A Preclinical Systematic Review of Ginsenoside-Rg1 in Experimental Parkinson’s Disease

Table 1

Characteristics of included studies.

Study (years)	Species ()	Weight	PD model	Anesthetic	Experimental group	Control group	Outcome measure (experimental: G-Rg1/control)	Intergroup difference (ID)
Heng et al., 2016	Male, C57BL/6 mice (10/10)	22–25 g	MPTP-induced PD	Chloral hydrate (400 mg/kg, ip)	G-Rg1 (10, 20, 40 mg/kg, ip) for 49 d + MPTP (25 mg/kg, ip) for 4 d	MPTP (25 mg/kg, ip) for 4 d	(1) Behavioral tests: rotarod test, pole test; (2) Numbers of TH(+) cells ↑; (3) TH protein expression ↑; (4) GFAP and IBA-1 expression ↓; (5) IBA-1 and GFAP(+) cells ↓; (6) Concentrations of TNF-α, IL-1β ↓; (7) Oligomeric α-synuclein expression ↓	(1) < 0.01; (2) < 0.01; (3) < 0.05; (4) < 0.01; (5) < 0.01; (6)
Jiang et al., 2015	C57BL/6 mice (10/10)	25–30 g	MPTP-induced PD	Urethane (Sigma) (1.5 g/kg)	G-Rg1 (10 mg/kg, ip) for 15 d + MPTP (30 mg/kg, ip) for 5 d	MPTP (30 mg/kg, ip) for 5 d	(1) Behavioral tests: rotarod test, pole test, wire suspension test; (2) TH(+) neurons ↑, TH protein expression ↑; (3) α-Synuclein expression ↓	(1) , < 0.05; (2) < 0.01; (3) < 0.05
Zhou et al., 2016	Male, C57BL/6J mice (10/10)	16–25 g	MPTP-induced PD	2% pentobarbital sodium (40 mg/kg)	G-Rg1 (5, 10, 20 mg/kg, ip) for 10 d + MPTP (30 mg/kg, ip) for 5 d	MPTP (30 mg/kg, ip) for 5 d	(1) Behavioral tests: pole test; (2) Numbers of TH(+) neurons ↑; (3) The protein levels of Wnt-1 and β-catenin ↑; GSK-3β and p-GSK-3β ↓; (4) Caspase-3 expression ↓, Bcl-xL ↑ protein levels of Wnt-1 ↑ and β-catenin ↑; GSK-3β ↓ and p-GSK- 3β ↓	(1) < 0.01; (2) < 0.01; (3) < 0.01; (4) < 0.01
Zhou et al., 2015	Male, C57BL/6J mice (5/5)	16–25 g	MPTP-induced PD	2% pentobarbital sodium (40 mg/kg)	G-Rg1 (5, 10, 20 mg/kg, ip) for 10 d + MPTP (30 mg/kg, ip) for 5 d	MPTP (30 mg/kg, ip) for 5 d	(1) The TH(+) neurons, levels of TH protein expression ↑; (2) T cell subsets: CD3^+CD4^+ T cells ↑, CD3^+CD8^+ T cells ↓; (3) Concentrations of TNF-α, IFN-γ, IL-1β, and IL-6 ↓; (4) Microglial cells not activated ↓	(1) < 0.01; (2) < 0.01, < 0.05; (3) < 0.01 or < 0.05
Chen et al., 2005	Male, C57BL mice (8/8)	18–22 g	MPTP-induced PD	NR	G-Rg1 (5, 10, 20 mg/kg, ip) for 8 d + MPTP (30 mg/kg, ip) for 5 d	MPTP (30 mg/kg, ip) for 5 d	(1) Numbers of TH(+) ↑ and Nissl(+) neurons ↑; TUNEL(+) neurons ↓; (2) GSH level ↑; T-SOD activity ↓ (3) Phospho-JNK ↓ and phospho-c-Jun protein levels ↓	(1) < 0.01; (2) < 0.01
Chen et al., 2002	Male, C57BL mice (6/6)	20 ± 2 g	MPTP-induced PD	2% pentobarbital sodium	G-Rg1 (2.5, 5, 10 mg/kg, ip) for 8 d + MPTP (30 mg/kg, ip) for 5 d	MPTP (30 mg/kg, ip) for 5 d	(1) TH(+) neurons ↑; TUNEL(+) neurons ↓; (2) Bcl-2 cells ↑; Bcl-xL cells ↑; Bax cells ↓; (3) Caspase-3 cells ↓; (4) iNOS cells ↓	(1) < 0.01; (2) < 0.01; (3) < 0.01; (4) < 0.01
Wei et al., 2015	C57BL/6 mice (9/9)	22–30 g	MPTP-induced PD	NR	G-Rg1 (10 mg/kg, ip) for 7 d + MPTP (20 mg/kg, ip) for 4 d	MPTP (20 mg/kg, ip) for 4 d	(1) EphA4 mRNA expression ↓; (2) EphA4 protein expression ↓	(1) < 0.01; (2) ,
