Аннотация

Hyperlipidemia is an enduring metabolic ailment that affects glucose and lipid processing.
The research objective was to measure the total phenolic, flavonoid, and tannin contents in Olea europaea L. leaves and to to identify their antioxidant and antihyperlipidemic potential. The study included an in silico model of interaction for hydroxytyrosol, oleuropein, and xanthine dehydrogenase. The in vivo experiment involved rabbits that received olive leaves (150 mg/kg) and 10 mL of egg yolk as a high-fat diet. At the end of the experimental period, blood samples were tested for lipid profile, and tissue specimens were used for liver histology.
The total phenolic content was 119.84 ± 3.86 mg GAE/g, the total flavonoid content was 2.22 ± 0.07 mg CE/g, and the total tannin content was 21.25 ± 1.24 mg REQ/g dry weight. According to DPPH and FRAP analyses, the antioxidant capacities were 0.34 ± 0.06 μg/mL and 6.35 ± 0.52 μmol Fe(II)/g dry weight, respectively. In the experimental animals, O. europaea leaves reduced such parameters as total cholesterol, low-density lipoprotein, total triglycerides, total cholesterol vs. high-density lipoprotein, and low-density lipoprotein vs. high-density lipoprotein. The histopathological liver assay showed no signs of tissue damage while the samples obtained from the control group demonstrated steatosis deposits and cellular necrosis. Based on the energy and RMSD results, hydroxytyrosol proved an effective xanthine dehydrogenase inhibition.
These findings constitute a good scientific basis for the complementary future research on the potential of O. europaea leaves as ingredients of functional foods or medical drugs.

Ключевые слова

Olea europaea L., hyperlipidemia, phenolic compounds, antioxidant activity, antihyperlipidemic activity, xanthine dehydrogenase

СПИСОК ЛИТЕРАТУРЫ

1. Makshood M, Post WS, Kanaya AM. Lipids in South Asians: Epidemiology and management. Current Cardiovascular Risk Reports. 2019;13. https://doi.org/10.1007/s12170-019-0618-9
2. Karr S. Epidemiology and management of hyperlipidemia. The American Journal of Managed Care. 2017;23(9):S139–S148.
3. Nelson RH. Hyperlipidemia as a risk factor for cardiovascular disease. Primary Care: Clinics in Office Practice. 2013;40(1):195–211. https://doi.org/10.1016/j.pop.2012.11.003
4. Ballantyne CM, Grundy SM, Oberman A, Kreisberg RA, Havel RJ, Frost PH, et al. Hyperlipidemia: Diagnostic and therapeutic perspectives. The Journal of Clinical Endocrinology and Metabolism. 2000;85(6):2089–2092. https://doi.org/10.1210/jcem.85.6.6642-1
5. Moszak M, Szulinska M, Bogdanski P. You are what you eat – The relationship between diet, microbiota, and metabolic disorders – A review. Nutrients. 2020;12(4). https://doi.org/10.3390/nu12041096
6. Wang K, Liao M, Zhou N, Bao L, Ma K, Zheng Z, et al. Parabacteroides distasonis alleviates obesity and metabolic dysfunctions via production of succinate and secondary bile acids. Cell Reports. 2019;26(1):222–235. https://doi.org/10.1016/j.celrep.2018.12.028
7. Wen J-J, Li M-Z, Chen C-H, Hong T, Yang J-R, Huang X-J, et al. Tea polyphenol and epigallocatechin gallate ameliorate hyperlipidemia via regulating liver metabolism and remodeling gut microbiota. Food Chemistry. 2023;404. https://doi.org/10.1016/j.foodchem.2022.134591
