CC BY-NC-ND 4.0 · Planta Med 2024; 90(11): 844-857
DOI: 10.1055/a-2353-1469
Biological and Pharmacological Activity
Original Papers

Two Olea europaea L. Extracts Reduce Harmful Effects in a Model of Neurotoxicity: Involvement of the Endoplasmic Reticulum

Jessica Maiuolo
1   Department of Health Sciences, School of Pharmacy, Magna Graecia University of Catanzaro, Catanzaro, Italy
,
Sonia Bonacci
1   Department of Health Sciences, School of Pharmacy, Magna Graecia University of Catanzaro, Catanzaro, Italy
,
Francesca Bosco
2   Department of Health Science, School of Medicine and Surgery, Magna Graecia University of Catanzaro, Catanzaro, Italy
,
Lorenza Guarnieri
2   Department of Health Science, School of Medicine and Surgery, Magna Graecia University of Catanzaro, Catanzaro, Italy
,
Stefano Ruga
2   Department of Health Science, School of Medicine and Surgery, Magna Graecia University of Catanzaro, Catanzaro, Italy
,
Antonio Leo
2   Department of Health Science, School of Medicine and Surgery, Magna Graecia University of Catanzaro, Catanzaro, Italy
3   System and Applied Pharmacology@University Magna Grecia, Science of Health Department, School of Medicine, Magna Graecia University of Catanzaro, Catanzaro, Italy
,
Rita Citraro
2   Department of Health Science, School of Medicine and Surgery, Magna Graecia University of Catanzaro, Catanzaro, Italy
3   System and Applied Pharmacology@University Magna Grecia, Science of Health Department, School of Medicine, Magna Graecia University of Catanzaro, Catanzaro, Italy
,
Salvatore Ragusa
4   PLANTA/Research, Documentation and Training Center, Palermo, Italy
,
Ernesto Palma
1   Department of Health Sciences, School of Pharmacy, Magna Graecia University of Catanzaro, Catanzaro, Italy
,
Vincenzo Mollace
1   Department of Health Sciences, School of Pharmacy, Magna Graecia University of Catanzaro, Catanzaro, Italy
,
Giovambattista De Sarro
2   Department of Health Science, School of Medicine and Surgery, Magna Graecia University of Catanzaro, Catanzaro, Italy
3   System and Applied Pharmacology@University Magna Grecia, Science of Health Department, School of Medicine, Magna Graecia University of Catanzaro, Catanzaro, Italy
› Author Affiliations
Work supported by #NEXTGENERATIONEU (NGEU) and fund. by the Ministry of Univ. and Research (MUR), Nat. Recov. and Resil. Plan (NRRP), project MNESYS (PE0000006) – a multisc. integr. approach to the study of the nervous system in health and disease (DN. 1553 11. 10.2022),and the European Commissionʼs FESR FSE 2014–2020 and POR CALABRIA FESR AZIONE 1.5.1 “Support for research infrastructures considered critical/crucial for regional systems” Nuova Piattaforma di Farmacologia Integrata e Tecnologie Avanzate.

Abstract

Prolonged exposure to lead has been recognized as harmful to human health as it may cause neurotoxic effects including mitochondrial damage, apoptosis, excitotoxicity, and myelin formation alterations, among others. Numerous data have shown that consuming olive oil and its valuable components could reduce neurotoxicity and degenerative conditions. Olive oil is traditionally obtained from olive trees; this plant (Olea europaea L.) is an evergreen fruit tree.

In this manuscript, two extracts have been used and compared: the extract from the leaves of Olea europaea L. (OE) and the extract derived from OE but with a further sonication process (s-OE). Therefore, the objectives of this experimental work were as follows: 1) to generate an innovative extract; 2) to test both extracts on a model of neurotoxicity of human neurons induced following lead exposure; and 3) to study the mechanisms behind lead-induced neurotoxicity.

The results showed that the mechanism involved in the neurotoxicity of lead included dysfunction of the cellular endoplasmic reticulum, which suffered oxidative damage. In addition, in all experiments, s-OE was more effective than OE, having greater and better effects against lead-induced damage and being dissolved in a smaller amount of EtOH, which promotes its sustainability.



