Selected trace metal concentrations in the soft tissue of wild mussel species from various regions worldwide.
\r\n\t
",isbn:"978-1-83968-924-6",printIsbn:"978-1-83968-923-9",pdfIsbn:"978-1-83968-925-3",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!1,hash:"ea4ec0d6ee01b88e264178886e3210ed",bookSignature:"Dr. Hiran Wimal Amarasekera",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/9500.jpg",keywords:"Bone Tumors, Oncology, Childhood Tumors, Cancer, Risk Factors, Modern Management, Benign Lesions, Tumor-Like Conditions, Immunology, Histochemistry, Cell Oncology, Tumor Markers",numberOfDownloads:389,numberOfWosCitations:0,numberOfCrossrefCitations:1,numberOfDimensionsCitations:1,numberOfTotalCitations:2,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"September 28th 2020",dateEndSecondStepPublish:"October 26th 2020",dateEndThirdStepPublish:"December 25th 2020",dateEndFourthStepPublish:"March 15th 2021",dateEndFifthStepPublish:"May 14th 2021",remainingDaysToSecondStep:"4 months",secondStepPassed:!0,currentStepOfPublishingProcess:4,editedByType:null,kuFlag:!1,biosketch:"Consultant Orthopaedic Surgeon from Sri Lanka currently working in University Hospitals of Coventry and Warwickshire, UK, trained at the National Hospital of Sri Lanka, at the Oldchurch Hospital in Essex UK and The Avenue Hospital Melbourne, Australia and University Hospitals of Coventry and Warwickshire, UK, obtained the FRCS from Royal College of Surgeons of Edinburgh, Scotland.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"67634",title:"Dr.",name:"Hiran",middleName:"Wimal",surname:"Amarasekera",slug:"hiran-amarasekera",fullName:"Hiran Amarasekera",profilePictureURL:"https://mts.intechopen.com/storage/users/67634/images/system/67634.jpg",biography:"Hiran Amarasekera is a Consultant Orthopaedic Surgeon from Sri Lanka currently working in University Hospitals of Coventry and Warwickshire, the UK as a hip preservation fellow. \r\nHis special interests include young adult hip and knee problems, sports injuries, Hip and knee arthroplasty, and complex arthroscopic procedures. \r\nHe completed the MBBS from Kasturba medical college Manipal, India and did his postgraduate in Trauma and Orthopaedics at the Post-graduate Institute of the Medicine University of Colombo obtained the MS. \r\nHe was initially trained at the National Hospital of Sri Lanka and then completed the further training at the Oldchurch Hospital in Essex UK and The Avenue Hospital Melbourne, Australia and University Hospitals of Coventry and Warwickshire, UK.\r\nHe obtained the FRCS from Royal College of Surgeons of Edinburgh in 2003 and was elected a fellow of Sri Lanka College of surgeons (FCSSL) 2012. \r\nHe has a keen interest in academia and research. 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Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"878",title:"Phytochemicals",subtitle:"A Global Perspective of Their Role in Nutrition and Health",isOpenForSubmission:!1,hash:"ec77671f63975ef2d16192897deb6835",slug:"phytochemicals-a-global-perspective-of-their-role-in-nutrition-and-health",bookSignature:"Venketeshwer Rao",coverURL:"https://cdn.intechopen.com/books/images_new/878.jpg",editedByType:"Edited by",editors:[{id:"82663",title:"Dr.",name:"Venketeshwer",surname:"Rao",slug:"venketeshwer-rao",fullName:"Venketeshwer Rao"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"61979",title:"Biomonitoring of Trace Metals in the Coastal Waters Using Bivalve Molluscs",doi:"10.5772/intechopen.76938",slug:"biomonitoring-of-trace-metals-in-the-coastal-waters-using-bivalve-molluscs",body:'\nMarine pollution is a major problem that has negative effects on the ocean’s ecosystems. Economic developments and urbanization are taking place at an accelerated rate in the coastal zones across the world, putting enormous pressures on coastal waters and marine habitats. Incidents of coastal and marine water pollution have increased throughout the world, mainly due to discharges from rivers, increased surface run-off, drainage from expanding port areas, oil spills, discharges from shipping activities, and domestic and industrial effluent discharges. Most of the world’s wastes around 20 billion tons per year end up in the sea, often without any preliminary processing.
\nTrace metals are introduced into the coastal waters through natural process and anthropogenic activities. The natural process includes river discharge, rock weathering, wind-generated dust from arid and semi-arid regions of the continents, and hydrothermal circulation at mid-ocean ridges. The anthropogenic sources of metals include agriculture, fossil fuel extraction, refining and burning, chemical production, and intentional and accidental discharges. Trace levels of trace metals naturally occur in the marine environment, and many of them at low concentrations are essential for marine life. However, if their concentrations exceed the natural levels, it will cause a serious threat to marine life. Monitoring and assessment programs are routinely conducted in the coastal waters for planning and implementing mitigation measures to control trace metal pollution. Historically as one of the simple and widely used monitoring techniques, sampling, and analysis of seawater and sediment are being employed for estimating the levels of contaminants including trace metals in coastal waters. Instead of using water or sediment samples, tissue concentrations of contaminants in marine organisms, especially bivalves, are being used as a reliable method for assessing the coastal water quality since 1960s [1–4].
