Safranal Ameliorates Renal Damage, Inflammation, and Podocyte Injury in Membranous Nephropathy via SIRT/NF-κB Signalling.

IF 2 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Current Medical Science Pub Date : 2025-04-01 Epub Date: 2025-03-04 DOI:10.1007/s11596-025-00020-8

Yan Bao, Ya-Mei Ge, Zheng Wang, Hong-Yun Wang, Qiong Wang, Jun Yuan

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引用次数: 0

Abstract

Objective: Safranal is a natural product from saffron (Crocus sativus L.) with anti-inflammatory and nephroprotective potential. This study aimed to explore the role of safranal in a cationic bovine serum albumin (C-BSA)-induced rat model of membranous glomerulonephritis (MGN).

Methods: After model establishment, Sprague-Dawley rats were administered 100 or 200 mg/kg safranal by gavage. A biochemical analyser was used to measure the urine protein levels and serum levels of renal function parameters. Hematoxylin-eosin and immunofluorescence staining of kidney tissues were performed to examine histopathological changes and assess the expression of IgG, C3, and Sirt1. Western blotting was performed to measure the protein levels of podocin, nephrin, Sirt1, and factors involved in the NF-κB/p65 pathway. Inflammatory cytokine levels in renal homogenates were determined by ELISA.

Results: Safranal at 100 or 200 mg/kg reduced kidney weight (2.07 ± 0.15 g and 2.05 ± 0.15 g) and the kidney somatic index (0.83 ± 0.08% and 0.81 ± 0.08%) in MGN rats compared with those in the model group without drug administration (2.62 ± 0.17 g and 1.05 ± 0.1%). C-BSA increased the urine protein level to 117.68 ± 10.52 mg/day (compared with the sham group, 5.03 ± 0.45 mg/day), caused dysregulation of renal function indicators, and induced glomerular expansion and inflammatory cell infiltration in the rat kidney samples. All the biochemical and histological changes were improved by safranal administration. Safranal at two doses also increased the fluorescence intensities of IgG (0.1 ± 0.009 and 0.088 ± 0.008) and C3 (0.065 ± 0.006 and 0.048 ± 0.004) compared with those in the MGN group (0.15 ± 0.013 and 0.086 ± 0.008). Additionally, safranal reversed the downregulation of podocin, nephrin, and Wilms tumor protein-1 (WT1) levels and reversed the high inflammatory cytokine levels in MGN rats. Mechanistically, safranal activated Sirt1 signalling to interfere with NF-κB signalling in the kidney tissues of MGN rats.

Conclusions: Safranal ameliorates renal damage, inflammation, and podocyte injury in MGN by upregulating SIRT1 and inhibiting NF-κB signalling.

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通过SIRT/NF-κB信号传导改善膜性肾病的肾损害、炎症和足细胞损伤

目的：藏红花醛是藏红花（Crocus sativus L.）的天然产物，具有抗炎和肾保护作用。本研究旨在探讨红花醛在阳离子型牛血清白蛋白（C-BSA）诱导的大鼠膜性肾小球肾炎（MGN）模型中的作用。方法：建立模型后，大鼠分别灌胃100、200 mg/kg的沙番醚。用生化分析仪测定尿蛋白水平和血清肾功能参数水平。采用苏木精-伊红染色和免疫荧光染色检测肾组织病理变化，并评估IgG、C3和Sirt1的表达。Western blotting检测podocin、nephrin、Sirt1和NF-κB/p65通路相关因子的蛋白水平。采用ELISA法检测肾匀浆中炎性细胞因子水平。结果：与未给药的模型组（2.62±0.17 g和1.05±0.1%）相比，100和200 mg/kg的番红花醚使MGN大鼠的肾脏重量（2.07±0.15 g和2.05±0.15 g）和肾体指数（0.83±0.08%和0.81±0.08%）降低。C-BSA使大鼠尿蛋白水平升高至117.68±10.52 mg/d（假药组为5.03±0.45 mg/d），引起肾功能指标失调，引起肾小球扩张和炎症细胞浸润。给药后各组生化及组织学变化均有改善。与MGN组（0.15±0.013和0.086±0.008）相比，两种剂量的Safranal也增加了IgG（0.1±0.009和0.088±0.008）和C3（0.065±0.006和0.048±0.004）的荧光强度。此外，safranal逆转了podocin、nephrin和Wilms tumor protein-1 （WT1）水平的下调，并逆转了MGN大鼠的高炎症细胞因子水平。机制上，safranal激活Sirt1信号通路，干扰MGN大鼠肾组织中NF-κB信号通路。结论：Safranal通过上调SIRT1和抑制NF-κB信号传导，改善MGN的肾损害、炎症和足细胞损伤。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current Medical Science Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

4.70

自引率

0.00%

发文量

126

期刊介绍： Current Medical Science provides a forum for peer-reviewed papers in the medical sciences, to promote academic exchange between Chinese researchers and doctors and their foreign counterparts. The journal covers the subjects of biomedicine such as physiology, biochemistry, molecular biology, pharmacology, pathology and pathophysiology, etc., and clinical research, such as surgery, internal medicine, obstetrics and gynecology, pediatrics and otorhinolaryngology etc. The articles appearing in Current Medical Science are mainly in English, with a very small number of its papers in German, to pay tribute to its German founder. This journal is the only medical periodical in Western languages sponsored by an educational institution located in the central part of China.