8. Poornima IG, Indaram M, Ross JD, Agarwala A, Wild RA. Hyperlipidemia and risk for preclampsia. Journal of Clinical Lipidology. 2022;16(3):253–260. https://doi.org/10.1016/j.jacl.2022.02.005
9. Nordestgaard BG, Langsted A, Freiberg JJ. Nonfasting hyperlipidemia and cardiovascular disease. Current Drug Targets. 2009;10(4):328–335. https://doi.org/10.2174/138945009787846434
10. Global Health Observatory [Internet]. [cited 15 Sep 2023]. Available from: https://www.who.int/data/gho
11. Uchendu IK, Ikebunwa OA, Okpagu CB. Cardiorenal protective effects of extracts of bitter leaf (Vernonia amygdalina L.) in animal model of metabolic syndrome. Foods and Raw Materials. 2024;12(2):264–272. https://doi.org/10.21603/2308-4057-2024-2-607
12. Gold ME, Nanna MG, Doerfler SM, Schibler T, Wojdyla D, Peterson ED, et al. Prevalence, treatment, and control of severe hyperlipidemia. American Journal of Preventive Cardiology. 2020;3. https://doi.org/10.1016/j.ajpc.2020.100079
13. Perez de Isla L, Alonso R, Watts GF, Mata N, Saltijeral-Cerezo A, Muñiz O, et al. Attainment of LDL-cholesterol treatment goals in patients with familial hypercholesterolemia: 5-year SAFEHEART Registry follow-up. Journal of the American College of Cardiology. 2016;67(11):1278–1285. https://doi.org/10.1016/j.jacc.2016.01.008
14. Yoshioka Y, Ohishi T, Nakamura Y, Fukutomi R, Miyoshi N. Anti-cancer effects of dietary polyphenols via ROS-mediated pathway with their modulation of microRNAs. Molecules. 2022;27(12). https://doi.org/10.3390/molecules27123816
15. Sharma P, Hajam YA, Kumar R, Rai S. Complementary and alternative medicine for the treatment of diabetes and associated complications: A review on therapeutic role of polyphenols. Phytomedicine Plus. 2022;2(1). https://doi.org/10.1016/j.phyplu.2021.10018
16. Harnafi H, Serghini-Caid H, El Houda Bouanani N, Aziz M, Amrani S. Hypolipemic activity of polyphenol-rich extracts from Ocimum basilicum in Triton WR-1339-induced hyperlipidemic mice. Food Chemistry. 2008;108(1):205–212. https://doi.org/10.1016/j.foodchem.2007.10.062
17. Aumeeruddy MZ, Mahomoodally MF. Global use of folk medicinal plants against hypercholesterolemia: A review of ethnobotanical field studies. Journal of Herbal Medicine. 2022;32. https://doi.org/10.1016/j.hermed.2022.100536
18. El SN, Karakaya S. Olive tree (Olea europaea) leaves: Potential beneficial effects on human health. Nutrition Reviews. 2009;67(11):632–638. https://doi.org/10.1111/j.1753-4887.2009.00248.x
19. Boss A, Bishop KS, Marlow G, Barnett MPG, Ferguson LR. Evidence to support the anti-cancer effect of olive leaf extract and future directions. Nutrients. 2016;8(8). https://doi.org/10.3390/nu8080513
20. Kabbash EM, Abdel-Shakour ZT, El-Ahmady SH, Wink M, Ayoub IM. Comparative metabolic profiling of olive leaf extracts from twelve different cultivars collected in both fruiting and flowering seasons. Scientific Reports. 2023;13. https://doi.org/10.1038/s41598-022-27119-5
21. Hassen I, Casabianca H, Hosni K. Biological activities of the natural antioxidant oleuropein: Exceeding the expectation – A mini review. Journal of Functional Foods. 2015;18:926–940. https://doi.org/10.1016/j.jff.2014.09.001
