Submitted Successfully!
To reward your contribution, here is a gift for you: A free trial for our video production service.
Thank you for your contribution! You can also upload a video entry or images related to this topic.
Version Summary Created by Modification Content Size Created at Operation
1 -- 1070 2023-06-08 12:31:23 |
2 only format change Meta information modification 1070 2023-06-09 04:22:04 |

Video Upload Options

Do you have a full video?


Are you sure to Delete?
If you have any further questions, please contact Encyclopedia Editorial Office.
Vijakumaran, U.; Goh, N.; Razali, R.A.; Abdullah, N.A.H.; Yazid, M.D.; Sulaiman, N. Olive Bioactive Compounds in Infectious Respiratory Diseases. Encyclopedia. Available online: (accessed on 14 June 2024).
Vijakumaran U, Goh N, Razali RA, Abdullah NAH, Yazid MD, Sulaiman N. Olive Bioactive Compounds in Infectious Respiratory Diseases. Encyclopedia. Available at: Accessed June 14, 2024.
Vijakumaran, Ubashini, Neng-Yao Goh, Rabiatul Adawiyah Razali, Nur Atiqah Haizum Abdullah, Muhammad Dain Yazid, Nadiah Sulaiman. "Olive Bioactive Compounds in Infectious Respiratory Diseases" Encyclopedia, (accessed June 14, 2024).
Vijakumaran, U., Goh, N., Razali, R.A., Abdullah, N.A.H., Yazid, M.D., & Sulaiman, N. (2023, June 08). Olive Bioactive Compounds in Infectious Respiratory Diseases. In Encyclopedia.
Vijakumaran, Ubashini, et al. "Olive Bioactive Compounds in Infectious Respiratory Diseases." Encyclopedia. Web. 08 June, 2023.
Olive Bioactive Compounds in Infectious Respiratory Diseases

The pathogenesis of respiratory diseases is centred around inflammation and oxidative stress. Plant-based alongside synthetic drugs were considered as therapeutics due to their proven nutraceutical value. One such example is the olive, which is a traditional symbol of the MedDiet. Olive bioactive compounds are enriched with antioxidant, anti-inflammatory, anticancer and antiviral properties.

olive respiratory disease

1. Introduction

The growing prevalence of chronic respiratory diseases (CRDs) has increased morbidity and mortality rates worldwide [1]. Chronic respiratory diseases include chronic obstructive pulmonary disease (COPD), asthma, pneumoconiosis, pneumonia, lung cancer, chronic bronchitis, pulmonary sarcoidosis and tuberculosis [2]. COPD causes 81.7% of CRD deaths and is the third-leading cause of death worldwide, killing almost 3.2 million people annually. Meanwhile, pneumonia is the leading cause of death among geriatric (>65 years old, elderly) and paediatric (<5 years old, children) patients [3]. The World Health Organization (WHO) reported that around 6.8 million people’s lives abruptly ended mainly due to respiratory illnesses during the COVID-19 pandemic era [4]. Thus, the management of CRDs was given priority, encompassing the invention of new drugs, vaccines, antibiotics, cortisone, ventilation tools, inhalation therapies and advanced lung surgical intervention [5]. However, developing drug-resistant organism strains and variants make available treatments less effective [6][7]. Hence, more efficient and atoxic drugs are preferable to ease CRD management, especially during the pandemic. Scientific interest is supported by the fact that more than thirty per cent of FDA-approved drugs are of natural origin [8]. Historically, natural-based therapies have long been incorporated into CRD treatment. More than 2000 years ago, drug delivery for respiratory diseases was performed via inhalation therapies in ayurvedic medicine [9]. Scientifically, Oriola et al. reviewed the potential of plant-derived natural chemicals, thus supporting their benefits for common respiratory disease treatment [10].
The olive has been one of the most researched plant varieties throughout the decades for its enormous health benefits [11][12]. It is a traditional symbol of Mediterranean culture. This is reflected by a quote from a famous French writer, Georges Duhamel, “There, where the olive tree gives up, is where the Mediterranean ends. The tree of light is the nature and culture of the Mediterranean” [13][14]. The olive fruit and olive oil are the largest products that are commercialised from the olive tree [14], which serve as primary sources of fat in the MedDiet [15]. In 2013, the United Nations Educational, Scientific and Cultural Organization (UNESCO) added the MedDiet to the “Representative List of the Intangible Cultural Heritage of Humanity”. The MedDiet was also specified as being a healthy diet in the 2015–2020 Dietary Guidelines for Americans [16]. Its nutritional values have been correlated with anti-inflammatory [17][18], cardio-protective [19][20][21], anticancer [22][23], anti-ageing [24][25] and neuroprotection [26][27][28] effects. Interestingly, a meta-analysis of cross-sectional studies demonstrated that the MedDiet was associated with longer telomere length and positive ageing [29].

