ENDOGENOUS MOLECULES
Endogenous Molecules are responsible for bio-regeneration and inhibition of fibrotic processes. According to the PNEI Clinic of Prof. Paolo Lissoni, “there are essentially three main sources of molecules capable of interrupting the aging process”:
- The Pineal Gland through Melatonin, its most well-known hormone.
- The Endocannabinoid System stimulated by PEA – Palmitoylethanolamide.
- The ACE-ACE2-Angiotensin 1-7 axis through the exogenous intake of Angiotensin 1-7 or alternatively Resveratrol which binds to its own receptor and increases its levels.
The reduction of the endogenous production of these molecules by the body can create deficits that contribute to the imbalance and neuro-immuno-chemical alterations typical of the aging process. Integrating these molecules can increase their concentration and bring it back to that of youth, thus benefiting from their rebalancing and regenerating action.
Endogenous molecules can be added to phytocomplexes and phytosynergics rich in vitamins, minerals and botanical extracts, all functional, effective and fundamental substances to counteract the alterations and deficits related to advancing age and regain physiological well-being.
Bibliographic reference:
An active and brilliant old age with PNEI. Natural approach to anti-aging. Nicoletta Merli, Paolo Lissoni, Walter Ardigò. Verdechiaro Edizioni
Melatonin
Melatonin is a hormone produced by the Pineal Gland and its main activity is to regulate the sleep-wake rhythm. According to scientific studies PNEI this hormone also performs other important functions and it is reductive to think only of its function on sleep.
Various studies have shown that Melatonin influences various biological processes. The presence of Melatonin receptors on certain tissues, such as lymph nodes, thymus and spleen, indicates that it is involved in various immunological processes.
It is considered the molecule capable of resynchronizing the human body and regulating the circadian rhythm and all the functions of the body that are related to the alternation of day and night.
In addition to regulating the sleep-wake cycle, Melatonin works as a real biological clock for the body, influencing various physiological processes. For example, the presence of Melatonin receptors in various tissues, such as lymph nodes, thymus and spleen, indicates its role also in immunological processes.
The numerous studies carried out in recent decades have demonstrated the importance of this molecule in the regulation of numerous physiological processes and its relationship with the Nervous System, the Immune System and the Endocrine System.
It is able to modulate the alternation between sleep and wakefulness, the mechanism of hunger and thirst, the production of urine, to regulate body temperature, basal metabolism and the release of hormones and even has a role in the emotional circuit.
The reduction in the production of Melatonin occurs already from the age of 25, a period in which the aging process begins, albeit slowly. It is a molecule produced naturally by our body and its integration has been widely studied even at high doses (10 mg per day) which have always shown a good tolerability profile. The numerous studies carried out on Melatonin have demonstrated the beneficial effects of the use of this substance in numerous pathologies and disorders other than sleep. In integrated medicine according to PNEI, the intake of food supplements with this molecule is recommended to maintain the concentration of the substance in the body at youthful levels, preserving the regularity of our daily biological rhythms and therefore counteracting aging and the pathological consequences that derive from alterations of circadian rhythms.
Melatonin is a powerful antioxidant capable of directly eliminating reactive oxygen and nitrogen species (free radicals) and enhancing the activity of antioxidant enzymes in our body.
Its reduction significantly affects the aging process, which is closely linked to the desynchronization of circadian hormonal cycles (day-night).
Melatonin delays aging by delaying the progressive deterioration (loss of sensitivity and therefore of bidirectional response) of the central control of hypothalamic-pituitary hormonal regulation, as demonstrated by the studies of the great Russian scientist Vladimir M. Dilman.
Melatonin can slow down aging because it also mitigates degenerative diseases typical of aging and that accelerate the process, such as hypertension, degeneration of vessels and arteries (arteriosclerosis), autoimmune diseases and prevents cancer.
Several studies, both in vivo and in vitro, have shown that Melatonin exerts various antineoplastic effects through multiple mechanisms, including the reduction of tumor cell proliferation and the inhibition of metastases. According to one study, Melatonin seems to sensitize tumor cells to the ionizing effects of radiation, improving the effectiveness of therapy. Studies have also shown the ability to reduce the side effects of chemotherapy and to enhance their effect, in particular of Cisplatin, Doxorubicin, Gefitinib and Tamoxifen. The main tumor types on which the antitumor effects of Melatonin have been observed are: breast, prostate, ovary, liver, kidney, lung, stomach, pancreas and colorectal cancer.
