Wide Biological Role of Hydroxytyrosol: Possible Therapeutic and Preventive Properties in Cardiovascular Diseases
Abstract
:1. Introduction
2. Methodology
3. Biochemical Properties of Hydroxytyrosol
4. Biological Effects of Hydroxytyrosol in Cellular In Vitro Models
4.1. HT as Radical Species Scavenger: Protective Role against Oxidative Stress Contributing to Atherosclerosis
4.2. Anti-Inflammatory Role of HT
4.3. Modulation of Endothelial and Macrophage Activation in Protection from Atherosclerosis
4.4. Antithrombotic Effect
4.5. Antiadipogenic Role
5. Health Beneficial Effects of Hydroxytyrosol Demonstrated in Animal In Vivo Models
5.1. Protection of Low-Density Lipoprotein (LDL) from Oxidation
5.2. Improvement of Blood Lipid Profile
5.3. Hypoglycemic Ability
5.4. Anti-Inflammatory Activity
5.5. Antithrombotic Effect
6. Health Beneficial Effects Demonstrated Through Clinical Trials in Humans
6.1. Protection of Low-Density Lipoprotein (LDL) from Oxidation
6.2. Modulation of Blood Lipid Profile
6.3. Increased Insulin Sensitivity
6.4. Anti-Inflammatory Activity
6.5. Antithrombotic Effect
7. Conclusions
Funding
Conflicts of Interest
References
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Study | In Vitro Model | Conditions | HT Health Benefits |
---|---|---|---|
Salami et al., 1995 [45] | CuS04-treated LDL samples | 10−5 M HT | ↓ F2-isoprostanes, ↑ Vit E |
Visioli et al., 1995 [46] | CuS04-treated LDL samples | HT range 10−6–10−4 M | ↑ Vit E, ↓ lipid peroxidation |
Carluccio et al., 2003 [66] | HUVECs and BAECs + LPS, IL-1β, TNFα, or PMA | 30 μM HT | ↓ VCAM-1, ↓ ICAM-1, ↓ NF-kB, ↓ AP-1, ↓ E-selectin |
O’Dowd et al., 2004 [49] | TNF and fMLP-stimulated human neutrophils | 10 μM HT | ↓ H2O2 |
Berrougui et al., 2005 [47] | [3H]-Cholesterol-loaded J774 macrophages | HT range 0–25 μM | ↑ ABCA1, ↑ apoA-I-mediated cholesterol efflux |
Schmitt et al., 2007 [41] | EA.hy926 | 0.1–100 µM HT for 24 h | No effect on endothelial NO bioavailability and eNOS activity |
Carluccio et al., 2007 [69] | Hcy-stimulated HUVECs | HT range 0.1–1 μM | ↓ VCAM-1, ↓ ROS, ↓ NF-κB |
Dell’Agli et al., 2008 [72] | Human platelets | 10 μM HT | ↓ cAMP-PDE, ↓ platelet aggregation |
Zrelli et al., 2011 [52] | VECs + H2O2 | 10, 30, 50 μM HT for 24 h | ↓ ROS, ↑ CAT, ↑ FOXO3a, ↑ pAMPK |
Richard et al., 2011 [62] | LPS-stimulated RAW264.7 | 25 μM HT | ↓ NO, ↓ PGE₂, ↓ IL-1α, ↓ IL-1β, ↓ IL-6, ↓ IL-12, ↓ TNFα, ↓ CXCL10/IP-10, ↓ CCL2/MCP-1, ↓ iNOS, ↓ MMP-9 |
