Background
Methods
Literature search
Inclusion criteria | Exclusion criteria |
---|---|
(1) TSG were administered. | (1) TSG were not administered. |
(2) Experimental AD was induced in rodents. | (2) Other types of animals (e.g., sheep, cats, and dogs) were used. |
(3) treatment group was treated with TSG, and control group was administered a placebo. | (3) Treatment group was administered another neuroprotective agent in addition to TSG. |
(4) Cognitive function was measured by the MWM, passageway water maze, passive avoidance task, Y maze experiment etc. | (4) Treatment group was administered another Chinese Traditional Medicine in addition to TSG. |
(5) Article was published in English or Chinese language. | (5) Only biochemical or physiological outcomes of treatment efficacy were assessed. |
(6) No control group was used. | |
(7) Duplicate publications or data presented in duplicate by additional publications. |
Data extraction
Methodological study quality
Authors & Year | ➀ | ➁ | ➂ | ➃ | ➄ | ➅ | ➆ | ➇ | ➈ | ➉ | Quality score |
---|---|---|---|---|---|---|---|---|---|---|---|
Zhang et al. 2006 [17] | √ | √ | √ | √ | √ | √ | √ | 7 | |||
Zhou et al. 2012 [13] | √ | √ | √ | √ | √ | √ | √ | 7 | |||
Zhang et al. 2006 [27] | √ | √ | √ | √ | √ | √ | 6 | ||||
Xing et al. 2006 [28] | √ | √ | √ | √ | √ | √ | 6 | ||||
Xie et al. 2005 [29] | √ | √ | √ | √ | 4 | ||||||
Chu et al. 2005 [30] | √ | √ | √ | √ | √ | √ | 6 | ||||
Huang et al. 2008 [31] | √ | √ | √ | √ | √ | 5 | |||||
Huang et al. 2008 [32] | √ | √ | √ | √ | √ | 5 | |||||
Liu et al. 2012 [33] | √ | √ | √ | √ | √ | √ | 6 | ||||
Chu et al. 2004 [34] | √ | √ | √ | √ | √ | 5 | |||||
Ye et al. 2003 [35] | √ | √ | √ | √ | √ | 5 | |||||
Ye et al. 2005 [36] | √ | √ | √ | √ | √ | √ | 6 | ||||
Wang et al. 2007 [12] | √ | √ | √ | √ | √ | 6 | |||||
Luo et al. 2009 [15] | √ | √ | √ | √ | √ | √ | √ | 7 | |||
Hou et al. 2011 [40] | √ | √ | √ | √ | √ | √ | √ | 7 | |||
Luo et al. 2010 [37] | √ | √ | √ | √ | √ | 5 | |||||
Zhao et al. 2004 [38] | √ | √ | √ | √ | √ | √ | √ | 7 | |||
Luo et al. 2012 [39] | √ | √ | √ | √ | √ | 5 |
Study Quality: | Zhang et al. 2006 [17] | Zhou et al. 2012 [13] | Zhang et al. 2006 [27] | Xing et al. 2006 [28] | Xie et al. 2005 [29] | Chu et al. 2005 [30] | Huang et al. 2008 [31] | Huang et al. 2008 [32] | Liu et al. 2012 [33] | Chu et al. 2004 [34] | Ye et al. 2003 [35] | Ye et al. 2005 [36] | Wang et al. 2007 [12] | Luo et al. 2009 [15] | Hou et al. 2011 [40] | Luo et al. 2010 [37] | Zhao et al. 2004 [38] | Luo et al. 2012 [39] |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Research question specified and clear? | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ |
Outcome measures relevant for AD research | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ |
Are the characteristics of study population clear? | ||||||||||||||||||
Species | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ |
Background/generation | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ |
Sex (and distribution) | √ | √ | √ | √ | √ | N | √ | N | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ |
