Olea25® Hydroxytyrosol is a polyphenol of Olive Leaf Extract that supports health benefits and scientific-based contribution to the Mediterranean Diet. Hydroxytyrosol(HT) is a potent antioxidant and anti-inflammatory that provides neuroprotective and cytoprotective support of neurodegenerative disease, and has added antimicrobial, anti-diabetic and heart health benefits.
This post reviews studies that support Hydroxytyrosol in the roles of neuroprotective and cytoprotective benefits, and its’ potential therapeutic contribution, as a polyphenolic compound, in neurodegenerative disease prevention.
Sources of Polyphenol- Hydroxytyrosol
There are two known sources of Hydroxytyrosol(3,4-dihydroxyphenylethanol; DOPET), the main phenolic compound found in olive oil and olive products that include olive leaf extract.
Exogenous: Ingestion of Natural Products that contain HT, or it’s precursors.
Endogenous: Derived from Dopamine Oxidative Metabolism
DOPET(HT), in it’s endogenous, form may provide neurotoxic protection involved in neurodegenerative diseases such as Parkinson’s Disease and Alzheimer’s Disease.
Dietary Polyphenols as Modulators of Brain Functions
The neuroprotective actions of dietary polyphenols impact on brain health have a number of actions.
- A potential to protect neurons against injury induced by neurotoxins.
- An ability to suppress neuroinflammation
- The potential to promote memory, learning and cognitive function.
While not fully clear, these beneficial effects are in part related to oxidative and inflammatory stress and protective signaling, and may involve hormetic effects to protect against oxidative and inflammatory stressors.
Hydroxytyrosol activates Sirt1 pathways.
Sirt1 guards against cellular oxidative stress and DNA damage.
Sirt1 activation shifts metabolisms away from using glucose as an energy source.
Neuroprotective and Cytoprotective Benefits of Hydroxytyrosol
Neuroprotective Support of Hydroxytyrosol
- Hydroxytyrosol promotes the cells own defenses against oxidative stress
- Protects neurogenesis
- Modulates mitochondrial function
Hydroxytyrosol provides mitochondrial protection by activating NrF2 in tissue and activating three glutathione related enzymes.
Glutathione (GSH) is an important antioxidant in plants, animals, fungi, and some bacteria , preventing damage to important cellular components caused by reactive oxygen species such as free radicals, peroxides, lipid peroxides and heavy metals.
HT enhanced the antioxidant defense system by preserving GSH levels and the activities of superoxide dismutase, GSH reductase, and GSH peroxidase.
Hydrosytyrosol alone or in combination with Polyunsaturated Fatty Acids provide cytoprotection as evidenced as an increased resistance of cellular DNA damage.
Hydroxytyrosol has been shown to cross the Blood-Brain barrier making it the brain antioxidant.
The Cytoprotective abilities of Hydroxytyrosol include:
Resistance to cellular damage in the brain through oxidative stress.
Protection of neuronal cells that may otherwise experience neurodegeneration.
Improved synaptic plasticity of neurons.
Down regulation of inflammatory activity.
Further effects of hydroxytyrosol include attenuation of neurotoxic activity that may lead to neurogenerative disease.
These activities act on:
- Reactive Oxygen Species(ROS)
- Nitric Oxide Overproduction
- Decreased Mitochondrial Membrane Potential
- Decreased Cellular Peroxide Formation
Antioxidant Properties of Hydroxytyrosol
From Scavenging Activity to Nrf2 Induction
Two mechanisms have been proposed with respect to HT antioxidant activity:
1. By directly scavenging Reactive Oxygen Species generated during oxidative stress
2. By activating different cellular signaling pathways that would increase the organism defenses against an oxidative stress.
The biotransformation properties of hydroxytyrosol activates cellular signaling pathways by induction of Phase II Detoxifying Enzymes via NrF2 Activation.
Nuclear factor (erythroid-derived 2)-related factor 2 (Nrf2) is a transcription factor that regulates expression of greater than 90% of antioxidant genes.
Phase II Detoxifying Enzymes provide a process by which toxins can be metabolized and later excreted.
There is growing scientific evidence suggesting that certain diseases are the direct result of damage to the body from poor Phase 2 detoxification. Diseases that may be caused by toxic intermediate metabolites and free radicals include:
- Parkinson’s Disease
- Chronic Fatigue
- Immune dysfunction
Studies indicate that HT activates Nfr2 in different tissues, and preliminary results in vivo suggest that through this activation beneficial effects in neurodegenerative diseases may be elicited.
