See discussions, stats, and author profiles for this publication at: https://www.researchgate.net/publication/275725771 Immunomodulation and Anti-Inflammatory Effects of Garlic Compounds Article in Journal of Immunology Research · May 2015 DOI: 10.1155/2015/401630 CITATIONS READS 83 666 7 authors, including: Rodrigo Arreola Saray Quintero-Fabián Instituto Nacional de Psiquiatría Instituto Nacional de Pediatría 24 PUBLICATIONS 411 CITATIONS 8 PUBLICATIONS 274 CITATIONS SEE PROFILE SEE PROFILE Lopez-Roa Rocio Ivette Juan Pablo Reyes-Grajeda University of Guadalajara Instituto Nacional de Medicina Genómica 23 PUBLICATIONS 305 CITATIONS 52 PUBLICATIONS 590 CITATIONS SEE PROFILE SEE PROFILE Some of the authors of this publication are also working on these related projects: Environmental enrichment and Epigenetics View project Polyphenols supplementation and physical exercise View project All content following this page was uploaded by Daniel Ortuño on 23 August 2015. 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Hindawi Publishing Corporation Journal of Immunology Research Volume 2015, Article ID 401630, 13 pages http://dx.doi.org/10.1155/2015/401630 Review Article Immunomodulation and Anti-Inflammatory Effects of Garlic Compounds Rodrigo Arreola,1 Saray Quintero-Fabián,2 Rocío Ivette López-Roa,3 Enrique Octavio Flores-Gutiérrez,4 Juan Pablo Reyes-Grajeda,5 Lucrecia Carrera-Quintanar,6 and Daniel Ortuño-Sahagún6 1 Psychiatric Genetics Department, National Institute of Psychiatry, “Ramon´ de la Fuente”, Clinical Research Branch, Calzada Mexico-Xochimilco101,ColoniaSanLorenzoHuipulco,Tlalpan,14370MexicoCity,DF,Mexico´ 2Unidad de Genetica´ de la Nutricion,´ Instituto de Investigaciones Biomedicas,´ Universidad Nacional Autonoma´ de Mexico,´ Instituto Nacional de Pediatr´ıa,AvendiadelImanNo.1,CuartoPiso,04530Mexico,DF,Mexico 3Departamento de Farmacobiolog´ıa, CUCEI, Universidad de Guadalajara, Boulevard Marcelino Garc´ıa Barragan,´ No. 1421, Esq. Calzada Ol´ımpica, 44430 Guadalajara, JAL, Mexico 4National Institute of Psychiatry, “Ramon´ de la Fuente”, Clinical Research Branch, Calzada Mexico-Xochimilco´ 101, Colonia San Lorenzo Huipulco, Tlalpan, 14370 Mexico City, DF, Mexico 5Instituto Nacional de Medicina Genomica,´ PerifericoSurNo.4809,ColoniaArenalTepepan,Delegaci´ on´ Tlalpan, 14610 Mexico,´ DF, Mexico 6Instituto de Investigacion´ en Ciencias Biomedicas´ (IICB), CUCS, Universidad de Guadalajara, Sierra Mojada No. 950, Colonia Independencia, 44340 Guadalajara, JAL, Mexico Correspondence should be addressed to Rodrigo Arreola; [email protected] and Daniel Ortuno-Sahag˜ un;´ [email protected] Received 20 October 2014; Revised 24 January 2015; Accepted 25 January 2015 Academic Editor: Oscar Bottasso Copyright © 2015 Rodrigo Arreola et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The benefits of garlic to health have been proclaimed for centuries; however, only recently have Allium sativum and its derivatives been proposed as promising candidates for maintaining the homeostasis of the immune system. The complex biochemistry of garlic makes it possible for variations in processing to yield different preparations with differences in final composition and compound proportion. In this review, we assess the most recent experimental results, which indicate that garlic appears to enhance the functioning of the immune system by stimulating certain cell types, such as macrophages, lymphocytes, natural killer (NK) cells, dendritic cells, and eosinophils, by mechanisms including modulation of cytokine secretion, immunoglobulin production, phagocytosis, and macrophage activation. Finally, because immune dysfunction plays an important role in the development and progress of several diseases, we critically examined immunoregulation by garlic extracts and compounds isolated, which can contribute to the treatment and prevention of pathologies such as obesity, metabolic syndrome, cardiovascular disorders, gastric ulcer, and even cancer. We concluded that A. sativum modulates cytokine secretion and that such modulation may provide a mechanism of action for many of their therapeutic effects. 