Age | √ | N | √ | √ | √ | √ | N | √ | N | √ | √ | √ | √ | N | √ | N | N | √ |
Presence and correct control group? | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ |
Where the groups similar at baseline (if not randomized think of weight and sex etc.)? | √ | √ | √ | √ | N | √ | √ | √ | √ | √ | N | √ | ? | √ | √ | √ | √ | √ |
Is the experiment randomized? | √ | √ | √ | √ | N | √ | √ | √ | √ | √ | N | √ | √ | √ | √ | √ | √ | √ |
Kind of supplement mentioned (TSG)? | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ |
Age when supplementation started mentioned? | √ | N | √ | √ | √ | √ | N | √ | N | √ | √ | √ | √ | N | √ | N | N | √ |
Duration of supplementation clear and specified? | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ |
Amount of TSG mentioned | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ |
Administration route specified | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ |
Is the timing of the supplementation during the day specified and similar in both groups? | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ |
Methods used for outcome assessment the same in both groups ? | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ |
Drop outs described for each group separately? | N | N | N | N | N | N | N | N | N | √ | N | N | N | N | N | N | N | N |
Blinded outcome assessment? | √ | N | N | N | N | N | N | N | N | N | N | N | N | N | N | N | N | N |
Was the outcome assessment randomized across the groups? | N | N | N | N | N | N | N | N | N | N | N | N | N | N | N | N | N | N |
Total number of animals included in statistical analyses clear? | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ | √ |
Age of sacrificing animals mentioned? | √ | N | √ | √ | √ | √ | N | √ | N | √ | N | √ | √ | N | √ | N | N | √ |
Quality score (items√) | 19 | 15 | 18 | 18 | 16 | 17 | 16 | 17 | 16 | 19 | 15 | 18 | 18 | 15 | 15 | 15 | 15 | 18 |
Statistical analysis
Results
Study inclusion
Study characteristics
Authors & Year | Species & sex (no.) | Sex | Type of mode | Drug (treated/control) | Main experimental groups | Dose of administration | Method/Time of TSG administration | Quality score | Outcome |
---|---|---|---|---|---|---|---|---|---|
Zhang et al. 2006 [17] | PDAPPV717I transgenic mouse (72) | Female & Male | Transgenic model | TSG/water | 1) AD plus water | 120 (TSG -L), & 240 (TSG-H) mg/kg body wt | Intragastrically/4 months | 7 | MWM |
2) AD plus TSG -L | |||||||||
3) AD plus TSG-H | |||||||||
Zhou et al. 2012 [13] | Sprague-Dawley rat (n = 12) | Male | Aβ infused rats | TSG/NS | 1) AD plus NS | 25 mg/kg body wt | Intragastrically/4 months | 7 | MWM |
2) AD plus TSG | |||||||||
Zhang et al. 2006 [27] | PDAPPV717I transgenic mouse (53) | Female & Male | Transgenic model | TSG/water | 1) AD plus water | 50 mg (TSG -L), 100 mg (TSG -M),& 200 mg (TSG-H) g/kg body wt | Intragastrically/4 months | 6 | MWM |
2) AD plus TSG -L | |||||||||
3) AD plus TSG -M | |||||||||
4) AD plus TSG-H | |||||||||