Publication History

Received: 18 March 2024

Accepted after revision: 10 June 2024

Accepted Manuscript online:
26 June 2024

Article published online:
06 August 2024

© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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  • References

  • 1 Cutuli D, Petrosini L, Gelfo F. Advance in neurotoxicity research from development to aging. Int J Mol Sci 2023; 24: 15112
  • 2 Lamoreaux J. “Passing Down Pollution”: (Inter)generational toxicology and (epi)genetic environmental health. Med Anthropol Q 2021; 35: 529-546
  • 3 Sayre LM, Perry G, Atwood CS, Smith MA. The role of metals in neurodegenerative diseases. Cell Mol Biol (Noisy-le-grand) 2000; 46: 731-741
  • 4 Al Osman M, Yang F, Massey IY. Exposure routes and health effects of heavy metals on children. Biometals 2019; 32: 563-573
  • 5 Babić Leko M, Mihelčić M, Jurasović J, Nikolac Perković M, Španić E, Sekovanić A, Orct T, Zubčić K, Langer Horvat L, Pleić N, Kiđemet-Piskač S, Vogrinc Ž, Pivac N, Diana A, Borovečki F, Hof PR, Šimić G. Heavy metals and essential metals are associated with cerebrospinal fluid biomarkers of alzheimerʼs disease. Int J Mol Sci 2022; 24: 467
  • 6 Vellingiri B, Suriyanarayanan A, Abraham KS, Venkatesan D, Iyer M, Raj N, Gopalakrishnan AV. Influence of heavy metals in Parkinsonʼs disease: An overview. J Neurol 2022; 269: 5798-5811
  • 7 Sarihi S, Niknam M, Mahjour S, Hosseini-Bensenjan M, Moazzen F, Soltanabadi S, Akbari H. Toxic heavy metal concentrations in multiple sclerosis patients: A systematic review and meta-analysis. EXCLI J 2021; 20: 1571-1584
  • 8 Farace C, Fenu G, Lintas S, Oggiano R, Pisano A, Sabalic A, Solinas G, Bocca B, Forte G, Madeddu R. Amyotrophic lateral sclerosis and lead: A systematic update. Neurotoxicology 2020; 81: 80-88
  • 9 de Paula Arrifano G, Crespo-Lopez ME, Lopes-Araújo A, Santos-Sacramento L, Barthelemy JL, de Nazaré CGL, Freitas LGR, Augusto-Oliveira M. Neurotoxicity and the global worst pollutants: Astroglial Involvement in arsenic, lead, and mercury intoxication. Neurochem Res 2023; 48: 1047-1065
  • 10 Ravipati ES, Mahajan NN, Sharma S, Hatware KV, Patil K. The toxicological effects of lead and its analytical trends: An update from 2000 to 2018. Crit Rev Anal Chem 2021; 51: 87-102
  • 11 Patrick L. Lead toxicity part II: The role of free radical damage and the use of antioxidants in the pathology and treatment of lead toxicity. Altern Med Rev 2006; 11: 114-127
  • 12 Hornedo-Ortega R, Cerezo AB, de Pablos RM, Krisa S, Richard T, García-Parrilla MC, Troncoso AM. Phenolic compounds characteristic of the mediterranean diet in mitigating microglia-mediated neuroinflammation. Front Cell Neurosci 2018; 12: 373
  • 13 Bucciantini M, Leri M, Nardiello P, Casamenti F, Stefani M. Olive polyphenols: Antioxidant and anti-inflammatory properties. Antioxidants (Basel) 2021; 10: 1044
  • 14 Vazquez-Aguilar A, Sanchez-Rodriguez E, Rodriguez-Perez C, Rangel-Huerta OD, Mesa MD. Metabolomic-based studies of the intake of virgin olive oil: A comprehensive review. Metabolites 2023; 13: 472
  • 15 Rodríguez-Juan E, Rodríguez-Romero C, Fernández-Bolaños J, Florido MC, Garcia-Borrego A. Phenolic compounds from virgin olive oil obtained by natural deep eutectic solvent (NADES): Effect of the extraction and recovery conditions. J Food Sci Technol 2021; 58: 552-561
  • 16 Silvestrini A, Giordani C, Bonacci S, Giuliani A, Ramini D, Matacchione G, Sabbatinelli J, Di Valerio S, Pacetti D, Procopio AD, Procopio A, Rippo MR. Anti-Inflammatory effects of olive leaf extract and its bioactive compounds oleacin and oleuropein-aglycone on senescent endothelial and small airway epithelial cells. Antioxidants (Basel) 2023; 12: 1509
