Figure 8.

Schematic of S-Equol protects chondrocyte against SNP’s damage. Treatment of chondrocyte with SNP could increase p53, intracellular NO and H₂O₂ levels and decrease mitochondrial membrane potential (ΔΨM). Furthermore, the NO could activate MMPs, resulting in type II collagen and aggrecan degradation. Simultaneously, p53 could increase expressions of pro-apopototic proteins including BIM, PUMA, NOXA, BAX, and BAK, and cause a decrease in anti-apoptotic proteins including Bcl-X_L and Bcl-2 expression, resulting in the release of cytochrome c, activation of caspase-9 and caspase-3, and finally the induction of apoptosis. The addition of S-Equol could lessen those effects caused by SNP. Moreover, S-Equol could active the PI₃K/Akt pathway, an upstream of apoptosis and NO production, including an increase in phosphorylation of Akt and Mdm2 to inhibit p53 and NO production, by which the apoptosis and matrix degradation caused by SNP are decreased. Red : enhanced by SNP; Red : decreased by SNP; Blue : enhanced by S-Equol; Blue : decreased by S-Equol.