With the deepening of the research, hydroxytyrosol olive leaf extract is much more active than olive bittersweet in antibacterial and antitumor activities. Hydroxytyrosol (hydroxytyrosol, HT) chemical name 3, 4 a dihydroxyphenylethanol. It has strong antioxidant activity. Mainly in the form of esters in the olive fruit and branches and leaves. HT monomer is obtained after hydrolysis of olive bittersweet, which has a simple structure and small molecular weight. It has good drug and health care functions. It has been widely concerned by domestic and foreign researchers.
• Research on anti-thrombosis, blood lipid regulation and anti-atherosclerosis effects
It is found that consumption of olive oil can greatly reduce the incidence of cardiovascular disease. Among them, HT plays an important role. It has been pointed out that the effect of HT on cardiovascular diseases is closely related to the inhibition of platelet aggregation, and GonzIlez-Correa et al. examined the anti-agglutination effect of HT on rat blood in vitro with salicylic acid as a reference. The results demonstrated that it inhibits thromboxane B synthesis. This increases the production of nitrous oxide, which leads to anticoagulant effect. deRoos et al. examined the anticoagulant effect of HT using human blood cells as a study subject. At a concentration of 100 mg/L, proteomic studies showed that it was involved in the regulation of nine proteins exerting anticoagulant effects. Such as platelet structure, activity and integrin aIIb/b3 transduction. From the results, it is clear that HT inhibits platelet activity and adhesion and can be used to prevent thrombosis .
The anticardiovascular effect of HT may be related to the reduction of blood glucose and lipid oxides concentration. It was proved that HT could reduce the concentration of blood glucose in plasma and the amount of triacylglycerol and total cholesterol in serum of diabetic rats. It also enhances SOD, catalase (CAT) and glutathione (GSH) peroxidase activities in liver and kidney. It reduces the levels of alkaline phosphatase and thiobarbituric acid reactants, among others, thus exhibiting a reduction in liver and kidney organ toxicity. The mechanism may be related to HT and LDL binding. It has also been shown that hydroxytyrosol olive leaf extract can treat hyperglycemia and oxidative stress conditions caused by diabetes .
HT can also prevent the development of atherosclerosis.Zrelli et al. demonstrated that olive leaf hydroxytyrosol can reduce the level of hydrogen peroxide-induced ROS in porcine pulmonary artery epithelial cells. It also enhanced the levels of mRNA enzymes, protein activity and intracellular transcriptional regulator 3a (FOXO3a), and induced adenosine monophosphate-activated protein kinase to translocate FOXO3a to the nucleus. Among other things FOXO3a is a transcriptional regulator. It is predominantly found in cardiac tissues, and its activated state has a significant effect on inhibiting vascular smooth muscle proliferation, cardiomyocyte hyperplasia and hypertrophy, and anti-oxidative stress. However, it is inactivated when it is transported from the nucleus to the cytoplasm. HT protects the body's epithelial cells from oxidative damage by inducing the expression of adenylate-activated protein kinase and activating the activity of the FOXO3a enzyme and prevents the development of atherosclerosis. In addition, HT is a potent intracerebral antioxidant. It has been shown to reduce the level of lipid peroxidation products in the striatum and the rest of the brain, and to impede the depletion of GSH. Consumption of foods containing HT reduces the risk of brain neuropathy. All of the above studies show that HT reduces the amount of reactive oxygen species in the brain and vascular endothelium, providing a molecular basis for the treatment of cardiovascular and cerebrovascular diseases.
• Study of antipathogenic microbial effects
HT may be developed as a drug for the treatment of intestinal and respiratory infections. It is highly effective and broad-spectrum. Taking Helicobacter pylori as an example, it has a variety of antibiotic-resistant strains worldwide. However, HT has a potent killing effect on both resistant and non-resistant strains. In another study, the lowest inhibitory concentration of HT on 5 standard strains (ATCC9006, ATCC8176, ATCC6539, ATCC17802, ATCC25923) and 44 strains obtained clinically were 0.24-7.85 g/mL, 0.97-31.25 g/mL, respectively. the inhibitory concentration was significantly lower than that of other plant extracts. And the activity of inhibiting Gram-positive bacteria was higher than that of Gram-negative bacteria. It is noteworthy that its antimicrobial activity was not only manifested against harmful species of bacteria in the intestinal tract. It also inhibited lactophilic bacteria and bifidobacteria.
