Therapeutic potential of triptolide in autoimmune diseases and strategies to reduce its toxicity

Abstract

With the increasing epidemiology of autoimmune disease worldwide, there is an urgent need for effective drugs with low cost in clinical treatment. Triptolide, the most potent bioactive compound from traditional Chinese herb Tripterygium Wilfordii Hook F, possesses immunosuppression and anti-inflammatory activity. It is a potential drug for the treatment of various autoimmune diseases, but its clinical application is still restricted due to severe toxicity. In this review, the pharmacodynamic effects and pharmacological mechanisms of triptolide in autoimmune diseases are summarized. Triptolide exerts therapeutic effect by regulating the function of immune cells and the expression of cytokines through inflammatory signaling pathways, as well as maintaining redox balance and gut microbiota homeostasis. Meanwhile, the research progress on toxicity of triptolide to liver, kidney, reproductive system, heart, spleen, lung and gastrointestinal tract has been systematically reviewed. In vivo experiments on different animals and clinical trials demonstrate the dose- and time- dependent toxicity of triptolide through different administration routes. Furthermore, we focus on the strategies to reduce toxicity of triptolide, including chemical structural modification, novel drug delivery systems, and combination pharmacotherapy. This review aims to reveal the potential therapeutic prospect and limitations of triptolide in treating autoimmune diseases, thus providing guiding suggestions for further study and promoting its clinical translation.

The therapeutic potential of triptolide and celastrol in neurological diseases

“…Although extracts of TWHF can be used to treat a variety of diseases, their toxicity limits clinical application ( Li et al, 2014 ). Among them, triptolide and celastrol have been reported to have hepatotoxicity, nephrotoxicity, cardiotoxicity, reproductive toxicity and hematological toxicity ( Table 2 ) ( Bai et al, 2021 ; Cheng et al, 2021 ). In addition, poor solubility and bioavailability have also limited the clinical application of triptolide and celastrol, and research on related derivatives ( Figure 4 ) and nanotechnology-based carrier system could improve this situation.…”

Therapeutic Effects of Triptolide on the Balance of Th17/Treg Cells via AKT/mTOR/p70S6k Signaling Pathway in Lupus-like Mice

“…Examples include artemisinin, tripterygium glycosides and total glucosides of paeony [36][37][38]. Previous studies have established that triptolide has immunomodulatory properties, including anti-in ammatory, antioxidant, immunomodulatory, antiproliferative and proapoptotic activities [24][25][26]. Triptolide has been found to be effective in treating autoimmune diseases such as SLE, rheumatoid arthritis, vasculitis and psoriasis [31][32][38][39].…”

Therapeutic Potential of Triptolide in Treating Bone-Related Disorders

“…The pharmacological influence of triptolide towards clinical progress showcases its role in different anti-inflammatory, immunomodulatory, antioxidant, and antiproliferation activities ( Tang et al, 2020 ; Tong et al, 2021 ; Yu et al, 2021 ; Yang et al, 2022 ). Furthermore, triptolide has been reported to play a critical role in various maladies, such as neurological disorders, respiratory illness, gastrointestinal disorders, renal diseases, endocrine diseases, autoimmune disorders, bone dysfunction, and cancer ( Yuan et al, 2019 ; Cheng et al, 2021 ). Herein, we focused on featuring the effects of chemical constituents, bioactivity, and therapeutic window of triptolide on treating bone defects and its related manifestations in inflammations and cancer, especially on bone cancer such as osteosarcoma.…”