Inhibitory effects of Ficus carica and Olea europaea on pro-inflammatory cytokines: A review

Document Type : Review Article


1 Department of Biochemistry, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran

2 School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran

3 Department of Physiology, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran

4 Department of Biochemistry, Faculty of Sciences, Payame Noor University, Tehran, Iran


Objective(s): Ficus carica (fig) and Olea europaea (olive) are valuable nutritional plants that are widely used in diet and traditional medicine. Different parts of the plants such as fruit and leaves contain beneficial compounds with diverse pharmacological properties, among which anti-inflammatory activities are remarkable. The purpose of this review is to discuss the anti-inflammatory effects of F. carica and O. europaea with emphasis on their impact on pivotal pro-inflammatory cytokines including IL-1, IL-6, and TNF-α. 
Materials and Methods: To prepare the present review, the sites utilized included Scopus, PubMed, Science Direct, and Google Scholar and studied relevant articles from 2000 until 2021. 
Results: As a result, we observed that most of the compounds in fig and olive including polyphenols, flavonoids, etc., exert their anti-inflammatory effects through inhibiting or decreasing pro-inflammatory cytokines. Moreover, some natural antioxidants are common between these two plants. 
Conclusion: We suggest that consuming figs and olives simultaneously or alone can be useful in the prevention or treatment of inflammatory diseases.


