References

medalphabet

Медицинский алфавит

Medical alphabet

2078-56312949-2807

ООО «Альфмед»

10.33667/2078-5631-2025-19-35-45

medalphabet-4515

Research Article

Статьи

Биологический возраст на паузе. Влияние нутрицевтиков на эндотелиальную дисфункцию и процессы старения организма

Biological age on pause. The effect of nutraceuticals on endothelial dysfunction and aging processes

https://orcid.org/0000-0002-4689-3591

Орлова

С. В.

Orlova

S. V.

Орлова Светлана Владимировна, д.м.н., проф., зав. кафедрой диетологии и клинической нутрициологии, главный научный сотрудник

Москва

Orlova Svetlana V., DM Sci (habil.), professor, head of Dept of Dietetics and Clinical Nutritiology, Chief Researcher

Moscow

orlova-sv@rudn.ru

https://orcid.org/0000-0002-3811-9459

Прокопенко

Е. В.

Prokopenko

E. V.

Прокопенко Елена Валерьевна, руководитель отдела развития и сопровождения МИС и сервисов департамента по развитию медицинской деятельности

Москва

Prokopenko Elena V., head of Dept for Development and Maintenance of Medical Information System and Services of the Department for Development of Medical Activities

Moscow

elvprokopenko@gmail.com

https://orcid.org/0000-0003-3220-0333

Никитина

Е. А.

Nikitina

E. A.

Никитина Елена Александровна, к.м.н., доцент кафедры диетологии и клинической нутрициологии, научный сотрудник, эксперт Методического аккредитационно-симуляционного центра

Москва

Nikitina Elena A., PhD Med, associate professor at Dept of Dietetics and Clinical Nutrition, research fellow, Expert of the Methodological Accreditation and Simulation Center

nikitina-ea1@rudn.ru

https://orcid.org/0000-0002-0548-3414

Балашова

Н. В.

Balashova

N. V.

Балашова Наталья Валерьевна, к.б.н., доцент кафедры диетологии и клинической нутрициологии, доцент кафедры клинической лабораторной диагностики факультета усовершенствования врачей

Author ID: 832745

Москва

Balashova Natalya V., PhD Bio, assistant professor at Dept of Clinical Laboratory Diagnostics of the Faculty of Advanced Training of Doctors5, assistant professor at Dept of Dietetics and Clinical Nutritiology

Author ID: 832745

BalashovaN77@mail.ru

ФГАОУ ВО «Российский университет дружбы народов имени Патриса Лумумбы» (РУДН) ; ГБУЗ «Научно-практический центр детской психоневрологии Департамента здравоохранения г. Москвы»РоссияPeoples’ Friendship University of Russia named after Patrice Lumumba ; Scientific and Practical Center for Pediatric Psychoneurology of the Moscow Department of HealthRussian Federation

ООО «ИНВИТРО»РоссияInvitro LLCRussian Federation

ФГАОУ ВО «Российский университет дружбы народов имени Патриса Лумумбы» (РУДН) ; ГБУЗ «Научно-практический центр детской психоневрологии Департамента здравоохранения г. Москвы» ; ФГБУ «Национальный медицинский исследовательский центр терапии и профилактической медицины» Минздрава РоссииРоссияPeoples’ Friendship University of Russia named after Patrice Lumumba ; Scientific and Practical Center for Pediatric Psychoneurology of the Moscow Department of Health ; National Medical Research Center for Therapy and Preventive MedicineRussian Federation

ФГАОУ ВО «Российский университет дружбы народов имени Патриса Лумумбы» (РУДН) ; ГБУЗ МО «Московский областной научно-исследовательский клинический институт имени М.Ф. Владимирского»РоссияPeoples’ Friendship University of Russia named after Patrice Lumumba ; M.F. Vladimirskii Moscow Regional Scientific Research Institute (MONIKI)Russian Federation

2025

30082025

119

«Диетология и нутрициология»

3545

2025

Орлова С.В., Прокопенко Е.В., Никитина Е.А., Балашова Н.В.

Orlova S.V., Prokopenko E.V., Nikitina E.A., Balashova N.V.

Данная работа распространяется под лицензией Creative Commons Attribution 4.0.

This work is licensed under a Creative Commons Attribution 4.0 License.

https://www.med-alphabet.com/jour/article/view/4515

Старение – неизбежный процесс, который включает дисбаланс между антиоксидантной защитой и активными формами кислорода, изменения в обновлении белков и митохондрий, укорочение теломер, клеточное старение, эпигенетические изменения и истощение стволовых клеток. Эти состояния связаны с легким или умеренным воспалением, которое всегда сопровождает процесс старения и возрастные заболевания. Результаты многочисленных исследований указывают на существование сложного биомолекулярного механизма, связанного с возрастной дисфункцией сосудов, которая приводит к окислительному стрессу, ремоделированию сосудов и дисфункции эндотелия.

Aging is an inevitable process that includes an imbalance between antioxidant defenses and reactive oxygen species, changes in protein and mitochondrial turnover, telomere shortening, cellular senescence, epigenetic changes, and stem cell exhaustion. These conditions are associated with mild to moderate inflammation, which always accompanies the aging process and age-related diseases. The results of numerous studies indicate the existence of a complex biomolecular mechanism associated with age-related vascular dysfunction, which leads to oxidative stress, vascular remodeling, and endothelial dysfunction.

эндотелийдисфункцияантиоксидантыполифенолыфлавоноидывитаминыминералыаминокислотырезвератролкуркуминтауринполиненасыщенные омега 3 жирные кислоты

endotheliumdysfunctionantioxidantspolyphenolsflavonoidsvitaminsmineralsamino acidsresveratrolcurcumintaurinepolyunsaturated omega‑3 fatty acids

Публикация выполнена при поддержке Программы стратегического академического лидерства РУДН.

The publication was supported by the RUDN University Strategic Academic Leadership Program.

References1

Matz RL, Schott C, Stoclet JC, Andriantsitohaina R. Age-related endothelial dysfunction with respect to nitric oxide, endothelium-derived hyperpolarizing factor and cyclooxygenase products. Physiol Res. 2000; 49: 11–18.

Li JM, Shah AM. Endothelial cell superoxide generation: regulation and relevance for cardiovascular pathophysiology. Am J Physiol Regul Integr Comp Physiol. 2004, 287: R1014–R1030. DOI: 10.1152/ajpregu.00124.2004

Stocker R, Keaney JF. Role of oxidative modifications in atherosclerosis. Physiol Rev. 2004; 84: 1381–1478. DOI: 10.1152/physrev.00047.2003

Lehoux S. Redox signalling in vascular responses to shear and stretch. Cardiovasc Res. 2006; 71: 269–279.

