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Ocimum basilicum L.: Antiinflammatory Actions and Potential Usage for Arthritic Conditions
CHAPTER 27
Ocimum basilicum L.: Antiinflammatory Actions and Potential Usage for Arthritic Conditions Michel Mansur Machado, Luís Flávio Souza de Oliveira, Luísa Zuravski Cellular Toxicology Research Group (ToxCel), Federal University of Pampa, Uruguaiana, Brazil
1. INTRODUCTION Arthritis is an inflammatory disease that leads to joint destruction and functional disability if not adequately treated.1 In this disease, autoantibodies such as rheumatoid factor or anticitrullinated peptide antibodies (ACPA) are typical serologic findings and are strongly associated with erosive disease.2 Aside from bone erosion, the pathognomonic features of arthritis comprise articular and periarticular bone loss and loss of trabeculation.3 A panel of effective and approved immunosuppressive drugs is available to treat inflammation and to avoid joint damage.4 Recent studies demonstrated poor adherence to these drugs, despite these treatment opportunities.5, 6 The reasons for this are multifactorial; however, they are mainly influenced by medical beliefs and lack of understanding of the disease.3 The use of natural products in folk medicine as a therapeutic resource is widely diffused in the population, and this inclination has contributed significantly to the consumption not only of natural products but also of herbal medicines. A work by the World Health Organization (WHO) that has evaluated the use of traditional medicine in different regions shows that the use of plants and their derivatives can reach more than 90% of certain regions of the world, such as China and Malaysia.7 Natural medicine is a very popular therapeutic resource in self-medication. However, due to the ease of access, it can aggravate its potential risks of toxicity. In addition, there is a large gap related to popular understanding that must be filled through actions that seek to improve the dissemination of knowledge about the safe and rational use of medicinal plants and herbal medicines. Among these is the availability of information with scientific evidence, which should be passed on to physicians, pharmacists, and users of these products.8 In this context, basil (Ocimum basilicum L.) appears as an alternative treatment, in addition to being widely used as an ornamental plant and a food condiment. This species belongs to the family Lamiaceae and originates from tropical Asia, but today it is Bioactive Food as Dietary Interventions for Arthritis and Related Inflammatory Diseases https://doi.org/10.1016/B978-0-12-813820-5.00027-1
© 2019 Elsevier Inc. All rights reserved.
481
482
Bioactive Food as Dietary Interventions for Arthritis and Related Inflammatory Diseases
cultivated worldwide.9 Among its popular uses, O. basilicum is used as an antioxidant, antiinflammatory, anticarcinogenic, antimicrobial, and cardiovascular agent.10 It is also used in abdominal discomfort caused by colic in addition to its use in respiratory problems such as cough and asthma11 and as an antiplatelet agent.12 Several secondary metabolites with antioxidant and antiinflammatory activities have been identified in this species with the main ones being polyphenols, flavonoids, and terpenes.13
2. BASIL (O. BASILICUM L.) Basil is an herbaceous, aromatic, and medicinal plant, known since antiquity by Indians, Greeks, Egyptians, and Romans. It is enveloped in spiritual culture and symbolism, and is even considered sacred among some Hindu peoples as it represents Tulasi, the wife of the god Vishnu. It is related to feelings of hatred, love, and mourning, but it is certainly more widely known for its culinary powers.14 The basil shows a straight and branched stem and reaches about 1 m in height. Its leaves are delicate, oval, pubescent, and bright green. The inflorescences are of the spike type and composed of white, lilac, or reddish flowers. Its pollination is crossed, and the fruits are of the type acheno with a black-blue coloration. There are more than 60 different varieties of basil, with variations in the color, size, and shape of the leaves, the size of the plant and the concentration of the aroma. The basil leaves have a characteristic sweet and spicy flavor and aroma. They are used dry or fresh in the preparation of several hot or cold dishes, and are closely related to Italian gastronomy 15.