The protective capacity of Melatonin against damage related to hypertension and obesity suggests that dietary supplementation with exogenous Melatonin in later years may be an effective therapeutic intervention for these age-related conditions.
Pea (Palmitoiletanolamide)
PEA is a physiological substance normally produced by many cells in our body. In particular, it is found in very high concentrations in brain tissue and is synthesized from the lipid components of cell membranes.
It is normally present in many of the foods we eat every day such as eggs, peas, tomatoes and soy. As an active ingredient it was identified in 1957 by Nobel Prize winner Rita Levi Montalcini who interpreted its mechanism of action in 1993. At the body level, PEA works as a biological modulator of chronic pain of various types linked to the activation of inflammatory and painful processes.
In particular, PEA limits the release of pro-inflammatory and pain mediators by blocking mast cells and the activation of cells at the spinal cord level: this makes it extremely effective in containing pain associated with an inflammatory state.
Since PEA is an endogenous modulator, i.e. a substance normally produced by our body, no side effects or interactions with other drugs have been reported, making it an effective remedy for the treatment of numerous pathologies with chronic pain that, as a rule, responds poorly to standard pharmacological therapies. The exogenous administration of PEA therefore allows to reintegrate the correct physiological reserves of this substance that can be altered or reduced by particular situations in the organism.
This molecule demonstrates numerous beneficial activities for the organism including:
• a modulating action on inflammatory processes that contributes to the control of unwanted inflammatory responses, thus promoting homeostasis;
• an effective analgesic action in conditions of chronic and neuropathic pain;
• antimicrobial properties that contribute to the response of the immune system against pathogens, including viral or drug-resistant agents;
• modulating the immune response helping to maintain balance in the immune system and reducing chronic inflammation.
The ability of PEA to protect nerve cells from damage and stress is particularly useful in preventing neurodegeneration. In chronic pathological situations, exogenous integration with PEA has proven beneficial for addressing imbalances and maintaining homeostasis.
Angiotension 1-7
is a peptide, produced in various organs through the ACE2 enzyme, which acts on the Mas receptor through which it carries out its protective action on the heart and blood vessels and normalizes blood pressure through a vasodilation mechanism.
The countless studies published in recent decades demonstrate the additional beneficial activities of the molecule including anti-inflammatory, anti-fibrotic, antiproliferative and anti-tumor protective and important capabilities in reducing metabolic syndrome. This endogenous molecule, working on blood vessels, the most important organ, can help protect the entire organism from physiopathological processes.
There are molecules, present in the products of the Niki Natural Alchemy line, that are able to interact with the ACE2-Angiotensin 1-7 axis and its Mas receptor, shifting the balance in favor of the action of Angiotensin 1-7, thus favoring its beneficial actions on the organism.
RESVERATROL: A NATURAL ALLY
OF ANGIOTENSIN 1-7
Resveratrol, a natural substance found mainly in the skin of grapes, blueberries, raspberries and mulberries, is able to lower blood levels of Angiotensin II and increase those of Angiotensin 1-7 because it has the ability to activate the same receptor as Angiotensin 1-7, the MAS.
More specifically, its action is expressed through the suppression of the ANG II/AT1R axis and the strengthening of the Ang (1-7)/Mas axis. This evidence has been demonstrated in numerous studies published in the most accredited international scientific journals.
In particular, the study “Resveratrol Confers Protection Against Ischemia/Reperfusion Injury by Increase of Angiotensin (1-7) Expression in a Rat Model of Myocardial Hypertrophy” published in the international scientific journal Journal of Cardiovascular Pharmacology highlighted the ability of Resveratrol to increase the expression of Ang 1-7 thus exerting its cardioprotective action.
Another study has shown that, following the intake of Resveratrol, plasma levels of Angiotensin 1-7 increase and this is also expressed through a protective effect at the renal level and an improvement in its functionality.
Among the numerous published studies we recall “The protective effect of resveratrol on vascular aging by modulation of the renin–angiotensin system” which demonstrated the important action of Resveratrol in protecting against arterial aging and this effect is associated, in particular, with the stimulation of the ACE2-Ang-(1-7)-ATR2-Mas axis.
