Dictamnine reduces chondrocyte ferroptosis and alleviates osteoarthritis through the HIF-1α/HO-1 pathway.

With the intensification of population aging in China, the incidence of osteoarthritis (OA) is increasing year by year among the middle-aged and elderly population, seriously affecting their health and quality of life. Currently, there is no specific treatment for OA, which makes it particularly important to seek new treatment strategies. Through literature review, we found a promising traditional Chinese medicine, the bark of Dictamnus dasycarpus Turcz, and extracted its active component dictamnine (DIC). For a long time, the biological activities of DIC, such as anti-inflammatory, anti-fungal, and anti-angiogenic, have been widely studied and recognized. Although we have some understanding of the anti-inflammatory effect of DIC, the specific effect on OA and its potential mechanism are still at the preliminary stage of research. To fill this research gap, we aim to explore the effectiveness of DIC in treating OA and reveal its potential anti-inflammatory mechanism. The research results show that DIC can exert pharmacological effects through multiple signaling pathways such as HIF-1α, NQO1, NRF2, and MAPK. Further mechanism studies reveal that DIC mainly inhibits the hypoxia-inducible factor-1α (HIF-1α)/heme oxygenase-1 (HO-1) signaling pathway and acts on chondrocytes to alleviate their ferroptosis phenomenon. This discovery provides a new idea for the treatment of OA and makes DIC a potential therapeutic candidate. Our research not only expands our understanding of the pharmacological effects of DIC, but also opens up a new direction for the drug development of OA, and is worthy of further in-depth exploration and development.