Table 2.

Characteristics of included publications.

Study	Animal Models and Species	Quantity Sex Age	Administration	Outcome
				Behavioral Change	Neuropathological Change	Biochemical Change
Ji-Jing Yan 2001 [11]	i.c.v. injection of Aβ1-42 ICR mice	10 M 18~26 g	0.002%, 0.004%, and 0.006% (w/v) Free drinking 1, 2, 3, 4 w	Improved memory (passive avoidance task; Y-maze tests; MWM)	Hippocampus GFAP and IL-1β immunoreactivities↑ (Immunocytochemistry)	Cortex Acetylcholine level↓ (colorimetry);
Hee-Sung KIM 2004 [12]	i.c.v. injection of Aβ1-42 ICR mice	6 M 18~26 g	0.006% (w/v) Free drinking 4 w	N/A?	Reduced microglial activation (Immunocytochemistry: OX-42 immunoreactivity↓)	Inhibition IFN-γ Immunoreactivity (Immunocytochemistry);
Jae-Young Cho 2005 [13]	i.c.v. injection of Aβ1-42 ICR mice	6 M 18~26 g	0.006% (w/v) Free drinking 4 w	N/A?	Reduced astrocytes activation	Alleviated oxidative stress in the hippocampus (eNOS and 3- NT immunoreactivity↓)
Takayoshi Mamiya 2008 [14]	i.c.v. injection of BSO ICR mice	10/15 M 25 w	0.5, 1, or 5 mg/kg sc 6 d	Improve recognition memory (the novel object recognition test); improve short-term memory (Y-maze);	extent of protein oxidation↓; carbonyl protein levels↓ in forebrains;	N/A?
Tsuyoshi Hamaguchi 2009 [15]	Mice double mutation K670N-M671L Tg2576 mice	10 F 5 mon	0.5% in food 10 mon	N/A?	Aβ deposits↓ (IHC)	N/A?
JIN Beibei 2011 [16]	Injected KA into hippocampus CA1 region KM mice	10 M&F 20~30 g	20, 40 and 80 mg/kg ig 30 d	Improved learning and cognitive skills (MWM)	Reduced expressions of GFAP in hippocampal CA1 region (Immunohistochemistry)	N/A?
Ji-Jing Yan 2013 [17]	APP/PS1 mice	5 F 6 mon	5.3 and 16 mg/kg/d Free drinking 6 mon	Improved memory (novel-object recognition test, Y-maze task)	Aβ1-42 and Aβ1-40 levels↓ (immunoassay kits)	Il-1β↓ (immunoassay kits)
Takashi Mori 2013 [18]	PSAPP C57BL/6J mice	12 M&F 6 mon	30 mg/kg ig 6 mon	Remediation of behavioral impairment (field activity testing; object recognition test; Y-maze test; MWM)	Cerebral Aβ deposits↓ (4G8 immunohistochemistry, ELISA)	Reduced neuroinflammation and Oxidative Stress: Iba1↑ (Immunohistochemistry); TNF-a, IL-1β, Sod1, catalase, and Gpx1 mRNA↓ (QRT-PCR)↓; reduced microglial and astroglial activation:GFAP↓ (Immunohistochemistry)
Fan-Shiu Tsai 2015 [19]	i.c.v. injection of Aβ1-42 SD rats	10~12 M 250~300 g	50 and 100 mg/kg ig 2 w	Attenuated impairment of cognitive function (Inhibitory Avoidance Test); improve memory (MWM);	N/A?	Cortical and hippocampal GSH↑, SOD↑, Cu, Zn-SOD↓ activity (spectrophotometrically); brain AChE Activity↓ (Ellman method)
Huang Hao 2016 [20]	LPS-induced SD rats	12 F 280~320 g	25, 50, 100 mg/kg ig 34 d	Improved learning and cognitive skills (MWM)	Protective effect on brain histopathology (HE staining, β-tubulin), PDE4B	Anti-oxidize effect (SOD↑); suppressed mRNA elevation of PDE4B, NLRP3, IL-1β and caspase-1(Q-PCR); PDE4B↓ (Immunohistochemistry, WB); NLRP3↓, CREB↑ and pCREB↑ (WB)
Masaki Kikugawa 2016 [21]	i.c.v. injection of Aβ25~35 C57BL/6 J mice	6 M 16–19 g	0.1 μmol/g/day po 42 d	Improved contextual freezing response impairment (fear conditioning test)	Protective effects on neurons survival (Nissl stain)	N/A?
