Li Kang, Wang Xiaoxue, Tang Huidi, Wang Feifan, Qu Zetong, Wang Xiaojie, Li Xiang, Cao Xiaoqing
Department of Pharmacology, School of Basic Medical Sciences, Shandong University, Jinan 250012, China.
Department of Pharmacy, Shandong Public Health Clinical Center, Shandong University, Jinan 250013, China.
Biology (Basel). 2025 May 17;14(5):560. doi: 10.3390/biology14050560.
Acute kidney injury (AKI) is associated with increased in-hospital mortality, yet effective therapeutic agents remain limited. Coixol, a polyphenolic compound derived from Coix, possesses anti-inflammatory properties, but its role in AKI remains unclear. In this study, we demonstrate that Coixol exerts protective effects against ischemia/reperfusion (I/R)-induced AKI by alleviating cellular senescence. Coixol treatment significantly reduced serum creatinine (SCr) and blood urea nitrogen (BUN) levels and decreased the expression of KIM1 and NGAL. RNA sequencing and validation experiments revealed that Coixol suppressed cellular senescence in AKI. Through a weighted gene co-expression network analysis and machine learning, we identified Plaur as a key target of Coixol, which was further validated using RNA-seq data. Notably, Plaur overexpression in AKI mice diminished the protective effects of Coixol, confirming its crucial role. Additionally, molecular docking and molecular dynamics simulations demonstrated strong binding affinity between Coixol and Plaur. These findings highlight Coixol as a promising renal protective agent targeting Plaur and cellular senescence in AKI.
急性肾损伤（AKI）与住院死亡率增加相关，但有效的治疗药物仍然有限。薏苡仁醇，一种从薏苡仁中提取的多酚类化合物，具有抗炎特性，但其在AKI中的作用仍不清楚。在本研究中，我们证明薏苡仁醇通过减轻细胞衰老对缺血/再灌注（I/R）诱导的AKI发挥保护作用。薏苡仁醇治疗显著降低了血清肌酐（SCr）和血尿素氮（BUN）水平，并降低了KIM1和NGAL的表达。RNA测序和验证实验表明，薏苡仁醇可抑制AKI中的细胞衰老。通过加权基因共表达网络分析和机器学习，我们确定Plaur是薏苡仁醇的关键靶点，并使用RNA-seq数据进一步验证。值得注意的是，在AKI小鼠中过表达Plaur可减弱薏苡仁醇的保护作用，证实了其关键作用。此外，分子对接和分子动力学模拟表明薏苡仁醇与Plaur之间具有很强的结合亲和力。这些发现突出了薏苡仁醇作为一种有前景的肾脏保护剂，可靶向AKI中的Plaur和细胞衰老。