3. ISOLATED COMPOUNDS IN BASIL Numerous studies have attempted to establish a composition pattern for basil, both in the extract and in the oil. The greatest difficulty is the diversity of this species. Today, more than 25 different types of O. basilicum are known, with numerous constitutional differences.16, 17 Because of the variety of compounds and variability of concentrations found in this cultivation, four chemotypes were established based on the compound’s highest concentration in the extracted oil of basil: chemotype linalool, methylchavicol, eugenol, and 1,8-cineole.16 Among the main compounds isolated so far in the oil are the compounds linalool, methyleugenol, eugenol, methylcinnamate, chavicol, 1,8-cineol, α-terpinol,13, 15, 18 camphor, limonene, geraniol, and farmaseno.19 In the extract, the compounds identified to date were novadensin, salvigenin, circiseol, eupatorin, gardenina B,20 chicoric acid, caftaric acid,13, 20a p-coumaric acid, peonidin-3, 5-diglycoside,20b and rosmarinic acid (RA).9, 20–22
Ocimum basilicum L.
Several studies report that among the components of this plant, RA is the most biologically active compound.9, 13, 21
4. IMMUNOLOGICAL AND ANTIINFLAMMATORY ACTIVITIES Certainly, the activities described for basil are varied, but those related to the effects on the immune system, especially the antiinflammatory effects, are, in the case of this chapter, the focus to be approached more vehemently. In this thinking, we list below a series of studies that demonstrate the effectiveness of this condiment as a potential agent to assist in the treatment of inflammatory diseases, as discussed below. Mueller, Hobiger, and Jungbauer23 evaluated the effects of aqueous extract of O. basilicum at 0.5 mg/mL on a macrophage culture. The results showed a 57% reduction in interleukin 6 concentration, a 24% reduction in tumor necrosis factor α (TNF-α), a 19% reduction in cyclooxygenase 2 (COX-2) activity, and an increase of 54% in the concentration of interleukin 10 (IL-10). Duraisamy et al.24 evaluated the effects of in vitro ethanolic extract on inflammatory parameters. The results showed that the extract was able to reduce lipoxygenase activity in vitro. Another study published in 2009 by Rakha et al.25 demonstrated that the basil seeds extract reduced carrageenan-induced paw edema by 10%, thus showing antiinflammatory activity. And more currently, a paper from our research group also addressed this topic. In 2017, a paper from Guez et al.26 demonstrated that the production of the proinflammatory cytokines such as TNF-α and IL-6 was not affected in different doses of O. basilicum extract. However, the percentage of production of IL-10, the antiinflammatory cytokine, shows an increase in the percentage of more than 60% at the highest dose of the extract when compared with the positive control (ibuprofen). The percentage of production of IL-10 was also demonstrated to be dose-dependent. Also, the ability of the extract from O. basilicum to inhibit COX-2, which acts as the inducible isoform and is regulated by growth factors and different cytokines (IL1β, IL6, or TNFα), was demonstrated. The inhibition of COX-2 in some tested concentrations approximates to the inhibition caused by RA in our study and in several other reports.27, 28 Additionally, in this same paper, we verified an inhibitory effect of O. basilicum over nitric oxide, a powerful mediator from the immune system.
