[Study on detoxification and mechanism of concoction with radix Rehmanniae praeparata juice on radix Tripterygium wilfordii-induced reproductive toxicity].

This study aims to explore the detoxification and mechanism of concoction with radix Rehmanniae praeparata(RRP) juice on radix Tripterygium wilfordii(RTW)-induced reproductive toxicity and its effect on the original anti-inflammatory efficacy of RTW while reducing toxicity for the first time. On the basis of the preparation of processed products of RTW concocted with RRP juice, the content of triptolide which is a main toxic component of RTW was measured by high performance liquid chromatography before and after processing, and the level of testosterone(T), creatinine(Cr), urea nitrogen(BUN), alanine aminotransferase(ALT), and aspartate aminotransferase(AST) in mouse serum was detected to evaluate the attenuation effect of concoction with RRP juice on multiorgan toxicity induced by RTW and to optimize the target organs for detoxification. The detoxification mechanism was evaluated by analyzing the level of ferrous ion(Fe~(2+)), malondialdehyde(MDA), superoxide dismutase(SOD), and reduced glutathione(GSH), as well as the expression level of solute carrier family 7 member 11(SLC7A11), ferritin heavy chain polypeptide 1(FTH1), and glutathione peroxidase 4(GPX4) proteins in mouse testis. In addition, the effect of concoction with RRP juice on the anti-inflammatory efficacy of RTW was evaluated by a mouse model with carrageenan foot swelling. RESULTS:: showed that the content of triptolide in the processed products of RTW concocted with RRP juice was significantly reduced(P<0.01). Compared with the normal group, the raw RTW group exhibited a significant decrease in the testicular coefficient and T level in serum, a significant increase in the level of Cr, BUN, ALT, and AST, as well as Fe~(2+) and MDA in testis, and a significant reduction in the level of SOD, GSH, SLC7A11, FTH1, and GPX4(P<0.01). Compared with the raw RTW group, the groups of RTW concocted with 20% and 25% RRP juice displayed a significant elevation of the testicular coefficient and T level in serum, a decrease in Cr and BUN levels in serum, as well as the Fe~(2+) and MDA levels in testis, and a significant increase in the level of SOD, GSH, SLC7A11, FTH1, and GPX4 in testis(P<0.01). Compared with the rheumatic heat stress group, the raw RTW group and the groups of RTW concocted with RRP juice exhibited a significant reduction in the foot swelling of mice(P<0.05, P<0.01). In conclusion, concoction with RRP juice can reduce the reproductive and renal toxicity induced by RTW, and the attenuation mechanism may be related to the inhibition of testicular ferroptosis in mice and preservation of the original anti-inflammatory effect of RTW in the process of toxicity reduction.