Anti-apoptosis mechanism of triptolide based on network pharmacology in focal segmental glomerulosclerosis rats
Authors: Mengdie Yang
Yayu Li
Xue Jiang
Jing Pan
Litao Song
Journal: Bioscience Reports (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: FSGS; IL4; apoptosis; network pharmacology; triptolide.
Affiliations: Department of Nephrology, Guangxing Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou Hospital of Traditional Chinese Medicine, No. 453, Tiyuchang Road, Hangzhou City, Zhejiang Province 310007, P. R. China, Department of Nephrology, Hangzhou Dingqiao Hospital, Dingqiao Branch of Hangzhou Hospital of Traditional Chinese medicine, No. 453, Tiyuchang Road, Hangzhou City, Zhejiang Province 310007, P. R. China, Department of Nephrology, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, No. 548, Binwen Road, Hangzhou City, Zhejiang Province 310000, P. R. China

Abstract:  Triptolide (TPL), the active component of Tripterygium wilfordii, exhibits anti-cancer and antioxidant functions. We aimed to explore the anti-apoptosis mechanism of TPL based on network pharmacology and in vivo and in vitro research validation using a rat model of focal segmental glomerulosclerosis (FSGS). The chemical structures and pharmacological activities of the compounds reported in T. wilfordii were determined and used to perform the network pharmacology analysis. The Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) was then used to identify the network targets for 16 compounds from Tripterygium wilfordii. Our results showed that 47 overlapping genes obtained from the GeneCards and OMIM databases were involved in the occurrence and development of FSGS and used to construct the protein-protein interaction (PPI) network using the STRING database. Hub genes were identified via the MCODE plug-in of the Cytoscape software. IL4 was the target gene of TPL in FSGS and was mainly enriched in the cell apoptosis term and p53 signaling pathway, according to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. TPL inhibited FSGS-induced cell apoptosis in rats and regulated IL4, nephrin, podocin, and p53 protein levels via using CCK8, TUNEL, and Western blot assays. The effects of IL4 overexpression, including inhibition of cell viability and promotion of apoptosis, were reversed by TPL. TPL treatment increased the expression of nephrin and podocin and decreased p53 expression in rat podocytes. In conclusion, TPL inhibited podocyte apoptosis by targeting IL4 to alleviate kidney injury in FSGS rats. 

Retracted: Yes

PubPeer comments:
 This article is being retracted from Bioscience Reports at the request of the authors. The authors have been unable to replicate the results produced in the study, in particular the quantity of podocytes undergoing apoptosis following treatment with Triptolide (TPL), causing the authors to doubt the original conclusion that TPL has no influence on the cell viability and apoptosis. The authors are still investigating the mechanism of TPL regulation on podocyte lesions and the reason for this discrepancy is currently unknown. The authors also note that there are errors in the units throughout the paper, as well as a u201cGlucose treatment and cell cultureu201d section in the methods, which did not form part of this study. The Editorial Board agrees to the retraction. ,