5. BIOLOGICAL ACTIVITY OF BASIL Basil has been a choice for a wide range of biological tests, usually in animals and experimental models in vitro. Among those that presented activities more related to the one proposed here are those related to free radicals, which are known to be involved in
483
484
Bioactive Food as Dietary Interventions for Arthritis and Related Inflammatory Diseases
numerous pathological conditions to the organism. Among the published studies on basil, the following stand out: Beric et al.29 showed that basil’s essential oil, the linalool chemotype, is effective to protect salmonella strains from the deleterious effects of hydrogen peroxide (H2O2). In the same line of action, Thirugnanasampandan and Jayakumar30 evaluated the effects of the ethanolic extract of O. basilicum at concentrations of 50–350 μg/mL in a human liver cell culture and observed a reduction in the production of nitric oxide with dose-dependent effects. Still on the antioxidant activity, Sakr and Al-Amoudi10 reported that the administration of 20 mL/kg of basil aqueous extract in albino rats for 6 weeks increased the superoxide dismutase (SOD) and catalase (CAT) activities, in addition to reducing lipid peroxidation caused by the administration of deltamethrin. Results showing the antioxidant activity of basil are frequent and widely reported.29, 31–39 The mechanisms of action involved in these activities are directly related to the stabilization of the free radical by the polyphenols present both in the extract and in the plant. This mechanism of inhibition is already well understood and well established.40
6. BASIL TOXICITY STUDIES Despite the widespread use of this species in cooking and of the various popular uses, studies involving toxicity are rare for this species. Among the studies published in recent years involving animals, we have the work of Shiga et al.,9 who used male rats and evaluated doses between 4000 and 6000 mg/kg. In this work, no death or sign of toxicity was recorded. Fandohan and colleagues in 200841 determined that O. basilicum oil had toxicity in rats after 14 days of doses of 1500 mg/kg/day. This resulted in a lethal dose (LD50) (dose responsible for the death of 50% of test animals) of 3250 mg/kg. Already with cell cultures, the literature is more restricted. Bravo and collaborators12 performed a work on cell culture with macrophages, evaluating only cell viability. The results showed that up to 60 μg/mL (maximum value tested) did not change in this parameter. Koko et al.42 evaluated the viability of lymphocytes in vitro, with concentrations of 25–100 μg/mL reducing cell viability by about 70%. As for proliferation, GomezFlores and his team43 determined that the aqueous extract presented lymphoproliferative activity from 31.25 μg/mL and the same occurred with the methanolic extract at concentrations of 125 μg/mL.
7. CONCLUSIONS A natural product is not a miracle solution. It is not the purpose of this text to make you believe that. However, we have provided scientific evidence to prove that basil, which
Ocimum basilicum L.
has been known in mythology as the “God of Spices,” can be an important adjunct in the treatment of numerous diseases that are based on the formation of free radicals and/or the inflammatory process. Because they are in vitro studies, the results cannot be completely extrapolated, but the evidence is strongly in favor of its use as a complement of treatment; besides it is very tasty.
ACKNOWLEDGMENTS The authors would like to thank the entire staff of the Cellular Toxicology Research Group, both old and current. You are a fundamental part of this work and the reason for our smiles. Thanks for everything!
