Jiedu Tongluo Baoshen formula enhances renal tubular epithelial cell autophagy to prevent renal fibrosis by activating SIRT1/LKB1/AMPK pathway

• Published in: Biomedicine & pharmacotherapy Vol. 160; p. 114340
• Main Authors: Jin, Di, Zhao, Yunyun, Sun, Yuting, Xue, Jiaojiao, Li, Xiangyan, Wang, Xiuge
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01.04.2023; Elsevier
• Subjects: AMP-Activated Protein Kinases - metabolism; Animals; Autophagy; Diabetic kidney disease; Diabetic Nephropathies - drug therapy; Diabetic Nephropathies - metabolism; Diabetic Nephropathies - prevention & control; Epithelial Cells; Epithelial-Mesenchymal Transition; Fibrosis; Jiedu Tongluo Baoshen formula; Rats; Renal fibrosis; Renal tubular epithelial cell; SIRT1/LKB1/AMPK; Sirtuin 1 - metabolism; ESRD; Renal fibrosis; HFD; FN; DM; Renal tubular epithelial cell; WB; LKB1; Autophagy; Col IV; α-SMA; SD; Jiedu Tongluo Baoshen formula; STZ; DKD; Diabetic kidney disease; STAT1; JTBF; EMT; ECM; SIRT1/LKB1/AMPK; UPLC; Irb; AMPK; GAPDH; TEM; HG; TCM
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2023.114340

Renal fibrosis, an important pathological change in the development of diabetic kidney disease (DKD), urgently needs new treatment methods clinically. The Jiedu Tongluo Baoshen (JTBF) formula was created based on the theory of toxic damage to the kidney collaterals, and a variety of active ingredients in JTBF have inhibitory effects on epithelial-mesenchymal transition (EMT) and extracellular matrix (ECM). In this study, the Ultra Performance Liquid Chromatography (UPLC) was employed to analyze the effective ingredients in the JTBF formula. After screening in the PubChem database, we identified 94 active compounds of JTBF and predicted the SIRT1 pathway as potential targets through network pharmacology. In addition, in the high fat diet (HFD)+Streptozocin (STZ)-induced DKD rat model and high glucose (HG)-induced NRK-52E cell model, JTBF treatment activates the phosphorylation of LKB1 and AMPK and enhances the autophagy activity of NRK-52E cells, thereby reducing the accumulation of EMT and ECM. These results have been confirmed in vivo and in vitro experiments. JTBF enhances the autophagy activity of renal tubular epithelial cells and inhibits the progression of DKD renal fibrosis by activating the SIRT1/LKB1/AMPK signal pathway. This study provides new insights into the molecular mechanism of JTBF to prevent and treat DKD renal fibrosis. [Display omitted] •Renal fibrosis is an important pathological change in the development of DKD.•Jiedu Tongluo Baoshen formula (JTBF) may inhibit DKD fibrosis.•JTBF enhances the autophagy of renal tubular epithelial cells and improves fibrosis.•SIRT1/LKB1/AMPK signaling is associated with renal fibrosis.•JTBF activates SIRT1/LKB1/AMPK pathway to enhance autophagy protection of kidney.