Tripterygium glycosides improve abnormal lipid deposition in nephrotic syndrome rat models

Abstract

Objective

The purpose of this study was to determine the effect of tripterygium glycosides (TGs) on regulating abnormal lipid deposition in nephrotic syndrome (NS) rats.

Methods

Sprague-Dawley (SD) rats were injected with 6 mg/kg doxorubicin to construct nephrotic syndrome models (n = 6 per group), and then administered with TGs (10 mg/kg·d⁻¹), prednisone (6.3 mg/kg·d⁻¹), or pure water for 5 weeks. Biomedical indexes, such as urine protein/creatinine ratio (PCR), blood urea nitrogen (BUN), serum creatinine (Scr), serum albumin (SA), triglycerides (TG), total cholesterol (TC)were investigated to evaluate the renal injury of rats. H&E staining experiment was used to assess the pathological alterations. Oil Red O staining was used to assess the level of renal lipid deposition. Malondialdehyde (MDA) and glutathione (GSH) were measured to assess the extent of oxidative damage to the kidney. TUNEL staining was used to assess the status of apoptosis in the kidney. Western blot analysis was performed to examine the levels of relevant intracellular signaling molecules.

Results

After treatment with TGs, those tested biomedical indexes were significantly improved, and the extent of kidney tissue pathological changes and lipid deposition in the kidney was diminished. Treatment with TGs decreased renal oxidative damage and apoptosis. Regarding the molecular mechanism, TGs significantly increased the protein expression levels of Bcl-2 but decreased the levels of CD36, ADFP, Bax, and Cleaved caspase-3.

Conclusion

TGs alleviates renal injury and lipid deposition induced by doxorubicin, suggesting that it may be a new strategy for reducing renal lipotoxicity in NS.

Graphical Abstract

Keywords:

• Doxorubicin
• nephrotic syndrome
• lipotoxicity
• tripterygium glycosides

Ethical approval

The animal protocol was reviewed and approved by the Experimental Animal Ethics Committee of Guangdong Provincial Hospital of Traditional Chinese Medicine, approval number (2020004).

Author contributions

Bo Liu, Aihua Wu, and Peng Xu conceived and designed the experiments. Bidan Zheng, Dongfang Lu, Xiuping Chen, Yinghua Yin, and Weiying Chen performed the experiments. Bidan Zheng, Huanmei Lin, and Dongfang Lu analyzed and interpreted the data. Bidan Zheng and Dongfang Lu wrote the manuscript. Bo Liu and Aihua Wu critically revised the manuscript. Bo Liu, Aihua Wu, Peng Xu, and Xiaowan Wang supervised the findings of the work and approved the manuscript for submission. All authors agreed with the final version of this manuscript.

Disclosure statement

The graphical abstract was created by Figdraw. The authors declare no conflicts of interest.

Data availability statement

All data generated during the study can be obtained upon reasonable request from the corresponding author.

Additional information

Funding

This work was supported by the Key-Area Research and Development Program of Guangdong Province (No. 2020B1111110007), Science and technology project of Guangzhou (Nos. 202002010004 and 202201020488), Natural Science Foundation of Guangdong Province (Nos. 2017B030314166, 2022A1515010103, and 2022A1515012443), the Specific Research Fund for TCM Science and Technology of Guangdong Provincial Hospital of Chinese Medicine (No. YN2020QN02), Research Fund for Bajian Talents of Guangdong Provincial Hospital of Chinese Medicine (No. BJ2022KY08), Collaborative innovation project of Guangzhou University of Chinese Medicine (Nos. 2021xk69 and 2021xk08), and Special Funds for State Key Laboratory of Dampness Syndrome of Chinese Medicine (Nos. SZ2021ZZ33 and SZ2021ZZ11).