1. Salma S, Shamsi Y, Ansari S, Nikhat S. Ficus carica L.: A Panacea of nutritional and medicinal benefits. Cellmed 2020;10:1-6. 
2. Farhangi H, Ajilian M, Saeidi M, Khodaei GH. Medicinal fruits in holy Quran. Int J Pediatr 2014;2:89-102.
3. Yi L, Ma S, Ren D. Phytochemistry and bioactivity of Citrus flavonoids: a focus on antioxidant, anti-inflammatory, anticancer and cardiovascular protection activities. Phytochem Rev 2017;16:479-511.
4. Netto RORF, Fernandes VAR, Belozo FL, Caldeira EJ. Anti-inflammatory and antioxidant effects of using alpha-tocopherol in cell culture of the parotid gland under conditions similar to diabetes mellitus. Rom J Diabetes Nutr Metab Dis 2020;27:274-280.
5. Ginwala R, Bhavsar R, Chigbu DGI, Jain P, Khan ZK. Potential role of flavonoids in treating chronic inflammatory diseases with a special focus on the anti-inflammatory activity of apigenin. Antioxidants 2019;8:35-63.
6. Kunnumakkara AB, Rana V, Parama D, Banik K, Girisa S, Sahu H, et al. COVID-19, cytokines, inflammation, and spices: How are they related? Life Sci 2021:119201.
7.    Mumoli N, Evangelista I, Colombo A, Conte G, Mazzone A, Barco S. Transient perivascular inflammation of the carotid artery (TIPIC) syndrome in a patient with COVID-19. Int J Infect Dis 2021;108:126-128.
8.    Garg M, Royce SG, Lubel JS. Letter: intestinal inflammation, COVID-19 and gastrointestinal ACE2-exploring RAS inhibitors. Aliment Pharmacol Ther 2020;52:569-570.
9.    Al-Snafi AE. Nutritional and pharmacological importance of Ficus carica-A. J Pharmacy 2017;7:22-48.
10.    Ali B, Mujeeb M, Aeri V, Mir S, Faiyazuddin M, Shakeel F. Anti-inflammatory and antioxidant activity of Ficus carica Linn. leaves. Nat Prod Res 2012;26:460-465.
11.    Badgujar SB, Patel VV, Bandivdekar AH, Mahajan RT. Traditional uses, phytochemistry and pharmacology of Ficus carica: A review. Pharm Biol 2014;52:1487-1503.
12.    García-Lafuente A, Guillamón E, Villares A, Rostagno MA, Martínez JA. Flavonoids as anti-inflammatory agents: implications in cancer and cardiovascular disease. Inflamm Res 2009;58:537-552.
13.    Liu Y-P, Guo J-M, Yan G, Zhang M-M, Zhang W-H, Qiang L, et al. Anti-inflammatory and antiproliferative prenylated isoflavone derivatives from the fruits of Ficus carica. J Agric Food Chem 2019;67:4817-4823.
14.    Miguel MG. Anthocyanins: Antioxidant and/or anti-inflammatory activities. J Appl Pharm Sci 2011;1:7-15.
15.    Sharma SH, Kumar JS, Chellappan DR, Nagarajan S. Molecular chemoprevention by morin–a plant flavonoid that targets nuclear factor kappa B in experimental colon cancer. Biomed Pharmacother 2018;100:367-373.
16.    Bouyahya A, Bensaid M, Bakri Y, Dakka N. Phytochemistry and ethnopharmacology of Ficus carica. Int J Biochem Res Rev 2016;14:1-12.
17.    Turkoglu M, Pekmezci E, Kilic S, Dundar C, Sevinc H. Effect of Ficus carica leaf extract on the gene expression of selected factors in HaCaT cells. J Cosmet Dermatol 2017;16:e54-e58.
18.    Sharma N, Palia P, Chaudhary A, Verma K, Kumar I. A review on pharmacological activities of lupeol and its triterpene derivatives. J Drug Deliv Ther 2020;10:325-332.
19.    Saleem M. Lupeol, a novel anti-inflammatory and anti-cancer dietary triterpene. Cancer Lett 2009;285:109-115.
20.    Abdel-Aty AM, Hamed MB, Salama WH, Ali MM, Fahmy AS, Mohamed SA. Ficus carica, Ficus sycomorus and Euphorbia tirucalli latex extracts: Phytochemical screening, antioxidant and cytotoxic properties. Biocatal Agric Biotechnol 2019;20:101199.
21.    Oliveira AP, Valentão P, Pereira JA, Silva BM, Tavares F, Andrade PB. Ficus carica L.: Metabolic and biological screening. Food Chem Toxicol 2009;47:2841-2846.
22.    Zhou Y, Wang J, Yang W, Qi X, Lan L, Luo L, et al. Bergapten prevents lipopolysaccharide-induced inflammation in RAW264. 7 cells through suppressing JAK/STAT activation and ROS production and increases the survival rate of mice after LPS challenge. Int Immunopharmacol 2017;48:159-168.
23.    Aidoo DB, Obiri DD, Osafo N, Antwi AO, Essel LB, Duduyemi BM, et al. Allergic airway-induced hypersensitivity is attenuated by bergapten in murine models of inflammation. Adv Pharmacol Sci 2019; 6097349.
24.    Li X, Yu C, Hu Y, Xia X, Liao Y, Zhang J, et al. New application of psoralen and angelicin on periodontitis with antibacterial, anti-inflammatory, and osteogenesis effects. Front Cell Infect Microbiol 2018;8:178-191.
25.    Cho UM, Choi DH, Yoo DS, Park SJ, Hwang HS. Inhibitory effect of ficin derived from fig latex on inflammation and melanin production in skin cells. Biotechnol Bioprocess Eng 2019;24:288-297.
26.    Ghanbari R, Anwar F, Alkharfy KM, Gilani A-H, Saari N. Valuable nutrients and functional bioactives in different parts of olive (Olea europaea L.)—a review. Int J Mol Sci 2012;13:3291-3340.
27.    Guo Z, Jia X, Zheng Z, Lu X, Zheng Y, Zheng B, et al. Chemical composition and nutritional function of olive (Olea europaea L.): A review. Phytochem Rev 2018;17:1091-1110.
28.    Otero DM, Oliveira FM, Lorini A, Antunes BdF, Oliveira RM, Zambiazi RC. Oleuropein: Methods for extraction, purifying and applying. Revista Ceres 2020;67:315-329.