Zou et al., 2012 [55] | VECs + H2O2 | 50 μM HT | ↑ pAkt, ↑ p-p38, ↑ pErK, ↑ Nrf2, ↑ HO-1, ↓ ROS |
Scoditti et al., 2012 [76] | HUVEC + PMA | 10 μM HT | ↓ MMP-9, ↓ COX-2, ↓ PGE2, ↓ NF-kB |
Rosignoli et al., 2013 [65] | PMA-activated PBMC | 100 μM HT | ↓ O2−, ↓ COX-2, ↓ PGE2 |
Scoditti et al., 2014 [63] | PMA-activated PBMC and U937 | HT range 1–10 μM | ↓ MMP-9, ↓ COX-2, ↓ PGE₂, ↓ NF-kB, ↓ PKCβ1, ↓ PKC-α |
Takeda et al., 2014 [64] | LPS-stimulated mouse peritoneal macrophages | 12.5 μg/mL HT | ↓ iNOS, ↓ NO |
Storniolo et al., 2014 [43] | HG-stimulated ECV304 | 10 µM HT for 48 h | ↓ ROS, ↑ ET-1, ↑ p-eNOS, ↑ NO |
Scoditti et al., 2015 [75] | SGBS cells + TNFα | HT range 0.1–20 μM | ↓ pJNK, ↑ adiponectin, ↑ PPARγ |
Catalán, et al., 2015 [71] | TNF-α-stimulated HAEC | 1, 2, 5, 10 μM HT for 24 h | ↓ E-selectin, ↓ P-selectin, ↓ VCAM-1, ↓ ICAM-1, ↓ MCP-1 |
Ozbek et al., 2015 [51] | H9c2 + O2− | HT range 0.1-10 µg/mL for 24 h | ↓ ROS, ↓ pMAPKAPK-2, ↓ pErk1/2, ↑ Hsp27, ↓ c-CASP3 |
Zrelli et al., 2015 [57] | VECs | HT range 10-100 μM | ↑ PI3K/Akt, ↑ pErK, ↑ Nrf2, ↑ HO-1 |
Tagliaferro et al., 2015 [53] | Hg induced hemolysis of human RBC | HT range 10-80 μM | ↓ ROS, ↑ GSH |
Officioso et al., 2016 [54] | Hg induced hemolysis of human RBC | HT range 0.1–5 μM | ↓ Eryptosis |
Atzeri et al., 2016 [48] | Caco-2 + oxidized cholesterol | HT range 2.5–10 μM | ↓ ROS, ↑ GSH, ↓ GPx activity |
Calabriso et al., 2018 [50] | PMA-stimulated HUVEC and HMEC-1 | HT range 1–30 μM | ↓TNFα, ↓IL-1β, ↓VCAM-1, ↓ ICAM-1, ↓ mtROS, ↓ ROS, ↓ MDA, ↓ MnSOD |
Manna et al., 2019 [67] | Hcy/TNFα-stimulated EA.hy 926 | HT range 0.5–2.5 μM | ↓ ICAM-1 |
Wang et al., 2019 [42] | HG-stimulated HUVECs | 25, 50, 100 µM HT-NO for 48 h | ↑ p-eNOS, ↑ NO, ↓ ROS, ↑ SIRT-1 |
Study | In Vivo Model | Conditions | HT Health Benefits |
---|---|---|---|
González-Santiago et al., 2006 [84] | Hyperlipemic rabbits, diet induced for 1 month | 4 mg/kg HT for 1 month | ↓ TC, ↓ TG, ↑ HDL, ↓ atherosclerotic lesion |
Fki et al., 2007 [80] | Wistar rats fed cholesterol-rich diet for 16 w | 2.5 mg/kg HT + 10 mg/kg OMW | ↓ TC, ↓ LDL, ↑ HDL, ↓ TBARS in liver, heart, kidney, and aorta, ↑ CAT, ↑ SOD1 |
Rietjens et al., 2007 [82] | Lewis rats, excised aorta | HT range 20–100 μM | Protection against induced impairment of NO-mediated aorta relaxation |
Jemai et al., 2008 [79] | Wistar rats fed cholesterol-rich diet for 16 w | 3 mg/kg/day HT and triacetylated HT | ↓ TC, ↓ TG, ↓ LDL, ↓ TBARS in liver, heart, kidney, and aorta, ↑ HDL, ↑ CAT, ↑ SOD1 |