Xing et al. 2006 [28] | PDAPPV717I transgenic mouse (46) | Female & Male | Transgenic model | TSG/water | 1) AD plus water | 0.05 (TSG -L), & 0.20 (TSG-H) g/kg body wt | Intragastrically/6 months | 6 | MWM |
2) AD plus TSG -L | |||||||||
3) AD plus TSG-H | |||||||||
Xie et al. 2005 [29] | BALB/c mouse (n = 12) | Female | D-galactose infused mice | TSG/water | 1) AD plus water | 0.05 g/kg body wt | Intragastrically/2 months | 4 | MWM |
2) AD plus TSG | |||||||||
Chu et al. 2005 [30] | Balb/c mouse (n = 52) | Female | D-galactose infused mice | TSG/water | 1) AD plus water | 33 mg (TSG-L), 100 mg (TSG-M),& 300 mg (TSG-H) g/kg body wt | Intragastrically/2 months | 6 | MWM |
2) AD plus TSG -L | |||||||||
3) AD plus TSG -M | |||||||||
4) AD plus TSG-H | |||||||||
Huang et al. 2008 [31] | Kunming mouse (n = 40) | Female & Male | D-galactose Infused mice | TSG/water | 1) AD plus water | 33 mg (TSG-L), 100 mg (TSG-M),& 300 mg (TSG-H) g/kg body wt | Intragastrically/2 months | 5 | MWM |
2) AD plus TSG –L | |||||||||
3) AD plus TSG –M | |||||||||
4) AD plus TSG-H | |||||||||
Huang et al. 2008 [32] | SMAP mouse | Male | Transgenic model | TSG/NS | 1) AD plus NS | 33 mg (TSG-L), 100 mg (TSG-M),& 300 mg (TSG-H) g/kg body wt | Intragastrically/50 days | 5 | MWM |
2) AD plus TSG –L | |||||||||
3) AD plus TSG –M | |||||||||
4) AD plus | |||||||||
TSG-H | |||||||||
Liu et al. 2012 [33] | SMAP mouse | Male | Transgenic model | TSG/NS | 1) AD plus NS | 33 mg (TSG-L), 100 mg (TSG-M),& 300 mg (TSG-H) g/kg body wt | Intragastrically/50 days | 6 | MWM |
2) AD plus TSG –L | |||||||||
3) AD plus TSG –M | |||||||||
4) AD plus TSG-H | |||||||||
Chu et al. 2004 [34] | Balb/c mouse (n = 52) | Female | Aβ infused mice | TSG/NS | 1) AD plus NS | 0.1 g/kg body wt | Intragastrically/8 weeks | 5 | MWM |
2) AD plus TSG | |||||||||
Ye et al. 2003 [35] | Sprague-Dawley rat (n = 43) | Male |
ibotenic acid infused rats | TSG/NS | 1) AD plus water | 30 mg (TSG-L), 60 mg (TSG-M),& 120 mg (TSG-H) g/kg body wt | Intraperitoneally/1 month | 5 | MWM |
2) AD plus TSG -L | |||||||||
3) AD plus TSG -M | |||||||||
4) AD plus TSG-H | |||||||||
Ye et al. 2005 [36] | Sprague-Dawley rat (n = 29) | Male | scopolamineinfused rats | TSG/NS | 1) AD plus water | 33 mg (TSG-L) & 100 mg (TSG-H) g/kg body wt | Intraperitoneally/2 months | 6 | MWM |
2) AD plus TSG -L | |||||||||
3) AD plus TSG-H | |||||||||
Wang et al. 2007 [12] | Sprague-Dawley rat | Male | Aged rats | TSG/water | 1) AD plus water | 30 mg(TSG-L), 60 mg (TSG-M) g/kg body wt | Intragastrically/12 W | 6 | PWM |
2) AD plus TSG -L | |||||||||
3) AD plus TSG-H | |||||||||
Luo et al. 2009 [15] | Sprague-Dawley rat | Male | aluminum chloride exposure rats | TSG/water | 1) AD plus water | 4000 mg g/kg body wt | Intragastrically/20 W | 7 | PAT |
2) AD plus TSG | |||||||||
Hou et al. 2011 [40] | Sprague-Dawley rat | Male | Aged rats | TSG/NS | 1) AD plus NS | 50 mg g/kg body wt | Intragastrically/20 W | 7 | MWM |
2) AD plus TSG | |||||||||
Luo et al. 2010 [37] | Sprague-Dawley rat | Male | Aβ infused rats | TSG/NS | 1) AD plus NS | 100 mg g/kg body wt | Intragastrically/3 W | 5 | YEM |
2) AD plus TSG | |||||||||