  • 17 Cirmi S, Celano M, Lombardo GE, Maggisano V, Procopio A, Russo D, Navarra M. Oleacein inhibits STAT3, activates the apoptotic machinery, and exerts anti-metastatic effects in the SH-SY5Y human neuroblastoma cells. Food Funct 2020; 11: 3271-3279
  • 18 Cirmi S, Maugeri A, Russo C, Musumeci L, Navarra M, Lombardo GE. Oleacein attenuates lipopolysaccharide-induced inflammation in THP-1-derived macrophages by the inhibition of TLR4/MyD88/NF-kappaB pathway. Int J Mol Sci 2022; 23: 1206
  • 19 Aydin C, Ozcan MM, Gümüş T. Nutritional and technological characteristics of olive (Olea europea L.) fruit and oil: Two varieties growing in two different locations of Turkey. Int J Food Sci Nutr 2009; 60: 365-373
  • 20 Azbar N, Keskin T, Yuruyen A. Enhancement of biogas production from olive mill effluent (OME) by co-digestion. Biomass Bioen 2008; 32: 1195-1201
  • 21 Nunes LJR, Loureiro LME, Sa LCR, Silva HFC. Evaluation of the potential for energy recovery from olive oil industry waste: Thermochemical conversion technologies as fuel improvement methods. Fuel (Lond) 2020; 279: 118536
  • 22 Wang W, Scali M, Vignani R, Spadafora A, Sensi E, Mazzuca S, Cresti M. Protein extraction for two-dimensional electrophoresis from olive leaf, a plant tissue containing high levels of interfering compounds. Electrophoresis 2003; 24: 2369-2375
  • 23 Gómez-González S, Ruiz-Jiménez J, Priego-Capote F, Luque de Castro MD. Qualitative and quantitative sugar profiling in olive fruits, leaves, and stems by gas chromatography-tandem mass spectrometry (GC-MS/MS) after ultrasound-assisted leaching. J Agric Food Chem 2010; 58: 12292-12299
  • 24 Jaber H, Ayadi M, Makni J, Rigane G, Sayadi S, Bouaziz M. Stabilization of refined olive oil by enrichment with chlorophyll pigments extracted from Chemlali olive leaves. Eur J Lipid Sci Technol 2012; 114: 1274-1283
  • 25 Talhaoui N, Taamalli A, Gomez-Caravaca AM, Fernandez-Gutierrez A, Segura-Carretero A. Phenolic compounds in olive leaves: Analytical determination, biotic and abiotic influence, and health benefits. Food Res Int 2015; 77: 92-108
  • 26 Romani A, Ieri F, Urciuoli S, Noce A, Marrone G, Nediani C, Bernini R. Health effects of phenolic compounds found in extra-virgin olive oil, by-products, and leaf of olea europaea L. Nutrients 2019; 11: 1776
  • 27 Lama-Muñoz A, Del Mar Contreras M, Espínola F, Moya M, de Torres A, Romero I, Castro E. Extraction of oleuropein and luteolin-7-O-glucoside from olive leaves: Optimization of technique and operating conditions. Food Chem 2019; 293: 161-168
  • 28 Selim S, Albqmi M, Al-Sanea MM, Alnusaire TS, Almuhayawi MS, Hussein S, Warrad M, El-Saadony MT. Valorizing the usage of olive leaves, bioactive compounds, biological activities, and food applications: A comprehensive review. Front Nutr 2022; 9: 1008349
  • 29 Sahin S, Bilgin M. Olive tree (Olea europaea L.) leaf as a waste by-product of table olive and olive oil industry: A review. J Sci Food Agric 2018; 98: 1271-1279
  • 30 Mohapatra D, Agrawal AK, Sahu AN. Exploring the potential of solid dispersion for improving solubility, dissolution & bioavailability of herbal extracts, enriched fractions, and bioactives. J Microencapsul 2021; 38: 594-612
  • 31 Procopio A, Alcaro S, Nardi M, Oliverio M, Ortuso F, Sacchetta P, Pieragostino D, Sindona G. Synthesis, biological evaluation, and molecular modeling of oleuropein and its semisynthetic derivatives as cyclooxygenase inhibitors. J Agric Food Chem 2009; 57: 11161-11167
  • 32 Frisina M, Bonacci S, Oliverio M, Nardi M, Vatrano TP, Procopio A. Storage effects on bioactive phenols in calabrian monovarietal extra virgin olive oils based on the efsa health claim. Foods 2023; 12: 3799
  • 33 Li T, Wu W, Zhang J, Wu Q, Zhu S, Niu E, Wang S, Jiang C, Liu D, Zhang C. Antioxidant capacity of free and bound phenolics from olive leaves: In vitro and in vivo responses. Antioxidants (Basel) 2023; 12: 2033
