Wang Hongbo, Wu Xiaoming, Li Ziyun, Rong Kuanrong, Gao Shan, Tang Wenjian, Zhang Jing
Department of Pharmacy, Shandong Medical College, Linyi 276000, People's Republic of China.
School of Pharmacy, Anhui Medical University, Hefei 230032, People's Republic of China.
ACS Omega. 2024 Nov 28;9(49):48821-48834. doi: 10.1021/acsomega.4c09003. eCollection 2024 Dec 10.
Glycyrrhetin urea has emerged as a privileged scaffold with anti-inflammatory activity for the treatment and prevention of acute kidney injury (AKI). In this study, structural modifications of the A ring of glycyrrhetinic acid yielded a series of urea derivatives, among which compound exhibited the most promising anti-inflammatory activity. was confirmed to interact with STING through a cellular heat shift assay and to inhibit the STING/NF-κB pathway in RAW264.7 cells. It acted on the STING pathway, inhibited NF-κB phosphorylation, and subsequently reduced the level of release of inflammatory factors. Additionally, significantly increased the survival rate of renal tubular epithelial cells, demonstrating a protective effect against cisplatin-induced cell death and mitigating inflammation activation. The AKI mouse model showed that significantly downregulated serum creatinine (Scr), blood urea nitrogen (BUN), and levels of inflammatory factors (IL-1β, IL-6, and TNF-α), thereby improving renal function. Morphological analysis revealed that attenuated the cisplatin-induced renal tubular injury. Therefore, represents a promising lead for the prevention and treatment of AKI.
甘草次酸尿素已成为一种具有抗炎活性的优势骨架，用于治疗和预防急性肾损伤（AKI）。在本研究中，对甘草次酸的A环进行结构修饰得到了一系列尿素衍生物，其中化合物表现出最有前景的抗炎活性。通过细胞热迁移分析证实其与STING相互作用，并在RAW264.7细胞中抑制STING/NF-κB通路。它作用于STING通路，抑制NF-κB磷酸化，随后降低炎症因子的释放水平。此外，显著提高了肾小管上皮细胞的存活率，显示出对顺铂诱导的细胞死亡的保护作用，并减轻炎症激活。AKI小鼠模型表明，显著下调血清肌酐（Scr）、血尿素氮（BUN）和炎症因子（IL-1β、IL-6和TNF-α）水平，从而改善肾功能。形态学分析显示，减轻了顺铂诱导的肾小管损伤。因此，代表了预防和治疗AKI的一个有前景的先导物。