Csiszar A, Labinskyy N, Orosz Z, Xiangmin Z, Buffenstein R, Ungvari Z. Vascular aging in the longest-living rodent, the naked mole rat. Am J Physiol Heart Circ Physiol. 2007; 293: H919–H927. DOI: 10.1152/ajpheart.01287.2006

Brandes RP, Fleming I, Busse R. Endothelial aging. Cardiovasc Res. 2005; 66: 286–294. DOI: 10.1016/j.cardiores.2004.12.027

Belik J, Jerkic M, McIntyre BA, Pan J, Leen J, Yu LX, Henkelman RM, Toporsian M, Letarte M. Age-dependent endothelial nitric oxide synthase uncoupling in pulmonary arteries of endoglin heterozygous mice. Am J Physiol Lung Cell Mol Physiol. 2009; 297: L1170–L1178. DOI: 10.1152/ajplung.00168.2009

Dikalov S. Cross talk between mitochondria and NADPH oxidases. Free Radic Biol Med. 2011; 51: 1289–1301. DOI: 10.1016/j.freeradbiomed.2011.06.033

Geng L, Cahill-Smith S, Li JM. 190 Nox2 activation and oxidative damage of cerebral vasculature and locomotor function in ageing mice. Heart. 2014; 100 (Suppl 3): A105–A106.

Paneni F, Osto E, Costantino S, Mateescu B, Briand S, Coppolino G, Perna E, Mocharla P, Akhmedov A, Kubant R, Rohrer L, Malinski T, Camici GG, Matter CM, Mechta-Grigoriou F, Volpe M, Lüscher TF, Cosentino F. Deletion of the activated protein‑1 transcription factor JunD induces oxidative stress and accelerates age-related endothelial dysfunction. Circulation. 2013; 127: 1229–1240. DOI: 10.1161/CIRCULATIONAHA.112.000826

Turgeon J, Haddad P, Dussault S, Groleau J, Maingrette F, Perez G, Rivard A. Protection against vascular aging in Nox2-deficient mice: Impact on endothelial progenitor cells and reparative neovascularization. Atherosclerosis. 2012; 223: 122–129. DOI: 10.1016/j.atherosclerosis.2012.05.003

Trott DW, Seawright JW, Luttrell MJ, Woodman CR. NAD(P)H oxidase-derived reactive oxygen species contribute to age-related impairments of endothelium-dependent dilation in rat soleus feed arteries. J Appl Physiol (1985). 2011; 110: 1171–1180. DOI: 10.1152/japplphysiol.01037.2010

Podlutsky A, Ballabh P, Csiszar A. Oxidative stress and endothelial dysfunction in pulmonary arteries of aged rats. Am J Physiol Heart Circ Physiol. 2010; 298: H346–H351. DOI: 10.1152/ajpheart.00972.2009

Simão S, Gomes P, Pinto V, Silva E, Amaral JS, Igreja B, Afonso J, Serrão MP, Pinho MJ, Soaresda-Silva P. Age-related changes in renal expression of oxidant and antioxidant enzymes and oxidative stress markers in male SHR and WKY rats. Exp Gerontol. 2011; 46: 468–474. DOI: 10.1016/j.exger.2011.02.003

Hecker L, Logsdon NJ, Kurundkar D, Kurundkar A, Bernard K, Hock T, Meldrum E, Sanders YY, Thannickal VJ. Reversal of persistent fibrosis in aging by targeting Nox4-Nrf2 redox imbalance. Sci Transl Med. 2014 Apr 9; 6 (231): 231ra47. DOI: 10.1126/scitranslmed.3008182. PMID: 24718857; PMCID: PMC4545252.

Donato A. J., Machin D. R., Lesniewski L. A. Mechanisms of dysfunction in the aging vasculature and role in age-related disease. Circ. Res. 2018; 123 (7): 825–848. DOI: 10.1161/CIRCRESAHA.118.312563

Park S., Lakatta E.G. Role of inflammation in the pathogenesis of arterial stiffness. Yonsei Med. J. 2012; 53 (2): 258–261. DOI: 10.3349/ymj.2012.53.2.258

Panche AN, Diwan AD, Chandra SR. Flavonoids: an overview. J Nutr Sci. 2016 Dec 29; 5: e47. DOI: 10.1017/jns.2016.41. Erratum in: J Nutr Sci. 2025 Jan 29; 14: e11. DOI: 10.1017/jns.2024.73. PMID: 28620474; PMCID: PMC5465813.

Zhuang C, Zhang W, Sheng C, Zhang W, Xing C, Miao Z. (2017) Chalcone: a privileged structure in medicinal chemistry. Chem Rev. 117 (12): 7762–7810.

Hernandez-Segura A, Nehme J, Demaria M. (2018) Hallmarks of cellular senescence. Trends Cell Biol. 28 (6): 436–453.

Barbosa MC, Grosso RA, Fader CM. Hallmarks of Aging: An Autophagic Perspective. Front Endocrinol (Lausanne). 2019 Jan 9; 9: 790. DOI: 10.3389/fendo.2018.00790. PMID: 30687233; PMCID: PMC6333684.

Höhn A, Weber D, Jung T, Ott C, Hugo M, Kochlik B, Kehm R, König J, Grune T, Castro JP. Happily (n)ever after: Aging in the context of oxidative stress, proteostasis loss and cellular senescence. Redox Biol. 2017 Apr; 11: 482–501. DOI: 10.1016/j.redox.2016.12.001. Epub 2016 Dec 7. PMID: 28086196; PMCID: PMC5228102.

Warnakulasuriya S.N., Ziaullah, Rupasinghe H.P. Long chain fatty acid acylated derivatives of quercetin‑3-O-glucoside as antioxidants to prevent lipid oxidation. Biomolecules. 2014; 4: 980–993. DOI: 10.3390/biom4040980

Wu C. M., Lin K. W., Teng C. H., Huang A. M., Chen Y. C., Yen M. H., Wu W. B., Pu Y. S., Lin C.N. Chalcone derivatives inhibit human platelet aggregation and inhibit growth in human bladder cancer cells. Biol. Pharm. Bull. 2014; 37: 1191–1198. DOI: 10.1248/bpb.b14–00099

Ahmad A., Khan R. M., Alkharfy K. M. Effects of selected bioactive natural products on the vascular endothelium. J. Cardiovasc. Pharmacol. 2013; 62: 111–121. DOI: 10.1097/FJC.0b013e3182927e47

Howitz K.T., Bitterman K.J., Cohen H.Y., Lamming, D.W., Lavu S., Wood J.G. et al. (2003). Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature. 425 (6954): 191–196. DOI: 10.1038/nature01960

Bonkowski M.S., Sinclair D.A. (2016). Slowing ageing by design: the rise of NAD+ and sirtuin-activating compounds. Nat. Rev. Mol. Cell Biol. 17 (11): 679–690. DOI: 10.1038/nrm.2016.93

Moiseeva A.M., Zheleznyak N.V., Generalova A.G., Moiseev D.V. Phytoalexin resveratrol: methods of determination, mechanisms of action, prospects for clinical use. Bulletin of Pharmacy. 2012; 1 (55): 63–73. (In Russ.).