2. Olive Bioactive Molecules in Infectious Respiratory Diseases

Respiratory infections occur due to bacteria or invading viruses. Antibiotic treatments tend to fail when dealing with antibiotic-resistant bacteria. Respiratory pathogens were reported to exacerbate chronic obstructive pulmonary disease [30]. A meta-analysis of 3338 COVID-19 patients reported that 6.9% of patients were coinfected with bacterial infections [31]. Seven compounds from olive (caffeic acid, verbascoside, oleuropein, luteolin 7-O-glucoside, rutin, apigenin 7-O-glucoside and luteolin 4’-O-glucoside) were found to have an antibacterial effect towards strains such as Bacillus cereus, Staphylococcus aureus, Pseudomonas aeruginosa and Klebsiella pneumoniae and antifungal strains such as Candida albicans [32]. Olive secoiridoides also inhibited five different bacterial strains (Haemophilus influenzae, Moraxella catarrhalis, Salmonella typhi, Vibrio parahaemolyticus and Staphylococcus aureus) that commonly cause intestinal and respiratory tract infections [33]. Moreover, aliphatic aldehydes from olives showed similar antibacterial activity [34][35] where alpha- and beta-unsaturated aldehydes were found to have broad-spectrum antibacterial activity, while saturated aldehydes did not show a significant antibacterial effect. Olive extract was reported as being one of the most potent antimycobacterial agents among 63 Mexican traditional medicines postulated as a potential drug for tuberculosis [36][37].
Viral infection is the major reason for respiratory diseases such as pneumonia, bronchitis and COVID-19. The most common viruses that invade the human respiratory system are human coronavirus, rhinovirus (RV), influenza, adenovirus, respiratory syncytial virus (RSV) and so on [38]. Olive compounds have been well reviewed and preferred as a functional food containing antiviral and immune-boosting effects [39]. Additionally, Hydroxytyrosol has been found to disrupt the viral envelope of influenza A viruses, including H1N1, H3N2, H5N1 and H9N2 [40]. Oleuropein has also been reported to inhibit the herpes simplex virus (HSV-1) via phosphorylating PKR, c-FOS and c-JUN in Hela cells [39]. Furthermore, purified HT from olive and a patented HT, HIDROX®, have been shown to inactivate SARS-CoV-2. They altered the spike protein, significantly impacting the viral genome [41]. A similar effect has been reported in molecular docking by Geromichalou et al. He demonstrated the EVOO compound’s potential to bind to inhibit the SARS-CoV-2 spike protein via targeting angiotensin-converting enzyme 2 (ACE2) and the receptor-binding domain (RBD) [42]. On the other hand, Nrf2 has also been revealed to have the ability to inhibit virus penetration by secreting anti-proteases in COVID-19 patients [43]. Nrf2 activates interferon gene expression to initiate antiviral activity [44]. The research collectively reported findings of olive-derived phytochemicals’ ability to activate the Nrf2 pathway [45][46][47]. Thus, they certainly could play a role in drug design for COVID-19 treatment.

