Figure 7.

Effects of anthocyanins on pro-survival and pro-apoptotic signaling pathways. Anthocyanins modulate several signaling pathways involved in cell survival and death. Anthocyanins inhibit the activity of c-Jun N-terminal kinase (JNK) and p53, which are responsible for activating pro-apoptotic family members of the Bcl-2 family of proteins, Bim, Bad, Puma, and Noxa. Bim, Puma, and Noxa are known to inhibit the pro-survival functions of B-cell lymphoma-2 (Bcl-2), causing activation of the pro-apoptotic protein, Bax. Bax can also be activated by interaction with Bad. Bax then forms pores in the mitochondrial membrane, allowing the release of cytochrome c from mitochondria. Cytochrome c interacts with apoptosis protease activating factor-1 (APAF-1) and caspase-9 to form the apoptosome. The apoptosome then cleaves procaspase-3 to form active caspase-3, stimulating apoptosis. Anthocyanins also enhance the activity of the phosphoinositide-3-kinase (PI3K)/Akt pro-survival signaling pathway, which inhibits activity of pro-apoptotic Bcl-2 family members including Bim, Bad, and Bax, in addition to inhibiting the activity of p53. This activity inhibits entry of neurons into caspase-dependent apoptosis. Alternatively, anthocyanins have also been shown to inhibit caspase-independent apoptosis by blocking the translocation of apoptosis inducing factor (AIF) from mitochondria to the cytosol and subsequently, the nucleus (dashed arrow).