REFERENCES 1. McInnes IB, Schett G. Pathogenetic insights from the treatment of rheumatoid arthritis. Lancet. 2017;389(10086):2328–2337. 2. Stach CM, B€auerle M, Englbrecht M, et al. Periarticular bone structure in rheumatoid arthritis patients and healthy individuals assessed by high-resolution computed tomography. Arthritis Rheum. 2010;62 (2):330–339. 3. Horne R, Chapman SC, Parham R, Freemantle N, Forbes A, Cooper V. Understanding patients’ adherence-related beliefs about medicines prescribed for long-term conditions: a meta-analytic review of the necessity-concerns framework. PLoS ONE. 2013;8(12)e80633. 4. Kleyer A, Finzel S, Rech J, et al. Bone loss before the clinical onset of rheumatoid arthritis in subjects with anticitrullinated protein antibodies. Ann Rheum Dis. 2014;73(5):854–860. 5. Rauscher V, Englbrecht M, van der Heijde D, Schett G, Hueber AJ. High degree of nonadherence to disease-modifying antirheumatic drugs in patients with rheumatoid arthritis. J Rheumatol. 2015;42 (3):386–390. 6. Waimann CA, Marengo MF, Achaval S, et al. Electronic monitoring of oral therapies in ethnically diverse and economically disadvantaged patients with rheumatoid arthritis: consequences of low adherence. Arthritis Rheum. 2013;65(6):1421–1429. 7. World Health Organization. Pharmacovigilance for traditional medicine products: why and how? 8. Farnsworth NR, Akerele O, Bingel AS, Soejarto DD, Guo Z. Medicinal plants in therapy. Bull World Health Organ. 1985;63(6):965. 9. Shiga T, Shoji K, Shimada H, Hashida S-n, Goto F, Yoshihara T. Effect of light quality on rosmarinic acid content and antioxidant activity of sweet basil, Ocimum basilicum L. Plant Biotechnol. 2009;26:255–259. 10. Sakr SA, Al-Amoudi WM. Effect of leave extract of Ocimum basilicum on deltamethrin induced nephrotoxicity and oxidative stress in albino rats. J Appl Pharm Sci. 2012;2(5). 11. Hussien J, Teshale C, Mohammed J. Assessment of the antimicrobial effects of some Ethiopian aromatic spice and herb hydrosols. Int J Pharmacol. 2011;7(5):635–640. 12. Bravo E, Amrani S, Aziz M, Harnafi H, Napolitano M. Ocimum basilicum ethanolic extract decreases cholesterol synthesis and lipid accumulation in human macrophages. Fitoterapia. 2008;79(7–8):515–523. 13. Lee J, Scagel CF. Chicoric acid found in basil (Ocimum basilicum L.) leaves. Food Chem. 2009;115 (2):650–656. 14. Akhtar MS, Munir M. Evaluation op the gastric antiulcerogenic effects of Solanum nigrum, Brassica oleracea and Ocimum basilicum in rats. J Ethnopharmacol. 1989;27(1–2):163–176. 15. Keita SM, Vincent C, Schmit J-P, Arnason JT, Belanger A. Efficacy of essential oil of Ocimum basilicum L. and O. gratissimum L. applied as an insecticidal fumigant and powder to control Callosobruchus maculatus (Fab.)[Coleoptera: Bruchidae]. J Stored Prod Res. 2001;37(4):339–349.
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Bioactive Food as Dietary Interventions for Arthritis and Related Inflammatory Diseases
16. Liber Z, Carovic-Stanko K, Politeo O, et al. Chemical characterization and genetic relationships among Ocimum basilicum L. cultivars. Chem Biodivers. 2011;8(11):1978–1989. 17. Lee S-J, Umano K, Shibamoto T, Lee K-G. Identification of volatile components in basil (Ocimum basilicum L.) and thyme leaves (Thymus vulgaris L.) and their antioxidant properties. Food Chem. 2005;91 (1):131–137. 18. Pascual-Villalobos M, Ballesta-Acosta M. Chemical variation in an Ocimum basilicum germplasm collection and activity of the essential oils on Callosobruchus maculatus. Biochem Syst Ecol. 2003;31 (7):673–679. 19. Labra M, Miele M, Ledda B, Grassi F, Mazzei M, Sala F. Morphological characterization, essential oil composition and DNA genotyping of Ocimum basilicum L. cultivars. Plant Sci. 2004;167(4):725–731. 