González-Correa et al., 2008 [85] | Wistar rats | 1, 5, 10, 20, 50, 100 mg/kg/day HT, HT-ac or acetylsalicylic acid for 1 w | ↓ platelet aggregation, ↓ thromboxane B2, ↓ prostacyclin, ↑ NO |
Cao et al., 2014 [81] | C57BL/6J mice high fat diet fed for 17 w | 10 and 50 mg/kg/day HT for 17 w | ↓ body and organs weight, ↓ HOMA-IR index, ↓ leptin, ↓ IL-6, ↓ CRP, ↓ TG, ↓ HDL, ↓ LDL, ↓ SREBP-1c, ↓ FAS, ↑ SOD1 |
db/db metabolic syndrome mice | 10 mg/kg/day HT or 225mg/kg/day metformin for 8 w | ↓ TG, ↓ TC, ↓ HDL, ↓ LDL, ↓ MDA, ↑ glucose tolerance | |
Tabernero et al., 2014 [83] | Wistar rats high cholesterol-fed | 25 mg/Kg/day HT, HT-ac, HT-et for 8 w | ↓ TC, ↓ LDL, ↓ glucose, ↓ insulin, ↓ leptin, ↓ MDA, ↓ TNFα, ↓IL-1β, ↓ MCP-1, ↑ ORAC |
Wang et al., 2019 [42] | KM diabetic mice, streptozotocin-induced | 77 mg/kg/day HT for 4 w | ↓ blood glucose, ↓ MDA, ↑ NO, ↑ SOD1 |
Study | Population | Conditions | HT Health Benefits |
---|---|---|---|
Camargo et al., 2010 [100] | No. 20 metabolic syndrome patients, age range 40–70 | 0.2 μmol g−1 and 45.4 μmol g−1 HT, single dose | ↓ IL-1β, ↓ IL-6, ↓ PTGS2, ↓NF-κB/MAPK/AP-1 pathway, ↓ chemokines |
de Bock et al., 2013 [99] | No. 46 overweight men, age range 35–55 | 9.7 mg/day HT and 51.1 mg/day oleuropein, for 12 w | ↑ insulin sensitivity, ↑ β-cell responsiveness |
Colica et al., 2017 [98] | No. 28 healthy subjects, age range 18–65 | 15 mg/day HT for 3 w | ↑ SOD1, ↑ thiol group, ↑ TSA, ↓ MDA, ↓ nitrite, ↓ nitrate, ↓ body fat mass, ↓ suprailiac skinfold, ↓ body weight |
Quirós-Fernández et al., 2019 [97] | No. 84 healthy subjects, age range 45–65 | 9.9 mg/day HT and 195 mg/day punicalagin, for 20 w | ↓ ox-LDL, ↓ SYS and DIA blood pressure |
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D’Angelo, C.; Franceschelli, S.; Quiles, J.L.; Speranza, L. Wide Biological Role of Hydroxytyrosol: Possible Therapeutic and Preventive Properties in Cardiovascular Diseases. Cells 2020, 9, 1932. https://doi.org/10.3390/cells9091932
D’Angelo C, Franceschelli S, Quiles JL, Speranza L. Wide Biological Role of Hydroxytyrosol: Possible Therapeutic and Preventive Properties in Cardiovascular Diseases. Cells. 2020; 9(9):1932. https://doi.org/10.3390/cells9091932
Chicago/Turabian StyleD’Angelo, Chiara, Sara Franceschelli, José Luis Quiles, and Lorenza Speranza. 2020. "Wide Biological Role of Hydroxytyrosol: Possible Therapeutic and Preventive Properties in Cardiovascular Diseases" Cells 9, no. 9: 1932. https://doi.org/10.3390/cells9091932