  • 34 Pereira SV, Colombo FB, de Freitas LAP. Ultrasound influence on the solubility of solid dispersions prepared for a poorly soluble drug. Ultrason Sonochem 2016; 29: 461-469
  • 35 Kumar TS, Shanmugam S, Palvannan T, Kumar VMB. Evaluation of antioxidant properties of Elaeocarpus ganitrus Roxb. 615 leaves. Iran J Pharm Res 2008; 7: 211-215
  • 36 Sandilya DK, Kannan A. Effect of ultrasound on the solubility limit of a sparingly soluble solid. Ultrason Sonochem 2010; 17: 427-434
  • 37 Hauptmann M, Frederickx F, Struyf H, Mertens P, Heyns M, Gendt S, Glorieux C, Brems S. Enhancement of cavitation activity and particle removal with pulsed high frequency ultrasound and supersaturation. Ultrason Sonochem 2013; 20: 69-76
  • 38 Babu VR, Areefulla SH, Mallikarjun V. Solubility and dissolution enhancement: An overview. J Pharm Res 2010; 3: 141-145
  • 39 Zhao D, Chang MW, Li JS, Suen W, Huang J. Investigation of ice-assisted sonication on the microstructure and chemical quality of Ganoderma lucidum spores. J Food Sci 2014; 79: E2253-E2265
  • 40 Maiuolo J, Maretta A, Gliozzi M, Musolino V, Carresi C, Bosco F, Mollace R, Scarano F, Palma E, Scicchitano M, Nucera S, Sergi D, Muscoli S, Gratteri S, Muscoli C, Mollace V. Ethanol-induced cardiomyocyte toxicity implicit autophagy and NFkB transcription factor. Pharmacol Res 2018; 133: 141-150
  • 41 James-Martin G, Baird DL, Hendrie GA, Bogard J, Anastasiou K, Brooker PG, Wiggins B, Williams G, Herrero M, Lawrence M, Lee AJ, Riley MD. Environmental sustainability in national food-based dietary guidelines: A global review. Lancet Planet Health 2022; 6: e977-e986
  • 42 Ayyalasomayajula N, Bandaru LJM, Chetty CS, Dixit PK, Challa S. Mitochondria-mediated moderation of apoptosis by EGCG in cytotoxic neuronal cells induced by lead (Pb) and amyloid peptides. Biol Trace Elem Res 2022; 200: 3582-3593
  • 43 Ibrahim IM, Abdelmalek DH, Elfiky AA. GRP78: A cellʼs response to stress. Life Sci 2019; 226: 156-163
  • 44 Maiuolo J, Macrì R, Bava I, Gliozzi M, Musolino V, Nucera S, Carresi C, Scicchitano M, Bosco F, Scarano F, Palma E, Gratteri S, Mollace V. Myelin disturbances produced by sub-toxic concentration of heavy metals: The role of oligodendrocyte dysfunction. Int J Mol Sci 2019; 20: 4554
  • 45 Zhao H, Pan X. Mitochondrial Ca(2+) and cell cycle regulation. Int Rev Cell Mol Biol 2021; 362: 171-207
  • 46 Brini M, Calì T, Ottolini D, Carafoli E. Neuronal calcium signaling: Function and dysfunction. Cell Mol Life Sci 2014; 71: 2787-2814
  • 47 Maiuolo J, Gliozzi M, Musolino V, Carresi C, Nucera S, Scicchitano M, Scarano F, Bosco F, Oppedisano F, Macrì R, Mollace V. Environmental and nutritional “stressors” and oligodendrocyte dysfunction: Role of mitochondrial and endoplasmatic reticulum impairment. Biomedicines 2020; 8: 553
  • 48 Oppedisano F, Maiuolo J, Gliozzi M, Musolino V, Carresi C, Nucera S, Scicchitano M, Scarano F, Bosco F, Macrì R, Ruga S, Zito MC, Palma E, Muscoli C, Mollace V. The potential for natural antioxidant supplementation in the early stages of neurodegenerative disorders. Int J Mol Sci 2020; 21: 2618
  • 49 Di Lorenzo C, Colombo F, Biella S, Stockley C, Restani P. Polyphenols and human health: The role of bioavailability. Nutrients 2021; 13: 273
  • 50 Ohnishi M, Morishita H, Iwahashi H, Shitzuo T, Yoshiaki S, Kimura M, Kido R. Inhibitory effects of chlorogenic acid on linoleic acid peroxidation and hemolysis. Phytochemistry 1994; 36: 579-583
  • 51 Oyaizu M. Studies on products of browning reaction: Antioxidative activities of products of browning reaction prepared from glucosamine. Jpn J Nutr Diet 1986; 44: 307-315
  • 52 Chou TC, Martin N. (Eds.) CompuSyn for Drug Combinations: PC Software and Userʼs Guide: A Computer Program for Quantitation of Synergism and Antagonism in Drug Combinations, and the Determination of IC50 and ED50 and LD50 Values. Paramus, NJ: ComboSyn Inc; 2005