Protective effects of Sulforaphene on kidney damage and gut dysbiosis in high-fat diet plus streptozotocin-induced diabetic mice

Bo Zhang; Kang Xu; Wenlei Deng; Ce Liu; Qianmin Xu; Huakang Sheng; Jialu Feng; Qipeng Yuan

doi:10.1016/j.foodchem.2024.142558

Protective effects of Sulforaphene on kidney damage and gut dysbiosis in high-fat diet plus streptozotocin-induced diabetic mice

Food Chem. 2024 Dec 19:469:142558. doi: 10.1016/j.foodchem.2024.142558. Online ahead of print.

Authors

Bo Zhang¹, Kang Xu², Wenlei Deng¹, Ce Liu¹, Qianmin Xu¹, Huakang Sheng¹, Jialu Feng³, Qipeng Yuan⁴

Affiliations

¹ State Key Laboratory of Chemical Resource Engineering, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China.
² School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China.
³ School of Medicine, Wuhan University of Science and Technology, Wuhan 430065, China.
⁴ State Key Laboratory of Chemical Resource Engineering, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China. Electronic address: yuanqp@mail.buct.edu.cn.

PMID: 39709924
DOI: 10.1016/j.foodchem.2024.142558

Abstract

Diabetic nephropathy (DN) is one of the most serious and prevalent complications associated with diabetes. Consequently, antidiabetic drugs or foods potentially protecting the kidneys are of significant therapeutic value. Sulforaphene (SFE) is a natural isothiocyanate derived from radish seeds, known for its anti-inflammatory and antioxidant properties. However, no studies have investigated on the ability of SFE to prevent or treat DN. This study established a high-fat diet combined with a streptozotocin-induced type II diabetes mellitus mouse model. We administered SFE treatment to examine its protective effects on renal and intestinal homeostasis in DN mice. After 4 weeks of treatment, SFE (50 mg/kg b.w.) not only reduced blood glucose concentration (20.3 %, P < 0.001), kidney to body weight ratio (26.2 %, P < 0.01), and levels of serum total cholesterol (40.6 %, P < 0.001), triglycerides (38.2 %, P < 0.01), creatinine (36.7 %, P < 0.01), and urea nitrogen (45.0 %, P < 0.001) in DN mice compared to control mice but also increased the kidney superoxide dismutase (72.7 %, P < 0.001), catalase (51.1 %, P < 0.001), and glutathione peroxidase activities (31.6 %, P < 0.01), as well as glutathione levels (39.2 %, P < 0.01) in comparison to DN mice. Furthermore, SFE decreased levels of reactive oxygen species (55.4 %, P < 0.01), 4-hydroxyalkenals (36.9 %, P < 0.001), malondialdehyde (42.6 %, P < 0.001), and 8-hydroxy-deoxyguanosine (26.3 %, P < 0.001), accompanied by a meliorating kidney morphological abnormalities. Notably, a reduction in renal inflammatory factors was also observed in SFE-treated DN mice compared to untreated DN mice, particularly in the C-X-C motif chemokine ligand 8 factors (54.8 %, P < 0.001). Western blotting results indicated that SFE significantly down-regulated the protein expression of TLR4 and MyD88 (1.9, 1.7-fold, P < 0.001). Additionally, SFE improved gut microbiota (GM) dysbiosis and intestinal homeostasis, as evidenced by increased expression of antimicrobial peptides and tight junction proteins in colon tissue. SFE appeared to enhance the proliferation of probiotics, such as Bacteroidota, Lachnospiraceae_NK4A136_group and norank_f__Muribaculaceae, while also decreasing harmful bacteria to a greater extent compared to STZ treatment. These findings suggest that SFE modulates GM and improves intestinal homeostasis, providing a theoretical basis for its use in the treatment of DN.

Keywords: Gut microbiota; Inflammation; Kidney protective effects; Oxidative stress; Streptozotocin; Sulforaphene.