molecules Review Naturally Lignan-Rich Foods: A Dietary Tool for Health Promotion? Carmen Rodríguez-García 1,2 , Cristina Sánchez-Quesada 1,2,3 , Estefanía Toledo 4,5,6 , Miguel Delgado-Rodríguez 1,2,7 and José J. Gaforio 1,2,3,7,* 1 Center for Advanced Studies in Olive Grove and Olive Oils, University of Jaen, Campus las Lagunillas s/n, 23071 Jaén, Spain; [email protected] (C.R.-G.); [email protected] (C.S.-Q.); [email protected] (M.D.-R.) 2 Department of Health Sciences, Faculty of Experimental Sciences, University of Jaén, 23071 Jaén, Spain 3 Agri-food Campus of International Excellence (ceiA3), 14071 Córdoba, Spain 4 Department of Preventive Medicine and Public Health, University of Navarra, 31008 Pamplona, Spain; [email protected] 5 CIBER Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III, 28029 Madrid, Spain 6 IdiSNA, Navarra Institute for Health Research, 31008 Pamplona, Spain 7 CIBER Epidemiología y Salud Pública (CIBER-ESP), Instituto de Salud Carlos III, 28029 Madrid, Spain * Correspondence: [email protected]; Tel.: +34-953-212-002 Academic Editor: David Barker Received: 28 January 2019; Accepted: 4 March 2019; Published: 6 March 2019 Abstract: Dietary guidelines universally advise adherence to plant-based diets. Plant-based foods confer considerable health benefits, partly attributable to their abundant micronutrient (e.g., polyphenol) content. Interest in polyphenols is largely focused on the contribution of their antioxidant activity to the prevention of various disorders, including cardiovascular disease and cancer. Polyphenols are classified into groups, such as stilbenes, flavonoids, phenolic acids, lignans and others. Lignans, which possess a steroid-like chemical structure and are defined as phytoestrogens, are of particular interest to researchers. Traditionally, health benefits attributed to lignans have included a lowered risk of heart disease, menopausal symptoms, osteoporosis and breast cancer. However, the intake of naturally lignan-rich foods varies with the type of diet. Consequently, based on the latest humans’ findings and gathered information on lignan-rich foods collected from Phenol Explorer database this review focuses on the potential health benefits attributable to the consumption of different diets containing naturally lignan-rich foods. Current evidence highlight the bioactive properties of lignans as human health-promoting molecules. Thus, dietary intake of lignan-rich foods could be a useful way to bolster the prevention of chronic illness, such as certain types of cancers and cardiovascular disease. Keywords: lignans; diet; antioxidants; health promotion; chronic diseases 1. Introduction Polyphenol-rich diets are suggested to possess health benefits. Polyphenols are micronutrients found in plants, and include flavonoids, stilbenes, phenolic acids, lignans and others [1]. They are secondary plant metabolites implicated in protection against pathogens and ultraviolet radiation [2]. Given their diverse chemical structures, different polyphenol classes likely possess differing health benefits [3]. It is therefore important to elucidate the specific potential benefits of each polyphenolic compound. Significant interest has been elicited by lignans, due to their steroid-analogous chemical structure. Accordingly, they are considered to be phytoestrogens. Lignans are bioactive compounds exhibiting various biological properties, including anti-inflammatory, antioxidant and antitumor Molecules 2019, 24, 917; doi:10.3390/molecules24050917 www.mdpi.com/journal/molecules Molecules 2019, 24, 917 2 of 25 activitiesMolecules 2019 [4]., 24 Additionally,, x some epidemiological studies have proposed that lignans decrease2 theof 24 risk of cardiovascular disease, but their effects on other chronic diseases (e.g., breast cancer) remain 46 controversialrisk of cardiovascular [5]. disease, but their effects on other chronic diseases (e.g., breast cancer) remain 47 controversialLignans are [5]. found in relatively low concentrations in various seeds, grains, fruits and vegetables, 48 and inLignans higher concentrations are found in relatively in sesame low and concentrations flax seeds [6]. in Therefore, various seeds, the level grains, of lignan fruits ingestion—and, and vegetables, 49 thus,and in lignan higher bioavailability, concentrations depends in sesame on theand type flax ofseeds diet [6]. consumed Therefore, [7, 8the] and level can of be lignan highly ingestion— variable. 50 Theand, present thus, lignan review bioavailability, attempts to describe depends the on potential the type beneficial of diet consumed effects of lignan [7,8] and intake can on be human highly 51 chronicvariable. disease, The present depending review on attempts the dietary to source.describe the potential beneficial effects of lignan intake on 52 human chronic disease, depending on the dietary source. 