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. 2023 Jan 13;9(1):e12963. doi: 10.1016/j.heliyon.2023.e12963

Table 2.

In vivo studies that investigated the effects of HT in animal models.

STUDY (year) Sample (size) Treatment Group Methodology Outcomes
[24] Male Wistar Rats (n = 40) Control group
Cholesterol group
HT group
HT-Ac group
HT-Et group
During 8 weeks: supplemented diet (2% cholesterol and 0.4% cholic acid) and 0.04% HT, HT-AC and HT-Et if corresponding LDL-col levels were reduced in Chol group.
Serum antioxidant activity were improved in HT and HT-Ac group in relation with Chol group.
[27] Female Wistar Rats (n = 12) Control group
HT group
SEC group
During 21 days: fed with 5 mg/kg SEC or HT.
Animals were weighted every 2 days to adjustment.
HT treatment could play a role in the modulation of several proteins closely related with CVDs.
[28] Wistar Rats (n = 70) Non-Diabetic rats
Diabetic rats
Diabetic + 0.5 mg/kg/day HT rats
Diabetic + 1 mg/kg/day HT rats
Diabetic + 2.5 mg/kg/day HT rats
Diabetic + 5 mg/kg/day HT rats
Diabetic + 10 mg/kg/day HT rats
HT was given once per day for 7 days before diabetes’ induction.
Then HT was given daily during 2 months.
HT treatment reduced platelet activity, thromboxane B2 and ox-LDL levels.
In addition, the treatment reduced MPOx, VCAM-1 and IL-6.
[29] ApoE−/− mice (n = 20) Control group
SEC treatment group
Control: standard diet.
SEC: standard diet 10 mg/kg SEC extract.
SEC treatment decreased the stain of E-selectin, MCP-1, ICAM-1, VCAM-1 and F4/80.
[30] BALB/c mice (n = 40) Control group 1
50 mg/ml LPS group, group 2
40 mg/kg HT group, group 3
80 mg/kg HT group, group 4
80 mg/kg HT at 5 times group, group 5
For 3 days: w/o polyphenols
Group 5 received HT
2 administrations 8 and 24 h post fasting
1 h after: LPS except group 1
At all doses tested of HT, COX-2 gene expression was reduced.
Plasma antioxidant power doubled basal levels after HT treatment.
[25] Sirtendo−/− mice and Sirt6flex/flex mice (WT mice) Control group
P-407 group
P-407 + HT group p-407 + HT-AC
WT group
WT + p-407 group
WT + p-407 + HT-AC group
Sirtendo−/− + p-407 + HT-AC
During 4 weeks: different concentrations of HT, HT-AC and peritoneal injection with p-407 HT treatment decreased TNF-α and 1L-1β levels.
IL-6 and Ccl2 mRNA levels decreased too.
[31] ApoE−/− mice with the C57BL/6 genetic background (n = 22) Control group
HT group
Daily HT: HT group
Daily saline gavage: Control group
HT treatment decreased plaque and atherosclerotic lesions while it improves lipid profile.
HT treatment upregulated ABCA1 and SR-BI expression while downregulates IL-2 and CRP expression.
[26] ApoE−/− mice in the C57/BL6 background (n = 40) ND
ND + HT-AC
HFD
HFD + HT-AC
For 12 weeks: HFD consumed western diet and/or HT-AC HT treatment decreased plaque formation and suppressed the expression of GSDMD.
HT suppressed TNF-α and IL-1β concentrations.
HT treatment decreased HDAC11 and HDAC11 mRNA expression.
[34] Wistar rats (n = 60) Non-Diabetic rats
Diabetic rats
Diabetic + 5 mg/kg/day HT rats
Diabetic + 0.5 mg/kg/day DHPG rats
Diabetic + 0.5 mg/kg/day DHPG + HT rats
Diabetic + 1 mg/kg/day DHPG + HT rats
Every treatment were administrated in the drinking water once a day during 7 days before diabetes’ induction.
Then, every treatment were administrated daily during 2 months.
HT increased HDL-chol levels while reduced platelet aggregation, thromboxane B2, MPOx and VCAM-1 levels.
[35] Swiss mice (n = 35) Control group
HT group
LPS group
20 mg HT + LPS group
40 mg HT + LPS group
For 10 days every group received their treatment HT treatment reduced CRP, MCP-1, MPO, IL-1β, IL-6, TNF-α and NF-kB

Abbreviations: ABCA1: ATP-binding cassette transporter 1; ApoE−/− mice: Apolipoprotein E knockout mice; Ccl2: Chemokine ligand 2; Con: Control; COX: cyclooxygenase; CRP: C-reactive protein; CVDs: Cardiovascular diesases; DHPG: 3,4-dyhydroxyphenylglycol; HDAC11: Histone deacetylase 11; HFD: High fat diet; HT-AC: Hydroxytyrosol acetate; HT-Et: Hydroxytyrosol ether; ICAM-1: Intercellular adhesion molecule-1; IL: Interleukin; Isop: Isoproterenol; LPS: Lipopolysaccharide; MCP-1: Monocyte chemoattractant protein-1; ND: Normal diet; NF-kB: Nuclear Factor kappa-light-chain-enhancer of activated B cells; OLE: Olive leaf extract; SD: Sprague-Dawley; SEC: Secoiridoids; Sirtendo−/− mice: Endothelium specific Sirt6 knockout; SR-BI: Scavenger receptor class B type 1; TNF-α: Tumor Necrosis Factor- α; VCAM-1: vascular cell adhesion molecule-1; WT: Wild-type.