<i>Tripterygium wilfordii</i>: An inspiring resource for rheumatoid arthritis treatment

<jats:title>Abstract</jats:title><jats:p><jats:italic>Tripterygium wilfordii</jats:italic> Hook F (<jats:italic>Tw</jats:italic>HF)‐based therapy is among the most efficient and crucial therapeutics for the treatment of rheumatoid arthritis (RA), which indicates that <jats:italic>Tw</jats:italic>HF is a potential source of novel anti‐RA drugs. However, accumulating studies have observed that <jats:italic>Tw</jats:italic>HF‐based therapy induces multi‐organ toxicity, which prevents the wide use of this herb in clinical practice, although several recent studies have attempted to reduce the toxicity of <jats:italic>Tw</jats:italic>HF. Notably, our research group developed a “Clinical Practice Guideline for <jats:italic>Tripterygium</jats:italic> Glycosides/<jats:italic>Tripterygium wilfordii</jats:italic> Tablets in the Treatment of Rheumatoid Arthritis” (No. T/CACM 1337‐2020) approved by the China Association of Chinese Medicine to standardize the clinical application of <jats:italic>Tw</jats:italic>HF‐based therapy and thus avoid adverse effects. Although great strides have been made toward the characterization of <jats:italic>Tw</jats:italic>HF‐based therapy and revealing its underlying pharmacological and toxicological mechanisms, several crucial gaps in knowledge remain as potential barriers to enhance its therapeutic effects on the premise of safety assurance. This review offers a global view of <jats:italic>Tw</jats:italic>HF, ranging from its chemical constituents, quality control, clinical observations, and underlying pharmacological mechanisms to toxic manifestations and mechanisms. We focus on the important and emerging aspects of this field and highlight the major challenges and strategies for using novel techniques and approaches to gain new insights into unresolved questions. We hope that this review will improve the understanding of <jats:italic>Tw</jats:italic>HF application and draw increasing interdisciplinary attention from clinicians that practice both Chinese and Western medicine, basic researchers, and computer scientists.</jats:p>