Department of Nephrology, Schneider Children's Medical Center, Petah Tikva, Israel.
School of Medicine, Tel Aviv University, Tel Aviv, Israel.
Sci Rep. 2024 Mar 30;14(1):7577. doi: 10.1038/s41598-024-58055-1.
Chronic Kidney Disease (CKD) associated complications are associated with increased inflammation through the innate immune response, which can be modulated with anti-inflammatory agents. An active ingredient derived from the Nuphar lutea aquatic plant, 6,6'-dihydroxythiobinupharidine (DTBN) has anti-inflammatory properties, mainly through the inhibition of NF-κB. We tested the effects of DTBN on mice with CKD. After preliminary safety and dosing experiments, we exposed 8 weeks old male C57BL/6J mice to adenine diet to induce CKD. Control and CKD animals were treated with IP injections of DTBN (25 μg QOD) or saline and sacrificed after 8 weeks. Serum urea and creatinine were significantly decreased in CKD-DTBN Vs CKD mice. Kidney histology showed a decrease in F4/80 positive macrophage infiltration, damaged renal area, as well as decreased kidney TGF-β in CKD-DTBN Vs CKD mice. Kidney inflammation indices (IL-1β, IL-6 and P-STAT3) were significantly decreased in CKD-DTBN as compared to CKD mice. DTBN treatment showed no apparent damage to tissues in control mice, besides a decrease in weight gain and mild hypoalbuminemia without proteinuria. Thus, DTBN significantly improved renal failure and inflammation indices in CKD mice. Therefore, this and similar substances may be considered as an additional treatment in CKD patients.
慢性肾脏病（CKD）相关并发症与固有免疫反应引起的炎症增加有关，可通过抗炎药物进行调节。一种来源于水生植物黄莲的活性成分 6,6'-二羟基硫代双叶豆堿（DTBN）具有抗炎特性，主要通过抑制 NF-κB 来实现。我们测试了 DTBN 对 CKD 小鼠的作用。在进行初步的安全性和剂量实验后，我们用腺嘌呤饮食诱导 8 周龄雄性 C57BL/6J 小鼠产生 CKD。对照和 CKD 动物接受 DTBN（25μg QOD）或生理盐水的腹腔注射，并在 8 周后处死。与 CKD 小鼠相比，CKD-DTBN 小鼠的血清尿素和肌酐显著降低。肾组织学显示 F4/80 阳性巨噬细胞浸润、受损的肾区以及 CKD-DTBN 小鼠的肾 TGF-β减少。与 CKD 小鼠相比，CKD-DTBN 小鼠的肾脏炎症指标（IL-1β、IL-6 和 P-STAT3）显著降低。与 CKD 小鼠相比，DTBN 治疗对对照组小鼠的组织没有明显损伤，除了体重增加减少和轻度低白蛋白血症而无蛋白尿。因此，DTBN 可显著改善 CKD 小鼠的肾衰竭和炎症指标。因此，这种物质和类似物质可被认为是 CKD 患者的附加治疗方法。
