凋亡和线粒体损伤,对I/ r诱导的AKI具有显著的保护作用。这些发现表明巴西林有望成为AKI的潜在治疗剂。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Brazilin attenuates kidney ischemia-reperfusion injury by regulating inflammation, oxidative stress, and mitochondrial dysfunction.

Brazilin, a natural homoisoflavonoid, is the primary bioactive ingredient derived from the bark and heartwood of Caesalpinia sappan L. It has been proven to exhibit multiple biological activities and therapeutic potential in chronic degenerative diseases, fibrotic disorders, inflammatory diseases, and cancers. However, whether it is involved in regulating the pathological process of acute kidney injury (AKI) is not fully understood. This study aimed to elucidate the role and key pharmacological molecular mechanisms of brazilin in AKI. Our data demonstrated that pretreatment with brazilin can significantly reduce the high expression of serum creatinine (Scr), blood urea nitrogen (BUN), and lipocalin-2 (LCN2) in mice exposed to ischemia/reperfusion (I/R) and alleviate kidney histopathological damage. Meanwhile, pretreatment with brazilin can alleviate apoptosis, inflammation, and oxidative stress injury in the kidney tissue cells by partially inhibiting the Toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB)/NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammatory pathway or activating the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) antioxidant pathway. In vitro, pretreatment with brazilin significantly downregulated pro-apoptotic Bax and upregulated anti-apoptotic Bcl-2 expression in human renal proximal tubular cells (HK-2) subjected to oxygen-glucose deprivation/reoxygenation (OGD/R). Besides, it ameliorated mitochondrial dysfunction by enhancing mitochondrial biogenesis and restoring mitochondrial membrane potential. These effects collectively suppressed oxidative stress injury and NLRP3 inflammasome signaling pathway activation. In summary, brazilin exhibits significant protective effects against I/R-induced AKI by attenuating inflammation, oxidative stress and cell apoptosis, and mitochondrial damage. These findings suggest that brazilin holds promise as a potential therapeutic agent for AKI.

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来源期刊
Histology and histopathology
Histology and histopathology 生物-病理学
CiteScore
3.90
自引率
0.00%
发文量
232
审稿时长
2 months
期刊介绍: HISTOLOGY AND HISTOPATHOLOGY is a peer-reviewed international journal, the purpose of which is to publish original and review articles in all fields of the microscopical morphology, cell biology and tissue engineering; high quality is the overall consideration. Its format is the standard international size of 21 x 27.7 cm. One volume is published every year (more than 1,300 pages, approximately 90 original works and 40 reviews). Each volume consists of 12 numbers published monthly online. The printed version of the journal includes 4 books every year; each of them compiles 3 numbers previously published online.
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