3. Olive Bioactive Molecules in Over-Proliferation of Respiratory Cells

Lung cancer is a leading cause of cancer death to date, which is due to the over-proliferation of respiratory cells [48]. Olive compounds, especially polyphenols, have been well studied for their anticancer effects [49][50][51]. A systematic search and meta-analysis of 45 studies [22] discovered that olive oil consumption prevents cancer. An olive extract and bromelain combination suppressed Benzo[a]pyrene (BaP)-induced lung carcinogenesis by decreasing the expression of inflammation and oxidative markers (Nrf2, NF-κB) [47]. In another study, oleic acid, and its metabolite oleoyl ethanolamide, induced apoptosis in lung carcinoma cell lines by decreasing programmed death-ligand 1 (PD-L1), the tumorigenesis marker and the phosphorylate STAT pathway [52]. An extract from olive mill wastewater (OMWW A009) limited lung cancer cell propagation by activating apoptosis. The extract was able to reduce CXCL12 and CXCR4 chemokines and STAT3 phosphorylation [53]. Besides, (-)-Oleocanthal (OC) disrupted metastasis by inhibiting the activation of mesenchymal-epithelial transition factor (c-MET) and cyclooxygenase 2 (COX2) in adenocarcinoma cells A549 and NCI-H322M [54]. The same study showed that eight weeks of OC supplementation prevented brain and other organ metastasis in mice models. The c-MET inhibitors showed promising results in lung cancer prevention in both animal models and clinical trials [55][56]. Hydroxytyrosol was also reported to have reversed TGFβ1-induced EMT in respiratory epithelial cells by inhibiting AKT and SMAD2/3 expression [57]. Thus, hydroxytyrosol could be exploited for cancer prevention by targeting c-MET inhibition.


