Yu Huifan, Huang Linsheng, Gui Lili, Wu Zhengkun, Luo Han, Xu Mao, Zhang Yan, Qian Yongshuai, Cao Wenjie, Liu Li, Li Fei
School of Pharmaceutical Sciences, Hubei Key Laboratory of Wudang Local Chinese Medicine Research Hubei University of Medicine Shiyan Hubei China.
Institute of Biomedicine Hubei University of Medicine Shiyan Hubei China.
Food Sci Nutr. 2024 Aug 20;12(10):8053-8066. doi: 10.1002/fsn3.4403. eCollection 2024 Oct.
Luteolin is a natural flavonoid, which exists in many plants, including onions, broccoli, carrots, peppers, celery, olive oil, and mint. Luteolin is a dietary flavonoid with potent uric acid-lowering and antioxidant bioactivities. To date, the mechanism by which luteolin alleviates hyperuricemia nephropathy (HN) still needs to be better defined. This study aims to evaluate the therapeutic efficacy of luteolin in a preclinical mouse model and in vitro. Luteolin was administered in the HN mice induced by the combination of potassium oxonate and hypoxanthine to evaluate the potential renoprotective effects in vivo. The NRK-52E cells were stimulated with adenosine for in vitro evaluation. Hematoxylin and eosin staining, biochemical analysis, immunoblotting, immunofluorescence, and immunohistochemistry were performed for the histopathologic and mechanistic investigations. The results suggest that luteolin attenuated tubular dilation and epithelial atrophy in the renal tissue of HN mice. Further, luteolin improved biochemical indicators concerning renal functions and oxidative stress in vivo. Mechanistically, luteolin reduced the renal expressions of KIM-1 and caspase-3. Luteolin activated renal SIRT1/6 cascade and its downstream Nrf2-mediated antioxidant pathway. Furthermore, luteolin elevated the renal expressions of ATP-binding cassette subfamily G isoform 2 protein (ABCG2) and organic anion/cation transporters. In addition, livers of luteolin-treated HN mice exhibited robust inhibition of xanthine oxidase. Together, our study shows that luteolin alleviates renal injury in the HN mice by activating urate excretion and Nrf2/HO-1/NQO1 antioxidant pathways and inhibiting liver xanthine oxidase activity. Thus, luteolin may be a potential agent for the treatment of HN.
木犀草素是一种天然黄酮类化合物，存在于许多植物中，包括洋葱、西兰花、胡萝卜、辣椒、芹菜、橄榄油和薄荷。木犀草素是一种具有强大降尿酸和抗氧化生物活性的膳食黄酮类化合物。迄今为止，木犀草素减轻高尿酸血症肾病（HN）的机制仍需进一步明确。本研究旨在评估木犀草素在临床前小鼠模型和体外实验中的治疗效果。将木犀草素给予由氧嗪酸钾和次黄嘌呤联合诱导的HN小鼠，以评估其在体内的潜在肾脏保护作用。用腺苷刺激NRK-52E细胞进行体外评估。进行苏木精和伊红染色、生化分析、免疫印迹、免疫荧光和免疫组化，以进行组织病理学和机制研究。结果表明，木犀草素减轻了HN小鼠肾组织中的肾小管扩张和上皮萎缩。此外，木犀草素改善了体内与肾功能和氧化应激相关的生化指标。从机制上讲，木犀草素降低了KIM-1和caspase-3在肾脏中的表达。木犀草素激活了肾脏SIRT1/6级联及其下游Nrf2介导的抗氧化途径。此外，木犀草素提高了ATP结合盒转运体G亚家族2蛋白（ABCG2）和有机阴离子/阳离子转运体在肾脏中的表达。此外，经木犀草素处理的HN小鼠的肝脏对黄嘌呤氧化酶表现出强烈的抑制作用。总之，我们的研究表明，木犀草素通过激活尿酸排泄和Nrf2/HO-1/NQO1抗氧化途径以及抑制肝脏黄嘌呤氧化酶活性来减轻HN小鼠的肾损伤。因此，木犀草素可能是治疗HN的潜在药物。
