GSH and OLEUROPEIN

 

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The provision of data on your part is optional, although failure to provide it may, in fact, make it impossible to pursue the contractual purposes.

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Your data will be processed by the owner, by the appointed data processors and by the strictly authorized data processors, in any case through the adoption of technical-organizational measures suitable for satisfying compliance with the privacy legislation.

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Your data may be communicated following inspections or checks, to supervisory bodies, judicial authorities as well as to all other subjects to whom the communication is mandatory by law.

It should be noted that the role of Data Processors is held by external companies with which a contractual relationship has been established and which need to receive your personal data to fulfill these agreements. To find out who is in charge of the treatment if they are appointed and to know the people who will be appointed in the future for this function, each interested party can send a letter of request to the owner of the personal data treatment, at the above address. It is intended to specify that the Managers indicated above do not deal with processing requests to exercise the rights of the interested parties pursuant to articles 15 et seq. of the Regulation. This activity is carried out exclusively by the undersigned as Data Controller.

 
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Thank you for reading this information which we have tried to make simple, complete, clear and transparent. In any case, we always try to improve: if you have any suggestions, write to us at info@innbiotecpharma.com. This information may change in the future: any changes will be communicated to you via e-mail, so that you can have the widest control of your data, in which case you will have the burden of reading it again, carefully

Innbiotec Pharma s.r.l.
Via Martiri di Civitella, 5, 52100 Arezzo (IT)
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info@innbiotecpharma.com
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OLEUROPEIN

The beneficial effects of oleuropein Oleuropein is the main polyphenol present in the leaves and fruits of the olive tree; it is found in extra virgin olive oil both in the form linked to a glucose molecule (glycated) and in the non-glycated form. For some time, natural polyphenols have attracted growing interest for their beneficial properties against numerous diseases, ranging from cancer to cardiovascular diseases, diabetes, neurodegenerative diseases and, more generally, for their ability to counteract the aging of cells, tissues and the whole organism. These properties are not limited to their known antioxidant power but go far beyond; the most recent studies have begun to demonstrate the effective clinical efficacy of the administration of polyphenols on humans and to reveal the molecular and cellular mechanisms with which these substances exert these effects and which are the basis of the nutritional virtues commonly associated with the so-called “Mediterranean Diet ”.

The results of the clinical trials conducted, together with the available epidemiological and experimental data consistently support the protective effect associated with the daily intake of oleuropein through the use of nutraceutical preparations consisting of olive leaf extracts enriched with the substance. 

The data provided by scientific research are particularly significant as regards the anti-neurodegenerative and anti-diabetic effects of oleuropein. The former were reported thanks to a series of studies carried out both on neuronal cells in culture and on model animals, in particular genetically modified mice in order to mimic a brain situation similar to that present in Alzheimer’s disease, the main form of dementia associated to aging in humans. In these mice, the administration of oleuropein with the normal meal in doses equivalent to approximately 200-°©-300 mg in humans has clearly beneficial effects in terms of cognitive performance, which are maintained at levels comparable with those of normal mice of the same age . At the histopathological and cellular level, this effect can be traced back to the reduction of the load of amyloid plaques (which characterize the disease) and of the inflammatory response and, in parallel, to a strong stimulation of the autophagic response, which protects the cell against the toxicity of the plaques and stimulates its reabsorption. These effects, which show a clear dose-°©-dependence, are similar to those produced by other polyphenols (resveratrol, curcumin, epigallocatechins) and can, at least in part, be traced back to the mobilization of calcium from intracellular deposits with the consequent activation of signals that result in the activation of autophagy. It has also been demonstrated that oleuropein can directly reduce the load of amyloid plaques by favoring a pathway that reduces the production of the precursor peptide of the same. Furthermore, recent studies on other polyphenols demonstrate effects of an epigenetic type, consisting in the modulation of the expression of particular sets of genes following reversible chemical modifications of the chromatin which do not alter the genetic heritage but the way in which it is expressed. These studies explain the anticancer effects of these polyphenols and, presumably, also those exerted by oleuropein, through the regulation of the activity of enzymes involved in the chemical modifications of chromatin.

