Ukr.Biochem.J. 2025; Volume 97, Issue 5, Sep-Oct, pp. 88-101
doi: https://doi.org/10.15407/ubj97.05.088
Historical overview of lipid biochemistry research: from initial hypotheses to understanding the biological role of N-acylethanolamines
H. V. Kosiakova*, A. G. Berdyshev, T. M. Horidko,
V. M. Klimashevsky, O. F. Meged, O. S. Tkachenko,
N. L. Kindruk, O. V. Zhukov, V. S. Asmolkova, N. M. Hula
Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine,
Department of Lipid Biochemistry, Kyiv;
*e-mail: kosiakova@hotmail.com
Received: 09 June 2025; Revised: 09 July 2025;
Accepted: 30 October 2025; Available on-line: 02 December 2025
In the Department of Lipid Biochemistry at the Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine, a systematic approach to studying the functional role of lipids and investigating the lipidome of mammals and humans was developed and implemented from 1988 to 2025. A new class of low-polarity lipids, N-acylethanolamines (NAE), was discovered, and a multifaceted detailed study of their biological activity and functional role in the body was conducted. This allowed the discovery of several new mechanisms for regulating vital processes both in normal conditions and in various pathological states. The relevance of these studies lies in the fact that they not only deepened fundamental knowledge in human and animal biology but also led to the development of several pharmacological agents for the therapy of a range of pathological conditions. The drugs are proposed for use in cardiovascular diseases, allergies, burns, type I and II diabetes, inflammatory processes, oncological diseases, organ transplantation, as well as chronic and acute stress, drug addiction, alcoholism, and post-traumatic stress disorder. Additionally, antiviral agents have been developed that are highly effective against influenza virus, hepatitis C virus, herpes simplex virus, and coronavirus. These agents have no side effects and are protected by 19 Ukrainian patents. The scientific results of the Department of Lipid Biochemistry have been published in over 200 scientific papers and presented at more than 130 international and domestic scientific forums. This article provides a brief review of the main achievements of the Department of Lipid Biochemistry in investigating the biological effects of NAE.
Keywords: endocannabinoid system, lipids, N-acylethanolamines, pathological conditions
References:
- Dykukha IS, Artamonov MV, Zhukov OD, Nizhenkivskyi OI, Rudenko SV, Lizohub VG, Gula NM. Phospholipids composition of the myocardium in patients with ischemic heart disease and its connection to arrhythmias. Ukr Biokhim Zhurn. 2008;80(3):118-123. (In Ukrainian). PubMed
- Gula NM, Margitych VM. Fatty acids and their derivatives in pathological conditions. K: Naukova Dumka, 2009. 346 p. (In Ukrainian).
- Gulaya NM, Melnik AA, Balkov DI, Volkov GL, Vysotskiy MV, Vaskovsky VE. The effect of long-chain N-acylethanolamines on some membrane-associated functions of neuroblastoma C1300 N18 cells. Biochim Biophys Acta. 1993;1152(2):280-288. PubMed, CrossRef
- Gula NM, Margitych VM, Goridko TM, Artamonov MV, Zhukov OD, Klimashevsky VM. Method for obtaining N-acylethanolamines. Patent of Ukraine 81861. 11 February 2008. (In Ukrainian).
- Gula NM, Komisarenko SV, Chumak AA, Artamonov MV, Zhukov OD, Meged OF, Petrova YI, Kindruk NL. A drug for suppressing allergic reactions and nonspecific inflammation, a method of its preparation and a method of its use. Patent of Ukraine 77278. 15.11.2006. (In Ukrainian).
- Gula NM, Margitych VM, Goridko TM, Artamonov MV, Zhukov OD, Klimashevsky VM. Application of N-acylethanolamines as medicinal products and method of their use Patent of Ukraine 77182. 15.11.2006. (In Ukrainian).
