Department of Medical Chemistry, Biochemistry and Clinical Chemistry, Faculty of Medicine, University of Rijeka, Rijeka, Croatia.
Department of Medical Chemistry, Biochemistry and Clinical Chemistry, Faculty of Medicine, University of Rijeka, Rijeka, Croatia.
Food Chem Toxicol. 2020 Aug;142:111472. doi: 10.1016/j.fct.2020.111472. Epub 2020 Jun 3.
Aucubin is pharmacologically active natural compound which possesses numerous beneficial properties. This study aimed to evaluate the protective effect of aucubin against cisplatin (CP)-induced acute kidney injury in mice and the mechanism of its action. Aucubin was administrated to mice orally or intraperitoneally (ip) (1.5 and 5 mg/kg) for two consecutive days, two days after ip injection of cisplatin (CP), 11 mg/kg. Treatment with aucubin by both routes of administration ameliorated histopathological changes and reduced elevated serum markers of kidney injury. CP administration increased renal expression of heme oxygenase-1 (HO-1) and 4-hydroxynonenal (4-HNE), as well as tumor necrosis factor-alpha (TNF-α), which was dose-dependently ameliorated by aucubin. Moreover, aucubin reduced increased renal expression of cleaved caspase-3 and -9 and decreased poly (ADP-ribose) polymerase (PARP) cleavage. Mechanistically, aucubin suppressed the activation of several signaling pathways involved in inflammation and apoptosis, including nuclear factor-kappa B (NF-κB), signal transducer and activator of transcription 3 (STAT3), Akt, extracellular signal-regulated kinase 1/2 (ERK1/2) and forkhead box O3a (FOXO3a). Parenteral application was marginally but statistically more effective in reducing CP-induced kidney injury than oral administration. The findings of this study suggest that aucubin acts as a protective agent against CP-induced nephrotoxicity, which should be further investigated.
桃叶珊瑚苷是一种具有多种有益特性的药理学活性天然化合物。本研究旨在评估桃叶珊瑚苷对顺铂（CP）诱导的小鼠急性肾损伤的保护作用及其作用机制。桃叶珊瑚苷通过口服或腹腔内（ip）给药（1.5 和 5mg/kg）连续两天，在腹腔注射顺铂（CP）（11mg/kg）两天后给予。两种给药途径的桃叶珊瑚苷治疗均改善了组织病理学变化，并降低了升高的血清肾损伤标志物。CP 给药增加了血红素加氧酶-1（HO-1）和 4-羟基壬烯醛（4-HNE）以及肿瘤坏死因子-α（TNF-α）的肾表达，而桃叶珊瑚苷则呈剂量依赖性地改善了这一表达。此外，桃叶珊瑚苷降低了肾中 cleaved caspase-3 和 -9 的表达增加，并减少了聚（ADP-核糖）聚合酶（PARP）的裂解。从机制上讲，桃叶珊瑚苷抑制了涉及炎症和细胞凋亡的几种信号通路的激活，包括核因子-κB（NF-κB）、信号转导和转录激活因子 3（STAT3）、Akt、细胞外信号调节激酶 1/2（ERK1/2）和叉头框 O3a（FOXO3a）。与口服给药相比，腹腔内给药在减轻 CP 诱导的肾损伤方面虽略有但具有统计学意义的更有效。本研究的结果表明，桃叶珊瑚苷作为一种对抗 CP 诱导的肾毒性的保护剂，值得进一步研究。