1. Introduction a broad spectrum of beneficial effects against microbial infections as well as cardioprotective, anticancerigenic, and Plants of the genus Allium are known for their produc- anti-inflammatory activity [1–5]. tion of organosulfur compounds, which possess interesting Preparations of garlic are mainly liquid (aqueous, oil, biological and pharmacological properties. Among these, or solvent extracts) or solid (dried garlic powder and fresh garlic (Allium sativum)isoneofthemostwidelyused cataplasm). These extractions can be based on water formu- ones. When extracted and isolated, these compounds exhibit lations, oils, or by using solvents as alcohols [6]. Composition 2 Journal of Immunology Research Table 1: Biological effects of different types of garlic preparations and extracts. Preparations/extract Effects References Dehydrated garlic powder/slices/crushed Diminish serum cholesterol [8] Antibacterial [9, 10] Antiparasitic [11] Aqueous extracts Modify immune response [12] Lipid metabolism [13] Cardiovascular-protective effects14 [ , 15] Antibacterial [16–19] Oil extracts Acaricidal [20] Modify Immune response [21, 22] Chloroform extract Inhibiting ROS formation and attenuating the activities of adhesion molecules [23] Cytotoxic [24] Hexane extract Modify immune response [25] Antioxidant [26, 27] AGE ROS scavenger and anti-inflammatory [28] Inhibits development of preneoplastic lesions [29] of the extracts depends on the source of the garlic strain, age, Garlic compounds can be divided in several groups or storage conditions, and type of processing, and the effects of families of compounds. Among these families, we find - the extracts are influenced by the method of consumption [7]. glutamyl cysteine derivatives, the primary precursor com- Biological effects of different garlic preparations and extracts ponents of the alliin and allyl methyl cysteine (methiin) are summarized in Table 1. compound families [6, 41], that produce, by enzymatic action The wide variety of effects that has been reported of garlic of alliinase (alliin lyase, EC: 4.4.1.4), the diallyl thiosulfinate preparations and extracts with beneficial and useful proper- (Allicin)andallylmethylthiosulfinate(AM)compound ties may be due to their numerous compounds (organosulfur families [41, 42], which are precursors of several organosulfur and others) contained in different concentrations, which is compound families (i.e., the ajoene and dithiin families) being a challenge to separate and identify compounds with [8]. Additionally, garlic preparations contain nonorgan sul- potential beneficial properties on the human immune and furedcompounds,suchastetrahydro-beta-carbolines[43, cardiovascular systems [7]. A comprehensive classification of 44], fructans, and glucose-linked -D-fructofuranosyl [45], the different compound derived from garlic, as well as their identified in AGE preparations [25]. biological effects reported, is actually in preparation and will be published elsewhere (Rodrigo-Arreola et al., in prepara- 3. Immunomodulatory Properties of tion). The presence and potency of garlic compounds vary Allium sativum with respect to mode of garlic preparation and extraction. Additionally, the proportion of these compounds is poorly Immunomodulation is one of the main targets for synthetic controlled with the methods used to generate different garlic drugs and chemicals. However, its high cost, anticipated preparations, the main problem being reproducibility and toxicity, and adverse event effects render it undesirable for validation of the real effects observed. the patients. In contrast, the use of herbal plants as health promoters is gaining increasing attention in both consumers 2. Main Organosulfur Compounds Purified and scientific circles. In the literature, several plants have been listed that exhibit immunomodulatory actions, like mod- from Garlic Preparations ulation of cytokine secretion; phagocytosis promotion and The presence of garlic compounds varies with respect to macrophage activation; immunoglobulin production; aller- mode of garlic preparation and extraction as follows: (1) gicreactionsandlymphocyteproliferation[46]. Recently, fresh bulbs main compounds are S-allyl-L-cysteine sulfoxide garlic has been suggested as a promising candidate for (alliin) and -glutamyl cysteine derivatives; (2) in steam maintaining the homeostasis of the immune system. Several distilled oils, sulfide family compounds are the main com- studieshavebeencarriedoutinanimalmodelstoexamine pounds; (3) powder from crushed and dried garlic contains the effect of different garlic components and formulations on alliin and diallyl disulfide (DADS); (4) macerates (ground immunomodulatory activities (summarized in Table 2). garlic) are enriched extractions with sulfide family com- pounds, dithiines, and (E–Z)-ajoene compounds, and (5) 3.1. Modulation of Cytokine Secretion by Garlic Deriva- AGE (soaked, sliced, aged garlic extract in ethanol solution) tives. Herbal medicines with immunomodulatory activity contains S-allyl-L-cysteine (SAC) and S-allyl mercaptocys- alter the immune function through the dynamic regulation teine (SAMC) [40]. of molecules such as cytokines and chemokines. Altering Journal of