Table 7.

The in vitro mechanism underlying the inhibition of MPTP opening-induced neuronal apoptosis by monomeric compounds in the treatment of ischemic stroke.

Agents	Cell lines	Model	Dose	Time periods	Mechanisms	References
Asiatic acid	HT-22	OGD (5 h)/R (24 h)	1 and 10 µg/ml	Posttreatment for 24 h	MMP↑, Cyto-c↓	Krishnamurthy et al., 2009
Tetrahydroxystilbene glucoside	PCN of neonatal SD rats	OGD (5% CO2 and 95% N2, 2 h)/R (24 h)	25 µM	Pretreatment for 24 h	MMP↑, SIRT1↑, Bcl-2/Bax↑; LDH↓, ROS↓, p-JNK↓, iNOS↓, nuclear p65↓, Ca2+↓, Hoechst 33258 positive staining↓	Wang et al., 2009
Mangiferin and Morin	PCN of embryonic SD rats	50 μM glutamate plus 10 μM glycine	1–104 nM	During and after glutamate exposure	SOD↑, CAT↑, p-Akt↑, cytoplasmic p65↑, MMP↑; Calpain↓, p-Erk1/2↓, nuclear p65↓, AIF↓, Bax↓, ROS↓	Campos-Esparza et al., 2009
Trans resveratrol	PC12	OGD (5% CO2, 94% N2, and 1% O2, 6 h)/R (24 h)	5, 10, and 25 μM	24 h before/post OGD	Bcl-2↑, GSH↑; Bax↓, HIF-1α↓, Caspase-3↓, ROS↓, LPO↓	Agrawal et al., 2011
Oxysophoridine	PHN of neonatal SD rats	OGD (2 h)/R (24 h)	5, 20, and 80 μM	OGD (2 h)/R (24 h)	Bcl-2/Bax↑; Caspase-3/8/9↓, Cyto-c↓, Hoechst-33342 fluorescence intensity↓ SOD↑, CAT↑, GSH-Px↑, MMP↑; NOS↓, glutamate↓, Ca2+↓, MDA↓, NO↓	Chen et al., 2013; Zhao et al., 2013
Gallic acid	SH-SY5Y	Hypoxia (Na2S2O4, 2 h)/R (2 h)	0.1, 1, and 10 μM	Pretreatment for 24 h	MMP↑, ATP↑, oxygen consumption↑; MDA↓, intracellular ROS↓, mtROS↓, MPTP opening↓	Sun et al., 2014
	SH-SY5Y	/	0.1, 1, and 10 mM	24 h before H2O2-induced MPTP opening	binding capacity of CypD and ANT-1↓, MPTP openinng↓, p-ERK↓, Cyto-c↓, cleaved Caspase-3/8/9↓	Sun et al., 2017
Oxysophocarpine	PHN of neonatal SD rats	OGD (5% CO2, and 95% N2, 2 h)/R (24 h)	1, 2, and 5 μmol/L	During reperfusion period	MMP↑; LDH↓, Ca2+↓, Caspase-3/12↓	Zhu et al., 2014
Epicatechin and Quercetin	PCN of embryonic CD1 mice	OGD (5% CO2, 5% H2, and 90% N2, 5 min)/R (1.5 h)	0.1–10 μM	Pretreatment for 24 h	OCRs↑, p-Akt/Akt↑, p-CREB/CREB↑, Bcl-2↑, PGC-1a↑, MT-ND2 (complex I)↑, MT-ATP6 (complex V)↑, MMP↑; Ca2+↓, NOS↓	Nichols et al., 2015
Aloperine	PHN of neonatal SD rats	OGD (5% CO2, and 95% N2, 2 h)/R (24 h)	25, 50, and 100 mg/L	During reperfusion period	CAT↑, SOD↑, GSH-Px↑, T-AOC↑, MMP↑; LDH↓, Ca2+↓, MDA↓, ROS↓, Hoechst 33342 positive staining↓	Ma et al., 2015
Aloin	PC12	OGD (5% CO2, and 95% N2, 4 h)/R (24 h)	10, 20, and 40 μg/ml	During OGD/R period	MMP↑, Bcl-2↑, SOD↑; LDH↓, MDA↓, ROS↓, Ca2+↓, Bax↓, Caspase-3↓, Hoechst 33342 positive staining↓, apoptosis under flow cytometry↓	Chang R. et al., 2016
Kaempferol	PCN of 17-d embryonic rats	OGD (2 h)	10 μM	Before OGD	OCRs↑, p-Akt/Akt↑, MMP↑, p-Drp1/Drp1↑, ATG5↑, ATP↑, HK-II↑, LC3 II/I ratios↑, mitochondrial Cyto-c/cytosolic Cyto-c↑; ROS↓, Ca2+↓, SDH↓, apoptosis under flow cytometry↓, MPTP openinng↓	Wu B. et al., 2017
Dehydrocostuslactone	hippocampal slices of SD rats	OGD (5% CO2, and 95% N2, 0.5 h)/R (1 h)	1, 5, and 10 µM	During OGD/R period	LC3 II/I ratios↑, Bcl-2↑; LDH↓, Bax↓, Cyto-c↓, Apaf-1↓, Caspase-3/7/9↓, p62↓	Zhao et al., 2018a
Icariside II	PC12	OGD (5% CO2, and 95% N2, 2 h)/R (24 h)	12.5, 25, and 50 μM	Posttreatment for 24 h	nuclear Nrf2↑, NQO-1↑, HO-1↑, Bcl-2/Bax↑, SIRT3↑, IDH2↑, MMP↑; LDH↓, ROS↓, cytoplasmic Nrf2↓, Keap1↓, cleaved Caspase-3↓, TUNEL-positive neurons↓	Feng et al., 2018
Astragaloside IV	PCN of 18-d embryonic SD rats	OGD (1% O2, 5% CO2, 3 h)/R (24 h)	6.25, 12.5, and 25 μmol/L	During OGD/R period	p-PKA/PKA and p-CREB/CREB↑, ATP↑, MMP↑; LDH↓, cleaved Caspase-3↓, ROS↓	Xue et al., 2019
Oxymatrine	PHN of newborn SD rats	OGD (5% CO2 and 95% N2, 2 h)/R (24 h)	0.2, 1, and 5 µg/ml	During reperfusion period	MCL-1↑, Bcl-2↑, p-Akt↑, p-PI3K↑, p-GSK3β↑, MMP↑; LDH↓, Ca2+↓, Caspase-3↓, NR2B↓ (NMDAR1), TUNEL-positive neurons↓, neuronal apoptosis under flow cytometry↓	Liu Y. et al., 2019
Salvinorin A	HBMECs	OGD (5% CO2 and 95% N2, 6 h)/R (24 h)	5 uM	During reperfusion period	p-AMPK↑, Mfn2↑, ATP↑, MMP↑; ROS↓, Ca2+↓, apoptosis under flow cytometry↓	Dong et al., 2019

↑, upgrade; ↓, downgrade.