  1. Xie, M.; Liu, X.; Cao, X.; Guo, M.; Li, X. Trends in prevalence and incidence of chronic respiratory diseases from 1990 to 2017. Respir. Res. 2020, 21, 49.
  2. Baptista, E.A.; Dey, S.; Pal, S. Chronic respiratory disease mortality and its associated factors in selected Asian countries: Evidence from panel error correction model. BMC Public. Health 2021, 21, 53.
  3. Levine, S.M.; Marciniuk, D.D. Global Impact of Respiratory Disease: What Can We Do, Together, to Make a Difference? Chest 2022, 161, 1153–1154.
  4. World Health Organization. Available online: (accessed on 21 March 2023).
  5. Geddes, D. The history of respiratory disease management. Medicine 2020, 48, 239–243.
  6. Behzadi, M.A.; Leyva-Grado, V.H. Overview of Current Therapeutics and Novel Candidates Against Influenza, Respiratory Syncytial Virus, and Middle East Respiratory Syndrome Coronavirus Infections. Front. Microbiol. 2019, 10, 1327.
  7. He, H.; Wunderink, R.G. Staphylococcus aureus Pneumonia in the Community. Semin. Respir. Crit. Care Med. 2020, 41, 470–479.
  8. Patridge, E.; Gareiss, P.; Kinch, M.S.; Hoyer, D. An analysis of FDA-approved drugs: Natural products and their derivatives. Drug. Discov. Today 2016, 21, 204–207.
  9. Sanders, M. Inhalation therapy: An historical review. Prim. Care Respir. J. 2007, 16, 71–81.
  10. Oriola, A.O.; Oyedeji, A.O. Plant-Derived Natural Products as Lead Agents against Common Respiratory Diseases. Molecules 2022, 27, 3054.
  11. Garcia-Martinez, O.; Ruiz, C.; Gutierrez-Ibanez, A.; Illescas-Montes, R.; Melguizo-Rodriguez, L. Benefits of Olive Oil Phenolic Compounds in Disease Prevention. Endocr. Metab. Immune Disord. Drug. Targets 2018, 18, 333–340.
  12. Barazani, O.; Dag, A.; Dunseth, Z. The history of olive cultivation in the southern Levant. Front. Plant. Sci. 2023, 14, 1131557.
  13. Letendre, D. Les mots de l’insoumis. Liberte 2014, 47. Available online:,+D.&publication_year=2014&journal=Liberte&volume=47&pages=278 (accessed on 26 March 2023).
  14. Jimenez-Lopez, C.; Carpena, M.; Lourenço-Lopes, C.; Gallardo-Gomez, M.; Lorenzo, J.M.; Barba, F.J.; Prieto, M.A.; Simal-Gandara, J. Bioactive Compounds and Quality of Extra Virgin Olive Oil. Foods 2020, 9, 1014.
  15. Widmer, R.J.; Flammer, A.J.; Lerman, L.O.; Lerman, A. The Mediterranean diet, its components, and cardiovascular disease. Am. J. Med. 2015, 128, 229–238.
  16. Romagnolo, D.F.; Selmin, O.I. Mediterranean Diet and Prevention of Chronic Diseases. Nutr. Today 2017, 52, 208–222.
  17. Che Man, R.; Sulaiman, N.; Ishak, M.F.; Bt Hj Idrus, R.; Abdul Rahman, M.R.; Yazid, M.D. The Effects of Pro-Inflammatory and Anti-Inflammatory Agents for the Suppression of Intimal Hyperplasia: An Evidence-Based Review. Int. J. Environ. Res. Public Health 2020, 17, 7825.
  18. Al-Aubaidy, H.A.; Dayan, A.; Deseo, M.A.; Itsiopoulos, C.; Jamil, D.; Hadi, N.R.; Thomas, C.J. Twelve-Week Mediterranean Diet Intervention Increases Citrus Bioflavonoid Levels and Reduces Inflammation in People with Type 2 Diabetes Mellitus. Nutrients 2021, 13, 1133.
  19. Martínez-González, M.A.; Gea, A.; Ruiz-Canela, M. The Mediterranean Diet and Cardiovascular Health. Circ. Res. 2019, 124, 779–798.
  20. Vijakumaran, U.; Yazid, M.D.; Hj Idrus, R.B.; Abdul Rahman, M.R.; Sulaiman, N. Molecular Action of Hydroxytyrosol in Attenuation of Intimal Hyperplasia: A Scoping Review. Front. Pharmacol. 2021, 12, 3266.
  21. Vijakumaran, U.; Shanmugam, J.; Heng, J.W.; Azman, S.S.; Yazid, M.D.; Haizum Abdullah, N.A.; Sulaiman, N. Effects of Hydroxytyrosol in Endothelial Functioning: A Comprehensive Review. Molecules 2023, 28, 1861.
  22. Morze, J.; Danielewicz, A.; Przybyłowicz, K.; Zeng, H.; Hoffmann, G.; Schwingshackl, L. An updated systematic review and meta-analysis on adherence to mediterranean diet and risk of cancer. Eur. J. Nutr. 2021, 60, 1561–1586.