Csiszar A, Labinskyy N, Podlutsky A, Kaminski PM, Wolin MS, Zhang C, Mukhopadhyay P, Pacher P, Hu F, De Cabo R, Ballabh P, Ungvari Z. Vasoprotective effects of resveratrol and SIRT1: attenuation of cigarette smoke-induced oxidative stress and proinflammatory phenotypic alterations. Am J Physiol Heart Circ Physiol. 2008; 294: H2721–H2735.

Csiszar A, Labinskyy N, Pinto JT, Ballabh P, Zhang H, Losonczy G, Pearson K, De Cabo R, Pacher P, Zhang C, Ungvari Z. Resveratrol induces mitochondrial biogenesis in endothelial cells. Am J Physiol Heart Circ Physiol. 2009; 297: H13–H20.

Brown K., Theofanous D., Britton R.G., Aburido G., Pepper C., Undru S.S. et al. (2024). Resveratrol for the management of human health: how far have we come? A systematic review of resveratrol clinical trials to highlight gaps and opportunities. Int. J. Mol. Sci. 25 (2): 747. DOI: 10.3390/ijms25020747

Nakmareong S, Kukongviriyapan U, Pakdeechote P, Donpunha W, Kukongviriyapan V, Kongyingyoes B, Sompamit K, Phisalaphong C. Antioxidant and vascular protective effects of curcumin and tetrahydrocurcumin in rats with L-NAME-induced hypertension. Naunyn Schmiedebergs Arch Pharmacol. 2011; 383: 519–29. DOI: 10.1007/s00210–011-0624-z

Coban D, Milenkovic D, Chanet A, Khallou-Laschet J, Sabbe L, Palagani A, Vanden Berghe W, Mazur A, Morand C. Dietary curcumin inhibits atherosclerosis by affecting the expression of genes involved in leukocyte adhesion and transendothelial migration. Mol Nutr Food Res. 2012; 56: 1270–81. DOI: 10.1002/mnfr.201100818

DiSilvestro RA, Joseph E, Zhao S, Bomser J. Diverse effects of a low dose supplement of lipidated curcumin in healthy middle aged people. Nutr J. 2012; 11: 79. DOI: 10.1186/1475‑2891‑11‑79

Panahi Y, Hosseini MS, Khalili N, Naimi E, Majeed M, Sahebkar A. Antioxidant and anti-inflammatory effects of curcuminoid-piperine combination in subjects with metabolic syndrome: A randomized controlled trial and an updated meta-analysis. Clin Nutr. 2015; 34: 1101–08. DOI: 10.1016/j.clnu.2014.12.019

Fleenor BS, Sindler AL, Marvi NK, Howell KL, Zigler ML, Yoshizawa M, Seals DR. Curcumin ameliorates arterial dysfunction and oxidative stress with aging. Exp Gerontol. 2013; 48: 269–76. DOI: 10.1016/j.exger.2012.10.008

J Santos-Parker JR, Strahler TR, Bassett CJ. et al. Curcumin supplementation improves vascular endothelial function in healthy middle-aged and older adults by increasing nitric oxide bioavailability and reducing oxidative stress. Aging (Albany NY). 2017; 9 (1): 187–208. https://doi.org/10.18632/aging.101149

Santos-Parker JR, Strahler TR, Bassett CJ. et al. Curcumin supplementation improves vascular endothelial function in healthy middle-aged and older adults by increasing nitric oxide bioavailability and reducing oxidative stress. Aging (Albany NY). 2017; 9 (1): 187–208. https://doi.org/10.18632/aging.101149

Kocher A., Behnam C., Frank D. The oral bioavailability of curcuminoids in healthy humans is markedly enhanced by micellar solubilisation but not further improved by simultaneous ingestion of sesamin, ferulic acid, naringenin and xanthohumol. J. Funct. Foods. 2015; 14: 183–191.

Yang Y, Li Y, Wang J, Sun K, Tao W, Wang Z. et al. Systematic investigation of Ginkgo biloba leaves for treating cardio-cerebrovascular diseases in an animal model. ACS Chem Biol. 2017; 12: 1363–72. DOI: 10.1021/acschembio.6b00762

Liu H, Wang X, Wang G, Cui P, Wu S, Ai C. et al. The nearly complete genome of Ginkgo biloba illuminates gymnosperm evolution. Nat Plants. 2021; 7: 748–56. DOI: 10.1038/s41477-021-00933-x

Kowalska I, Adach W, Stochmal A, Olas B. A comparison of the effects of apigenin and seven of its derivatives on selected biomarkers of oxidative stress and coagulation in vitro. Food Chem Toxicol. 2020; 136: 111016. DOI: 10.1016/j.fct.2019.111016

Ude C, Schubert-Zsilavecz M, Wurglics M. Ginkgo biloba extracts: a review of the pharmacokinetics of the active ingredients. Clin Pharmacokinet. 2013; 52: 727–49. DOI: 10.1007/s40262‑013‑0074‑5

Kuznetsova S.M., Glazovskaya I.I. Use of Tanakan for Neuropharmacological Rehabilitation of Patients After Stroke: Report Abstract. Proceedings of the Scientific and Practical Symposium «Tanakan». Kiev. 1997. P. 7.

Yuryev D.V., Eller K.I., Arzamastsev A.P. Analysis of Flavonol Glycosides in Ginkgo Biloba-Based Preparations and Dietary Supplements. Pharmacy. 2003; 2: 7. (In Russ.).

Zuzuk B.M., Kutsik R.V., Tomchuk Yu. et al. Ginkgo Biloba (Analytical Review). Pharmacist. 2001; 19: 34; Zuzuk B.M., Kutsik R.V., Tomchuk Yu. et al. Ginkgo biloba (analytical review). Pharmacist. 2001; 21: 25. (In Russ.).

Clayton ZS, Hutton DA, Brunt VE, VanDongen NS, Ziemba BP, Casso AG, et al. Apigenin restores endothelial function by ameliorating oxidative stress, reverses aortic stiffening, and mitigates vascular inflammation with aging. Am J Physiol Heart Circ Physiol. 2021; 321: H185–96. DOI: 10.1152/ajpheart.00118.2021

Soehnlein O, Libby P. Targeting inflammation in atherosclerosis – from experimental insights to the clinic. Nat Rev Drug Discov. 2021; 20: 589–610. DOI: 10.1038/s41573‑021‑00198‑1

Zuzuk B.M., Kutsik R.V., Tomchuk Yu. et al. Ginkgo biloba (analytical review). Pharmacist. 2001; 19: 34.

