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The strong role of severe oxidative stress, reduced antioxidant defenses like GSH with increased lipid peroxidation and malondialdehyde generation (213), lipid, protein and DNA oxidation with increased apoptosis and necrosis in atherosclerosis as a major cause of cardiovascular diseases and stroke, supports the use of complementary and alternative medicines, dietary supplements, and antioxidants with hardly any adverse effect, able to restore homeostasis reversing oxidative stress (214)

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However, the protective effect of icariin is countered by the ferroptosis activator erastin and the SIRT1 inhibitor EX527 (Yu et al., 2023a)