 The antidiabetic action of oleuropein is supported by recent clinical trials. One of these showed that the daily administration of about 50 mg of the polyphenol for 12 weeks to a group of middle-aged, overweight subjects at risk for developing type 2 diabetes reduced blood sugar and improved both the secretion and insulin sensitivity. Another study conducted in human subjects with type 2 diabetes given 500 mg of oleuropein per day for 14 weeks showed a significant improvement in glucose homeostasis, with reductions in glycosylated hemoglobin and fasting insulin levels, while a reduction in starch digestion and absorption was noted in rats treated with oleuropein. Other studies have shown that in vitro oleuropein prevents the amyloid aggregation of amylin, a peptide secreted together with insulin by pancreatic beta cells, the aggregates of which are believed to be co-responsible for the cellular suffering that accompanies the onset of diabetes type 2. The efficacy of oleuropein in contrasting both the onset of type 2 diabetes and some of its consequences can be seen in a broader protective effect against the metabolic syndrome. In fact, other studies have shown that in mice, oleuropein attenuates fatty liver disease and reduces obesity induced by a high-fat diet. The anti-°©-obesity effect and the modulation of glucose homeostasis had previously been reported also for other plant polyphenols. In conclusion, the available scientific data convincingly support the efficacy of the daily intake of large doses of oleuropein for the prevention of pathologies linked to aging such as senile dementia and cancer, or to metabolic disorders such as type 2 diabetes and the metabolic syndrome. The constant daily intake of large doses of oleuropein through the supplementation, with nutraceutical products, of the normal content of the substance in the diet therefore appears useful and recommendable in order to prevent and treat the metabolic syndrome and type 2 diabetes mellitus, also in consideration of the absence of side effects related to the intake of oleuropein. 