Olive leaf extract hydroxytyrosol can also inhibit the activity of many viruses. These include HIV-1, H1N1, H3N2, H5N1 and H9N2 subtypes and Newcastle fowl plague virus. However, it is not effective against bovine rotavirus and adenovirus.Lee.Huang et al. "found that HT can reduce the activity of HIV-1 fusion enzyme. And can hinder the fusion of the active core of gp by forming hydrogen bonds with the hydrophobic groups in the outer layer of the viral envelope . Subsequently Yamada et al. experimentally found that pretreatment of dog kidney cells (MDCK) with HT did not affect the proliferation of H9N2 on MDCK. However, after infusing HT into the cells and inactivating H9N2, the results showed that neither viral DNA nor protein could be detected. Moreover, the morphology of H9N2 virus changed after HT treatment was observed by electron microscopy. This shows that the target is the envelope or other parts of the virus itself, not the host cell. Thus, hydroxytyrosol olive leaf extract can not only be used as an antibacterial and antiviral drug. And it can also enhance the body's defense function. Highlighting its potential for development as an antipathogenic microbial drug .
• Research on cartilage protection and anti-osteoporosis effects
Cartilage is a dense connective tissue composed of osteoblastic soft cells or chondrocytes and other components. Embedded in the extracellular matrix, it is an important component of bone. Because of its low metabolism, cartilage recovery after injury or breakage is slow.HT induces and enhances chondrocyte proliferation and increases its ability to produce extracellular matrix components, thereby promoting cartilage repair and regeneration.Hagiwara et al. examined the effects of HT on bone formation and bone loss after removal of the ovaries, using osteoblasts and osteoclasts as the targets. At concentrations of 10-100 mol/L, hydroxytyrosol in food stimulated calcium deposition in a dose-dependent manner. However, it had no effect on collagen and alkaline phosphatase in primary osteoblasts. At concentrations of 50-100 mol/L, HT prevented the formation of multinucleated osteoclasts in a dose-dependent manner, and HT inhibited bone loss in de-ovulated femoral trabecular osteoblasts. It also reduced H₂O₂ levels in pro-osteoblasts, which prevented osteoporosis caused by oxidative stress.HT plays a key role in bone formation and maintenance of bone health, and can be used as an effective drug in the treatment of osteoporosis. It is suitable for inducing or enhancing cartilage repair or cartilage regeneration, especially for athletes and people with active lifestyles.
• Study on the effect on retinal macular degeneration prevention and treatment
HT prevents oxidative damage to the retinal epithelium caused by acrolein, environmental toxicity, oxidized fatty particles and aging. It is especially suitable for the elderly to maintain eye health and high resolution and improve vision. In human retinal epithelial cells APRE I 19, HT protects both the Nrf2 cellular pathway and activates the coenzyme PPARGC1 receptor.Nrf2 activates phase II purifying enzymes. Nrf2 activates phase II purifying enzymes, such as monoglutamyl and cysteinyl ligases, NADPH quinone oxidoreductase 1, erythrocyte synthase 1, and other antioxidant enzymes, which "bind" to the free radicals and convert other toxic compounds into less reactive molecules. PPARGC1, on the other hand, uncoils protein 2 and the mitochondrial complex to enhance the expression of mitochondrial transporter A to protect against mitochondrial dysfunction. This enhances cell survival. Thus hydroxytyrosol powder olive leaf extract induces phase II purifying enzyme activity and enhances mitochondrial production, thereby preventing or treating macular degeneration .
• Other health effects studies
HT reduces the production of intracellular COX I-2 and the expression of 5-monooxygenase, and decreases the synthesis of prostaglandin E-2. It can be used as an anti-inflammatory and analgesic.HT helps to repair mitochondria damaged by over-exercise or exertion, which can lead to rapid recovery of physical fitness and enhance resistance and athletic ability. It can also reduce the formation of fat droplets in C3H10T1/2 cells of mice, so as to achieve the purpose of weight loss.
Foreign scholars have made good research on the pharmacological effects of HT in regulating blood lipids and anti-atherosclerosis, anti-pathogenic microorganisms, preventing and controlling retinal macular degeneration, protecting cartilage and anti-osteoporosis and other aspects. Some studies have also explored the pharmacological mechanism of HT at the molecular level. Domestic research on HT is mainly in health products and food additives. It has less research on its medicinal use. Recently, Liu Health et al. applied for a patent for hydroxytyrosol olive leaf extract for the treatment of prostate cancer.
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