Friend or foe? The dual role of triptolide in the liver, kidney, and heart

Triptolide, a controversial natural compound due to its significant pharmacological activities and multiorgan toxicity, has gained much attention since it was isolated from the traditional Chinese herb Tripterygium wilfordii Hook F. However, in addition to its severe toxicity, triptolide also presents powerful therapeutic potency in the same organs, such as the liver, kidney, and heart, which corresponds to the Chinese medicine theory of You Gu Wu Yun (anti-fire with fire) and deeply interested us. To determine the possible mechanisms involved in the dual role of triptolide, we reviewed related articles about the application of triptolide in both physiological and pathological conditions. Inflammation and oxidative stress are the two main ways triptolide exerts different roles, and the cross-talk between NF-κB and Nrf2 may be one of the mechanisms responsible for the dual role of triptolide and may represent the scientific connotation of You Gu Wu Yun. For the first time, we present a review of the dual role of triptolide in the same organ and propose the possible scientific connotation of the Chinese medicine theory of You Gu Wu Yun, hoping to promote the safe and efficient use of triptolide and other controversial medicines.