Lo Yi-Hsin, Yang Shun-Fa, Cheng Ching-Chang, Hsu Kuo-Chiang, Chen Yu-Syuan, Chen Yu-Ya, Wang Chun-Wei, Guan Siao-Syun, Wu Cheng-Tien
Department of Nutrition, China Medical University, Taichung 406040, Taiwan.
Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan.
Biomedicines. 2022 Mar 3;10(3):595. doi: 10.3390/biomedicines10030595.
Nobiletin (Nob), a critical active flavonoid of citrus fruits, has received attention for its superior physical functions, which have shown to improve the progression of diseases. Chronic kidney disease (CKD) is recognized as a global health problem, and its mortality and morbidity rates are worsened with an increased risk of accompanying disorders. In this study, we aimed to elucidate whether Nob treatment ameliorates kidney fibrosis and also to identify the potential signaling networks in a unilateral ureteral obstructive (UUO) mouse model, which was used to mimic the progression of CKD. Six-week-old C57BL/6J mice were orally treated with 50 mg/kg of Nob for 14 constitutive days after UUO surgery. We found that the administration of Nob diminished kidney fibrosis and the expression of EMT markers, ameliorated oxidative stress and ferroptosis-associated injury, and mitigated the inflammatory response in the kidneys of UUO mice. Our results suggested that Nob treatment has antiferroptosis, anti-inflammatory, and antifibrotic effects, improving the progression of CKD in UUO mice. Nob may serve as a potential therapeutic candidate for the improvement of progressive CKD in further studies.
诺米林（Nob）是柑橘类水果中的一种关键活性黄酮类化合物，因其卓越的生理功能而受到关注，这些功能已被证明可改善疾病进展。慢性肾脏病（CKD）是一个全球性的健康问题，其死亡率和发病率会随着伴随疾病风险的增加而恶化。在本研究中，我们旨在阐明诺米林治疗是否能改善肾纤维化，并确定在单侧输尿管梗阻（UUO）小鼠模型中的潜在信号网络，该模型用于模拟CKD的进展。六周龄的C57BL/6J小鼠在UUO手术后连续14天口服50mg/kg的诺米林。我们发现，给予诺米林可减少肾纤维化和EMT标志物的表达，改善氧化应激和铁死亡相关损伤，并减轻UUO小鼠肾脏中的炎症反应。我们的结果表明，诺米林治疗具有抗铁死亡、抗炎和抗纤维化作用，可改善UUO小鼠的CKD进展。在进一步的研究中，诺米林可能作为改善进行性CKD的潜在治疗候选药物。
