Besides, a number of related indicators suggested that Loureirin A has a strong antioxidant activity in the treatment of osteoarthritis via increasing content of SOD2 and suppressing MDA and ROS.
The finding in mice that deletion of SOD2 or the anti-oxidant gene transcriptional regulator nuclear factor-erythroid 2- related factor (Nrf2) result in more severe OA, while overexpression or treatment with mitochondrial targeted anti-oxidants reduces OA, further support a role for excessive ROS in the pathogenesis of OA.
Expression of Nrf2 and its target genes HO-1, NQO1 and SOD2 was significantly high in OA cartilage compared to normal cartilage and was also higher in damaged area compared to smooth area of OA cartilage of the same patient.
Instead, Wogonin induced mild oxidative stress through the generation of ROS and depletion of cellular GSH, thereby modulating the cellular redox leading to the induction of Nrf2/ARE pathways through activation of ROS/ERK/Nrf2/HO-1-SOD2-NQO1-GCLC signaling axis in OA chondrocytes.
SOD2 depletion led to a significant increase in mtDNA strand breaks in chondrocytes, but there was no notable difference in the level of strand breaks between OA and control chondrocytes.
Real time PCR, Western blot, and immunohistofluorescence assays confirmed a significant decrease of the major mitochondrial antioxidant protein manganese-superoxide dismutase (SOD2) in the superficial layer of OA cartilage.