Onbysh T.E., Makarova L.M., Pogorely V.E. Mechanisms of realization of pharmacological activity of ginkgo biloba extract. Modern science-intensive technologies. 2005; 5: 22–25. URL: https://top-technologies.ru/ru/article/view?id=22912 (date of access: 17.07.2025).

Brinkhaus B, Lindner M, Schuppan D, et al. Chemical, pharmacological, and clinical profile of the East Asian medicinal plant. Centella Asiatica Phytomedicine. 2000; 7 (5): 427–448. DOI:10.1016/S0944–7113(00)80065‑3

James JT, Dubery IA. Pentacyclic triterpenoids from the medicinal herb, Centella asiatica (L.) Urban. Molecules. 2009; 14 (10): 3922–3941. DOI: 10.3390/molecules14103922

Kim WJ, Kim JD, Veriansyah B, Kim J, Oh SG, Tjandrawinata RR. Extraction of Asiaticoside from Centella asiatica: effects of solvents and extraction methods. Biochemistry. 2004; 23: 339–344.

Gupta YK, Kumar MHV, Srivastava AK. Effect of Centella asiatica on pentylenetetrazole-induced kindling, cognition, and oxidative stress in rats. Pharmacol Biochem Behav. 2003; 74 (3): 579–585. DOI: 10.1016/S0091-3057(02)01044‑4

Rao SB, Chetana M, Uma DP. Centella asiatica treatment during postnatal period enhances learning and memory in mice. Physiol Behav. 2005; 86 (4): 449–457. DOI: 10.1016/j.physbeh.2005.07.019

Chen Y, Han T, Rui Y. et al. Effects of total triterpenes of Centella asiatica on the Depression behavior and concentration of amino acid in forced swimming mice. Zhong Yao Cai. 2003; 26 (12): 870–873.

Fitrawan LO, Ariastuti R, Tjandrawinata RR, Nugroho AE, Pramono S. Antidiabetic effect of combination of fractionated-extracts of Andrographis paniculata and Centella asiatica: in vitro study. Asian Pac J of Trop Biomed. 2018; 8 (11): 527. DOI: 10.4103/2221-1691.245957

Abdul Khisam E. E., Rofi M. S., Khalid A. M., Dzhalaluddin A. F., Mokhamad Yusof M. I., Idris M.KH. i dr. Kombinirovannyy ekstrakt Moringi maslichnoy.i tsentella aziatskaya moduliruyet okislitel’nyy stress i stareniyev fibroblastakh dermy cheloveka, indutsirovannykh perekis’yu vodoroda. Turk J. Biol. 2018; 42 (1): 33–44.

Cesarone MR, Laurora G, De Sanctis MT, Incandela L, Grimaldi R, Marelli C. et al. The microcirculatory activity of Centella asiatica in venous insufficiency.A double-blind study. Minerva Cardioangiol. 1994; 42: 299–304.

Belcaro GV, Grimaldi R, Guidi G. Improvement of capillary permeability in patients with venous hypertension after treatment with TTFCA. Angiology. 1990; 41: 533–40. DOI: 10.1177/000331979004100705

De Sanctis MT, Incandela L, Cesarone MR, Grimaldi R, Belcaro G Marelli C. Acute Effects of TTFCA on capillary filtration in severe venous Hypertension. Panminerva Med. 1994; 36: 87–90.

McKay D.L., Blumberg J.B. The role of tea in human health: An update. J. Am. Coll. Nutr. 2002; 21: 1–13. DOI: 10.1080/07315724.2002.10719187

Cabrera C., Giménez R., López M.C. Determination of tea components with antioxidant activity. J. Agric. Food Chem. 2003; 51: 4427–4435. DOI: 10.1021/jf0300801

Graham H.N. Green tea composition, consumption, and polyphenol chemistry. Prev. Med. 1992; 21: 334–350. DOI: 10.1016/0091-7435(92)90041-F

Del Rio D., Stewart A.J., Mullen W., Burns J., Lean M.E., Brighenti F., Crozier A. HPLC–MSn analysis of phenolic compounds and purine alkaloids in green and black tea. J. Agric. Food Chem. 2004; 52: 2807–2815. DOI: 10.1021/jf0354848

Jiang D.J., Jiang J.L., Tan G.S., Huang Z.Z., Deng H.W., Li Y.J. Demethylbellidifolin inhibits adhesion of monocytes to endothelial cells via reduction of tumor necrosis factor alpha and endogenous nitric oxide synthase inhibitor level. Planta Med. 2003; 69: 1150–1152. DOI: 10.1055/s‑2003-818008

Böger R.H., Sydow K., Borlak J., Thum T., Lenzen H., Schubert B., Tsikas D., Bode-Böger S.M. LDL cholesterol upregulates synthesis of asymmetrical dimethylarginine in human endothelial cells: Involvement of S-adenosylmethionine-dependent methyltransferases. Circ. Res. 2000; 87: 99–105. DOI: 10.1161/01.RES.87.2.99

Xuan C., Tian Q. W., Li H., Zhang B. B., He G. W., Lun L. M. Levels of asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase inhibitor, and risk of coronary artery disease: A meta-analysis based on 4713 participants. Eur. J. Prev. Cardiol. 2015. DOI: 10.1177/2047487315586094

Tang W.J., Hu C.P., Chen M.F., Deng P.Y., Li Y.J. Epigallocatechin gallate preserves endothelial function by reducing the endogenous nitric oxide synthase inhibitor level. Can. J. Physiol. Pharmacol. 2006; 84: 163–171. DOI: 10.1139/y05-156

Wang X., Ouyang Y. Y., Liu J., Zhao G. Flavonoid intake and risk of CVD: A systematic review and meta-analysis of prospective cohort studies. Br.J. Nutr. 2014; 111: 1–11. DOI: 10.1017/S000711451300278X

Enseleit F, Sudano I, Periat D, Winnik S, Wolfrum M, Flammer AJ. et al. Effects of Pycnogenol on endothelial function in patients with stable coronary artery disease: A double-blind, randomized, placebo-controlled, cross-over study. Eur Heart J. 2012; 33: 1589–97. DOI: 10.1093/eurheartj/ehr482

Ryan J, Croft K, Mori T, Wesnes K, Spong J, Downey L. et al. An examination of the effects of the antioxidant Pycnogenol® on cognitive performance, serum lipid profile, endocrinological and oxidative stress biomarkers in an elderly population. J Psychopharmacol. 2008; 22: 553–62. DOI: 10.1177/0269881108091584

Canali R, Comitato R, Schonlau F, Virgili F. The anti-inflammatory pharmacology of Pycnogenol in humans involves COX‑2 and 5-LOX mRNA expression in leukocytes. Int Immunopharmacol. 2009; 9: 1145–9. DOI: 10.1016/j.intimp.2009.06.001

