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Piperlongumine (PL), an oxidative stress inducer, inhibits ZIKV replication in various cells, including the human brain microvascular, Vero, and human umbilical vein endothelial cells 129

These are mediated by 11-hydroxylase (P450c11 or CYP11B1), which generates cortisol (followed by activities of the ER enzymes P450c21 and P450c17), and aldosterone synthase (P450c11AS or CYP11B2) which produces aldosterone 91,92,93,94

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It is important to underline that although ALA has been investigated in cytokine-induced inflammation for its antioxidant characteristics (enhanced oxidative stress is essential for persistent inflammation), its inhibitory effects on TNF--induced endothelial activation are thought to be due to its metal chelating activity rather than a general antioxidant effect