20. Grayer RJ, Kite GC, Goldstone FJ, Bryan SE, Paton A, Putievsky E. Infraspecific taxonomy and essential oil chemotypes in sweet basil, Ocimum basilicum. Phytochemistry. 1996;43(5):1033–1039. 20a. Kwee EM, Niemeyer ED. Variations in phenolic composition and antioxidant properties among 15 basil (Ocimum basilicum L.) cultivars. Food Chem. 2011;28(4):1044–1050. 20b. Phippen WB, Simon JE. Anthocyanins in basil (Ocimum basilicum L.). J Agric Food Chem. 1998;46 (5):1734–1738. 21. Javanmardi J, Khalighi A, Kashi A, Bais H, Vivanco J. Chemical characterization of basil (Ocimum basilicum L.) found in local accessions and used in traditional medicines in Iran. J Agric Food Chem. 2002;50 (21):5878–5883. 22. Nguyen PM, Niemeyer ED. Effects of nitrogen fertilization on the phenolic composition and antioxidant properties of basil (Ocimum basilicum L.). J Agric Food Chem. 2008;56(18):8685–8691. 23. Mueller M, Hobiger S, Jungbauer A. Anti-inflammatory activity of extracts from fruits, herbs and spices. Food Chem. 2010;122(4):987–996. 24. Duraisamy A, Narayanaswamy N, Sebastian A, Balakrishnan K. Sun protection and anti-inflammatory activities of some medicinal plants. Int J Res Cosmet Sci. 2011;1(1):13–16. 25. Rakha P, Nagpal M, Sharma S, Parle M. Anti-inflammatory activity of petroleum ether extract of seeds of Ocimum Basilicum Linn. Res J Pharm Technol. 2009;2(3):589–591. 26. G€ uez CM, Souza ROD, Fischer P, et al. Evaluation of basil extract (Ocimum basilicum L.) on oxidative, anti-genotoxic and anti-inflammatory effects in human leukocytes cell cultures exposed to challenging agents. Braz J Pharm Sci. 2017;53(1). 27. Kelm M, Nair M, Strasburg G, DeWitt D. Antioxidant and cyclooxygenase inhibitory phenolic compounds from Ocimum sanctum Linn. Phytomedicine. 2000;7(1):7–13. 28. Petersen M, Simmonds MS. Rosmarinic acid. Phytochemistry. 2003;62(2):121–125. 29. Beric T, Nikolic B, Stanojevic J, Vukovic-Gacˇic B, Knezˇevic-Vukcˇevic J. Protective effect of basil (Ocimum basilicum L.) against oxidative DNA damage and mutagenesis. Food Chem Toxicol. 2008;46(2):724–732. 30. Thirugnanasampandan R, Jayakumar R. Protection of cadmium chloride induced DNA damage by Lamiaceae plants. Asian Pac J Trop Biomed. 2011;1(5):391–394. 31. Koroch AR, Simon JE, Juliani HR. Essential oil composition of purple basils, their reverted green varieties (Ocimum basilicum) and their associated biological activity. Ind Crop Prod. 2017;107:526–530. 32. Touiss I, Khatib S, Bekkouch O, Amrani S, Harnafi H. Phenolic extract from Ocimum basilicum restores lipid metabolism in Triton WR-1339-induced hyperlipidemic mice and prevents lipoprotein-rich plasma oxidation. Food Sci Human Wellness. 2017;6(1):28–33. 33. Teofilovic B, Grujic-Letic N, Golocˇorbin-Kon S, Stojanovic S, Vastag G, Gadzˇuric S. Experimental and chemometric study of antioxidant capacity of basil (Ocimum basilicum) extracts. Ind Crop Prod. 2017;100:176–182. 34. Pirbalouti AG, Malekpoor F, Salimi A, Golparvar A. Exogenous application of chitosan on biochemical and physiological characteristics, phenolic content and antioxidant activity of two species of basil (Ocimum ciliatum and Ocimum basilicum) under reduced irrigation. Sci Hortic. 2017;217:114–122. 35. Stanojevic LP, Marjanovic-Balaban ZR, Kalaba VD, Stanojevic JS, Cvetkovic DJ, Cakic MD. Chemical composition, antioxidant and antimicrobial activity of basil (Ocimum basilicum L.) essential oil. J Essent Oil Bear Plants. 2017;20(6):1557–1569. 36. Khodabakhshi T, Beheshti F, Hosseini M, et al. Effect of Ocimum basilicum hydro-alcoholic extract on oxidative damage of brain tissue following seizures induced by pentylenetetrazole in mice. Physiol Pharmacol. 2017;295–303.
Ocimum basilicum L.