22. Bhatia A, Singh B, Arora R, Arora S. In vitro evaluation of the α-glucosidase inhibitory potential of methanolic extracts of traditionally used antidiabetic plants. BMC Complementary Medicine and Therapies. 2019;19. https://doi.org/10.1186/s12906-019-2482-z
23. Al-Farsi M, Alasalvar C, Morris A, Baron M, Shahidi F. Comparison of antioxidant activity, anthocyanins, carotenoids, and phenolics of three native fresh and sun dried date (Phoenix dactylifera L.) varieties grown in Oman. Journal of Agricultural and Food Chemistry. 2005;53(19):7592−7599. https://doi.org/10.1021/jf050579q
24. Biglari F, Alkarkhi AFM, Easa AM. Antioxidant activity and phenolic content of various date palm (Phoenix dactylifera) fruits from Iran. Food Chemistry. 2008;107(4):1636–1641. https://doi.org/10.1016/j.foodchem.2007.10.033
25. Qaisar MN, Chaudhary BA, Sajid MU, Hussain N. Evaluation of α-glucosidase inhibitory activity of dichloromethane and methanol extracts of Croton bonplandianum Baill. Tropical Journal of Pharmaceutical Research. 2014;13(11):1833–1836. https://doi.org/10.4314/tjpr.v13i11.9
26. Blois MS. Antioxidant determinations by the use of a stable free radical. Nature. 1958;181:1199–1200. https://doi.org/10.1038/1811199a0
27. Benzie IFF, Strain JJ. The ferric reducing ability of plasma (FRAP) as a measure of “antioxidant power”: The FRAP assay. Analytical Biochemistry. 1996;239(1):70–76. https://doi.org/10.1006/abio.1996.0292
28. Djerrou Z. Anti-hypercholesterolemic effect of Pistacia lentiscus fatty oil in egg yolk-fed rabbits: A comparative study with simvastatin. Chinese Journal of Natural Medicines. 2014;12(8):561–566. https://doi.org/10.1016/S1875-5364(14)60086-8
29. Patel H, Kukol A. Integrating molecular modelling methods to advance influenza A virus drug discovery. Drug Discovery Today. 2021;26(2):503–510. https://doi.org/10.1016/j.drudis.2020.11.014
30. Fki I, Sayadi S, Mahmoudi A, Daoued I, Marrekchi R, Ghorbel H. Comparative study on beneficial effects of hydroxytyrosol- and oleuropein-rich olive leaf extracts on high-fat diet-induced lipid metabolism disturbance and liver injury in rats. BioMed Research International. 2020;2020. https://doi.org/10.1155/2020/1315202
31. Wang B, Qu J, Feng S, Chen T, Yuan M, Huang Y, et al. Seasonal variations in the chemical composition of Liangshan olive leaves and their antioxidant and anticancer activities. Foods. 2019;12(8). https://doi.org/10.3390/foods8120657
32. Acar-Tek N, Ağagündüz D. Olive leaf (Olea europaea L. folium): Potential effects on glycemia and lipidemia. Annals of Nutrition and Metabolism. 2020;76(1):10–15. https://doi.org/10.1159/000505508
33. Anwar S, Saleem H, Khurshid U, Ansari SY, Alghamdi S, Al-Khulaidi AWA, et al. Comparative phytochemical composition, oleuropein quantification, antioxidant and cytotoxic properties of Olea europaea L. leaves. Natural Product Research. 2023;37(6):1023–1029. https://doi.org/10.1080/14786419.2022.2097230
34. Morsy NFS, Abdel-Aziz ME. Efficiency of olive (Olea europaea L.) leaf extract as antioxidant and anticancer agents. Journal of Agroalimentary Processes and Technologies. 2014;20(1):46–53.