Schäfer A, Chovanova Z, Muchova J, Sumegova K, Liptakova A, Durackova Z. et al. Inhibition of COX‑1 and COX‑2 activity by plasma of human volunteers after ingestion of French maritime pine bark extract (Pycnogenol). Biomed Pharmacother. 2005; 60: 5–9. DOI: 10.1016/j.biopha.2005.08.006

Uhlenhut K, Högger P. Facilitated cellular uptake and suppression of inducible nitric oxide synthase by a metabolite of maritime pine bark extract (Pycnogenol). Free Radic Biol Med. 2012; 53: 305–13. DOI: 10.1016/j.freeradbiomed.2012.04.013

Kurlbaum M, Mülek M, Högger P. Facilitated uptake of a bioactive metabolite of maritime pine bark extract (Pycnogenol) into human erythrocytes. PLoS One. 2013; 8: e63197. DOI: 10.1371/journal.pone.0063197

Marini A, Grether-Beck S, Jaenicke T, Weber M, Burki C, Formann P. et al. Pycnogenol(R) effects on skin elasticity and hydration coincide with increased gene expressions of collagen type I and hyaluronic acid synthase in women. Skin Pharmacol Physiol. 2012; 25: 86–92. DOI: 10.1159/000335261

Grether-Beck S, Marini A, Jaenicke T, Krutmann J. French maritime pine bark extract (Pycnogenol(R)) effects on human skin: Clinical and molecular evidence. Skin Pharmacol Physiol. 2016; 29: 13–7. DOI: 10.1159/000441039

Nattagh-Eshtivani E, Gheflati A, Barghchi H, Rahbarinejad P, Hachem K, Shalaby MN. et al. The role of Pycnogenol in the control of inflammation and oxidative stress in chronic diseases: Molecular aspects. Phytother Res. 2022; 36: 2352–74. DOI: 10.1002/ptr.7454

Trebaticky B, Muchova J, Ziaran S, Bujdak P, Breza J, Durackova Z. Natural polyphenols improve erectile function and lipid profile in patients suffering from erectile dysfunction. Bratisl Med J. 2019; 120: 941–4. DOI: 10.4149/BLL_2019_158

Arcangeli P. Pycnogenol in chronic venous insufficiency. Fitoterapia. 2000; 71: 236–44. DOI: 10.1016/S0367-326X(99)00164–1

Petrassi C, Mastromarino A, Spartera C. Pycnogenol in chronic venous insufficiency. Pyctomedicine. 2000; 7: 383–8. DOI: 10.1016/S0944-7113(00)80059‑8

Weyns A-S, Verlaet AAJ, Breynaert A, Naessens T, Fransen E, Verhelst H. et al. Clinical investigation of French maritime pine bark extract on attention-deficit hyperactivity disorder as compared to methylphenidate and placebo: Part 1: Efficacy in a randomised trial. J Funct Foods. 2022; 97: 105246. DOI: 10.1016/j.jff.2022.105246

Weyns A-S, Verlaet AAJ, Van Herreweghe M, Breynaert A, Fransen E, De Meester I. et al. Clinical investigation of French maritime pine bark extract on attention-deficit hyperactivity disorder as compared to methylphenidate and placebo: Part 2: Oxidative stress and immunological modulation. J Funct Foods. 2022; 97: 105247. DOI: 10.1016/j.jff.2022.105247

Donovan EK, Kekes-Szabo S, Lin JC, Massey RL, Cobb JD, Hodgin KS. et al. A placebo-controlled, pseudo-randomized, crossover trial of botanical agents for gulf war illness: Curcumin (Curcuma longa), Boswellia (Boswellia serrata), and French maritime pine bark (Pinus pinaster). Int J Environ Res Public Health. 2021; 18: 2468. DOI: 10.3390/ijerph18052468

Belcaro G, Cesarone MR, Errichi S, Zulli C, Errichi BM, Vinciguerra G. et al. Treatment of osteoarthritis with Pycnogenol. The SVOS (San Valentino Osteo-arthrosis Study). Evaluation of signs, symptoms, physical performance and vascular aspects. Phytother Res. 2008; 22: 518–23. DOI: 10.1002/ptr.2376

Zhao H, Wu J, Wang N, Grether-Beck S, Krutmann J, Wei L. Oral Pycnogenol(R) intake benefits the skin in urban Chinese outdoor workers: A randomized, placebo-controlled, double-blind, and crossover Intervention study. Skin Pharmacol Physiol. 2021; 56: 1–11. DOI: 10.1159/000514323

Cai C, Zeng B, Lin L, Zheng M, Burki C, Grether-Beck S. et al. An oral French maritime pine bark extract improves hair density in menopausal women: A randomized, placebo-controlled, double blind intervention study. Health Sci Rep. 2023; 6: e1045. DOI: 10.1002/hsr2.1045

Steigerwalt R., Belcaro G., Cesarone M.R., Di Renzo A., Grossi M.G., Ricci A., et al. Pycnogenol improves microcirculation, retinal edema, and visual acuity in early diabetic retinopathy. J Ocul Pharmacol Ther. 2009; 25: 537–40. DOI: 10.1089/jop.2009.0023

Kohama T, Negami M. Effect of low-dose French maritime pine bark extract on climacteric syndrome in 170 perimenopausal women. J Reprod Med. 2013; 58: 39–46.

Wilson D, Evans M, Guthrie N, Sharma P, Baisley J, Schonlau F. et al. A randomized, double-blind, placebo-controlled exploratory study to evaluate the potential of Pycnogenol for improving allergic rhinitis symptoms. Phytother Res. 2010; 24: 1115–9. DOI: 10.1002/ptr.3232

Watanabe K, Hiramine H, Hamada N. Effects of French pine bark extract chewing gum on oral Malodor and salivary bacteria. J Nutr Sci Vitaminol. 2018; 64: 185–91. DOI: 10.3177/jnsv.64.185

Ackerman J, Clifford T, McNaughton LR, Bentley DJ. The effect of an acute antioxidant supplementation compared with placebo on performance and hormonal response during a high volume resistance training session. J Int Soc Sports Nutr. 2014; 11: 10. DOI: 10.1186/1550‑2783‑11‑10

Hosseini S, Lee J, Sepulveda RT, Rohdewald P, Watson RR. A randomized, double-blind, placebo-controlled, prospective, 16 week crossover study to determine the role of Pycnogenol in modifying blood pressure in mildly hypertensive patients. Nutr Res. 2001; 21: 1251–60. DOI: 10.1016/S0271-5317(01)00342‑6

Nishioka K, Hidaka T, Nakamura S, Umemura T, Jitsuiki D, Soga J. et al. Pycnogenol, French maritime pine bark extract, augments endothelium-dependent vasodilation in humans. Hypertens Res. 2007; 30: 775–80. DOI: 10.1291/hypres.30.775