- Goridko TM, Gula NM, Stohniy NA, Meged OF, Klimashevsky VM, Shovkun SA, Kindruk NL, Berdyshev AH. Influence of N-stearoylethanolamine on the lipid peroxidation process and lipid composition of the rat liver under acute morphine intoxication. Ukr Biokhim Zhurn. 2007;79(5):175-185. (In Ukrainian). PubMed
- Bondarenko OV, Hula NM, Makarchuk MYu, Horid’ko TM. Effects of N-stearoylethanolamine on anxiety-like behavioral reactions of rats after chronic alcoholization. Biologija. 2014;60(1):23-31. CrossRef
- Bondarenko OV, Hula NM, Makarchuk MIu, Horid’ko TM, Kovalenko OA. Effects of N-stearoylethanolamine on the emotionality and learning ability of rats. Fiziol Zh. 2014;60(5):52-61. (In Ukrainian). CrossRef
- Artamonov M, Zhukov O, Shuba I, Storozhuk L, Khmel T, Klimashevsky V, Mikosha A, Gula N. Incorporation of labelled N-acylethanolamine (NAE) into rat brain regions in vivo and adaptive properties of saturated NAE under X-ray irradiation. Ukr Biokhim Zhurn. 2005;77(6):51-62. PubMed
- Zhukov AD, Berdyshev AG, Kosiakova GV, Klimashevskiy VM, Gorid’ko TM, Meged OF, Hula NM. N-stearoylethanolamine effect on the level of 11-hydroxycorticosteroids, cytokines IL-1β, IL-6 and TNFα in rats with nonspecific inflammation caused by thermal burn of skin. Ukr Biochem J. 2014;86(3):88-97. CrossRef
- Storozhuk LM, Zhukov OD, Artamonov MN, Gula NM, Mikosha OS. Pathways of N-acylethanolamine action on the adrenal cortex function. Endokrynologia. 2005;10(1):63-68. (In Ukrainian).
- Ibrahimov KV, Kosiakova HV, Horid’ko TM. The effect of N-stearoylethanolamine on the stress hormones levels in old rats with induced chronic inflammation. Biotechnologia Acta. 2024;17(2):49-51. CrossRef
- Kosiakova GV, Gulaya NM. The N-stearoylethanolamine effect on the NO-synthase way of nitrogen oxide formation and phospholipid composition of erythrocyte membranes in rats with streptozotocine diabetes. Ukr Biokhim Zhurn. 2007;79(6):53-59. (In Ukrainian). PubMed
- Gulaya NM, Kosiakova GV, Berdyshev AG. The effects of N-stearoylethanolamine on the NO-synthase way of NO generation in the aorta and heart of streptozotocin-induced diabetic rats. Ukr Biokhim Zhurn. 2007;79(5):153-158. (In Ukrainian). PubMed
- Goridko TM, Kosiakova GV, Berdyshev AG, Bazylyanska VR, Margitich VM, Gula NM. The influence of N-stearoylethanolamine on the activity of antioxidant enzymes and on the level of stable NO metabolites in the rat testes and blood plasma at the early stages of streptozotocine-іnduced diabetes. Ukr Biokhim Zhurn. 2012; 84(3):37-43. (In Ukrainian). PubMed
- Gulaya NM, Berdyshev AG, Chumak AA, Meged EF, Kindruk NL, Goridko TN. Cardioprotective effect of N-stearoylethanolamine under the anaphylactic shock in guinea pigs. Biomed Khim. 2009;55(6):743-749. (In Russian). PubMed
- Gula NM, Chumak AA, Meged EF, Goridko TM, Kindruk NL, Berdyshev AG. Immunosuppressive properties of N- stearoylethanolamine a stable compound with cannabimimetic properties characteristics. Ukr Biokhim Zhurn. 2008;80(1):57-67. (In Ukrainian). PubMed
- Hula NM, Chumak AA, Berdyshev AH, Mehed EF, Goridko TM, Kindruk NL, Kosyakova GV, Zhukov OD. Anti-inflammatory effect of N-stearoylethanolamine on experimental burn wound in rats. Ukr Biokhim Zhurn. 2009; 81(2):107-116. (In Ukrainian). PubMed
- Berdyshev AG, Gulaya NM, Chumak AA, Kindruk NL. The effect of N-stearoylethanolamine on free amino acid levels in plasma and liver of rats with an experimental burn. Biochem. 2011;5:44-50. CrossRef
- Onopchenko OV, Kosiakova GV, Goridko TM, Berdyschev AG, Meged OF, Hula NM. The effect of N-stearoylethanolamine on the activity of antioxidant enzymes, content of lipid peroxidation products and nitric oxide in the blood plasma and liver of rats with induced insulin-resistance. Ukr Biochem J. 2013;85(5):88-96. PubMed, CrossRef
- Gula NM, Chumak AA, Berdyshev AG, Kosyakova GV, Goridko TM, Meged OF, Onopchenko OV. Use of N-stearoylethanolamine as a drug with a complex effect for the treatment of thermal burns of the skin of the III degree and the prevention and treatment of burn disease. Patent of Ukraine 113605. 10.02.2017. (In Ukrainian).
- Gulaya NM, Babich LG, Shlykov SG, Margitich VM, Govseeva NN, Klimashevsky VM, Kosterin SA. Effect of N-palmitoylethanolamine on energy-dependent transport of Ca2+ in myometrium cells and their phospholipid composition. Ukr Biokhim Zhurn. 1997;69(5-6):75-84. (In Russian). PubMed
- Voitychuk OI, Asmolkova VS, Gula NM, Sotkis GV, Galadari S, Howarth FC, Oz M, Shuba YM. Modulation of excitability, membrane currents and survival of cardiac myocytes by N-acylethanolamines. Biochim Biophys Acta. 2012;1821(9):1167-1176. PubMed, CrossRef
- Gula NM, Kosyakova GV, Berdyshev AG. Application of N- stearoylethanolamine as a medicinal product for the treatment of diabetes mellitus types I and II. Patent of Ukraine 85523. 26.01.2009. (In Ukrainian).