THE BIOCHEMISTRY OF LIFE AND DEATH WITH THE THREE MAJOR REGENERATIVE SYSTEMS
(PINEAL, CARDIAC ANP AND ACE 2 – ANG 1-7 AXIS)
Discover the products
-
Pea
31,90 €
NOTE: Supplements are not intended as a substitute for a varied and balanced diet and a healthy lifestyle. Do not exceed the recommended daily doses. The information in the product sheets should not be interpreted as medical advice and is not intended to and cannot replace medical prescriptions. The information provided is for informational and educational purposes only and concerns the ingredients contained in food supplements. Supplements are not intended as a means of treating, preventing, diagnosing or alleviating pathologies.
Angiotensina 1-7
Robson Augusto Souza Santos, “Angiotensin-(1-7) A Comprehensive Review”. Springer, 2019 – Link
Lelis DF, Freitas DF, Machado AS, Crespo TS, Santos SHS. Angiotensin-(1-7), Adipokines and Inflammation. Metabolism. 2019 Jun;95:36-45. doi: 10.1016/j.metabol.2019.03.006. Epub 2019 Mar 21. PMID: 30905634 – Link
Medina D, Arnold AC. Angiotensin-(1-7): Translational Avenues in Cardiovascular Control. Am J Hypertens. 2019 Nov 15;32(12):1133-1142. doi: 10.1093/ajh/hpz146. PMID: 31602467; PMCID: PMC6856625 – Link
Luna P, Fernanda Pérez M, Castellar-Lopez J, Chang A, Montoya Y, Bustamante J, Rosales-Rada W, Mendoza-Torres E. Potential of Angiotensin-(1-7) in COVID-19 Treatment. Curr Protein Pept Sci. 2023;24(1):89-97. doi: 10.2174/1389203724666221130140416. PMID: 36453502 – Link
de Souza-Neto FP, Carvalho Santuchi M, de Morais E Silva M, Campagnole-Santos MJ, da Silva RF. Angiotensin-(1-7) and Alamandine on Experimental Models of Hypertension and Atherosclerosis. Curr Hypertens Rep. 2018 Mar 14;20(2):17. doi: 10.1007/s11906-018-0798-6. PMID: 29541937 – Link
de Paula Gonzaga ALAC, Palmeira VA, Ribeiro TFS, Costa LB, de Sá Rodrigues KE, Simões-E-Silva AC. ACE2/Angiotensin-(1-7)/Mas Receptor Axis in Human Cancer: Potential Role for Pediatric Tumors. Curr Drug Targets. 2020;21(9):892-901. doi: 10.2174/1389450121666200210124217. PMID: 32039680 – Link
Derkachev IA, Popov SV, Maslov LN, Mukhomedzyanov AV, Naryzhnaya NV, Gorbunov AS, Kan A, Krylatov AV, Podoksenov YK, Stepanov IV, Gusakova SV, Fu F, Pei JM. Angiotensin 1-7 increases cardiac tolerance to ischemia/reperfusion and mitigates adverse remodeling of the heart-The signaling mechanism. Fundam Clin Pharmacol. 2024 Jun;38(3):489-501. doi: 10.1111/fcp.12983. Epub 2024 Feb 4. PMID: 38311344 – Link
Liu J, Li X, Wang X, Peng L, Song G, He J. Angiotensin(1-7) Improves Islet Function in Diabetes Through Reducing JNK/Caspase-3 Signaling. Horm Metab Res. 2022 Apr;54(4):250-258. doi: 10.1055/a-1796-9286. Epub 2022 Apr 12. PMID: 35413746 – Link
João Marcus Oliveira Andrade , Alanna Fernandes Paraíso , Zélia Menezes Garcia , Adaliene Versiani Matos Ferreira , Ruben D M Sinisterra , Frederico B Sousa , André Luiz Sena Guimarães , Alfredo Maurício Batista de Paula , Maria José Campagnole-Santos , Robson Augusto dos Santos , Sérgio Henrique Sousa Santos “Cross talk between angiotensin-(1-7)/Mas axis and sirtuins in adipose tissue and metabolism of high-fat feed mice” PubMed 2014 – Link
In-Ae Jang , Eun Nim Kim , Ji Hee Lim, Min Young Kim , Tae Hyun Ban , Hye Eun Yoon , Cheol Whee Park , Yoon Sik Chang , Bum Soon Choi “Effects of Resveratrol on the Renin-Angiotensin System in the Aging Kidney” PubMed 2019 – Link
