Review Article

Efficacy of Terpenoid in Attenuating Aortic Atherosclerosis in Apolipoprotein-E Deficient Mice: A Meta-Analysis of Animal Studies

Table 1

Characteristics of the included studies.

StudyTerpenoidAgeSexDietStudy lengthDoseRouteLocation of
lesion area
AnalysisStainingGroups and sample size

Jiang et al., 2016 [19]Sesquiterpenoid,
artesunate
4W?HFD24W1.5 mg/kg/d
5 mg/kg/d
15 mg/kg/d
i.p.Thoracic aortaEn face (longitudinal)Oil red OControl=6
Sesquiterpenoid low=6
Sesquiterpenoid medium=6
Sesquiterpenoid high=6

Lopez-Franco et al., 2006 [20]Sesquiterpenoid,
parthenolide
12WMaleHFD(1) 10W
(2) 20W
4 mg/kg/d
10 mg/kg/d
2 mg/kg/d
i.p.Aortic rootCross-sectionalOil red OControl=6, 6
Sesquiterpenoid low=4
Sesquiterpenoid medium=9
Sesquiterpenoid high=8

Wang et al., 2016 [21]Sesquiterpenoid,
patchouli
8WFemaleHFD10W40 mg/kg/dIG(1) Thoracic and abdominal aorta
(2) Aortic root
(1) En face (longitudinal) 
(2) Cross-sectional
Oil red OControl=10, 10
Sesquiterpenoid=10, 10

Li et al., 2018 [22]Diterpenoid,
pseudolaric acid B
8WMaleHFD4W5 mg/kg/dIG(1) Thoracic and abdominal aorta
(2) Aortic root
(1) En face (longitudinal)  
(2) Cross-sectional
Oil red OControl=12, 12
Diterpenoid=12, 12

Liu et al., 2012 [23]Diterpenoid,
ginkgolide B
8WMaleHFD8W20 mg/kg/dIG(1) Thoracic aorta
(2) Aortic sinus
(1) En face (longitudinal)  
(2) Cross-sectional
Oil red OControl=3, 10
Diterpenoid treatment=3, 10

Liu et al., 2015 [24]Diterpenoid,
cryptotanshinone
6WMaleHFD16W15 mg/kg/d
45 mg/kg/d
IG(1) Aortic root to iliac branches
(2) Aortic sinus
(1) En face (longitudinal)  
(2) Cross-sectional
Oil red OControl=6, 6
Diterpenoid low=6, 6
Diterpenoid high=6, 6

Steffens et al., 2005 [25]Diterpenoid,
delta-9-tetrahydrocannabinol
10WMaleHFD6W1 mg/kg/dIGAortic rootCross-sectionalSudan IVControl=8
Diterpenoid treatment=6

Tang et al., 2011 [26]Diterpenoid,
tanshinone IIA
6WMaleNCD20W10 mg/kg/d
30 mg/kg/d
90 mg/kg/d
IG(1) Aortic arch
(2) Aortic root
(1) En face (longitudinal)  
(2) Cross sectional
(1) Oil red O
(2) HE
Control=10, 10
Diterpenoid low=10, 10
Diterpenoid medium=10, 10
Diterpenoid high=10, 10

Xu et al., 2011 [27]Diterpenoid,
tanshinone IIA
6WMaleHCD16W10 mg/kg/d
30 mg/kg/d
IG(1) Aortic root to iliac branches
(2) Aortic sinus
(1) En face (longitudinal)
(2) Cross-sectional
Oil red OControl=6, 6
Diterpenoid low=6, 6
Diterpenoid high=6, 6

Xu et al., 2012 [28]Diterpenoid,
tanshinone IIA
6WMaleHCD16W30 mg/kg/dIGAortic rootsCross-sectionalOil red OControl=6
Diterpenoid treatment=6

Zhao et al., 2016 [29]Diterpenoid,
tanshinone IIA
8WMaleHFD8W30 mg/kg/dIGThoracic aorta(1) En face (longitudinal)
(2) Cross-sectional
Oil red OControl=8, 8
Diterpenoid treatment=9, 8

