Table 6.

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

Agents	Objects	Gender	Weight (g)	Animal model	Dose	Time periods	Mechanisms	References
Asiatic acid	C57BL/6	male	22–27	pMCAO	30, 75, and 165 mg/kg, i.g.	1 h before and 3, 10, and 20 h after pMCAO	Cyto-c↓, BBB permeability (IgG)↓	Krishnamurthy et al., 2009
Ginsenoside Rd	SD	male	270–320	MCAO	50 mg/kg, i.p.	30 min before MCAO	MMP↑, aconitase↑, mitochondrial complexes I-IV↑; ROS↓, lactate/pyruvate ratio↓, cleaved Caspase-3, Cyto-c↓, AIF↓	Ye et al., 2011b
Genistein	C57/BL6J	male	24–28	MCAO (1 h)/R (24 h)	2.5, 5, and 10 mg/kg, i.g.	Pretreatment once daily for 2 w	SOD↑, GSH-Px↑, mitochondrial Cyto-c↑; MDA↓, mtROS↓, cytosolic Cyto-c↓, Caspase-3↓, TUNEL-positive neurons↓, p-NF-κB p65 subunit↓, p-IκBα↓	Qian et al., 2012
Oxysophoridine	ICR	male	20–25	MCAO (2 h)/R (24 h)	62.5, 125, and 250 mg/kg, i.p.	Pretreatment once daily for 1 w	SOD↑, GSH-Px↑, Bcl-2↑; MDA↓, Caspase-3↓, Bax↓, TUNEL-positive neurons↓	Wang et al., 2013
Echinacoside	SD	both	12–17	Permanent ligation of the left CCA plus low oxygen atmosphere (8% O2, 92% N2) for 2.5 h	40, 80, and 160 mg/kg, i.p.	Every 12 h after operation, a total of 4 times	SOD↑, GSH-Px↑, CAT↑, T-AOC↑, Bcl-2/Bax↑; MDA↓, Caspase-3↓, TUNEL-positive neurons↓	Wei W. et al., 2019
Gallic acid	SD	male	250–300	MCAO (2 h)/R (24 h)	25 and 50 mg/kg, i.v.	20 min before MCAO	MMP↑, mitochondrial Cyto-c↑; MDA↓, ROS↓, cytosolic Cyto-c↓, TUNEL-positive neurons↓	Sun et al., 2014
	SD	male	250–300	MCAO	50 mg/kg		binding capacity of CypD and ANT-1↓, MPTP openinng↓, p-ERK↓, Cyto-c↓, cleaved Caspase-3/8/9↓	Sun et al., 2017
Oxymatrine	SD	both	——	Permanent ligation of the left CCA plus low oxygen atmosphere (8% O2, 92% N2) for 2.5 h	30, 60, and 120 mg/kg, i.p.	Every 12 h after operation, a total of 2 times	SOD↑, GSH-Px↑, CAT↑, T-AOC↑, Bcl-2/Bax↑, MDA↓, Caspase-3↓, neuronal apoptosis under flow cytometry↓	Zhao et al., 2015a
Matrine	ICR	male	20–25	MCAO (2 h)/R (24 h)	7.5, 15, and 30 mg/kg, i.p.	Pretreatment once daily for 1 w	SOD↑, GSH-Px↑, CAT↑, T-AOC↑, Bcl-2/Bax↑, MDA↓, Caspase-3↓, neuronal apoptosis under flow cytometry↓	Zhao et al., 2015b
Taurine	SD	both	——	Permanent ligation of the left CCA plus low oxygen atmosphere (8% O2, 92% N2) for 2 h	30, 60, and 120 mg/kg, i.p.	Every 12 h after operation, a total of 2 times	SOD↑, GSH-Px↑, T-AOC↑, Bcl-2/Bax↑, ATP↑; LA↓; MPO↓, MDA↓, AIF↓, Cyto-c↓	Zhu et al., 2016
HSYA	Wistar	male	220–250	MCAO (1 h)/R (24 h)	8 mg/kg, i.v.	After reperfusion	GSH↑, CAT↑; MDA↓, TNF-α↓, MPTP opening↓	Ramagiri and Taliyan, 2016
Curcumin	Wistar	male	180–200	MCAO/R	25 mg/kg, i.p.		Bcl-↑, Sirt1↑, MMP ↑; p53↓, Bax↓, IL-6↓, TNF-α↓, ROS↓	Zhang et al., 2017
Picroside II	Wistar	male	240–260	MCAO (2 h)/R (24 h)	20 mg/kg, i.p.	15 min before MCAO/R.	VDAC1↓, cytoplasmic and nuclear EndoG↓, ROS↓, MPTP opening↓, TUNEL-positive neurons↓	Li S. et al., 2018
Rhein	SD	male	260–300	MCAO (2 h)/R (72 h)	25, 50, and 100 mg/kg, i.g.	3 days following MCAO/R	SOD↑, GSH-Px↑, CAT↑, Bcl-2/Bax ratio↑; MDA↓, Caspase-3/9↓, cleaved Caspase-3↓	Zhao et al., 2018b
Genipin	C57BL/6	male	25–30	MCAO (1 h)/R (24 h)	50 mg/kg, i.g.	Pretreatment once daily for 3 d	ATP↑, SOD↑, GSH↑; UCP2↓, SIRT3↓, NAD+/NADH↓, LDH↓, cleaved Caspase-3↓, TUNEL-positive neurons↓	Zhao B. et al., 2019
Swertiamain	ICR	male	20–25	MCAO (2 h)/R (24 h)	25, 100, and 400 mg/kg, i.p.	Pretreatment once daily for 1 w	Bcl-2/Bax↑, SOD↑, GSH-Px↑, CAT↑, GSH↑, nulcear Nrf2↑, HO-1↑, NQO1↑; MDA↓, Keap1↓, cytoplasmic Nrf2↓, TUNEL-positive neurons↓	Wang et al., 2019b

↑, upgrade; ↓, downgrade.