Syed Rahamat Unissa, Moni Sivakumar S, Hussein Weiam, Alhaidan Taghreed Mohammad Saad, Abumilha Sondos Mohammed Y, Alnahdi Lama Khalid, Wong Ling Shing, Subramaniyan Vetriselvan, Kumarasamy Vinoth
Department of Pharmaceutics, College of Pharmacy, University of Ha'il, Ha'il, 81442, Saudi Arabia.
Department of Pharmaceutics, College of Pharmacy, Jazan University, Jazan, 45142, Saudi Arabia.
Sci Rep. 2025 Feb 5;15(1):4369. doi: 10.1038/s41598-025-87319-7.
Cubebin, a dibenzyl butyrolactone lignan belonging to several distinct families, including Aristolochiaceae, Myristicaceae, Piperaceae, and Rutaceae, and possesses several pharmacological activities, including analgesic, anti-inflammatory, antioxidant, and vasodilatory. The current study aimed to evaluate the effect of cubebin on streptozotocin (STZ)-evoked diabetic nephropathy (DN). DN is a well-identified complication of diabetes mellitus (DM) characterized by renal hypertrophy that progressively declines kidney function. Wistar rats were randomly divided into groups- normal, STZ control (65 mg/kg/body weight), and STZ + cubebin (10 and 20 mg/kg). Biochemical parameters such as glucose levels, kidney parameters, lipid profile, oxidative stress, endogenous antioxidant markers, inflammatory cytokines and histopathology were performed. Molecular docking [(PDB ID: TNF-α (7JRA), NF-κB (1SVC), TGF-β1 (3TZM)] and dynamic simulation (MDS) were also performed with the selected target. STZ-induced DN was changes in these parameters. In contrast, DN + cubebin at 10 and 20 mg/kg doses improved the biochemical parameters and histological changes. Furthermore, molecular docking and simulation studies showed a binding affinity with negative binding energy with TNF-α (7jra, - 11.342 kcal/mol), TGF-β1 (3tzm, - 9.162 kcal/mol) and NF-κB (1svc, - 6.665 kcal/mol). The results of MDS provided insight into the mechanisms that associate proteins TNF-α, NF-κB, and TGF-β1 in conformational dynamics upon binding to cubebin. In conclusion, these findings exhibit a potential effect of cubebin in STZ-evoked DN rats.
荜澄茄素是一种二苄基丁内酯木脂素，属于多个不同的科，包括马兜铃科、肉豆蔻科、胡椒科和芸香科，具有多种药理活性，包括镇痛、抗炎、抗氧化和血管舒张作用。本研究旨在评估荜澄茄素对链脲佐菌素（STZ）诱发的糖尿病肾病（DN）的影响。DN是糖尿病（DM）一种公认的并发症，其特征是肾肥大，肾功能逐渐下降。将Wistar大鼠随机分为正常组、STZ对照组（65mg/kg体重）和STZ+荜澄茄素组（10和20mg/kg）。检测了血糖水平、肾脏参数、血脂谱、氧化应激、内源性抗氧化标志物、炎性细胞因子等生化参数，并进行了组织病理学检查。还对选定的靶点进行了分子对接[（PDB ID：TNF-α（7JRA）、NF-κB（1SVC）、TGF-β1（3TZM）]和动态模拟（MDS）。STZ诱导的DN使这些参数发生了变化。相比之下，10和20mg/kg剂量的DN+荜澄茄素改善了生化参数和组织学变化。此外，分子对接和模拟研究表明，荜澄茄素与TNF-α（7jra，-11.342kcal/mol）、TGF-β1（3tzm，-9.162kcal/mol）和NF-κB（1svc，-6.665kcal/mol）具有负结合能的结合亲和力。MDS结果深入了解了蛋白TNF-α、NF-κB和TGF-β1与荜澄茄素结合时在构象动力学中的相关机制。总之，这些发现显示了荜澄茄素对STZ诱发的DN大鼠具有潜在作用。