HT and tyrosol were able to protect neuronal cells against Aβ induced toxicity and prevented the nuclear translocation of transcription factor NF-κB .
Effects of Hydroxytyrosol on Mitochondrial Biogenesis
The effects of strenuous or extreme exercise can cause fatigue and damage to muscle and immune function. In a study by Feng and associates, found that excessive exercise was susceptible to reduced aerobic capacity and induce damage to renal and immune system function. They were able to show that oxidation and mitochondrial function were confirmed.
Hydroxytyrosol (HT), a natural olive polyphenol, efficiently enhanced endurance capacity and prevented Exe-induced renal and immune system damage. Also, HT treatment inhibited both the Exe-induced increase in autophagy and mitochondrial fission and the decrease in PGC-1α expression. In addition, HT enhanced mitochondrial fusion and mitochondrial complex I and II activities in muscle of Exe rats. These results demonstrate that Exe-induced fatigue and damage to muscle and immune functions may be mediated via the regulation of mitochondrial dynamic remodeling, including the downregulation of mitochondrial biogenesis and upregulation of autophagy.
In research by Hao, et al., data suggested that HT is able to promote mitochondral function by stimulating mitochondrial biogenesis.
The mechanistic study of the PPARGC1α activation signaling pathway demonstrated that HT is an activator of 5′AMP-activated protein kinase(AMPK) and also up-regulates gene expression of PPARα, CPT-1 and PPARγ.
The analysis of the pharmacokinetic properties and safety profile, as well as the in vitro and in vivo neuroprotective actions, make Hydroxytyrosol a potential therapeutic candidate for the prevention of neurodegenerative diseases.
- Zhu, Lu et al. Hydroxytyrosol protects against oxidative damage by simultaneous activation of mitochondrial biogenesis and phase II detoxifying enzyme systems in retinal pigment epithelial cells. Journal of Nutritional Biochemistry,Volume 21,Issue 11,1089 – 1098.
Bulotta S, Celano M, Lepore SM, Montalcini T, Pujia A, Russo D. Beneficial effects of the olive oil phenolic components oleuropein and hydroxytyrosol: focus on protection against cardiovascular and metabolic diseases. Journal of Translational Medicine. 2014;12:219. doi:10.1186/s12967-014-0219-9.
- Young, Julie, Klaus WJ Wahle, and Susanne P. Boyle. “Cytoprotective effects of phenolic antioxidants and essential fatty acids in human blood monocyte and neuroblastoma cell lines: Surrogates for neurological damage in vivo.” Prostaglandins, Leukotrienes and Essential Fatty Acids 78.1 (2008): 45-59.
Tuck, Kellie L., and Peter J. Hayball. “Major phenolic compounds in olive oil: metabolism and health effects.” The Journal of nutritional biochemistry 13.11 (2002): 636-644.
D’Angelo, S., et al. “Pharmacokinetics and metabolism of hydroxytyrosol, a natural antioxidant from olive oil.” Drug metabolism and disposition: the biological fate of chemicals 29.11 (2001): 1492.
- Schaffer, Sebastian, and Barry Halliwell. “Comment on hydroxytyrosol induces proliferation and cytoprotection against oxidative injury in vascular endothelial cells: role of Nrf2 activation and HO-1 induction.” Journal of agricultural and food chemistry 59.19 (2011): 10770-10771.
- Shenoy S, Chowanadisai W, Sharman E, Keen C, Liu J, Rucker R. 2011. Biofactors in food promote health by enhancing mitochondrial function. Cal Ag 65(3):141-147. DOI: 10.3733/ca.v065n03p141.
- Hao, Jie jie et al.”Hydroxytyrosol promotes mitochondrial biogenesis and mitochondrial function in 3T3-L1 adipocytes.” Journal of Nutritional Biochemistry, Volume 21 , Issue 7 , 634 – 644
Acteoside and its aglycones protect primary cultures of rat cortical cells from glutamate-induced excitotoxicityKA Koo, SH Kim, TH Oh, YC Kim – Life sciences, 2006
- Rodríguez-Morató, Jose, et al. “Potential role of olive oil phenolic compounds in the prevention of neurodegenerative diseases.” Molecules 20.3 (2015): 4655-4680.
- Kathrin Pallauf, Katrin Giller, Patricia Huebbe, and Gerald Rimbach, “Nutrition and Healthy Ageing: Calorie Restriction or Polyphenol-Rich “MediterrAsian” Diet?,” Oxidative Medicine and Cellular Longevity, vol. 2013, Article ID 707421, 14 pages, 2013. doi:10.1155/2013/707421