  23. Porciello, G.; Montagnese, C.; Crispo, A.; Grimaldi, M.; Libra, M.; Vitale, S.; Palumbo, E.; Pica, R.; Calabrese, I.; Cubisino, S.; et al. Mediterranean diet and quality of life in women treated for breast cancer: A baseline analysis of DEDiCa multicentre trial. PLoS ONE 2020, 15, e0239803.
  24. Mazzocchi, A.; Leone, L.; Agostoni, C.; Pali-Schöll, I. The Secrets of the Mediterranean Diet. Does Olive Oil Matter? Nutrients 2019, 11, 2941.
  25. Fernández del Río, L.; Gutiérrez-Casado, E.; Varela-López, A.; Villalba, J.M. Olive Oil and the Hallmarks of Aging. Molecules 2016, 21, 163.
  26. Kamil, K.; Yazid, M.D.; Idrus, R.B.; Kumar, J. Hydroxytyrosol Promotes Proliferation of Human Schwann Cells: An In Vitro Study. Int. J. Environ. Res. Public Health 2020, 17, 4404.
  27. Naureen, Z.; Dhuli, K.; Medori, M.C.; Caruso, P.; Manganotti, P.; Chiurazzi, P.; Bertelli, M. Dietary supplements in neurological diseases and brain aging. J. Prev. Med. Hyg. 2022, 63, E174–E188.
  28. Foscolou, A.; Critselis, E.; Panagiotakos, D. Olive oil consumption and human health: A narrative review. Maturitas 2018, 118, 60–66.
  29. Canudas, S.; Becerra-Tomás, N.; Hernández-Alonso, P.; Galié, S.; Leung, C.; Crous-Bou, M.; De Vivo, I.; Gao, Y.; Gu, Y.; Meinilä, J.; et al. Mediterranean Diet and Telomere Length: A Systematic Review and Meta-Analysis. Adv. Nutr. 2020, 11, 1544–1554.
  30. Euba, B.; López-López, N.; Rodríguez-Arce, I.; Fernández-Calvet, A.; Barberán, M.; Caturla, N.; Martí, S.; Díez-Martínez, R.; Garmendia, J. Resveratrol therapeutics combines both antimicrobial and immunomodulatory properties against respiratory infection by nontypeable Haemophilus influenzae. Sci. Rep. 2017, 7, 12860.
  31. Langford, B.J.; So, M.; Raybardhan, S.; Leung, V.; Westwood, D.; MacFadden, D.R.; Soucy, J.R.; Daneman, N. Bacterial co-infection and secondary infection in patients with COVID-19: A living rapid review and meta-analysis. Clin. Microbiol. Infect. 2020, 26, 1622–1629.
  32. Pereira, A.P.; Ferreira, I.C.; Marcelino, F.; Valentão, P.; Andrade, P.B.; Seabra, R.; Estevinho, L.; Bento, A.; Pereira, J.A. Phenolic compounds and antimicrobial activity of olive (Olea europaea L. Cv. Cobrançosa) leaves. Molecules 2007, 12, 1153–1162.
  33. Bisignano, G.; Tomaino, A.; Lo Cascio, R.; Crisafi, G.; Uccella, N.; Saija, A. On the in-vitro antimicrobial activity of oleuropein and hydroxytyrosol. J. Pharm. Pharm. 1999, 51, 971–974.
  34. Bisignano, G.; Laganà, M.G.; Trombetta, D.; Arena, S.; Nostro, A.; Uccella, N.; Mazzanti, G.; Saija, A. In vitro antibacterial activity of some aliphatic aldehydes from Olea europaea L. FEMS Microbiol. Lett. 2001, 198, 9–13.
  35. Waterman, E.; Lockwood, B. Active components and clinical applications of olive oil. Altern. Med. Rev. 2007, 12, 331–342.
  36. Alkhatib, A. Antiviral Functional Foods and Exercise Lifestyle Prevention of Coronavirus. Nutrients 2020, 12, 2633.
  37. Bertelli, M.; Kiani, A.K.; Paolacci, S.; Manara, E.; Kurti, D.; Dhuli, K.; Bushati, V.; Miertus, J.; Pangallo, D.; Baglivo, M.; et al. Hydroxytyrosol: A natural compound with promising pharmacological activities. J. Biotechnol. 2020, 309, 29–33.
  38. Troy, N.M.; Bosco, A. Respiratory viral infections and host responses; insights from genomics. Respir. Res. 2016, 17, 156.
  39. Pennisi, R.; Ben Amor, I.; Gargouri, B.; Attia, H.; Zaabi, R.; Chira, A.B.; Saoudi, M.; Piperno, A.; Trischitta, P.; Tamburello, M.P.; et al. Analysis of Antioxidant and Antiviral Effects of Olive (Olea europaea L.) Leaf Extracts and Pure Compound Using Cancer Cell Model. Biomolecules 2023, 13, 238.
  40. Yamada, K.; Ogawa, H.; Hara, A.; Yoshida, Y.; Yonezawa, Y.; Karibe, K.; Nghia, V.B.; Yoshimura, H.; Yamamoto, Y.; Yamada, M.; et al. Mechanism of the antiviral effect of hydroxytyrosol on influenza virus appears to involve morphological change of the virus. Antivir. Res. 2009, 83, 35–44.
