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
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.