37. Ali A, Qasim M, Aftab MN, et al. Effects of Ocimum basilicum extract on hematological and serum profile of male albino mice after AlCl3 induced toxicity. Pure Appl Biol. 2017;6(2):505–510. 38. Elgndi MA, Filip S, Pavlic B, et al. Antioxidative and cytotoxic activity of essential oils and extracts of Satureja montana L., Coriandrum sativum L. and Ocimum basilicum L. obtained by supercritical fluid extraction. J Supercrit Fluids. 2017;128:128–137. 39. Drees F, Rafieian-Kopaei M, Salehi E, Rokni N, Sharafati-Chaleshtori R. Antioxidant and antibacterial activity of basil (Ocimum basilicum L.) essential oil in beef burger. 2018. 40. Ricciardi V, Portaccio M, Piccolella S, Manti L, Pacifico S, Lepore M. Study of SH-SY5Y cancer cell response to treatment with polyphenol extracts using FT-IR spectroscopy. Biosensors. 2017;7(4):57. 41. Fandohan P, Gnonlonfin B, Laleye A, Gbenou J, Darboux R, Moudachirou M. Toxicity and gastric tolerance of essential oils from Cymbopogon citratus, Ocimum gratissimum and Ocimum basilicum in Wistar rats. Food Chem Toxicol. 2008;46(7):2493–2497. 42. Koko W, Mesaik MA, Yousaf S, Galal M, Choudhary MI. In vitro immunomodulating properties of selected Sudanese medicinal plants. J Ethnopharmacol. 2008;118(1):26–34. 43. Gomez-Flores R, Vera´stegui-Rodrı´guez L, Quintanilla-Licea R, Tamez-Guerra P, Tamez-Guerra R, Rodrı´guez-Padilla C. In vitro rat lymphocyte proliferation induced by Ocinum basilicum, Persea americana, Plantago virginica, and Rosa spp. extracts. J Med Plants Res. 2008;2(1):005–010.
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Ocimum basilicum L.: Antiinflammatory Actions and Potential Usage for Arthritic Conditions Michel Mansur Machado, Luís Flávio Souza de Oliveira, Luísa Zuravski Cellular Toxicology Research Group (ToxCel), Federal University of Pampa, Uruguaiana, Brazil
1. INTRODUCTION Arthritis is an inflammatory disease that leads to joint destruction and functional disability if not adequately treated.1 In this disease, autoantibodies such as rheumatoid factor or anticitrullinated peptide antibodies (ACPA) are typical serologic findings and are strongly associated with erosive disease.2 Aside from bone erosion, the pathognomonic features of arthritis comprise articular and periarticular bone loss and loss of trabeculation.3 A panel of effective and approved immunosuppressive drugs is available to treat inflammation and to avoid joint damage.4 Recent studies demonstrated poor adherence to these drugs, despite these treatment opportunities.5, 6 The reasons for this are multifactorial; however, they are mainly influenced by medical beliefs and lack of understanding of the disease.3 The use of natural products in folk medicine as a therapeutic resource is widely diffused in the population, and this inclination has contributed significantly to the consumption not only of natural products but also of herbal medicines. A work by the World Health Organization (WHO) that has evaluated the use of traditional medicine in different regions shows that the use of plants and their derivatives can reach more than 90% of certain regions of the world, such as China and Malaysia.7 Natural medicine is a very popular therapeutic resource in self-medication. However, due to the ease of access, it can aggravate its potential risks of toxicity. In addition, there is a large gap related to popular understanding that must be filled through actions that seek to improve the dissemination of knowledge about the safe and rational use of medicinal plants and herbal medicines. Among these is the availability of information with scientific evidence, which should be passed on to physicians, pharmacists, and users of these products.8 In this context, basil (Ocimum basilicum L.) appears as an alternative treatment, in addition to being widely used as an ornamental plant and a food condiment. This species belongs to the family Lamiaceae and originates from tropical Asia, but today it is Bioactive Food as Dietary Interventions for Arthritis and Related Inflammatory Diseases https://doi.org/10.1016/B978-0-12-813820-5.00027-1
© 2019 Elsevier Inc. All rights reserved.
