Table 1.

Examples of natural antioxidants candidates for improving clinical outcomes in patients undergoing MIRI and/or cerebral IRI.

Antioxidant Family	Antioxidant	Formula	Prevention Proposed	Target
Polyphenols	Resveratrol		MIRI [60] and CIRI [61]	Ameliorate OS by increase in Nrf2 expression [61,62]. Also, decrease inflammation through TLR4/NF-κB signaling pathway [61,63].
	Quercetin		MIRI [64] and CIRI [65,66]	Scavenging and inhibition of ROS, and induction of Nrf2/HO-1 expression [65].
	Curcumin		MIRI [67] and CIRI [68]	Decrease myocardial apoptosis by activating JAK2/STAT3 pathway, thus reducing OS-damage [67]; while neuroprotection could be due to inhibition of pyroptosis by suppressing the p38 MAPK pathway [69].
Carotenoids	Lycopene		MIRI [33] and CIRI [70]	Inhibit mPTP opening via modulation of Bax and Bcl-2 [33,70].
	Crocin		MIRI [71] and CIRI [58]	In the heart, there is a regulation of SIRT1/Nrf2 signaling and related endoplasmic reticulum stress [71], while in the brain, a reduction in HIF-1α and caspase-3 was seen [58].
	β-carotene		MIRI [72] and CIRI [73]	Inhibit NF-κB pathway [73].
	Astaxanthin		MIRI [74] and CIRI [75]	Activate Nrf2/HO-1 pathway, regulate the miR-138/HIF-1α axis [74]. Enhance the expressions of SOD1 and 2 [75]
	Lutein		CIRI [76]	Decrease SOD, CAT and GTX activity [76].
Vitamins	All-trans retinoic acid (ATRA)		MIRI [77] and CIRI [78]	Downregulation of MAPK signaling [77,78].
	Vitamin C		MIRI [79] and CIRI [80]	Decrease SOD activity [81] and PI3K-Akt signaling pathway [79].
	Vitamin D (α-tocopherol)		MIRI [82] and CIRI [83]	Reduce inflammation RhoA/ROCK/NF-ĸB pathway [82], activate Nrf2/HO-1 pathway, and suppress NLRP3-mediated pyroptotic pathway [83].
	Vitamin E		MIRI [84] and CIRI [85]	Downregulation of GPX (1, 5 and 6) and MPO [84].
	Folic acid		CIRI [86]	Inhibition of NMDAR [86].
Others	Ginsenoside Rg1		CIRI [87]	Activation of Nrf2/ARE pathway [88].
	Ginsenoside Rb1		MIRI [89,90]	Reduce succinate-driven ROS production by inhibiting NADH dehydrogenase in mitochondrial complex I [91].

Akt: protein kinase B; ARE: antioxidant response elements; CIRI: cerebral ischemia–reperfusion injury; GPX: glutathione peroxidase; HO-1: heme oxygenase-1; MIRI: myocardial ischemia–reperfusion injury; MPO: myeloperoxidase; mPTP: mitochondrial permeability transition pore; NF-κB: nuclear factor kappa B; NMDAR: N-methyl-D-aspartate receptor; Nrf2: Nuclear factor erythroid 2-related factor 2; PI3K: phosphoinositide 3-kinase; ROS: reactive oxygen species; SIRT1: sirtuin 1; SOD: superoxide dismutase; TLR4: Toll-like receptor 4.