Bibliography

  • Phenols and Polyphenols from Argania spinosa. Z. Charrouf and D. Guillaume, American Journal of Food Technology, 2007, 2, pages 679-683, 
  • Prossnitz, Eric R.; Barton, Matthias (2014). “Estrogen biology: New insights into GPER function and clinical opportunities”. Molecular and Cellular Endocrinology 389 (1-2): 71–83. 
  • Haris Omar, Syed (2010). “Oleuropein in Olive and its Pharmacological Effects”. Scientia Pharmaceutica 78 (2): 133–54. 
  • Sudjana, Aurelia N.; D’Orazio, Carla; Ryan, Vanessa; Rasool, Nooshin; Ng, Justin; Islam, Nabilah; Riley, Thomas V.; Hammer, Katherine A. (2009). “Antimicrobial activity of commercial Olea europaea (olive) leaf extract”. International Journal of Antimicrobial Agents 33 (5): 461–3. 
  • Barbaro, Barbara; Toietta, Gabriele; Maggio, Roberta; Arciello, Mario; Tarocchi, Mirko; Galli, Andrea; Balsano, Clara (2014). “Effects of the olive-derived polyphenol oleuropein on human health”. International Journal of Molecular Sciences 15 (10): 18508–18524. 
  • Tripoli, Elisa; Giammanco, Marco; Tabacchi, Garden; Di Majo, Danila; Giammanco, Santo; La Guardia, Maurizio (2009). “The phenolic compounds of olive oil: Structure, biological activity and beneficial effects on human health”. Nutrition Research Reviews 18 (1): 98–112. 
  • Walter Jr, WM; Fleming, HP; Etchells, JL (1973). “Preparation of antimicrobial compounds by hydrolysis of oleuropein from green olives”. Applied microbiology 26 (5): 773–6. 
  • Andreadou, Ioanna; Iliodromitis, Efstathios K.; Mikros, Emmanuel; Constantinou, Maria; Agalias, Apostolos; Magiatis, Prokopios; Skaltsounis, Alexios Leandros; Kamber, Elli; et al. (2006). “The Olive Constituent Oleuropein Exhibits Anti-Ischemic, Antioxidative, and Hypolipidemic Effects in Anesthetized Rabbits”. The Journal of Nutrition 136 (8): 2213–9. 
  • Leehuang, S; Huang, P; Zhang, D; Lee, J; Bao, J; Sun, Y; Chang, Y; Zhang, J; Huang, P (2007). “Discovery of small-molecule HIV-1 fusion and integrase inhibitors oleuropein and hydroxytyrosol: Part I. Integrase inhibition”. Biochemical and Biophysical Research Communications 354 (4): 872–8. 
  • Lee-Huang S, Huang P, Huang P (July 11–16, 2004). “Anti-HIV activity of olive leaf extract and synergism with HAART”. Int Conf AIDS 15th. Bangkok.
  • Leri M, Natalello A, Bruzzone E, Stefani M, Bucciantini M. Oleuropein aglycone and hydroxytyrosol interfere differently with toxic Aβ1-42 aggregation. Food Chem Toxicol. 2019 Apr 14. pii: S0278-6915(19)30214-5. 
  • Palazzi L, Bruzzone E, Bisello G, Leri M, Stefani M, Bucciantini M, Polverino de Laureto P.  Oleuropein aglycone stabilizes the monomeric α-synuclein and favours the growth of non-toxic aggregates.  Sci Rep. 2018 May 29;8(1):8337.     
  • Miceli C, Santin Y, Manzella N, Coppini R, Berti A, Stefani M, Parini A, Mialet-Perez J, Nediani C.  Oleuropein Aglycone Protects against MAO-A-Induced Autophagy Impairment and Cardiomyocyte Death through Activation of TFEB.  Oxid Med Cell Longev. 2018 Mar 26;2018:8067592.     
  • Nardiello P, Pantano D, Lapucci A, Stefani M, Casamenti F.  Diet Supplementation with Hydroxytyrosol Ameliorates Brain Pathology and Restores Cognitive Functions in a Mouse Model of Amyloid-β Deposition.  J Alzheimers Dis. 2018;63(3):1161-1172.     
  • Leri M, Oropesa-Nuñez R, Canale C, Raimondi S, Giorgetti S, Bruzzone E, Bellotti V, Stefani M, Bucciantini M.  Oleuropein aglycone: A polyphenol with different targets against amyloid toxicity.  Biochim Biophys Acta Gen Subj. 2018 Jun;1862(6):1432-1442.     
  • Casamenti F, Stefani M.  Olive polyphenols: new promising agents to combat aging-associated neurodegeneration.  Expert Rev Neurother. 2017 Apr;17(4):345-358.     
  • Luccarini I, Pantano D, Nardiello P, Cavone L, Lapucci A, Miceli C, Nediani C, Berti A, Stefani M, Casamenti F.  The Polyphenol Oleuropein Aglycone Modulates the PARP1-SIRT1 Interplay: An In Vitro and In Vivo Study.  J Alzheimers Dis. 2016 Sep 6;54(2):737-50.     
  • Rigacci S, Stefani M.  Nutraceutical Properties of Olive Oil Polyphenols. An Itinerary from Cultured Cells through Animal Models to Humans.  Int J Mol Sci. 2016 May 31;17(6). pii: E843.     
  • Pantano D, Luccarini I, Nardiello P, Servili M, Stefani M, Casamenti F.  Oleuropein aglycone and polyphenols from olive mill waste water ameliorate cognitive deficits and neuropathology.  Br J Clin Pharmacol. 2017 Jan;83(1):54-62.     
  • Leri M, Nosi D, Natalello A, Porcari R, Ramazzotti M, Chiti F, Bellotti V, Doglia SM, Stefani M, Bucciantini M.  The polyphenol Oleuropein aglycone hinders the growth of toxic transthyretin amyloid assemblies.  J Nutr Biochem. 2016 Apr;30:153-66.     
  • Rigacci S, Miceli C, Nediani C, Berti A, Cascella R, Pantano D, Nardiello P, Luccarini I, Casamenti F, Stefani M.  Oleuropein aglycone induces autophagy via the AMPK/mTOR signalling pathway: a mechanistic insight.  Oncotarget. 2015 Nov 3;6(34):35344-57.     
  • Casamenti F, Grossi C, Rigacci S, Pantano D, Luccarini I, Stefani M.  Oleuropein Aglycone: A Possible Drug against Degenerative Conditions. In Vivo Evidence of its Effectiveness against Alzheimer’s Disease.  J Alzheimers Dis. 2015;45(3):679-88.     
  • Rigacci S, Stefani M.  Nutraceuticals and amyloid neurodegenerative diseases: a focus on natural phenols.  Expert Rev Neurother. 2015 Jan;15(1):41-52.     
  • Luccarini I, Grossi C, Rigacci S, Coppi E, Pugliese AM, Pantano D, la Marca G, Ed Dami T, Berti A, Stefani M, Casamenti F.  Oleuropein aglycone protects against pyroglutamylated-3 amyloid-ß toxicity: biochemical, epigenetic and functional correlates.  Neurobiol Aging. 2015 Feb;36(2):648-63.     
  • Luccarini I, Ed Dami T, Grossi C, Rigacci S, Stefani M, Casamenti F.  Oleuropein aglycone counteracts Aβ42 toxicity in the rat brain.  Neurosci Lett. 2014 Jan 13;558:67-72.     
  • Grossi C, Ed Dami T, Rigacci S, Stefani M, Luccarini I, Casamenti F.  Employing Alzheimer disease animal models for translational research: focus on dietary components.  Neurodegener Dis. 2014;13(2-3):131-4.     
  • Grossi C, Rigacci S, Ambrosini S, Ed Dami T, Luccarini I, Traini C, Failli P, Berti A, Casamenti F, Stefani M.  The polyphenol oleuropein aglycone protects TgCRND8 mice against Aß plaque pathology.  PLoS One. 2013 Aug 8;8(8):e71702.     
  • Diomede L, Rigacci S, Romeo M, Stefani M, Salmona M.  Oleuropein aglycone protects transgenic C. elegans strains expressing Aβ42 by reducing plaque load and motor deficit.  PLoS One. 2013;8(3):e58893.     
  • Rigacci S, Guidotti V, Bucciantini M, Nichino D, Relini A, Berti A, Stefani M.  Aβ(1-42) aggregates into non-toxic amyloid assemblies in the presence of the natural polyphenol oleuropein aglycon.  Curr Alzheimer Res. 2011 Dec;8(8):841-52.    
  • Rigacci S, Guidotti V, Bucciantini M, Parri M, Nediani C, Cerbai E, Stefani M, Berti A.  Oleuropein aglycon prevents cytotoxic amyloid aggregation of human amylin.  J Nutr Biochem. 2010 Aug;21(8):726-35.     