Zhou et al., 2015 [30]Diterpenoid,
retinoic acid
8WMaleHFD8W2 mg/kg/di.p.Aortic sinusCross-sectionalOil red OControl=10
Diterpenoid treatment=10

Buus et al., 2011 [31]Triterpenoid,
oleanolic acid
12WMaleHFD8W100 mg/kg/dIGAortic root to thoracic aortaEn face (longitudinal)Oil red OControl=10
Triterpenoid =10

Chen et al., 2012 [32]Triterpenoid,
corosolic acid
8WMaleHFD12W10 mg/kg/dChow(1) Aortic root to abdominal aorta
(2) Aortic root
(1) En face (longitudinal)
(2) Cross-sectional
(1) Sudan IV
(2) HE
Control=8, 8
Triterpenoid=8, 8

Gu et al., 2013 [33]Triterpenoid,
celastrol
8WMaleHFD4W1 mg/kg/d
2 mg/kg/d
i.p.Aortic sinusCross-sectionalOil red OControl=5
Triterpenoid low=5
Triterpenoid high=5

Gui et al., 2016 [34]Triterpenoid,
betulin
6WMaleHFD12W20 mg/kg/d
40 mg/kg/d
Chow(1) Aortic root to iliac branches
(2) Aortic sinus
(1) En face (longitudinal)
(2) Cross-sectional
(1) Sudan IV
(2) Oil red O
Control=6, 6
Triterpenoid low=8, 8
Triterpenoid high=6, 6

Jia et al., 2014 [35]Triterpenoid,
notoginsenoside R1
9WMaleHFD8W25 mg/kg/di.p.Aortic rootCross-sectionalHEControl=9
Triterpenoid treatment=9

Li et al., 2011 [36]Triterpenoid,
ginsenoside-Rd
6W?HFD12W20 mg/kg/di.p.Aortic root to iliac branchesEn face (longitudinal)Oil red OControl=10
Triterpenoid=10

Liu et al., 2016 [37]Triterpenoid,
ilexgenin A
8WMaleHFD16W12 mg/kg/dChowAortic sinusCross-sectionalHEControl=10
Triterpenoid =10

Messner et al., 2011 [38]Triterpenoid,
ursolic acid
8WMaleHFD24W0.9 mg/kg/d
2.7 mg/kg/d
DrinkAortic root to iliac branchesEn face (longitudinal)Sudan IVControl=5
Triterpenoid low=4
Triterpenoid high=5

Tang et al., 2018 [39]Triterpenoid,
celosins
12WMaleHFD4W10 mg/kg/d
30 mg/kg/d
90 mg/kg/d
ChowAortic root to iliac branchesEn face (longitudinal)Oil red OControl=9
Triterpenoid low=9
Triterpenoid medium=10
Triterpenoid high=10

Zhou et al., 2016 [40]Triterpenoid,
compound K
10WMaleHFD8W1 mg/kg/d
3 mg/kg/d
9 mg/kg/d
i.p.(1) Aortic root to abdominal aorta
(2) Aortic root
(1) En face (longitudinal)
(2) Cross-sectional
(1) Oil red O
(2) HE
Control=6, 6
Triterpenoid low=6, 6
Triterpenoid medium=6, 6
Triterpenoid high=6, 6

Dwyer et al., 2001 [41]Tetraterpenoid,
lutein
12WFemaleNCD8W2000 mg/kg/dChowAortic rootCross-sectionalOil red OControl=7
Tetraterpenoid=9

Han et al., 2015 [42]Tetraterpenoid,
lutein
8WMaleHFD24W25 mg/kg/d
50 mg/kg/d
100 mg/kg/d
ChowAortic sinusCross-sectionalOil red OControl=3
Tetraterpenoid low=3
Tetraterpenoid medium=3
Tetraterpenoid high=3

Zou et al., 2017 [43]Tetraterpenoid,
astaxanthin
6WMaleNCD12W500 mg/kg/dChowAortic sinusCross-sectionalOil red OControl=6
Tetraterpenoid treatment=6

Note: NCD, normal-chow diet; HCD, high-cholesterol diet; HFD, high-fat diet; IG, intragastric; i.p., intraperitoneal injection; HE, hematoxylin and eosin; ? = not reported.