OBJECTIVE To explore the molecular mechanism of glycyrrhizic acid antagonizing nephrotoxicity induced by tripterygium glycosides from the perspective of transporters.
METHODS The targets of tripterygium glycosides and glycyrrhizic acid on nephrotoxicity were predicted by network pharmacology, and the targets related to renal transporters were selected and verified by animal experiments. The contents of BUN and Scr in rat serum were measured by ELISA, the pathological condition of rat kidney was detected by HE staining, and the expressions of transporter gene and protein were detected by qPCR and Western blot.
RESULTS Network pharmacology predicted that there were 73 targets and 81 molecular functions of the two drugs on nephrotoxicity, which were mainly concentrated in protein binding, involving transporters ABCB1 and ABCC2. Animal experiments showed that tripterygium glycosides significantly increased the contents of BUN and Scr in rat kidney, the renal pathological results showed that the kidney was severely injured; Compatibility of tripterygium glycosides and glycyrrhizic acid significantly reduced the contents of BUN and Scr and alleviated kidney damage. qPCR and Western blot showed that tripterygium glycosides significantly down-regulated the gene and protein expressions of P-gp and MRP2; Compatibility of tripterygium glycosides and glycyrrhizic acid significantly up-regulated the gene and protein expressions of P-gp and MRP2.
CONCLUSION Glycyrrhizic acid can accelerate the excretion of toxic substances and antagonize the nephrotoxicity caused by tripterygium glycosides by affecting P-gp and MRP2 transporters. This study provides experimental evidence for the combination of two drugs in clinical treatment of nephropathy and alleviation of toxic reactions.
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