Bacopa monnieri

Bacopa monnieri is a nootropic herb that has been used for longevity and cognitive enhancement. Supplementation with its extracts can improve memory, especially in the short term, and bring benefits for mental health. Bacopa monnieri, commonly known as water hyssop, is an herb often used in Ayurvedic medicine. It is taken in various formats with the aim of improving cognitive functions, relieving stress and promoting an overall improvement in vitality. Bacosides, the main active substances of Bacopa monnieri, interact with the dopamine and serotonin systems, but the main mechanism concerns neuronal communication, stimulating the growth of neuronal dendrites. Bacopa monnieri also has antioxidant effects.

The benefits of Bacopa monnieri

An improvement in memory is the main known effect of Bacopa. Although effects of this nature are usually studied in the elderly, Bacopa monnieri appears to be effective in young people as well. Some preliminary research suggests it may reduce cortisol secretion and depletion of dopamine and serotonin during chronic stress. It may have antidepressant effects, but more confirmatory research is needed.

Side effects of Bacopa monnieri

Taking Bacopa monnieri on an empty stomach can cause nausea, cramping, bloating and diarrhea. Since Bacopa monnieri can have anxiolytic (anxiety reducing) effects, it is not advisable to take it in combination with other anxiolytics.

Bibliography

CUCURBITA, D.E.

Pumpkin seeds (Cucurbita maxima) have been used in ethnic and traditional medicine as a remedy for kidney, bladder and prostate disorders. Pumpkin seed oil has several phenolic compounds such as vanillic acid, vanillin, luteolin and sinapic acid . Pumpkin seed consumption reduces markers of inflammation, increases lymphocyte count, improves phagocytic activity, and inhibits the progression of fatty liver disease into steatohepatitis.