2. Biosynthesis, Classification and Presence of Lignans in Foods 53 2. Biosynthesis, Classification and Presence of Lignans in Foods Lignans are a type of secondary plant metabolite exhibiting diverse structures [9]. Plants derive a 54 complexLignans array are of secondary a type of secondary metabolites plant from metabolite only a handful exhibiting of relatively diverse simple structures propenyl [9]. phenolsPlants derive [10]. 55 Biosynthesisa complex array of lignans of secondary is characterized metabolites by afrom remarkable only a handful increase of in relatively molecular simple complexity propenyl [10]. phenols 56 [10].Lignans Biosynthesis share of common lignans biosynthetic is characterized pathways, by a remarkable consist of two increase propyl-benzene in molecular units complexity coupled by[10]. a 57 β,β0-bondLignans [11], share and thuscommon belong biosynthetic to the group pathways, of diphenolic consist compounds of two propyl-benzene [12]. units coupled by 58 a β,β′Lignans-bond [11], may and be organizedthus belong into to eightthe group structural of diphenolic subgroups compounds (according [12]. to the manner in which 59 oxygenLignans is incorporated may be organized and the pattern into eight of cyclization): structural subgroups Dibenzylbutyrolactol, (according dibenzocyclooctadiene,to the manner in which 60 dibenzylbutyrolactone,oxygen is incorporated dibenzylbutane, and the pattern arylnaphthalene,of cyclization): Dibenzylbutyrolactol, aryltetralin, furan and dibenzocyclooctadiene, furofuran (Figure1). 61 Eachdibenzylbutyrolactone, subgroup can be further dibenzylbu subdividedtane, accordingarylnaphthalene, to lignan aryltetralin, molecule oxidation furan and level furofuran and identities (Figure 62 of1). non-propyl Each subgroup aromatic can rings be further present subdivided on side chains according [13,14]. to lignan molecule oxidation level and 63 identities of non-propyl aromatic rings present on side chains [13,14]. dibenzylbutirolactol dibe nzocyclooctadiene dibenzylbutirolactone dibenzylbutane arylnapththalene arylte tralin furan furofuran 64 65 FigureFigure 1. 1.Structural Structural subgroups subgroups of of lignans lignans (Ar=Aryl). (Ar=Aryl). 66 OfOf the the eight eight lignan lignan subclasses, subclasses, synthesis synthesis of furofurans—which of furofurans—which exhibit a 2,6-diaryl-3,7- exhibit a 67 2,6-diaryl-3,7-dioxabicyclooctanedioxabicyclooctane skeleton—is initiated skeleton—is by the initiated enantioselective by the enantioselectivedimerization of dimerizationtwo coniferyl 68 ofalcohol two coniferyl units derived alcohol from units the shikimate derived from biosynthetic the shikimate pathway biosynthetic (Figure 2) [14]. pathway To date, (Figure 53 species2)[ 14 ].of 69 Tofurofuran date, 53 specieslignans of have furofuran been reported lignans have in 41 been genera reported of 27 in plant 41 genera families, of 27 including plant families, Thymelaeaceae, including 70 Thymelaeaceae,Styracaceae, Scrophulariaceae, Styracaceae, Scrophulariaceae, Saururaceae, Rutaceae, Saururaceae, Rhizophoraceae, Rutaceae, Rhizophoraceae, Piperaceae, Pedaliaceae, Piperaceae, 71 Pedaliaceae,Orobanchaceae, Orobanchaceae, Myristicaceae, Myristicaceae, Magnoliaceae, Magnoliaceae, Lauraceae, Lamiaceae, Lauraceae, Geraniaceae, Lamiaceae, Dioscoreaceae, Geraniaceae, 72 Dioscoreaceae,Cyperaceae, Cupressaceae, Cyperaceae, Cupressaceae, Compositae, Compositae,Combretaceae, Combretaceae, Cactaceae, Cactaceae,Aristolochiaceae, Aristolochiaceae, Arecaceae, 73 Arecaceae,Araliaceae, Araliaceae, Aquifoliaceae, Aquifoliaceae, Apocynaceae, Apocynaceae, Acoraceae Acoraceaeand Acanthaceae. and Acanthaceae. Furofuran Furofuranlignans are lignans present 74 arein the present bark, in bulbs, the bark, leaves, bulbs, seeds, leaves, stems seeds, and stemsroots of and these roots plants of these [14]. plants [14]. 75 However,However, depending depending onon thethe enzymeenzyme that catalyzescatalyzes modification modification of of the the precursor precursor metabolite, metabolite, a 76 avariety variety of of lignans lignans can be synthesizedsynthesized (Figure(Figure2 ).2). TheThe major major lignans—which lignans—which possess possess numerous numerous 77 pharmacologicalpharmacological properties—areproperties—are artigenin,artigenin, enterodiol,enterodiol, enterolactone,enterolactone, sesamin,sesamin, syringaresinol,syringaresinol, 78 medioresinol,medioresinol, ( (−−)-matairesinol,)-matairesinol, (−)-secoisolariciresinol, (−)-secoisolariciresinol, (+)-laricire (+)-lariciresinolsinol and (+)-pinoresinol, and (+)-pinoresinol, among 79 amongothers others[15]. [15]. Molecules 2019, 24, 917 3