35. Vogel P, Machado IK, Garavaglia J, Zani VT, de Souza D, Bosco SMD. Polyphenols benefits of olive leaf (Olea europaea L) to human health. Nutricion Hospitalaria. 2015;31(3):1427–1433. https://doi.org/10.3305/nh.2015.31.3.8400
36. Mansour HMM, Zeitoun AA, Abd-Rabou HS, El Enshary HA, Dailin DJ, Zeitoun MAA, et al. Antioxidant and anti-diabetic properties of olive (Olea europaea) leaf extracts: In vitro and in vivo evaluation. Antioxidants. 2023;12(6). https://doi.org/10.3390/antiox12061275
37. Orak HH, Karamać M, Amarowicz R, Orak A, Penkacik K. Genotype-related differences in the phenolic compound profile and antioxidant activity of extracts from olive (Olea europaea L.) leaves. Molecules. 2019;24(6). https://doi.org/10.3390/molecules24061130
38. Zhang C, Xin X, Zhang J, Zhu S, Niu E, Zhou Z, et al. Comparative evaluation of the phytochemical profiles and antioxidant potentials of olive leaves from 32 cultivars grown in China. Molecules. 2022;27(4). https://doi.org/10.3390/molecules27041292
39. Alesci A, Miller A, Tardugno R, Pergolizzi S. Chemical analysis, biological and therapeutic activities of Olea europaea L. extracts. Natural Product Research. 2021;36(11):2932–2945. https://doi.org/10.1080/14786419.2021.1922404
40. Batçıoğlu K, Küçükbay F, Alagöz MA, Günal S, Yilmaztekin Y. Antioxidant and antithrombotic properties of fruit, leaf, and seed extracts of the Halhalı olive (Olea europaea L.) native to the Hatay region in Turkey. Foods and Raw Materials. 2023;11(1):84–93. https://doi.org/10.21603/2308-4057-2023-1-557
41. Cheurfa M, Abdallah HH, Allem R, Noui A, Picot-Allain CMN, Mahomoodally F. Hypocholesterolaemic and antioxidant properties of Olea europaea L. leaves from Chlef province, Algeria using in vitro, in vivo and in silico approaches. Food and Chemical Toxicology. 2019;123:98–105. https://doi.org/10.1016/j.fct.2018.10.002
42. Fernández-Poyatos MP, Ruiz-Medina A, Llorent-Martínez EJ. Phytochemical profile, mineral content, and antioxidant activity of Olea europaea L. cv. Cornezuelo table olives. Influence of in vitro simulated gastrointestinal digestion. Food Chemistry. 2019;297. https://doi.org/10.1016/j.foodchem.2019.05.207
43. Lins PG, Pugine SMP, Scatolini AM, de Melo MP. In vitro antioxidant activity of olive leaf extract (Olea europaea L.) and its protective effect on oxidative damage in human erythrocytes. Heliyon. 2018;4(9). https://doi.org/10.1016/j.heliyon.2018.e00805
44. Malhotra HS, Goa KL. Atorvastatin: an updated review of its pharmacological properties and use in dyslipidaemia. Drugs. 2001;61(12):1835–1881. https://doi.org/10.2165/00003495-200161120-00012
45. Jang A, Srinivasan P, Lee NY, Song HP, Lee JW, Lee M, Jo C. Comparison of hypolipidemic activity of synthetic gallic acid-linoleic acid ester with mixture of gallic acid and linoleic acid, gallic acid, and linoleic acid on high-fat diet induced obesity in C57BL/6 Cr Slc mice. Chemico-Biological Interactions. 2008;174(2):109–117. https://doi.org/10.1016/j.cbi.2008.05.018
46. Hadrich F, Mahmoudi A, Bouallagui Z, Feki I, Isoda H, Feve B, et al. Evaluation of hypocholesterolemic effect of oleuropein in cholesterol-fed rats. Chemico-Biological Interactions. 2016;252:54–60. https://doi.org/10.1016/j.cbi.2016.03.026
47. Guex CG, Reginato FZ, Figueredo KC, da Silva ARH, Pires FB, Jesus RS, et al. Safety assessment of ethanolic extract of Olea europaea L. leaves after acute and subacute administration to Wistar rats. Regulatory Toxicology and Pharmacology. 2018;95:395–399. https://doi.org/10.1016/j.yrtph.2018.04.013