29.    Velázquez-Palmero D, Romero-Segura C, García-Rodríguez R, Hernández ML, Vaistij FE, Graham IA, et al. An oleuropein β-glucosidase from olive fruit is involved in determining the phenolic composition of virgin olive oil. Front Plant Sci 2017;8:1902-1914.
30.    Wongwarawipat T, Papageorgiou N, Bertsias D, Siasos G, Tousoulis D. Olive oil-related anti-inflammatory effects on atherosclerosis: potential clinical implications. Endocr Metab Immune Disord Drug Targets 2018;18:51-62.
31.    Burja B, Kuret T, Janko T, Topalović D, Živković L, Mrak-Poljšak K, et al. Olive leaf extract attenuates inflammatory activation and DNA damage in human arterial endothelial cells. Front Cardiovasc Med 2019;6:56.
32.    Özcan MM, Matthäus B. A review: benefit and bioactive properties of olive (Olea europaea L.) leaves. Eur Food Res Technol 2017;243:89-99.
33.    Serra G, Incani A, Serreli G, Porru L, Melis MP, Tuberoso CI, et al. Olive oil polyphenols reduce oxysterols-induced redox imbalance and pro-inflammatory response in intestinal cells. Redox Biol 2018;17:348-354.
34.    Yonezawa Y, Miyashita T, Nejishima H, Takeda Y, Imai K, Ogawa H. Anti-inflammatory effects of olive-derived hydroxytyrosol on lipopolysaccharide-induced inflammation in RAW264. 7 cells. J Vet Med Sci 2018;80:1801-1807.
35.    Richard N, Arnold S, Hoeller U, Kilpert C, Wertz K, Schwager J. Hydroxytyrosol is the major anti-inflammatory compound in aqueous olive extracts and impairs cytokine and chemokine production in macrophages. Planta Med 2011;77:1890-1897.
36.    da Silva ECO, dos Santos FM, Ribeiro ARB, de Souza ST, Barreto E, da Silva Fonseca EJ. Drug-induced anti-inflammatory response in A549 cells, as detected by Raman spectroscopy: A comparative analysis of the actions of dexamethasone and p-coumaric acid. Analyst 2019;144:1622-1631.
37.    Kheiry M, Dianat M, Badavi M, Mard SA, Bayati V. p-Coumaric acid attenuates lipopolysaccharide-induced lung inflammation in rats by scavenging ROS production: An in vivo and in vitro study. Inflammation 2019;42:1939-1950.
38.    Mazani M, Rezagholizadeh L, Shamsi S, Mahdavifard S, Ojarudi M, Salimnejad R, et al. Protection of CCl(4)-induced hepatic and renal damage by linalool. Drug Chem Toxicol 2020; 6097349.
39.    Pourfarjam Y, Rezagholizadeh L, Nowrouzi A, Meysamie A, Ghaseminejad S, Ziamajidi N, et al. Effect of Cichorium intybus L. seed extract on renal parameters in experimentally induced early and late diabetes type 2 in rats. Ren Fail 2017;39:211-221.
40.    Rezagholizadeh L, Pourfarjam Y, Nowrouzi A, Nakhjavani M, Meysamie A, Ziamajidi N, et al. Effect of Cichorium intybus L. on the expression of hepatic NF-κB and IKKβ and serum TNF-α in STZ- and STZ+ niacinamide-induced diabetes in rats. Diabetol Metab Syndr 2016;8:11.
41.    Shin HS, Satsu H, Bae M-J, Totsuka M, Shimizu M. Catechol groups enable reactive oxygen species scavenging-mediated suppression of PKD-NFkappaB-IL-8 signaling pathway by chlorogenic and caffeic acids in human intestinal cells. Nutrients 2017;9:165.
42.    Yarla NS, Polito A, Peluso I. Effects of olive oil on TNF-α and IL-6 in humans: implication in obesity and frailty. Endocr Metab Immune Disord Drug Targets 2018;18:63-74.
43.    Marquez-Martin A, De La Puerta R, Fernandez-Arche A, Ruiz-Gutierrez V, Yaqoob P. Modulation of cytokine secretion by pentacyclic triterpenes from olive pomace oil in human mononuclear cells. Cytokine 2006;36:211-217.
44.    Lozano-Castellón J, López-Yerena A, Rinaldi de Alvarenga JF, Romero del Castillo-Alba J, Vallverdú-Queralt A, Escribano-Ferrer E, et al. Health-promoting properties of oleocanthal and oleacein: Two secoiridoids from extra-virgin olive oil. Crit Rev Food Sci Nutr 2020;60:2532-2548.
45.    Carpi S, Scoditti E, Massaro M, Polini B, Manera C, Digiacomo M, et al. The extra-virgin olive oil polyphenols oleocanthal and oleacein counteract inflammation-related gene and mirna expression in adipocytes by attenuating NF-κB activation. Nutrients 2019;11:2855.
46.    Chebbi Mahjoub R, Khemiss M, Dhidah M, Dellaï A, Bouraoui A, Khemiss F. Chloroformic and methanolic extracts of Olea europaea L. leaves present anti-inflammatory and analgesic activities. Int Sch Res Notices 2011;564972.
47.    Wang L, Geng C, Jiang L, Gong D, Liu D, Yoshimura H, et al. The anti-atherosclerotic effect of olive leaf extract is related to suppressed inflammatory response in rabbits with experimental atherosclerosis. Eur J Nutr 2008;47:235-243.
48.    Qabaha K, AL-Rimawi F, Qasem A, Naser SA. Oleuropein is responsible for the major anti-inflammatory effects of olive leaf extract. J Med Food 2018;21:302-305.
49.    Pamukçu B. Inflammation and thrombosis in patients with COVID-19: A prothrombotic and inflammatory disease caused by SARS coronavirus-2. Anatol J Cardiol 2020;24:224-234.
50.    Mehta P, Haskard DO, Laffan MA, Chambers RC, Hunt BJ. Thromboses and COVID-19: reducing inflammation in addition to thromboprophylaxis. Lancet Rheumatol 2021;3:e171-e172.