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

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.

Keywords

Inflammation / Membranous nephropathy / Nuclear factor kappa B / Safranal / Sirtuin type-1

© The Author(s) 2025

Authors’ Contributions Yan Bao and Ya-mei Ge conceived and designed the experiments. Yan Bao, Ya-mei Ge, Zheng Wang, Hongyun Wang, Qiong Wang and Jun Yuan carried out the experiments. Yan Bao, Ya-mei Ge and Jun Yuan drafted the manuscript. Yan Bao, Ya-mei Ge, Zheng Wang and Jun Yuan revised the manuscript. All authors agreed to be accountable for all aspects of the work. All authors have read and approved the final manuscript.

Funding This study was supported by the National Natural Science Foundation of China (Nos. 82474412 and 82074364), the Innovation Program of Wuhan-Basic Research in 2022 (No. 2022020801020506) and the Natural Science Foundation of Hubei Province (No. 2022CFC024).

Availability of Data and Materials The raw sequence data reported in this paper and detailed information will be available from the authors on request.

Declarations

Ethical Approval The protocol for animal experiments in this study was under approval of the Animal Ethics Committee of Wuhan Myhalic Biotechnology Co., Ltd (No. HLK-202309078).

Consent for Publication Not applicable.

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third-party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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