Tiao MM, Lin YJ, Yu HR, et al. Resveratrol ameliorates maternal and post-weaning high-fat diet-induced nonalcoholic fatty liver disease via renin-angiotensin system. Lipids Health Dis. 2018 doi: 10.1186/s12944-018-0824-3 – Link
Kim, Eun Nim, et al. “The protective effect of resveratrol on vascular aging by modulation of the renin–angiotensin system.” Atherosclerosis 270 (2018): 123-131 – Link
Fahimeh Soltan , Mansour Esmaili Dahej , Maryam Yadegari , Ali Moradi , Zeinab Hafizi Barjin , Fatemeh Safari “Resveratrol Confers Protection Against Ischemia/Reperfusion Injury by Increase of Angiotensin (1-7) Expression in a Rat Model of Myocardial Hypertrophy” PubMed 2021 – Link
Maria Esther Rubio-Ruiz, Verónica Guarner-Lans , Agustina Cano-Martínez , Eulises Díaz-Díaz, Linaloe Manzano-Pech, Anel Gamas-Magaña, Vicente Castrejón-Tellez, Concepción Tapia-Cortina and Israel Pérez-Torres 3, “Resveratrol and Quercetin Administration Improves Antioxidant DEFENSES and reduces Fatty Liver in Metabolic Syndrome Rats” PubMed 2019 – Link
Models You-Lin Tain and Chien-Ning Hsu “Novel Insights on Dietary Polyphenols for Prevention in Early-Life Origins of Hypertension: A Review Focusing on Preclinical Animal” PubMed 2022 – Link
Melatonina
Pandi-Perumal SR, Srinivasan V, Maestroni GJ, Cardinali DP, Poeggeler B, Hardeland R. Melatonin: Nature’s most versatile biological signal? FEBS J. 2006 Jul;273(13):2813-38. doi: 10.1111/j.1742-4658.2006.05322.x. PMID: 16817850 – Link
Mahmood D. Pleiotropic Effects of Melatonin. Drug Res (Stuttg). 2019 Feb;69(2):65-74. doi: 10.1055/a-0656-6643. Epub 2018 Jul 30. PMID: 30060265 – Link
Chitimus 1, Mihaela Roxana Popescu 2, Suzana Elena Voiculescu 1, Anca Maria Panaitescu 3, Bogdan Pavel 1, Leon Zagrean 1, Ana-Maria Zagrean 1 “Melatonin’s Impact on Antioxidative and Anti-Inflammatory Reprogramming in Homeostasis and Diseas” PubMed 2020 – Link
Rivkees SA. Developing circadian rhythmicity. Basic and clinical aspects. Pediatr Clin North Am. 1997 Apr;44(2):467-87. doi: 10.1016/s0031-3955(05)70486-7. PMID: 9130930 – Link
Karasek M, Winczyk K. Melatonin in humans. J Physiol Pharmacol. 2006 Nov;57 Suppl 5:19-39. PMID: 17218758 – Link
Tan DX, Xu B, Zhou X, Reiter RJ. Pineal Calcification, Melatonin Production, Aging, Associated Health Consequences and Rejuvenation of the Pineal Gland. Molecules. 2018; 23(2):301 – Link
https://doi.org/10.3390/molecules23020301 – Link
Polevshchikov AV, Nazarov PG. [Immunity, aging and works of V.M.Dilman.]. Adv Gerontol. 2020;33(5):838-853. Russian. PMID: 33550738 – Link
Meng X, Li Y, Li S, Zhou Y, Gan RY, Xu DP, Li HB. Dietary Sources and Bioactivities of Melatonin. Nutrients. 2017 Apr 7;9(4):367. doi: 10.3390/nu9040367. PMID: 28387721; PMCID: PMC5409706 – Link
Minich DM, Henning M, Darley C, Fahoum M, Schuler CB, Frame J. Is Melatonin the “Next Vitamin D”?: A Review of Emerging Science, Clinical Uses, Safety, and Dietary Supplements. Nutrients. 2022 Sep 22;14(19):3934. doi: 10.3390/nu14193934. PMID: 36235587; PMCID: PMC9571539 – Link
Oncotarget. 2017 Jun 13. Melatonin for the prevention and treatment of cancer. Ya Li, Sha Li, Yue Zhou, Xiao Meng, Jiao-Jiao Zhang, Dong-Ping Xu, Hua-Bin Li – Link
J Pineal Res. 2015 Mar. Melatonin sensitizes human breast cancer cells to ionizing radiation by downregulating proteins involved in double-strand DNA break repair. Alonso-Gonzalez C, Gonzalez A, Martinez-Campa C, Gomez-Arozamena J, Cos S – Link