Liu X, Wei J, Tan F, Zhou S, Wurthwein G, Rohdewald P. Pycnogenol, French maritime pine bark extract, improves endothelial function of hypertensive patients. Life Sci. 2004; 74: 855–62. DOI: 10.1016/j.lfs.2003.07.037

Zibadi S, Rohdewald PJ, Park D, Watson RR. Reduction of cardiovascular risk factors in subjects with type 2 diabetes by Pycnogenol supplementation. Nutr Res. 2008; 28: 315–20. DOI: 10.1016/j.nutres.2008.03.003

100

Schäfer A, Högger P. Oligomeric procyanidins of French maritime pine bark extract (Pycnogenol) effectively inhibit alpha-glucosidase. Diabetes Res Clin Pract. 2007; 77: 41–6. DOI: 10.1016/j.diabres.2006.10.011

101

Laidlaw S.A., Shultz T.D., Cecchino J.T., Kopple J.D. Plasma and urine taurine levels in vegans. Am.J. Clin. Nutr. 1988; 47: 660–663.

102

Chang Y.C., Ding S.T., Lee Y.H., Wang Y.C., Huang M.F., Liu I.H. Taurine homeostasis requires de novo synthesis via cysteine sulfinic acid decarboxylase during zebrafish early embryogenesis. Amino Acids 2013; 44: 615–629.

103

Zhang, D.; Fan, J.; Liu, H.; Qiu, G.; Cui, S. Testosterone enhances taurine synthesis by upregulating androgen receptor and cysteine sulfinic acid decarboxylase expressions in male mouse liver. Am.J. Physiol. Gastrointest. Liver Physiol. 2023; 324: G295–G304.

104

Sharma S., Sahoo B.M., Banik B.K. Biological Effects and Mechanisms of Taurine in Various Therapeutics. Curr. Drug Discov. Technol. 2023, online ahead of print.

105

Sbodio J.I., Snyder S.H., Paul B.D. Regulators of the transsulfuration pathway. Br.J. Pharmacol. 2019; 176: 583–593.

106

Park E., Park S.Y., Cho I.S., Kim B.S., Schuller-Levis G. A Novel Cysteine Sulfinic Acid Decarboxylase Knock-Out Mouse: Taurine Distribution in Various Tissues with and without Taurine Supplementation. Adv. Exp. Med. Biol. 2017; 975 Pt 1: 461–474.

107

Guizoni D.M, Vettorazzi J.F, Carneiro E.M., Davel A.P. Modulation of endothelium-derived nitric oxide production and activity by taurine and taurine-conjugated bile acids. Nitric Oxide. 2020; 94: 48–53. (PDF) Functional role of Taurine in aging and cardiovascular health: An updated overview.

108

Gambardella J., Khondkar W., Morelli M.B., Wang X., Santulli G., Trimarco V. Arginine and Endothelial Function. Biomedicines. 2020; 8: 277.

109

Fennessy F.M., Moneley D.S., Wang J.H., Kelly C.J., Bouchier-Hayes D.J. Taurine and vitamin C modify monocyte and endothelial dysfunction in young smokers. Circulation. 2003; 107: 410–415.

110

El Idrissi A., Okeke E., Yan X., Sidime F., Neuwirth L.S. Taurine regulation of blood pressure and vasoactivity. Adv. Exp. Med. Biol. 2013; 775: 407–425.

111

Yildiz O., Ulusoy K.G. Effects of taurine on vascular tone. Amino Acids. 2022; 54: 1527–1540.

112

Sun B., Maruta H., Ma Y., Yamashita H. Taurine Stimulates AMP-Activated Protein Kinase and Modulates the Skeletal Muscle Functions in Rats via the Induction of Intracellular Calcium Influx. Int. J. Mol. Sci. 2023; 24: 4125.

113

Ra S.G., Choi Y., Akazawa N.., Kawanaka K., Ohmori H., Maeda S. Effects of Taurine Supplementation on Vascular EndothelialFunction at Rest and After Resistance Exercise. Adv. Exp. Med. Biol. 2019; 1155: 407–414.

114

Katakawa M., Fukuda N., Tsunemi A., Mori M., Maruyama T., Matsumoto T.., Abe M.., Yamori Y. Taurine and magnesium supplementation enhances the function of endothelial progenitor cells through antioxidation in healthy men and spontaneouslyhypertensive rats. Hypertens. Res. 2016; 39: 848–856.

115

Guizoni D. M., Freitas I. N., Victorio J. A., Possebom I. R., Araujo T. R., Carneiro E. M., Davel A.P. Taurine treatment reversesprotein malnutrition-induced endothelial dysfunction of the pancreatic vasculature: The role of hydrogen sulfide. Metabolism. 2021; 116: 154701.

116

Ferreira Abud G., Giolo De Carvalho F., Batitucci G., Travieso S.G., Bueno Junior C.R., Barbosa Junior F., Marchini J.S., de Freitas E.C. Taurine as a possible antiaging therapy: A controlled clinical trial on taurine antioxidant activity in women ages55 to 70. Nutrition. 2022; 101; 111706.

117

Jong C.J., Azuma J., Schaffer S. Mechanism underlying the antioxidant activity of taurine: Prevention of mitochondrial oxidantproduction. Amino Acids. 2012; 42: 2223–2232.

118

Kang Y.J., Choi M.J. Liver Antioxidant Enzyme Activities Increase After Taurine in Ovariectomized Rats. Adv. Exp. Med. Biol. 2017; 975 Pt 2: 1071–1080.

119

Sun Q., Wang B., Li Y., Sun F., Li P., Xia W., Zhou X., Li Q., Wang X., Chen J. et al. Taurine Supplementation Lowers Blood Pressure and Improves Vascular Function in Prehypertension: Randomized, Double-Blind, Placebo-Controlled Study. Hypertension. 2016; 67: 541–549.

120

Scabora J.E., de Lima M.C., Lopes A., de Lima I.P., Mesquita F.F., Torres D.B., Boer P.A., Gontijo J.A. Impact of taurinesupplementation on blood pressure in gestational protein-restricted offspring: Effect on the medial solitary tract nucleus cellnumbers, angiotensin receptors, and renal sodium handling. J. Renin-Angiotensin-Aldosterone Syst. 2015; 16: 47–58.

121

Abebe W., Mozaffari M.S. Effects of chronic taurine treatment on reactivity of the rat aorta. Amino Acids 2000; 19: 615–623.

122

Sener G., Ozer Sehirli A., Ipci Y., Cetinel S., Cikler E., Gedik N., Alican I. Taurine treatment protects against chronicnicotine-induced oxidative changes. Fundam. Clin. Pharmacol. 2005; 19: 155–164.