Recent studies have shown how oral intake of Cucurbita extract reduces patients’ bladder hyperactivity, preventing urinary disorders and producing an effect on urinary health; it also reduces the risk of bladder and kidney stones.

The lipid extract of Cucurbita maxima seeds slows the progress of hypertension and decreases hypercholesterolemia due to the content of unsaturated fatty acids and phytosterols. Furthermore, Cucurbita seed extracts show hypoglycaemic activity, contributing to the prevention of diabetes mellitus.

Bibliography

  • Effects of dietary milled seed mixture on fatty acid status and inflammatory markers in patients on Hemodialysis Sci. World J, 2014
  • Edible Seeds from Cucurbitaceae Family as Potential Functional Foods: Immense Promises, Few Concerns – Biomed Pharmacother, 2017
  • A Review on Pharmacological Activities and Utilization Technologies of Pumpkin – Plant Foods Hum Nutr, 2006
  • Nutrientes e propriedades funcionais em sementes de abóbora (Cucurbita maxima) submetidas a diferentes processamentos. Ciênc Tecnol Aliment 2010; (30): 185-190.

EPILOBIUM

Epilobium angustifolium L. is a well-known medicinal plant traditionally used in the treatment of urogenital diseases, stomach and liver disorders, skin problems, etc. E. angustifolium extracts exhibit antiproliferative, cytotoxic, antioxidant, anti-inflammatory, immunomodulatory and antimicrobial activities. The unique combination of biological properties demonstrated by the results of some studies indicates that its extracts exert a positive effect in benign prostatic hyperplasia (BPH) and potentially in the prevention of prostate cancer.

The efficacy of phytotherapy with E. angustifolium is still poorly tested in clinical trials, while numerous beneficial effects of the extracts on prostate function have been documented in in vitro and in vivo tests.

Bibliografia

    • Products as Sources of New Drugsfrom 1981 to 2014. J Nat Prod 2016; 79(3): 629-661.2. 
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    • Analgesic properties of Epilobium angustifolium, evaluated by the hot platetest and the writhing test. Farmaco 2001; 56(5-7): 341-343.
    • Anti-inflammatory effects ofa substance extracted from Epilobium angustifolium. AgentsActions 1988; 23(1-2): 106-107.
    • Isolation of the antiphlogistic principle from Epilobium angustifolium. PlantaMed 1991;57(4): 357-360.
    • Anti-proliferative effect on a prostatic epithelial cell line (PZ-HPV-7) byEpilobium angustifolium L. Farmaco 2001; 56 (5-7): 483–489.
    • Extracts of various speciesof Epilobium inhibit proliferation of human prostate cells. J PharmPharmacol 2003; 55(5): 683–690.
    • Extracts from Epilobium sp.herbs induce apoptosis in human hormone-dependent prostatecancer cells by activating the mitochondrial pathway. J PharmPharmacol 2013; 65(7): 1044-1054.
    • Effects of catechin on the phenolic content and antioxidant properties oflow-fat cheese. Int J Food Sci Tech 2013; 48: 2448-2455.
    • Evaluation of theantioxidant properties and oxidative stability of Pecorino cheesemade from the raw milk of ewes fed Rosmarinus officinalis L.leaves. Int J Food Sci Tech 2015; 50: 558-565.
    • Assays for hydrophilic andlipophilic antioxidant capacity (oxygen radical absorbancecapacity (ORACFL) of plasma and other biological and foodsamples. J Agr Food Chem 2003; 51(11): 3273-3279.
    • Antioxidant capacity of cow milk, whey and deproteinized milk.Int Dairy J 2009; 19: 380–385.
  • In Vitro Protective Effectsof Lycium barbarum Berries Cultivated in Umbria (Italy) onHuman Hepatocellular Carcinoma Cells. Biomed Res Int. 2016;2016:7529521.

Milk thistle

The use of Silybum marianum for therapeutic purposes of this plant has been known since ancient times. Silymarin is extracted from the pericarp of milk thistle fruits, a mixture of flavonolignans known for their purifying and protective properties on the liver.