Oxid Med Cell Longev. 2020. Utilizing Melatonin to Alleviate Side Effects of Chemotherapy: A Potentially Good Partner for Treating Cancer with Ageing. Zhiqiang Ma, Liqun Xu, Dong Liu, Xiaoyan Zhang, Shouyin Di, Weimiao Li, Jiao Zhang, Russel J. Reiter, Jing Han, Xiaofei Li, Xiaolong Yan – Link
Cell Prolif. 2015 Feb. Melatonin potentiates cisplatin-induced apoptosis and cell cycle arrest in human lung adenocarcinoma cells. P. Plaimee, N. Weerapreeyakul, S. Barusrux, N. P. Johns – Link
J Membr Biol. 2016 Apr. Synergic Effects of Doxorubicin and Melatonin on Apoptosis and Mitochondrial Oxidative Stress in MCF-7 Breast Cancer Cells: Involvement of TRPV1 Channels. Koşar PA, Nazıroğlu M, Övey İS, Çiğ B – Link
Cell Physiol Biochem. 2014. Melatonin sensitizes H1975 non-small-cell lung cancer cells harboring a T790M-targeted epidermal growth factor receptor mutation to the tyrosine kinase inhibitor gefitinib. Yun M, Kim EO, Lee D, Kim JH, Kim J, Lee H, Lee J, Kim SH – Link
Mol Pharmacol. 2019 Aug. Pharmacological, Mechanistic, and Pharmacokinetic Assessment of Novel Melatonin-Tamoxifen Drug Conjugates as Breast Cancer Drugs. Mahmud Hasan, Mohamed Akmal Marzouk, Saugat Adhikari, Thomas D. Wright, Benton P. Miller, Margarite D. Matossian, Steven Elliott, Maryl Wright, Madlin Alzoubi, Bridgette M. Collins-Burow, Matthew E. Burow, Ulrike Holzgrabe, Darius P. Zlotos, Robert E. Stratford, Paula A. Witt-Enderby – Link
Sangiliyandi Gurunathan 1, Muhammad Qasim 2, Min-Hee Kang 1, Jin-Hoi Kim 1 !Role and Therapeutic Potential of Melatonin in Various Type of Cancers! PubMed 2021 – Link
PEA (Palmitoiletanolamide)
Skaper S.D., Buriani A., Dal Toso R., Petrelli L., Romanello S., Facci L., Leon A. 1996 – Link
The ALIAmide palmitoylethanolamide and cannabinoids, but not anandamide, are protective in a delayed postglutamate paradigm of excitotoxic death in cerebellar granule neurons – Link
Proc Natl Acad Sci U S A. 30;93(9):3984-9. Luongo L, Starowicz K, Maione S, Di Marzo V. Allodynia Lowering Induced by Cannabinoids and Endocannabinoids (ALICE). Pharmacol Res. 2017;119:272-277 – Link
Levi-Montalcini R1, Skaper SD, Dal Toso R, Petrelli L, Leon A. Nerve growth factor: from neurotrophin to neurokine. Trends Neurosci. 1996;19(11):514-20 – Link
Paul Clayton, Mariko Hill, Nathasha Bogoda, Silma Subah, and Ruchitha Venkatesh. Palmitoylethanolamide: A Natural Compound for Health Management. Int J Mol Sci. 2021 May; 22(10): 5305 – Link
Bekir Berker Artukoglu, Chad Beyer, Adi Zuloff-Shani, Ephraim Brener, Michael Howard Bloch. Efficacy of Palmitoylethanolamide for Pain: A Meta-Analysis. Pain Physician. 2017 Jul;20(5):353-362 – Link
Lo Verme J., Fu J., Astarita G., La Rana G., Russo R., Calignano A., Piomelli D. 2005. The nuclear receptor peroxisome proliferator-activated receptor-alpha mediates the antiinflammatory actions of palmitoylethanolamide. Mol Pharmacol. 67(1):15-9. 1 – Link
Skaper S.D., Buriani A., Dal Toso R., Petrelli L., Romanello S., Facci L., Leon A. 1996. The ALIAmide palmitoylethanolamide and cannabinoids, but not anandamide, are protective in a delayed postglutamate paradigm of excitotoxic death in cerebellar granule neurons. Proc Natl Acad Sci U S A. 30;93(9):3984-9 – Link
Paul Clayton 1, Mariko Hill 2, Nathasha Bogoda 2, Silma Subah 2, Ruchitha Venkatesh 3 “Palmitoylethanolamide: A Natural Compound for Health Management” PubMed 2021 – Link