481
482
Bioactive Food as Dietary Interventions for Arthritis and Related Inflammatory Diseases
cultivated worldwide.9 Among its popular uses, O. basilicum is used as an antioxidant, antiinflammatory, anticarcinogenic, antimicrobial, and cardiovascular agent.10 It is also used in abdominal discomfort caused by colic in addition to its use in respiratory problems such as cough and asthma11 and as an antiplatelet agent.12 Several secondary metabolites with antioxidant and antiinflammatory activities have been identified in this species with the main ones being polyphenols, flavonoids, and terpenes.13
2. BASIL (O. BASILICUM L.) Basil is an herbaceous, aromatic, and medicinal plant, known since antiquity by Indians, Greeks, Egyptians, and Romans. It is enveloped in spiritual culture and symbolism, and is even considered sacred among some Hindu peoples as it represents Tulasi, the wife of the god Vishnu. It is related to feelings of hatred, love, and mourning, but it is certainly more widely known for its culinary powers.14 The basil shows a straight and branched stem and reaches about 1 m in height. Its leaves are delicate, oval, pubescent, and bright green. The inflorescences are of the spike type and composed of white, lilac, or reddish flowers. Its pollination is crossed, and the fruits are of the type acheno with a black-blue coloration. There are more than 60 different varieties of basil, with variations in the color, size, and shape of the leaves, the size of the plant and the concentration of the aroma. The basil leaves have a characteristic sweet and spicy flavor and aroma. They are used dry or fresh in the preparation of several hot or cold dishes, and are closely related to Italian gastronomy 15.
3. ISOLATED COMPOUNDS IN BASIL Numerous studies have attempted to establish a composition pattern for basil, both in the extract and in the oil. The greatest difficulty is the diversity of this species. Today, more than 25 different types of O. basilicum are known, with numerous constitutional differences.16, 17 Because of the variety of compounds and variability of concentrations found in this cultivation, four chemotypes were established based on the compound’s highest concentration in the extracted oil of basil: chemotype linalool, methylchavicol, eugenol, and 1,8-cineole.16 Among the main compounds isolated so far in the oil are the compounds linalool, methyleugenol, eugenol, methylcinnamate, chavicol, 1,8-cineol, α-terpinol,13, 15, 18 camphor, limonene, geraniol, and farmaseno.19 In the extract, the compounds identified to date were novadensin, salvigenin, circiseol, eupatorin, gardenina B,20 chicoric acid, caftaric acid,13, 20a p-coumaric acid, peonidin-3, 5-diglycoside,20b and rosmarinic acid (RA).9, 20–22
Ocimum basilicum L.
Several studies report that among the components of this plant, RA is the most biologically active compound.9, 13, 21
4. IMMUNOLOGICAL AND ANTIINFLAMMATORY ACTIVITIES Certainly, the activities described for basil are varied, but those related to the effects on the immune system, especially the antiinflammatory effects, are, in the case of this chapter, the focus to be approached more vehemently. In this thinking, we list below a series of studies that demonstrate the effectiveness of this condiment as a potential agent to assist in the treatment of inflammatory diseases, as discussed below. Mueller, Hobiger, and Jungbauer23 evaluated the effects of aqueous extract of O. basilicum at 0.5 mg/mL on a macrophage culture. The results showed a 57% reduction in interleukin 6 concentration, a 24% reduction in tumor necrosis factor α (TNF-α), a 19% reduction in cyclooxygenase 2 (COX-2) activity, and an increase of 54% in the concentration of interleukin 10 (IL-10). Duraisamy et al.24 evaluated the effects of in vitro ethanolic extract on inflammatory parameters. The results showed that the extract was able to reduce lipoxygenase activity in vitro. Another study published in 2009 by Rakha et al.25 demonstrated that the basil seeds extract reduced carrageenan-induced paw edema by 10%, thus showing antiinflammatory activity. And more currently, a paper from our research group also addressed this topic. In 2017, a paper from Guez et al.26 demonstrated that the production of the proinflammatory cytokines such as TNF-α and IL-6 was not affected in different doses of O. basilicum extract. However, the percentage of production of IL-10, the antiinflammatory cytokine, shows an increase in the percentage of more than 60% at the highest dose of the extract when compared with the positive control (ibuprofen). The percentage of production of IL-10 was also demonstrated to be dose-dependent. Also, the ability of the extract from O. basilicum to inhibit COX-2, which acts as the inducible isoform and is regulated by growth factors and different cytokines (IL1β, IL6, or TNFα), was demonstrated. The inhibition of COX-2 in some tested concentrations approximates to the inhibition caused by RA in our study and in several other reports.27, 28 Additionally, in this same paper, we verified an inhibitory effect of O. basilicum over nitric oxide, a powerful mediator from the immune system.
