CASP3, TP53, and MYC Targeted by Triptolide towards Ovary Induce Female Reproductive Toxicity

Triptolide is an important active compound derived from Chinese herbal medicine Tripterygium wilfordii Hook f. Despite its positive therapeutic effects, the female reproductive toxicity is still blocking its clinical application with its toxicity mechanism is still obscure. In order to tackle the mechanism of female reproductive toxicity, one intuitive approach is to explore the biological molecule network involving targeted proteins and associated ovary expressed proteins. In this study, triptolide's target proteins and their biological functions were analyzed first. Then, focused on the enriched process of negative regulation of cell cycle, targeted proteins, together with proteins expressed in ovary which are contributed in negative regulation of cell cycle were extracted so as to form the female reproductive toxicity molecule network. Finally, three targeted proteins of CASP3, TP53, and MYC were highlighted as the leading causation of female reproductive toxicity. Further analysis indicated that these 3 target proteins can further regulate 21 ovary expressed proteins which also participate in associated processes. This study provides specified molecule level mechanism the female reproductive toxicity of triptolide which can be used to prevent toxicity while keeping its therapeutic effects.