Table 1.

Summary of studies on the protective functions of nicorandil in myocardial microcirculation.

Authors	Type of study	Models	Mechanism
Ozcan et al., 2002 [101]	Basic study	Rats	Functions as a K+ channel opener and directly attenuates mitochondrial oxidative stress at reoxygenation.
Ishida et al., 2004 [103]	Basic study	Rats	Attenuates matrix Ca2+ overload with accompanying depolarization of the mitochondrial membrane.
Ono, 2004 [17]	Clinical study		Improvement in cardiac function and clinical outcomes in patients with AMI with nicorandil may be associated with the suppression of ROS formation.
Kim, 2006 [120]	Basic study	Rats	Mitochondrial ROS promotes MPT onset and subsequent myocyte death after reperfusion.
Lu, 2006 [102]	Basic study	Rats	Nicorandil protects against postischemic left ventricular dysfunction by opening the mito-KATP channels, decreasing hydroxyl radicals, and increasing the coronary flow in the isolated rat heart.
Nishikawa, 2006 [98]	Basic study	Rats	Nicorandil regulates the Bcl-2 family proteins by opening the mito-KATP channels, induces NO-cGMP signaling, and inhibits the hypoxia-induced mitochondrial death pathway.
Tsujimoto, 2006 [108]	Basic study	Rats	Bcl-2 and Bcl-x(L) blocked MPT by directly inhibiting the VDAC activity.
Azadeh, 2009 [104]	Basic study	Rats	NO donation and free-radical scavenging properties of nicorandil may upregulate endothelial NO synthase.
Li, 2010 [123]	Basic study	Rats	DNA fragmentation is regulated by the mitochondrial fission machinery.
Maloyan, 2010 [124]	Basic study	Mice	Overexpression of Bcl-2 increases the lifespan of cardiomyocytes and ameliorates cardiac dysfunction, prevents mitochondrial swelling, and inhibits the apoptotic response in CryABR120G mice.
Ahmed, 2011 [105]	Basic study	Rats	Nicorandil (3 mg/kg) improves energy production and lowers the elevated myeloperoxidase activity.
Ahmed, 2013 [95]	Basic study	Rats	Nicorandil reduces albuminuria and ameliorates renal injury by blocking oxidative stress in chronic kidney disease.
Shahzad, 2013 [125]	Basic study	Rats	Postconditioning by hypoxia/reoxygenation prevents reperfusion injury by limiting mitochondrial Ca2+ load and thus opening MPTP in isolated cardiomyocytes.
Zhang, 2016 [29]	Basic study	Rats	H/R induces CMEC oxidative damage through the SR-Ca2+-XO-ROS injury signals.
Zollbrecht, 2016 [63]	Basic study	Rats	Nitrite-induced inhibition of NOX activity may be related to changes in NOX2 expression and XOR function.
Chan, 2017 [83]	Basic study	Rats	SIRT1 expression was repressed, acetylated p53 expression was enhanced, LOX-1/oxidative stress was upregulated in monocytes of patients with CAD, thereby increasing proapoptotic events and proinflammatory responses.
Jin, 2017 [66]	Basic study	Mice	ATF6 decreases myocardial I/R damage by linking ER stress and oxidative stress gene programs.
Zhang, 2017 [100]	Basic study	Mice	Nicorandil effectively inhibits the NF-κb signaling pathway during the pathogenesis of MI by regulating the M1/M2 status and promoting angiogenesis.
Su, 2018 [99]	Basic study	Rats	Nicorandil protected cardiomyocytes from CME-induced myocardial injury primarily by inhibiting TLR4/MyD88/NF-κB signaling.
Zhu, 2018 [23]	Basic study	Mice	XO-dependent oxidative damage and filopodia-related cellular migration, ultimately leading to endothelial apoptosis and migratory inhibition.
Sánchez-Duarte, 2020 [119]	Basic study	Chicken	Nicorandil affects the mitochondrial respiratory chain function by increasing the complex III activity and ROS production in skeletal muscle mitochondria.

MPT: mitochondrial permeability transition; H/R: hypoxia/reoxygenation; CMECs: cardiac microvascular endothelial cells.