Wang et al., 2015	Male, C57BL/6 mice (9/9)	22–30 g	MPTP-induced PD	NR	G-Rg1 (10 mg/kg, ip) for 8 d + MPTP (20 mg/kg, ip) for 5 d	MPTP (20 mg/kg, ip) for 5 d	(1) Behavioral tests: the swim-score ↑; (2) TH protein expression ↑; (3) P-c-Jun protein expression ↓; (4) Numbers of EphB1(+) cells ↓	(1) < 0.05; (2) < 0.05; (3) < 0.05; (4)
Zhu et al., 2014	Male, C57BL/6 mice (9/9)	22–30 g	MPTP-induced PD	6% chloral hydrate (30 mg/kg)	G-Rg1 (10 mg/kg, ip) for 8 d + MPTP (20 mg/kg, ip) for 5 d	MPTP (20 mg/kg, ip) for 5 d	(1) Behavioral tests: pole test; (2) TH mRNA ↑; (3) Ephrin-B2(+) cells ↓(4) P-c-Jun(+) cells ↓	(1) < 0.05; (2) < 0.05; (3) < 0.05; (4)
Wang et al., 2014	Male, C57BL/6 mice (9/9)	25–30 g	MPTP-induced PD	Anesthetized	G-Rg1 (10 mg/kg, ip) for 8 d + MPTP (30 mg/kg, ip) for 5 d	MPTP (30 mg/kg, ip) for 5 d	(1) Behavioral exhibition; (2) Number of TH(+), FLIP(+), FADD(+), and caspase-3(+) cells; (3) Expression level of TH, FLIP, FADD, and caspase-3 protein	(1) Not found; (2) < 0.01; (3)
Yan et al., 2014	Female, C57BL mice (10/10)	20 ± 2 g	MPTP-induced PD	NR	G-Rg1 (10 mg/kg, ip) for 8 d + MPTP (30 mg/kg, ip) for 5 d	MPTP (15 mg/kg, ip) for 5 d	(1) DA ↑; (2) Number of TH neurons ↑	(1) < 0.01; (2)
Liu et al., 2008	Male, C57BL/6 mice (15/15)	18–23 g	MPTP-induced PD	20% urethane	G-Rg1 for 8 d + MPTP (30 mg/kg, ip) for 5 d	MPTP (30 mg/kg, ip) for 5 d	(1) Behavioral exhibition; (2) Number of TH(+) cells ↑; (3) Number of caspase-3(+) cells ↓; (4) Number of TUNEL(+) cells ↓; (5) Caspase-3 protein ↓	(1) Not found; (2) < 0.05; (3) < 0.05; (4) < 0.05; (5) < 0.05
Yang et al., 2009	Male, C57BL/6 mice (12/12)	17 ± 5 g	MPTP-induced PD	10% chloral hydrate (0.04 mg/kg)	G-Rg1 (70 mg/kg, ip) for 20 d + MPTP (30 mg/kg, ip) for 5 d	MPTP (30 mg/kg, ip) for 5 d	(1) Number of BrdU(+) cells ↑; (2) Number of Nestin(+) cells ↓; (3) BrdU+/Nestin+ cells ↑	(1) < 0.01; (2) P < 0.01; (3)
Ji, 2008	Male, C57BL/6 mice (9/9)	25 ± 2 g	MPTP-induced PD	10% chloral hydrate (0.3 ml/kg)	G-Rg1 (5 mg/kg, ip) for 8 d + MPTP (30 mg/kg, ip) for 5 d	MPTP (30 mg/kg, ip) for 5 d	(1) Behavioral exhibition; (2) Number of TH(+) cells ↑	(1) Not found; (2) Not found
Wang et al., 2008	Male, C57BL/6 mice (10/10)	25–30 g	MPTP-induced PD	Anesthetized	G-Rg1 (10 mg/kg, ip) for 8 d + MPTP (30 mg/kg, ip) for 5 d	MPTP (30 mg/kg, ip) for 5 d	(1) Behavioral exhibition; (2) Number of TH(+) cells ↑; number of COX-2 and PGE2(+) cells ↓; (3) Number of p-P38(+) cells ↓; (4) p-P38, COX-2, and PGE2 proteins ↓; TH proteins expression ↑	(1) Not found; (2) < 0.01; (3) < 0.01; (4)
Yang et al., 2007	Male, C57BL/6 mice (6/6)	21 ± 2 g	MPTP-induced PD	Chloral hydrate	G-Rg1 (5 mg/kg, ip) for 8 d + MPTP (30 mg/kg, ip) for 5 d	MPTP (30 mg/kg, ip) for 5 d	(1) Number of TH(+) cells ↑; TH mRNA ↑; (2) DA, DOPAC, and HVA ↑; (3) Number of Fe(+) cells ↓; (4) Bcl-2 cells ↑, Bcl-2 mRNA ↑; (5) Caspase-3 and Bax(+) cells ↓, Bax and caspase-3 mRNA proteins ↓	(1) , < 0.05; (2) < 0.05; (3) < 0.05; (4) , < 0.05; (5) , < 0.05