- Onopchenko OV, Kosiakova GV, Goridko TM, Klimashevsky VM, Hula NM. The effect of N-stearoylethanolamine on liver phospholipid composition of rats with insulin resistance caused by alimentary obesity. Ukr Biochem J. 2014;86(1):101-110. PubMed, CrossRef
- Onopchenko OV, Kosiakova GV, Meged EF, Klimashevsky VM, Hula NM. The effect of N-stearoylethanolamine on cholesterol content, fatty acid composition and protein carbonylation level in rats with alimentary obesity-induced insulin resistance. Ukr Biochem J. 2014;86(1):119-128. PubMed, CrossRef
- Onopchenko OV, Kosiakova GV, Klimashevsky VM, Hula NM. The effect of N-stearoylethanolamine on plasma lipid composition in rats with experimental insulin resistance. Ukr Biochem J. 2015;87(1):46-54. PubMed, CrossRef
- Onopchenko OV, Kosiakova GV, Oz M, Klimashevsky VM, Gula NM. N-stearoylethanolamine restores pancreas lipid composition in obesity-induced insulin resistant rats. Lipids. 2015;50(1):13-21. PubMed, CrossRef
- Kvitnitskaya-Ryzhova TYu, Kosiakova HV, Lugovskoy SP, Mykhalskiy SA, Klymenko PP, Malysheva SP, Tkachenko OS. Age-related morpho-functional changes in rats’ pancreas under high-fat diet-induced insulin resistance and its pharmacological treatment. Wiad Lek. 2021;74(2):241-246. CrossRef
- Onopchenko OV, Horid’ko TM, Kosiakova HV, Berdyshev AG, Klimashevsky VM, Hula NM. The effect of N-stearoylethanolamine on the lipid composition of the rat testes and testosterone level during the early stages of streptozotocin-іnduced diabetes. Ukr Biochem J. 2020;92(2):45-58. CrossRef
- Tkachenko O, Kosiakova H, Klimashevsky V, Berdyshev A, Hula N. The effect of N-stearoylethanolamine on the adipocyte fatty acid composition of different age rats with obesity-induced insulin resistance. EUREKA: Life Sciences. 2020;(2):10-23. CrossRef
- Onopchenko O, Kosiakova H, Berdyshev A, Hula N. Anti-inflammatory action of N-stearoylethanolamine in rat peritoneal macrophages during high fat feeding. Atherosclerosis. 2018;275:e194. CrossRef
- Berdyshev AG, Kosiakova HV, Onopchenko OV, Panchuk RR, Stoika RS, Hula NM. N-Stearoylethanolamine suppresses the pro-inflammatory cytokines production by inhibition of NF-κB translocation. Prostaglandins Other Lipid Mediat. 2015;121(Pt A):91-96. PubMed, CrossRef
- Berdyshev AG, Kosiakova HV, Hula NM. Modulation of LPS-induced ROS production and NF-κB nuclear translocation by N-stearoylethanolamine in macrophages. Ukr Biochem J. 2017;89(5):62-69. CrossRef
- Kosiakova H, Berdyshev A, Dosenko V, Drevytska T, Herasymenko O, Hula N. The involvement of peroxisome proliferator-activated receptor gamma (PPARγ) in anti-inflammatory activity of N-stearoylethanolamine. Heliyon. 2022;8(11):e11336. PubMed, PubMedCentral, CrossRef
- Horid’ko TM, Kosiakova HV, Berdyshev AG, Meged OF, Gudz EA, Onopchenko OV, Asmolkova VS, Lozova VM, Tukalenko EV, Bondarenko OV, Tubalzeva II, Kovalenko OA, Makarchuk MY, Hula NM. Antistress effects of N-stearoylethanolamine in rats with chronic social stress. Ukr Biochem J. 2017;89(4):68-76. CrossRef
- Lykhmus O, Kalashnyk O, Uspenska K, Horid’ko T, Kosyakova H, Komisarenko S, Skok M. Different effects of nicotine and N-stearoyl-ethanolamine on episodic memory and brain mitochondria of α7 nicotinic acetylcholine receptor knockout mice. Biomolecules. 2020;10(2):226. PubMed, PubMedCentral, CrossRef
- Gula NM, Goridko TM, Kosyakova GV, Berdyshev AG, Meged OF, Asmolkova VS, Makarchuk MYu, Lozova VM, Tukalenko EV, Bondarenko OV, Tubaltseva II, Kovalenko OA. N-Stearoylethanolamine as a remedy with a complex effect for the treatment of chronic stress. Patent of Ukraine 121595. 25.06.2020. (In Ukrainian).