48. Taamalli A, Feriani A, Lozano-Sanchez J, Ghazouani L, El Mufti A, Allagui MS, et al. Potential hepatoprotective activity of super critical carbon dioxide olive leaf extracts against CCl4-induced liver damage. Foods. 2020;9(6). https://doi.org/10.3390/foods9060804
49. Jemai H, Mahmoudi A, Feryeni A, Fki I, Bouallagui Z, Choura S, et al. Hepatoprotective effect of oleuropein-rich extract from olive leaves against cadmium-induced toxicity in mice. BioMed Research International. 2020;2020. https://doi.org/10.1155/2020/4398924
50. Uyanoğlu M. Prevention of tissue injury with Olea europaea L. leaf extract after partial liver ischemia/reperfusion. Biology Bulletin. 2021;48(5):536–545. https://doi.org/10.1134/S1062359021050150
51. Vidičević S, Tošić J, Stanojević Ž, Isaković A, Mitić D, Ristić D, et al. Standardized Olea europaea L. leaf extract exhibits protective activity in carbon tetrachloride-induced acute liver injury in rats: The insight into potential mechanisms. Archives of Physiology and Biochemistry. 2020;126(5):399–407. https://doi.org/10.1080/13813455.2018.1550095
52. Omagari K, Kato S, Tsuneyama K, Hatta H, Sato M, Hamasaki M, et al. Olive leaf extract prevents spontaneous occurrence of non-alcoholic steatohepatitis in SHR/NDmcr-cp rats. Pathology. 2010;42(1):66–72. https://doi.org/10.3109/00313020903434389
53. Ahmed M, Shakeel M, Raza MA, Kumar U, Ansar M, Shah GA, et al. Models calibration and evaluation. In: Ahmed M, editors. Systems modeling. Singapore: Springer; 2020. pp. 151–178. https://doi.org/10.1007/978-981-15-4728-7_5
54. Yang K-J, Choi WJ, Chang Y-K, Park CW, Kim SY, Hong YA. Inhibition of xanthine oxidase protects against diabetic kidney disease through the amelioration of oxidative stress via VEGF/VEGFR axis and NOX-FoxO3a-eNOS signaling pathway. International Journal of Molecular Sciences. 2023;24(4). https://doi.org/10.3390/ijms24043807
55. Mohamed MZ, Abed El Baky MF, Hassan OA, Mohammed HH, Abdel-Aziz AM. PTEN/PI3K/VEGF signaling pathway involved in the protective effect of xanthine oxidase inhibitor febuxostat against endometrial hyperplasia in rats. Human and Experimental Toxicology. 2020;39(9):1224–1234. https://doi.org/10.1177/0960327120914977
56. Ngoc TM, Khoi NM, Ha DT, Nhiem NX, Tai BH, Don DV, et al. Xanthine oxidase inhibitory activity of constituents of Cinnamomum cassia twigs. Bioorganic and Medicinal Chemistry Letters. 2012;22(14):4625–4628. https://doi.org/10.1016/j.bmcl.2012.05.051
57. Hendriani R, Nursamsiar, Tjitraresmi A. In vitro and in silico evaluation of xanthine oxidase inhibitory activity of quercetin contained in Sonchus arvensis leaf extract. Asian Journal of Pharmaceutical and Clinical Research. 2017;10(14):50–53. https://doi.org/10.22159/ajpcr.2017.v10s2.19486
58. Serrano JL, Figueiredo J, Almeida P, Silvestre, S. From xanthine oxidase inhibition to in vivo hypouricemic effect: An integrated overview of in vitro and in vivo studies with focus on natural molecules and analogues. Evidence-Based Complementary and Alternative Medicine. 2020;2020. https://doi.org/10.1155/2020/9531725
59. Mehmood A, Li J, Rehman AU, Kobun R, Llah IU, Khan I, et al. Xanthine oxidase inhibitory study of eight structurally diverse phenolic compounds. Frontiers in Nutrition. 2022;9. https://doi.org/10.3389/fnut.2022.966557