Tongluo Yishen Decoction Ameliorates Renal Fibrosis via Regulating Mitochondrial Dysfunction Induced by Oxidative Stress in Unilateral Ureteral Obstruction Rats

Abstract

Tongluo Yishen (TLYS) decoction is an herb that is extensively applied for the treatment of chronic kidney disease (CKD) in traditional Chinese medicine. In this study, 37 different dominant chemical constituents of TLYS were identified. Rats with unilateral ureteral obstruction (UUO) were used as animal models, and TLYS decoction was administered orally for 14 days. TLYS decoction reduced the levels of renal function indicators, serum creatinine levels and blood urea nitrogen levels and alleviated renal pathological changes. Gene Ontology (GO) and KEGG pathway analyses of RNA sequencing data showed that TLYS decoction had significant effects on biological processes, cellular components and molecular functions in UUO rats and that the phagosome (a membrane source in the early stages of autophagy), lysosome (an important component of autolysosome), and oxidation pathways (which contribute to mitochondrial function) might be related to the antifibrotic effects of TLYS decoction. Moreover, we found significant mitochondrial function impairment, including a decreased mitochondrial membrane potential (MMP) and an imbalance in mitochondrial dynamics, excessive oxidative stress, and activation of Pink1/Parkin-mediated mitophagy in UUO rats. Treatment with TLYS decoction significantly increased the MMP, normalized mitochondrial dynamics and ameliorated renal injury. Moreover, TLYS alleviated the mitophagy clearance deficiency. In conclusion, our study showed that TLYS decoction can ameliorate mitochondrial dynamics by reducing oxidative stress and regulating mitophagy, thereby relieving renal injury, protecting renal function, and reducing renal fibrosis. This study provides support for the application of and further research on TLYS decoction.

Tongluo Yishen Decoction Ameliorates Renal Fibrosis via NLRP3-Mediated Pyroptosis In Vivo and In Vitro

“…Our previous research has proved that TLYS has a good therapeutic effect on RIF ( Jia et al, 2021 ). The present experimental study also found that TLYS could protect the kidney function and improve the histopathological damage of the kidney in UUO rats.…”

“…Our team conducted the TLYS decoction fingerprint study by UHPLC-MS. A total of 37 compounds were identified ( Jia et al, 2021 ). Studies have also shown that Salvianolic acid B can alleviate I/R injury in mice by inhibiting caspase-1/GSDMD-mediated pyroptosis via the Nrf2/NLRP3 signaling pathway ( Pang et al, 2020 ).…”

“…Several components of TLYS have been shown in numerous studies to have anti-inflammatory and antioxidant properties ( Zhang et al, 2014 ; Xu et al, 2017 ; Ye T. et al, 2020 ; Tang et al, 2020 ). Our previous research found that TLYS alleviated renal pathological damage by improving oxidative stress in the kidneys of UUO rats ( Jia et al, 2021 ). However, the mechanism of whether TLYS plays a role in pyroptosis remains unclear.…”

Development of a reporting guideline for systematic reviews of animal experiments in the field of traditional Chinese medicine

“…However, through the application of modern experimental methods and technologies in animals, deeper as well as important information that cannot be obtained by the direct observation can be collected 4 . Second, in TCM, functions and therapeutic mechanisms of different drugs, their pharmacokinetics, safety and other issues are still not clear 5–7 . This is more applicable particularly in those cases where the research question involves potential harm without expected benefit (e.g., toxicology, environmental epidemiology), 8,9 research methods on the basis of animal experiment are very necessary.…”

“…4 Second, in TCM, functions and therapeutic mechanisms of different drugs, their pharmacokinetics, safety and other issues are still not clear. [5][6][7] This is more applicable particularly in those cases where the research question involves potential harm without expected benefit (e.g., toxicology, environmental epidemiology), 8,9 research methods on the basis of animal experiment are very necessary.…”