Pharmacokinetic and Toxicological Characteristics of Tripterigium Glycosides and Their Derivatives

Background: Tripterigium wilfordii glycosides (TWG) demonstrate paramount bioactive effectiveness in the management of many autoimmune diseases. However, its side effects on the hepatic, nephrotic, reproductive, and cardiovascular systems have limited its immense therapeutic potentials. Triptolide (TP) and Celastrol (CL), the leading bioactive as well as toxic constituents of TWG, have been widely studied. This review aims to summarize the key mechanisms that TWG trigger the toxic reactions and the precautionary measures that could prevent and reduce such reactions. Method: We undertook a systemic search of bibliographic databases for peer-reviewed research literature about the toxic mechanisms and pharmacokinetic profiles of TWG. The key points of screened papers were described and combined together to make up whole. Results: Totally 125 papers were referred in this paper, the majority were from Chinese academic associations. It has been reported that reactive oxygen species generation, mitochondrial respiratory chain inhibition, and metabolizing enzyme inhibition are the leading factors of the toxic reactions. The bioactive effects and toxicities of TWG are closely related to its metabolic profiles. It has been confirmed that TP and CL inhibit CYP450 and the transporters. This paper reviews and summarizes the pharmacokinetic parameters of TWG. Antioxidants, polymeric micelle and topical nanoparticle formulations have exhibited potentials in toxicity circumvention. Conclusion: A thorough understanding of the pharmacokinetic and toxicological characteristics of TWG combined with further in-depth study will enhance the efficacy and safety in using TWG, which would augment and improve its clinical application in the future. Keywords: Toxic mechanism, pharmacokinetics, tripterigium glycosides, triptolide, celastrol, metabolite.