5. BIOLOGICAL ACTIVITY OF BASIL Basil has been a choice for a wide range of biological tests, usually in animals and experimental models in vitro. Among those that presented activities more related to the one proposed here are those related to free radicals, which are known to be involved in
483
484
Bioactive Food as Dietary Interventions for Arthritis and Related Inflammatory Diseases
numerous pathological conditions to the organism. Among the published studies on basil, the following stand out: Beric et al.29 showed that basil’s essential oil, the linalool chemotype, is effective to protect salmonella strains from the deleterious effects of hydrogen peroxide (H2O2). In the same line of action, Thirugnanasampandan and Jayakumar30 evaluated the effects of the ethanolic extract of O. basilicum at concentrations of 50–350 μg/mL in a human liver cell culture and observed a reduction in the production of nitric oxide with dose-dependent effects. Still on the antioxidant activity, Sakr and Al-Amoudi10 reported that the administration of 20 mL/kg of basil aqueous extract in albino rats for 6 weeks increased the superoxide dismutase (SOD) and catalase (CAT) activities, in addition to reducing lipid peroxidation caused by the administration of deltamethrin. Results showing the antioxidant activity of basil are frequent and widely reported.29, 31–39 The mechanisms of action involved in these activities are directly related to the stabilization of the free radical by the polyphenols present both in the extract and in the plant. This mechanism of inhibition is already well understood and well established.40
6. BASIL TOXICITY STUDIES Despite the widespread use of this species in cooking and of the various popular uses, studies involving toxicity are rare for this species. Among the studies published in recent years involving animals, we have the work of Shiga et al.,9 who used male rats and evaluated doses between 4000 and 6000 mg/kg. In this work, no death or sign of toxicity was recorded. Fandohan and colleagues in 200841 determined that O. basilicum oil had toxicity in rats after 14 days of doses of 1500 mg/kg/day. This resulted in a lethal dose (LD50) (dose responsible for the death of 50% of test animals) of 3250 mg/kg. Already with cell cultures, the literature is more restricted. Bravo and collaborators12 performed a work on cell culture with macrophages, evaluating only cell viability. The results showed that up to 60 μg/mL (maximum value tested) did not change in this parameter. Koko et al.42 evaluated the viability of lymphocytes in vitro, with concentrations of 25–100 μg/mL reducing cell viability by about 70%. As for proliferation, GomezFlores and his team43 determined that the aqueous extract presented lymphoproliferative activity from 31.25 μg/mL and the same occurred with the methanolic extract at concentrations of 125 μg/mL.
7. CONCLUSIONS A natural product is not a miracle solution. It is not the purpose of this text to make you believe that. However, we have provided scientific evidence to prove that basil, which
Ocimum basilicum L.
has been known in mythology as the “God of Spices,” can be an important adjunct in the treatment of numerous diseases that are based on the formation of free radicals and/or the inflammatory process. Because they are in vitro studies, the results cannot be completely extrapolated, but the evidence is strongly in favor of its use as a complement of treatment; besides it is very tasty.
ACKNOWLEDGMENTS The authors would like to thank the entire staff of the Cellular Toxicology Research Group, both old and current. You are a fundamental part of this work and the reason for our smiles. Thanks for everything!
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