Zhou et al., 2003	Male, C57BL mice (8/8)	20 ± 2 g	MPTP-induced PD	2% pentobarbital	G-Rg1 (5, 10, 20 mg/kg, ip) for 8 d + MPTP (30 mg/kg, ip) for 5 d	MPTP (30 mg/kg, ip) for 5 d	(1) Number of TH(+) and Nissl(+) cells ↑; (2) Number of caspase-3(+) and TUNEL(+) cells ↓; (3) p-JNK and p-c-Jun protein expression ↓	(1) < 0.01; (2) < 0.01; (3)
Meng et al., 2001	Male, C57BL/6 mice (15/15)	25–30 g	MPTP-induced PD	10% chloral hydrate (0.3 ml/kg)	G-Rg1 (10, 20 mg/kg, ip) for 9 d + MPTP (30 mg/kg, ip) for 5 d	MPTP (30 mg/kg, ip) for 5 d	(1) Behavioral exhibition: pole test; (2) Number of TH(+) cells ↑; number of GRP78(+), caspase-l2(+), and caspase-3(+) cells ↓; (3) TH protein expression ↑; GRP78, caspase-l2, and caspase-3 protein expression ↓	(1) Not found; (2) < 0.01; (3)
Yang, 2014	Male, C57BL/6 mice (15/15)	22–30 g	MPTP-induced PD	Ethyl ether	G-Rg1 (10 mg/kg, ip) for 9 d + MPTP (30 mg/kg, ip) for 7 d	MPTP (20 mg/kg, ip) for 7 d	(1) Behavioral assessments: the swim-score; (2) EphB6 and Ephrin-B1 mRNA expression ↓; (3) EphB6 and Ephrin-B1 protein expression ↓	(1) < 0.01; (2) < 0.01; (3)
Wang et al., 2009	Male, C57BL/6 mice (15/15)	25–30 g	MPTP-induced PD	Anesthetized	G-Rg1 (10 mg/kg, ip) for 8 d + MPTP (30 mg/kg, ip) for 5 d	MPTP (30 mg/kg, ip) for 5 d	(1) Behavioral assessments; (2) Number of TH(+) cells ↑; number of COX-2(+) cells ↓; (3) TH proteins expression ↑; COX-2 protein expression ↓	(1) Not found; (2) < 0.01; (3)
Xu et al., 2009	Female ovariectomized Wistar rats (12/12)	220–250 g	6-OHDA induced PD	Chloral hydrate (400 mg/kg)	G-Rg1 (10 mg/kg, ip) for 14 d + 6-OHDA (3.6 g/l, ip)	6-OHDA (3.6 mg/ml, ip)	(1) Reduced apomorphine-induced rotarod test; (2) Number of TH(+) neurons ↑; (3) Gene expression of TH ↑; (4) The Bcl-2 protein and gene expression ↑	(1) < 0.01; (2) < 0.01; (3) < 0.01; (4)
Jie, 2010	Male ovariectomized Wistar rats (10/10)	200–250 g	6-OHDA induced PD	10% chloral hydrate (3 ml/kg)	G-Rg1 (3 μg/μl, ip) + 6-OHDA (2 mg/ml, ip) for 7 d	6-OHDA (2 mg/ml, ip) for 7 d	(1) Behavioral tests: decreased apomorphine-induced rotarod test; (2) SOD ↑, GSH level ↑, MDA ↓, LDH ↓	(1) Not found; (2)
Xu et al., 2008	Female ovariectomized Wistar rats (6/6)	200–250 g	6-OHDA induced PD	8% chloral hydrate	G-Rg1 (10 mg/kg, ip) for 14 d + 6-OHDA (3.6 g/l, ip)	6-OHDA (3.6mg/ml, ip)	(1) Behavioral tests: decreased apomorphine-induced rotarod test; (2) DA ↑, DOPAC ↑	(1) < 0.01; (2)
Xu and Chen, 2007	Female ovariectomized Wistar rats (12/12)	200–250 g	6-OHDA induced PD	8% chloral hydrate	G-Rg1 (10 mg/kg, ip) for 14 d + 6-OHDA (3.6 mg/ml, ip)	6-OHDA (3.6 mg/ml, ip)	(1) Number of TH(+) neurons ↑; (2) TH gene expression ↑	(1)
Sun et al., 2016	Female ovariectomized Wistar rats (18/18)	250–300 g	LPS-induced PD	400 mg/kg chloral hydrate	G-Rg1 (10 mg/kg, ip) for 14 d + LPS (5.0 μg, ip)	LPS 5.0 μg dissolved in 2 μl of 0.9% saline	(1) DA, DOPAC, and HVA ↑; (2) TNF-α and IL-1β ↓	(1) < 0.01; (2) Not found