College of Food Science and Engineering, Ocean University of China, No. 5 Yushan Road, Qingdao 266003, P. R. China.
Laboratory for Marine Drugs and Bioproducts, Pilot National Laboratory for Marine Science and Technology (Qingdao), Qingdao 266237, Shandong Province, P. R. China.
Food Funct. 2022 Jun 6;13(11):6103-6117. doi: 10.1039/d1fo04178a.
An increasing number of studies have reported the effects of curcumin (Cur) and docosahexaenoic acid (DHA) on alleviating acute kidney injury (AKI). In this work, we have performed a comparative investigation to determine the effect of dietary DHA-acylated Cur esters, ester derivatives of Cur, and recombination of curcumin and DHA on alleviating acute kidney injury in a mouse model induced by a single intraperitoneal injection with cisplatin (20 mg kg). The results showed that the DHA-acylated Cur diesters significantly decreased the abnormally increased blood urea nitrogen, creatinine, lipopolysaccharide (LPS) and trimethylamine--oxide (TMAO) in serum caused by AKI. Histopathological results confirmed that DHA-acylated Cur diesters clearly reduced the degree of renal tubular injury. The renal protective effect of the DHA-acylated Cur diester was better than that of the monoester and the recombination of Cur and DHA. Notably, we found that the DHA-acylated Cur diester treatment remarkably changed the relative abundance of microbiota related to LPS and TMAO/trimethylamine (TMA) metabolism. Moreover, dietary DHA-acylated Cur diesters clearly reduced the MDA content and elevated GSH levels in the kidney of AKI mice, as well as changed the fatty acid composition in the kidney. Further mechanism studies showed that DHA-acylated Cur diesters significantly inhibited inflammation, apoptosis and oxidative stress by preventing the LPS and TMAO-mediated PI3K/Akt/NF-κB signaling pathway. The above results indicate that DHA-acylated Cur diesters are a potentially novel candidate or targeted dietary pattern to prevent and treat drug-induced acute kidney injury.
越来越多的研究报告了姜黄素（Cur）和二十二碳六烯酸（DHA）对缓解急性肾损伤（AKI）的作用。在这项工作中，我们进行了对比研究，以确定膳食 DHA 酰化 Cur 酯、Cur 的酯衍生物以及姜黄素和 DHA 的重组对顺铂（20mg/kg）单次腹腔注射诱导的小鼠模型 AKI 的缓解作用。结果表明，DHA 酰化 Cur 二酯可显著降低 AKI 引起的血清中异常升高的血尿素氮、肌酐、脂多糖（LPS）和三甲胺氧化物（TMAO）。组织病理学结果证实 DHA 酰化 Cur 二酯明显减轻了肾小管损伤的程度。DHA 酰化 Cur 二酯的肾保护作用优于单酯和姜黄素与 DHA 的重组。值得注意的是，我们发现 DHA 酰化 Cur 二酯处理可显著改变与 LPS 和 TMAO/三甲胺（TMA）代谢相关的微生物群落的相对丰度。此外，膳食 DHA 酰化 Cur 二酯可明显降低 AKI 小鼠肾脏中的 MDA 含量和 GSH 水平，并改变肾脏中的脂肪酸组成。进一步的机制研究表明，DHA 酰化 Cur 二酯通过抑制 LPS 和 TMAO 介导的 PI3K/Akt/NF-κB 信号通路显著抑制炎症、细胞凋亡和氧化应激。上述结果表明，DHA 酰化 Cur 二酯是一种潜在的新型候选物或靶向饮食模式，可预防和治疗药物引起的急性肾损伤。