123

Fennessy F.M., Moneley D.S., Wang J.H., Kelly C.J., Bouchier-Hayes D.J. Taurine and vitamin C modify monocyte andendothelial dysfunction in young smokers. Circulation. 2003; 107: 410–415.

124

125

Liang W., Yang Q., Wu G., Lin S., Yang J., Feng Y., Hu J. Effects of Taurine and L-Arginine on the Apoptosis of VascularSmooth Muscle Cells in Insulin Resistance Hypertensive Rats. Adv. Exp. Med. Biol. 2017; 975 Pt 2: 813–819.

126

Forzano I., Avvisato R., Varzideh F., Jankauskas S.S., Cioppa A., Mone P., Salemme L., Kansakar U., Tesorio T., Trimarco V. et al. L-Arginine in diabetes: Clinical and preclinical evidence. Cardiovasc. Diabetol. 2023; 22: 89.

127

Trimarco V. Izzo R., Lombardi A., Coppola A., Fiorentino G., Santulli G. Beneficial effects of L-Arginine in patients hospitalizedfor COVID‑19: New insights from a randomized clinical trial. Pharmacol. Res. 2023; 191: 106702.

128

Gambardella J., Fiordelisi A., Spigno L., Boldrini L., Lungonelli G., Di Vaia E., Santulli G., Sorriento D., Cerasuolo F.A., Trimarco V. et al. Effects of Chronic Supplementation of L-Arginine on Physical Fitness in Water Polo Players. Oxid. Med. Cell. Longev. 2021.

129

Vormann J. Magnesium: Nutrition and Homeostasis. AIMS Public Health. 2016; 3 (2): 329–340.

130

Cosaro E, Bonafini S, Montagnana M. et al. Effects of magnesium supplements on blood pressure, endothelial function and metabolic parameters in healthy young men with a family history of metabolic syndrome. Nutr Metab Cardiovasc Dis. 2014; 24 (11): 1213–1220.

131

Shechter M, Sharir M, Labrador MJ, Forrester J, Silver B, Bairey Merz CN. Oral magnesium therapy improves endothelial function in patients with coronary artery disease. Circulation. 2000; 102 (19): 2353–2358.

132

Darooghegi Mofrad M, Djafarian K, Mozaffari H, Shab-Bidar S. Effect of magnesium supplementation on endothelial function: A systematic review and meta-analysis of randomized controlled trials. Atherosclerosis. 2018; 273: 98–105.

133

134

Barbagallo M, Dominguez LJ, Galioto A, Pineo A, Belvedere M. Oral magnesium supplementation improves vascular function in elderly diabetic patients. Magnes Res. 2010; 23 (3): 131–137.

135

Cunha AR, D’El-Rei J, Medeiros F. et al. Oral magnesium supplementation improves endothelial function and attenuates subclinical atherosclerosis in thiazide-treated hypertensive women. J Hypertens. 2017; 35 (1): 89–97.

136

Shen H, Oesterling E, Stromberg A, Toborek M, MacDonald R, Hennig B: Zinc deficiency induces vascular pro-inflammatory parameters associated with NF-kappaB and PPAR signaling. Journal of the American College of Nutrition. 2008; 27 (5): 577–587.

137

138

Shen H, Oesterling E, Stromberg A, Toborek M, MacDonald R, Hennig B. Zinc deficiency induces vascular pro-inflammatory parameters associated with NF-kappaB and PPAR signaling. Journal of the American College of Nutrition. 2008; 27 (5): 577–587.

139

Reiterer G, Toborek M, Hennig B: Peroxisome proliferator activated receptors alpha and gamma require zinc for their antiinflammatory properties in porcine vascular endothelial cells. The Journal of nutrition 2004; 134 (7): 1711–1715.

140

141

Connell P, Young VM, Toborek M, Cohen DA, Barve S, McClain CJ, Hennig B. Zinc attenuates tumor necrosis factor- mediated activation of transcription factors in endothelial cells. Journal of the American College of Nutrition. 1997; 16 (5): 411–417.

142

Hennig B, Meerarani P, Ramadass P, Toborek M, Malecki A, Slim R, McClain CJ. Zinc nutrition and apoptosis of vascular endothelial cells: implications in atherosclerosis. Nutrition (Burbank, Los Angeles County, Calif). 1999; 15 (10): 744–748.

143

Kondo Y, Rusnak JM, Hoyt DG, Settineri CE, Pitt BR, Lazo JS. Enhanced apoptosis in metallothionein null cells. Molecular pharmacology. 1997; 52 (2): 195–201.

144

Zhuang X, Pang X, Zhang W, Wu W, Zhao J, Yang H, Qu W. Effects of zinc and manganese on advanced glycation end products (AGEs) formation and AGEs-mediated endothelial cell dysfunction. Life sciences 2012; 90 (3–4): 131–139.

145

Wei S, Huang J, Li Y, Zhao J, Luo Y, Meng X, Sun H, Zhou X, Zhang M, Zhang W. Novel zinc finger transcription factor ZFP580 promotes differentiation of bone marrow-derived endothelial progenitor cells into endothelial cells via eNOS/NO pathway. Journal of molecular and cellular cardiology. 2015; 87: 17–26.

146

Tinggi, U. Selenium: its role as antioxidant in human health. Environ Health Prev Med. 2008; 13: 102–108. https://doi.org/10.1007/s12199‑007‑0019‑4

147

Tapiero H, Townsend DM, Tew KD. The antioxidant role of selenium and seleno-compounds. Biomed Pharm. 2003; 57: 134–44.

148

DP, Sies H. Role of copper, zinc, selenium, tellurium in the cellular defense against oxidative and nitrosative stress. J Nutr. 2003; 133: 1448S‑51S. Return to ref 8 in article.

149

Valko M, Rhodes CJ, Moncol J, Izakovic M, Mazur M. Free radicals, metals, antioxidants in oxidative stress-induced cancer. Chem Biol Interact. 2006; 160: 1–40.

150

Andersen O., Nielsen J.B. Effect of simultaneous low level dietary supplementation with inorganic selenium in whole-body, blood and organ levels of toxic metals in mice. Environ. Health Perspect. 1994; 102: 321–324. DOI: 10.1289/ehp.94102s3321

151

Guseinov T.M., Yakhyaeva F.R. Selenium and aging, the role of selenium in gerontological processes // Biomedicine. 2015; 4: 3–7.

