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Insights into the mechanisms of triptolide nephrotoxicity through network pharmacology-based analysis and RNA-seq

Introduction: Triptolide (TPL) is a promising plant-derived compound for clinical therapy of multiple human diseases; however, its application was limited considering its toxicity.

Methods: To explore the underlying molecular mechanism of TPL nephrotoxicity, a network pharmacology based approach was utilized to predict candidate targets related with TPL toxicity, followed by deep RNA-seq analysis to characterize the features of three transcriptional elements include protein coding genes (PCGs), long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) as well as their associations with nephrotoxicity in rats with TPL treatment.

Results & discussion: Although the deeper mechanisms of TPL nephrotoxcity remain further exploration, our results suggested that c-Jun is a potential target of TPL and Per1 related circadian rhythm signaling is involved in TPL induced renal toxicity.

Comments：

It is interesting to see the use of a network pharmacology approach followed by deep RNA-seq analysis to explore the molecular mechanism of TPL nephrotoxicity. The identification of candidate targets related to TPL toxicity and the characterization of transcriptional elements, including PCGs, lncRNAs, and circRNAs, provide a comprehensive view of the molecular changes associated with TPL treatment. The finding of c-Jun as a potential target of TPL and the involvement of Per1 related circadian rhythm signaling in TPL induced renal toxicity suggests potential avenues for further research on the mechanisms underlying TPL nephrotoxicity. However, it is important to note that these results are based on a rat model and may not necessarily translate to humans, and additional studies are needed to confirm and extend these findings.

Related Products

Cat.No. Product Name Information
S3604 Triptolide Triptolide is a diterpene triepoxide, immunosuppresive agent extracted from the Chinese herb Tripterygium wilfordii. It functions as a NF-κB inhibitor with dual actions by disruption of p65/CBP interaction and by reduction of p65 protein. Triptolide (PG490) abrogates the transactivation function of heat shock transcription factor 1 (HSF1). Triptolide inhibits MDM2 and induces apoptosis through a p53-independent pathway.

Related Targets

NF-κB MDM2/MDMX Apoptosis related HSP (HSP90) ADC Cytotoxin