Isoorientin inhibits NLRP3 inflammasome activation by activating Nrf2 signaling to delay the progression of osteoarthritis

Osteoarthritis (OA) is a common condition worldwide and one of the leading causes of disability. At present, there is no clear pathological mechanism or treatment to slow disease progression. ISO (Isoorientin) is a dietary flavonoid that has anti-inflammatory properties, it can also be present in edible plants and beverages. However, its effects on OA chondrocytes are not fully articulated. This study aims to investigate how ISO delays OA progression and its specific mechanism. The salvaging effects of ISO on extracellular matrix degradation and its protective effects against pyroptosis were studied. It was discovered that these effects might be mediated through the Nrf2/HO-1 and NQO1/NF-κB pathways. Nrf2-siRNA was then used for validation. Subsequently, the effects and mechanisms of ISO were evaluated in a mouse model of OA induced by surgery, and a certain degree of improvement in OA conditions due to ISO was observed.In conclusion, ISO may be a promising candidate drug for alleviating OA.