152

Bjorklund G., Shanaida M., Lysiuk R. et al. Selenium: An Antioxidant with a Critical Role in AntiAging. Molecules. 2022; 27 (19): 6613–6623. DOI: 10.3390/molecules27196613

153

Fairweather-Tait S.J., Bao Y., Broadley M.R. et al. Selenium in human health and disease. Antioxid Redox Signal. 2011; 14 (7): 1337–1383. DOI: 10.1089/ars.2010.3275

154

Hori E., Yoshida S., Fuchigami T. et al. Cardiac myoglobin participates in the metabolic pathway of selenium in rats. Metallomics. 2018; 10 (4): 614–622. DOI: 10.1039/c8mt00011e

155

Leiter O., Zhuo Z., Rust R. et al. Selenium mediates exercise-induced adult neurogenesis and reverses learning deficits induced by hippocampal injury and aging. Cell Metab. 2022; 34 (3): 408–423. DOI: 10.1016/j.cmet.2022.01.005

156

Maeda N, Hagihara H, Nakata Y, Hiller S, Wilder J, Reddick R. Aortic wall damage in mice unable to synthesize ascorbic acid. Proc Natl Acad Sci USA. 2000; 97: 841–846.

157

Armour J, Tyml K, Lidington D, Wilson JX. Ascorbate prevents microvascular dysfunction in the skeletal muscle of the septic rat. J Appl Physiol (1985). 2001; 90: 795–803.

158

Lebedeva O.V., Cherkasov N.S., Chechukhin V.M. Clinical significance of reamberin use in prevention of cerebral and cardiovascular complications in newborns with very low and extremely low body weight. Rossiyskiy Vestn. Perinatol. i Pediatrii. 2010; 2: 19–29.

159

Buvaltsev V.I. Endothelial dysfunction as a new concept of prevention and treatment of cardiovascular diseases. Int. Med. J. 2001; 3: 202–209.

160

Rodriguez J.A., Grau A., Eguinoa E. et al. Dietary supplementation withvitamins C and E prevents downregulation of endothelial NOS expressionin hypercholesterolemia in vivo and in vitro. Atherosclerosis. 2002; 165 (1): 33–40.

161

Huang A., Vita J.A., Venema R.C., Keaney J.F. Jr. Ascorbic acid enhances endothelial nitric-oxide synthase activity by increasing intracellular tetrahydrobiopterin. J Biol Chem. 2000; 275 (23): 17399–406. https://doi.org/10.1074/jbc.M002248200

162

Bondar I.A., Klimontov V.V. Antioxidants in the treatment and prevention of diabetes mellitus. Diabetes mellitus. 2001; 1: 47–53.

163

Stanhewicz A.E., Kenney W.L. Role of folic acid in nitric oxide bioavailability and vascular endothelial function. Nutr Rev. 2017; 75 (1): 61–70. https://doi.org/10.1093/nutrit/nuw053

164

Antoniades C., Shirodaria C., Warrick N. et al. 5-methyltetrahydrofolate rapidly improves endothelial function and decreases superoxide production in human vessels: effects on vascular tetrahydrobiopterin availability and endothelial nitric oxide synthase coupling. Circulation. 2006; 114 (11): 1193–201. https://doi.org/10.1161/CIRCULATIONAHA.106.612325

165

Artunc F., Essig M., Artunc N. et al. Effects of tetrahydrobiopterin on nitric oxide bioavailability and renal hemodynamics in healthy volunteers. J Nephrol. 2008; 21 (6): 850–60.

166

Shikh EV, Makhova AA. Prob lems in the choice of a folate formulation for correction of folate status. Obstetrics and Gynecology. 2018;8:304. DOI: 10.18565/aig.2018.8.3340. (In Russ.).

167

Jain S.K., Krueger K.S. et al. Relationship of blood thromboxane-B2 (TxB2) with lipid peroxides and effect of vitamin E and placebo supplementation on TxB2 and lipid peroxide levels in type 1 diabetic patients // Diabetes Care. 1998; 21 (9): 1511–1516.

168

Heller R., Werner-Felmayer G., Werner E.R. Alpha-tocopherol and endothelial nitric oxide synthesis. Ann NY Acad Sci. 2004; 1031: 74–85. https://doi.org/10.1196/annals.1331.007

169

M.G. Ipatova, PhD, D.S. Bordin, PhD, Prof. The Role of Nutrition, Nutrients, and Lifestyle Changes in the Treatment of Non-Alcoholic Fatty Liver Disease. Effective Pharmacotherapy. 2025; 21 (2): 58–64. DOI 10.33978/2307‑3586‑2025‑21‑2‑58‑64. (In Russ.).

170

Skakun N.P., Shmanko V.V., Okhrimovich L.M. Clinical pharmacology of hepatoprotectors. Ternopil: Zbruch, 1995. P. 272.

171

Omura M., Kobayashi S., Mizukami Y. et al. Eicosapentaenoic acid (EPA) induces Ca(2+)-independent activation and translocation of endothelial nitric oxide synthase and endothelium-dependent vasorelaxation. FEBS Lett. 2001; 487 (3): 361–6. https://doi.org/10.1016/s0014-5793(00)02351‑6

172

Zgheel F., Perrier S., Remila L. et al. EPA: DHA 6:1 is a superior omega‑3 PUFAs formulation attenuating platelets-induced contractile responses in porcine coronary and human internal mammary artery by targeting the serotonin pathway via an increased endothelial formation of nitric oxide. Eur J Pharmacol. 2019; 853: 41–8. https://doi.org/10.1016/j.ejphar.2019.03.022

173

Vaisar T, Pennathur S, Green PS. Shot gun proteomics implicates protease inhibition and com-plement activation in the antiin ammatory properties of HDL. J Clin Investigation. 2007; 117 (3): 746–56.

174

Sena CM, Pereira AM, Seiça R. Endothelial dysfunction – a major mediator of diabetic vascular disease. Biochim Biophys Acta. 2013 Dec; 1832 (12): 2216–31. DOI: 10.1016/j.bbadis.2013.08.006. Epub 2013 Aug 29. PMID: 23994612.

175

Ungvari Z, Orosz Z, Labinskyy N, Rivera A, Xiangmin Z, Smith K, Csiszar A. Increased mitochondrial H2O2 production promotes endothelial NF-kappaB activation in aged rat arteries. Am J Physiol Heart Circ Physiol. 2007; 293: H37–H47.

176

Pearson KJ, Baur JA, Lewis KN, Peshkin L, Price NL, Labinskyy N, Swindell WR, Kamara D, Minor RK, Perez E, Jamieson HA, Zhang Y, Dunn SR, Sharma K, Pleshko N, Woollett LA, Csiszar A, Ikeno Y, Le Couteur D, Elliott PJ, Becker KG, Navas P, Ingram DK, Wolf NS, Ungvari Z, Sinclair DA, De Cabo R. Resveratrol delays age-related deterioration and mimics transcriptional aspects of dietary restriction without extending life span. Cell Metab. 2008; 8: 157–168.

177

Weiss N, Ide N, Abahji T, Nill L, Keller C, Hoffmann U. Aged garlic extract improves homocysteine-induced endothelial dysfunction in macro- and microcirculation. J Nutr. 2006; 136: 750S‑754S.

The authors declare that there are no conflicts of interest present.