  41. de Oliveira, J.R.; Antunes, B.S.; do Nascimento, G.O.; Kawall, J.C.S.; Oliveira, J.V.B.; Silva, K.; Costa, M.A.T.; Oliveira, C.R. Antiviral activity of medicinal plant-derived products against SARS-CoV-2. Exp. Biol. Med. 2022, 247, 1797–1809.
  42. Geromichalou, E.G.; Geromichalos, G.D. In Silico Approach for the Evaluation of the Potential Antiviral Activity of Extra Virgin Olive Oil (EVOO) Bioactive Constituents Oleuropein and Oleocanthal on Spike Therapeutic Drug Target of SARS-CoV-2. Molecules 2022, 27, 7572.
  43. Schultz, M.A.; Hagan, S.S.; Datta, A.; Zhang, Y.; Freeman, M.L.; Sikka, S.C.; Abdel-Mageed, A.B.; Mondal, D. Nrf1 and Nrf2 transcription factors regulate androgen receptor transactivation in prostate cancer cells. PLoS ONE 2014, 9, e87204.
  44. Hassan, S.M.; Jawad, M.J.; Ahjel, S.W.; Singh, R.B.; Singh, J.; Awad, S.M.; Hadi, N.R. The Nrf2 Activator (DMF) and COVID-19: Is there a Possible Role? Med. Arch. 2020, 74, 134–138.
  45. Lee, W.; Kim, J.; Park, E.K.; Bae, J.S. Maslinic Acid Ameliorates Inflammation via the Downregulation of NF-kappaB and STAT-1. Antioxidants 2020, 9, 106.
  46. Wang, W.C.; Xia, Y.M.; Yang, B.; Su, X.N.; Chen, J.K.; Li, W.; Jiang, T. Protective Effects of Tyrosol against LPS-Induced Acute Lung Injury via Inhibiting NF-κB and AP-1 Activation and Activating the HO-1/Nrf2 Pathways. Biol. Pharm. Bull. 2017, 40, 583–593.
  47. Majumder, D.; Debnath, R.; Nath, P.; Libin Kumar, K.V.; Debnath, M.; Tribedi, P.; Maiti, D. Bromelain and Olea europaea (L.) leaf extract mediated alleviation of benzo(a)pyrene induced lung cancer through Nrf2 and NFκB pathway. Env. Sci. Pollut. Res. Int. 2021, 28, 47306–47326.
  48. Demerlé, C.; Gorvel, L.; Olive, D. BTLA-HVEM Couple in Health and Diseases: Insights for Immunotherapy in Lung Cancer. Front. Oncol. 2021, 11, 682007.
  49. Gorzynik-Debicka, M.; Przychodzen, P.; Cappello, F.; Kuban-Jankowska, A.; Marino Gammazza, A.; Knap, N.; Wozniak, M.; Gorska-Ponikowska, M. Potential Health Benefits of Olive Oil and Plant Polyphenols. Int. J. Mol. Sci. 2018, 19, 686.
  50. Torić, J.; Marković, A.K.; Brala, C.J.; Barbarić, M. Anticancer effects of olive oil polyphenols and their combinations with anticancer drugs. Acta Pharm. 2019, 69, 461–482.
  51. Moral, R.; Escrich, E. Influence of Olive Oil and Its Components on Breast Cancer: Molecular Mechanisms. Molecules 2022, 27, 477.
  52. Yamagata, K.; Uzu, E.; Yoshigai, Y.; Kato, C.; Tagami, M. Oleic acid and oleoylethanolamide decrease interferon-γ-induced expression of PD-L1 and induce apoptosis in human lung carcinoma cells. Eur. J. Pharm. 2021, 903, 174116.
  53. Gallazzi, M.; Festa, M.; Corradino, P.; Sansone, C.; Albini, A.; Noonan, D.M. An Extract of Olive Mill Wastewater Downregulates Growth, Adhesion and Invasion Pathways in Lung Cancer Cells: Involvement of CXCR4. Nutrients 2020, 12, 903.
  54. Siddique, A.B.; Kilgore, P.C.S.R.; Tajmim, A.; Singh, S.S.; Meyer, S.A.; Jois, S.D.; Cvek, U.; Trutschl, M.; Sayed, K.A.E. (−)-Oleocanthal as a Dual c-MET-COX2 Inhibitor for the Control of Lung Cancer. Nutrients 2020, 12, 1749.
  55. Pasquini, G.; Giaccone, G. C-MET inhibitors for advanced non-small cell lung cancer. Expert. Opin. Investig. Drugs 2018, 27, 363–375.
  56. Recondo, G.; Che, J.; Jänne, P.A.; Awad, M.M. Targeting MET Dysregulation in Cancer. Cancer Discov. 2020, 10, 922–934.
  57. Razali, R.A.; Yazid, M.D.; Saim, A.; Idrus, R.B.H.; Lokanathan, Y. Approaches in Hydroxytyrosol Supplementation on Epithelial&mdash;Mesenchymal Transition in TGF&beta;1-Induced Human Respiratory Epithelial Cells. Int. J. Mol. Sci. 2023, 24, 3974.
Subjects: Respiratory System
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to : , , , , ,
View Times: 297
Revisions: 2 times (View History)
Update Date: 09 Jun 2023
Video Production Service