Milk thistle is traditionally used in acute or chronic liver disease. Research indicates that this extract is able to perform a regenerative action on the liver cell and counteract the effects of hepatotoxic agents. Furthermore, it is an effective antioxidant.

Bibliography

Efficacy of lifestyle changes in subjects with non-alcoholic liver steatosis and metabolic syndrome may be improved with an antioxidant nutraceutical: a controlled clinical study. Drugs R. D. 2015 Mar;15(1):21-5.
Hepatoprotective herbal drug, silymarin from experimental pharmacology to clinical medicine. Indian J Med Res. 2006 Nov;124(5):491-504.

Silymarin as Supportive Treatment in Liver Diseases: A Narrative Review Adv Ther. 2020; 37(4): 1279–1301.

Dandelion

Taraxacum officinale, also known as dandelion, is a vegetable that has limited traditional use in East Asian countries. It is used worldwide for its diuretic effect.

Animal studies and in vitro tests indicate that dandelion extract exerts beneficial effects on human health, although more research is needed to attribute these effects to the individual active ingredients

Research in rodents suggests that dandelion may facilitate digestion by increasing the transit of food between the stomach and small intestine. Dandelion root extract may also exert a protective effect on the pancreas and exhibit antiallergenic properties.

Recent studies indicate efficacy of dandelion extracts in conferring protective effects in the liver in mouse models of ethyl alcohol, CCl4 and acetominophen hepatotoxicity secondary to its antioxidant properties, since these toxic substances exert hepatotoxicity by oxidative mechanisms. Feeding dandelion extract to mice with a high-fat diet attenuates fatty liver production and liver inflammation, and subsequent insulin resistance, through modulation of AMP-dependent protein kinase (AMPK) in liver tissue.

According to other studies, oral ingestion of dandelion appears to confer some protective effects on the liver of rodents; the mechanism seems to be due to the antioxidant properties of the dandelion extract.

Bibliography

Mahesh A1, et al. Hepatocurative potential of sesquiterpene lactones of Taraxacum officinale on carbon tetrachloride induced liver toxicity in mice. Acta Biol Hung. (2010)
Davaatseren M1, et al. Taraxacum official (dandelion) leaf extract relieves high-fat diet-induced nonalcoholic fatty liver. Food Chem Toxicol. (2013)
Colle D1, et al. Antioxidant properties of Taraxacum officinale leaf extract are involved in the protective effect against hepatoxicity induced by acetaminophen in mice. J Med Food. (2012)
González-Castejón M1, et al. Reduction of adipogenesis and lipid accumulation by Taraxacum officinale (Dandelion) extracts in 3T3L1 adipocytes: an in vitro study. Phytother Res. (2014)

Curcumin

Curcumin – a yellow pigment found mainly in turmeric (Curcuma longa, Turmerinc English, a flowering plant of the ginger family better known as a spice used in curry) quantity of antioxidants produced by the body.

Curcumin and curcuminoids present in turmeric can be extracted to produce supplements with higher potency than turmeric. However, curcumin is poorly absorbed during digestion, so different formulations have been created to improve its bioavailability.

Main benefits of curcumin

Curcumin supplementation reliably reduces inflammation markers and increases the levels of endogenous antioxidants in the body. Available research supports small to moderate improvements in symptoms of depression and anxiety and in pain and function in osteoarthritis. Research also indicates its effectiveness in reducing LDL cholesterol, blood sugar and blood pressure as well.

Main disadvantages of curcumin

One of the major disadvantages of curcumin is that it is poorly absorbed when orally ingested on its own. As for potential adverse effects, doses of up to 8 grams of curcuminoids have not been associated with serious adverse effects in humans. However, longer-term studies that are more comprehensive in their assessments are needed. Studies using high doses of curcumin have reported some mild adverse effects, including nausea, diarrhea, headache, skin rashes.

How does curcumin work?

The potential beneficial effects of curcumin appear to be primarily a result of its anti-inflammatory and antioxidant properties. These properties are mediated by the direct or indirect interaction of curcumin with various molecular targets, including transcription factors, enzymes, cell cycle proteins, receptors, cell surface adhesion molecule, growth factors, and protein kinases.