- Gula NM, Goridko TM, Kosyakova GV, Berdyshev AG, Meged’ OF, Skok MV, Lykhmus OYu, Komisarenko SV, Kholin VO, Peschana KO. N-stearoylethanolamine as a remedy with a complex effect for the treatment of diseases accompanied by neuroinflammation and cognitive impairment. Patent of Ukraine 122252. 12.10.2020. (In Ukrainian).
- Kosiakova H, Berdyshev A, Horid’ko T, Meged O, Klimashevsky V, Matsokha R, Tkachenko O, Asmolkova V, Kvitnitskaya-Ryzhova T, Luhovskyi S, Klymenko P, Hula N. N-Stearoylethanolamine exerts cardioprotective effects in old rats. Curr Aging Sci. 2024;17(2):144-155. PubMed, CrossRef
- Lykhmus O, Uspenska K, Koval L, Lytovchenko D, Voytenko L, Horid’ko T, Kosiakova H, Gula N, Komisarenko S, Skok M. N-Stearoylethanolamine protects the brain and improves memory of mice treated with lipopolysaccharide or immunized with the extracellular domain of α7 nicotinic acetylcholine receptor. Int Immunopharmacol. 2017;52:290-296. PubMed, CrossRef
- Romanenko KS, Horid’ko TM. Еffect of N-stearoylethanolamine on the lipid composition of the frontal cortex and hippocampus of the rat’s brain at the aging. Biotechnologia Acta. 2022;15(2):66-67. CrossRef
- Gula NM, Asmolkova VS, Rybalko SL, Dyadyun ST, Starosila DB, Komisarenko SV, Chumak AA, Berdyshev AG. Application of N-stearoylethanolamine as a substance with active anti-influenza effect. Patent of Ukraine 79010. 10.04.2013. (In Ukrainian).
- Gula NM, Asmolkova VS, Rybalko SL, Dyadyun ST, Starosila DB, Komisarenko SV, Chumak AA, Berdyshev AG. A drug with antineuraminidase and interferon-inducing action for the prevention and treatment of influenza infection. Patent of Ukraine 75632. 10.12.2012. (In Ukrainian).
- Hula NM, Chumak AA, Rybalko SL, Diadiun ST, Asmolkova VS, Berdyshev AH, Kosiakova HV, Starosyla DB, Benkovskaia LK, Bashta YuM. Anti-influenza effect of N-stearoilethanolamine. J NAMS Ukraine. 2014;20(4):393-401. (In Ukrainian).
- Gula NM, Asmolkova VS, Rybalko VL, Dyadyun ST, Starosila DB, Komisarenko SV, Chumak AA, Berdyshev AG. Application of N-stearoylethanolamine as a substance with active anti-influenza, antiviral, antineuraminidase, interferon-inducing and anti-hemagglutination action and a means for the prevention and treatment of influenza infection. Patent of Ukraine 104650. 25.02.2014. (In Ukrainian).
- Hula NM, Chumak AA, Berdyshev AG, Kosiakova GV, Goridko TM, Meged’ OF, Asmolkova VS, Porva YuI, Rybalko SL, Dyadun ST, Starosyla DB, Deryabin OM. N-stearoylethanolamine – a new inhibitor of the hepatitis C virus reproduction. Biopolym Cell. 2021;37(3):167-176. CrossRef
- Gula NM, Chumak AA, Berdyshev AG, Kosyakova GV, Horidko TM, Meged OF, Asmolkova VS, Porva YuI, Rybalko SL, Dyadyun ST, Starosila DB. A remedy for the treatment of human hepatitis C. Patent of Ukraine 119584.10.07.2019. (In Ukrainian).
- Gula NM, Chumak AA, Berdyshev AG, Kosyakova GV, Goridko TM, Meged OF, Asmolkova VS, Porva YI, Rybalko SL, Dyadyun ST, Starosila DB. Means for the prevention and treatment of infections caused by herpes simplex viruses of types 1 and 2. Patent of Ukraine 119380. 10.06.2019. (In Ukrainian).
- Gula NM, Chumak AA, Goridko TM, Kosyakova GV, Berdyshev AG, Meged OF, Asmolkova VS, Chernyshenko VO, Rybalko SL, Starosila DB, Deryabin OM, Arhipova MA. A remedy with a complex effect for the treatment of coronavirus disease. Patent of Ukraine 129241. 19.02.2025. (In Ukrainian).
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