Exploring Triptolide's Dual Role in Inflammation and Oxidative Stress: Responses of Organelles

ABSTRACT Triptolide (TPL), isolated from the traditional Chinese herb Tripterygium wilfordii Hook. f., is a natural compound with complex pharmacological activities. TPL has significant therapeutic effects in rheumatoid arthritis, Alzheimer's disease, diabetic nephropathy, and other diseases through anti‐inflammatory and antioxidant effects. However, its pro‐inflammatory and antioxidant effects produce toxicity to multiple organs such as kidney, liver, and the reproductive organs. Thus, the effects of TPL on inflammation and oxidative stress broaden the therapeutic scope of TPL, but also limit its clinical application. In recent years, studies have shown that TPL can significantly affect the structure and function of multiple organelles such as endoplasmic reticulum, mitochondria and lysosomes. The presence of some special structures among these organelles, which are involved in the exchange of substances and information, may be an important reason for that TPL can cause alterations in multiple organelles. This review systematically summarizes the dual role and molecular mechanisms of TPL in inflammation and oxidative stress, and analyzes the cytological basis for the dual role of TPL from the aspects of organelles and their cross‐talk, so as to provide a comprehensive and in‐depth investigation for the fundamental research and clinic application of TPL.