Zhao et al. 2004 [38] | Wistar rat | Male | Hypercholestero-lemia rats | TSG/NS | 1) AD plus NS | 30 mg (TSG-L), 60 mg (TSG-M),& 120 mg (TSG-H) g/kg body wt | Intragastrically/10 W | 7 | MWM |
2) AD plus TSG -L | |||||||||
3) AD plus TSG -M | |||||||||
4) AD plus TSG-H | |||||||||
Luo et al. 2012 [39] | Sprague-Dawley rat | Male | Aβ infused rats | TSG/NS | 1) AD plus NS | 50 mg g/kg body wt | Intragastrically/3 W | 4 | YEM |
2) AD plus TSG |
Study quality
Overall efficacy
Stratified meta-analysis
Subgroups | Acquisition memory | Retention memory | ||||||
---|---|---|---|---|---|---|---|---|
Studies | Participants | Effect size [95 % CI] | Subgroup differences | Dtudies | Participants | Effect size [95 % CI] | Subgroup differences | |
Animal species | ||||||||
APP mice | 11 | 349 | −1.84 [−2.62, −1.05] |
P = 0.0002 | 4 | 144 | 2.84 [1.35, 4.32] |
P < 0.00001 |
Balb/c mice | 5 | 124 | −0.45 [−0.80, −0.09] | |||||
Kunming mice | 5 | 98 | −0.84 [−1.27, −0.42] | 3 | 60 | 1.12 [0.56, 1.67] | ||
SMP8 mice | 6 | 120 | −0.79 [−1.17, −0.41] | 6 | 120 | 1.36 [0.95, 1.77] | ||
SD rats | 9 | 208 | −2.78 [−4.06, −1.51] | 2 | 48 | 3.60 [2.63, 4.57] | ||
Wistar rats | 3 | 105 | −1.35 [−1.17, −0.41] | |||||
Sex | ||||||||
Male | 20 | 471 | −1.59 [−2.12, −1.06] |
P < 0.00001 | 8 | 168 | 1.61 [1.17, 2.45] |
P = 0.65 |
Female | 5 | 124 | −0.45 [−0.80, −0.09] | |||||
Female & Male | 14 | 409 | −1.68 [−2.31, −1.05] | 7 | 204 | 2.06 [1.15, 2.98] | ||
Model | ||||||||
Untransgenic | 22 | 535 | −1.46 [−1.94, −0.98] |
P = 0.99 | 5 | 108 | 1.98 [0.88,3.08] |
P = 0.93 |
Transgenic | 17 | 469 | −1.46 [−2.00, −0.91] | 10 | 264 | 1.92 [1.28, 2.56] | ||
Dose | ||||||||
Less 100 mg | 21 | 582 | −1.92 [−2.52, −1.32] |
P = 0.04 | 8 | 216 | 2.23 [1.34, 3.11] |
P = 0.15 |
100 mg | 11 | 270 | −0.91 [−1.37, −0.45] | 3 | 60 | 1.25 [0.69, 1.82] | ||
200 mg | 2 | 64 | 0.92 [−1.46, −0.39] | |||||
300 mg | 4 | 88 | −1.01 [−1.46, −0.56] | 4 | 96 | 1.98 [0.92, 3.05] | ||
Quality | ||||||||
4 | 2 | 60 | −2.10 [−5.27, −1.08] |
P < 0.00001 | 1 | 12 | 3.86 [1.66, 6.05] |
P = 0.006 |
5 | 15 | 361 | −1.26 [−1.64, −0.81] | 6 | 120 | 1.15 [0.76, 1.55] | ||
6 | 15 | 387 | −0.63 [−0.83, −0.42] | 3 | 60 | 1.56 [0.96, 2.16] | ||
7 | 7 | 196 | −3.82 [−4.41, −3.23] | 5 | 180 | 2.97 [1.71, 4.22] |
Covariates | Coef. | Std. err. | t |
P > |t| | [95 % conf. interval] | |
---|---|---|---|---|---|---|
(a) Acquisition memory | ||||||
Quality score | −.8748308 | .2568104 | −3.41 | 0.002 | −1.400067 | −.3495946 |
sex | .6720335 | .4156478 | 1.62 | 0.117 | −.1780618 | 1.522129 |
dose | .1827889 | . 2101048 | 0.87 | 0.391 | −.2469237 | .6125015 |
special | .24532 | .1328595 | 1.85 | 0.075 | −.0264082 | .5170483 |
model | .8326842 | .7477604 | 1.11 | 0.294 | −.8588674 | 2.524236 |
(b) Retention memory | ||||||
Quality score | .4047783 | .3156139 | 1.28 | 0.224 | −.2828853 | 1.092442 |
sex | .7864006 | .291455 | 2.70 | 0.019 | 1.421426 | .1513747 |
dose | −.4543919 | .3441781 | −1.32 | 0.211 | −1.204292 | .2955078 |
special | .7864006 | .291455 | 2.70 | 0.019 | .1513747 | 1.421426 |