Takashi Mori 2017 [22]	APP/PS1 C57BL/6J mice	8 M&F 12 mon	30 mg/kg ig 3 mon	Improved memory (assess novel object recognition memory, the novel object recognition test and retention test phases; Y-maze test, RAWM)	Cerebral parenchymal A β deposits↓and size↓ (IHC), A β 1-40, A β 1-42↓ (ELISA); vascular A β deposits↓ (IHC); attenuated astrocytosis and microgliosis (IHC of GFAP and Iba1); Attenuated Synaptotoxicity: synaptophysin immunoreactivity↑ (IHC)	Promoted nonamyloidogenic and inhibited amyloidogenic APP processing: sAPP-α/holo-APP↓ (WB), β-oligomers↓ (ELISA); activated ADAM10 and inhibits BACE1(WB); attenuated neuroinflammation and oxidative stress: TNF-α↓, IL-1β↓, SOD1↓, GPx1↓ (Q-PCR); attenuated Synaptotoxicity: synaptophysin immunoreactivity↑ (IHC)
Wang Yue 2017 [23]	APP/PS1 C57BL/6 mice	10 15~20 g	20, 40, 100 mg/kg ig 7 d	N/A?	N/A?	Reduced apoptosis (WB: Bcl-2↑, Bax↓, p-JNK↓, p-C-Jun↓, Caspase3↓), Reduces oxidative stress in the brain (MDA↓, SOD↑)
MING Rui 2018 [24]	Injected KA into hippocampus CA1 region KM mice	M&F 26 ± 4 g	20, 40, and 80 mg/kg 30 d	N/A?	Reduced number of positive GFAP cells in cerebral cortical glial cells (Immunofluorescence)	Reduced inflammatory cytokines (ELISA: IL-1β↓, IL-6↓, TNF-α↓)
Mohd Faraz Zafeer 2019 [25]	ICV-STZ Wistar rats	6 M 350 ± 25 g	100 mg/kg po 21 d	Attenuated spatial memory and learning loss (MWM)	Protective effect on brain histopathology (HE staining of coronal sections)	Mitigation of AD-related oxidative stress (DCFDA: ROS↓); mito-protective efficacy (flow cytometric: Δψm; Calcein-AM/CoCl2 assay: mPTP; WB: Drp-1↑, Mfn2↓, PGC1-α↑, BAX↓, Cytochrome-C↓, LPO↓); DNA fragmentation↓ (comet assay)
Takashi Mori 2019 [26]	APP/PS1 mice	8 M&F 12 mon	30 mg/kg ig 3 mon	Improved memory (Y-maze, RAWM; novel object recognition test; alternation Y-maze task)	Cerebral Aβ deposits↓ (4G8 immunostain); Aβ1-40 and Aβ1-42 levels↓ (ELISA)	Promoted nonamyloidogenic and inhibited amyloidogenic APP cleavage (WB); ADAM10 ↓, BACE1 ↓ (WB); mitigated astrocytosis and microgliosis (IHC of GFAP and Iba1); dampened neuroinflammation and oxidative stress: TNF-α↓, IL-1β↓ (Q-PCR), SOD1↓, GPx1↓ (Q-PCR and WB); attenuated Synaptotoxicity: synaptophysin immunoreactivity↑ (IHC)
WANG Qian 2019 [27]	Injecting Aβ1-42 into the lateral ventricle KM mice	10 M 18~22 g	0.1 and 0.4 g/kg ig	Improved spatial positioning memory (MWM). No effect on the excitability of the central nervous system (spontaneous activity experiment)	Improved morphological changes (HE Staining); Tau; pS396 protein phosphorylated, total Tau protein↓ and S396↓; reduced Aβ generation	Improved abnormal mitochondrial division (RT-PCR: Drp1↓, CnAα↓, CnAβ↓mRNA); Bace1↓