\nMost of the marine bivalves such as mussels, oysters, and clams are commercially important groups, and several of them are being used for coastal farming around the globe and as popular seafood. Since late 1960s and early 1970s, bivalves such as mussels were used for biomonitoring trace metals in coastal waters [3, 5]. In biomonitoring, tissue burden of trace metals in marine organisms are analyzed, and the biological responses of organisms are measured to assess changes in the environmental quality caused by toxic contaminants [6–8]. This chapter will attempt to provide an overview of the basic concept, methods and the present status of the biomonitoring of trace metals in the coastal waters using bivalve molluscs.
\nGenerally, bivalves are suspension feeders or deposit feeders, or even utilize both feeding methods. They feed on microscopic algae, bacteria, and detritus through filter feeding process. They draw water from the posterior ventral side through the inhalant siphon, and the water passes through the gills and gets expelled through the exhalent siphon. In this process, they filter large quantities of seawater, and the water filtering capacity of typical natural mussel beds has been calculated as 7–12 m3, m−1, h−1 [9, 10]. One single adult blue mussel pumps around 50 ml of seawater per minute during active feeding [11]. As bivalves filter large quantiles of seawater, their tissues absorb some of the contaminants present in water and food particles. Bivalves accumulate trace metals from the surrounding aquatic medium across the cellular membrane (dissolved source) and from the food materials (dietary source) [12].
\nHistorically, bivalve molluscs are considered as valuable marine organisms for environmental monitoring and used as biomonitors of chemical pollution of coastal waters [3, 5, 13]. Bivalves are widely distributed from the North Pole to the South Pole, sessile in nature, and easy to sample and available in a suitable size for chemical analysis. Bivalves are also resistant to a wide range of contaminants and may thrive even in highly polluted environments [3, 14]. These qualities make them a group of candidate species for biomonitoring programs across the globe. As filter feeders, they bioaccumulate various contaminants and their tissue concentrations provide a time-integrated picture of contaminants in the environment [15, 16]. It has been reported that bivalves accumulate trace metals in their tissues at levels up to 100–100,000 times higher than the concentrations observed in the seawater in which they live [5, 17]. Therefore, several chemical contaminants, including trace metals, present at undetectable levels in seawater can be detected in bivalve tissues. Different species of clams, mussels, and oysters have widespread distribution across the continents (Figure 1), and many of those species have been successfully used for monitoring the concentrations of contaminants in the marine environment [5].
\nCommon marine bivalves and their habitats from the Indian coast. (A) Intertidal rocky area showing green mussel beds from the south west coast of India; (B) green mussel Perna viridis; (C) enlarged view of green mussels; (D) oyster bed consisting of Crassostrea madrasensis and Saccostrea cucullata exposed during low tide; and (E) enlarged view of C. madrasensis and S. cucullata; (E) clam bed consisting of Meretrix casta and (F) enlarged view of the clam Paphia malabarica.
Cobalt, copper, chromium, iron, magnesium, manganese, molybdenum, nickel, selenium, and zinc are essential metals that are required for various biochemical and physiological functions of animals [18] while other metals such as aluminum, antinomy, arsenic, barium, cadmium, gold, lead, lithium, mercury, nickel, platinum, silver, strontium, tin, titanium, and vanadium have no established biological functions and are considered as non-essential metals [19]. However, the essential metals will be harmful to the organisms if their concentrations exceed the natural levels. The expert’s group of International Council for the Exploration of the Sea (ICES) and Oslo and Paris Conventions (OSPAR) highlighted the trace metals such as arsenic, cadmium, chromium, copper, mercury, nickel, lead, and zinc in the marine environment as key substances of concern [20].
\nBivalves accumulate both essential and non-essential metals in their soft tissues above the background levels in seawater or sediments, and this process is called bioaccumulation. Bioaccumulation is a good integrative indicator of the chemical exposures of marine organisms such as bivalves in polluted waters [21]. Trace metals cannot be metabolized by organisms, and hence bioaccumulation of trace metals is of particular value as an exposure indicator. However, metal bioaccumulation can be complex. The bioaccumulation levels in mollusks differ among metals in the same bivalve species and among species [13, 21–23] due to the biological role of different metals and to specific strategies of accumulation [23]. In addition, the metal bioaccumulation in bivalves depends on the marine environmental factors (temperature, pH, salinity, co-occurrence of metals, etc.) and the biological conditions (age, sex, sexual maturity stage, etc.) of the species [24, 25].
\nThe gill tissue of bivalves constitutes a key interface for the uptake of dissolved metal ions from water followed by the mantle tissue, and the uptake of metals bound to particulate material is achieved via the digestive tract, in particular, via the digestive gland [23]. Generally, in bivalves, maximum concentrations of metals have been reported in the digestive gland and/or gill tissue followed by mantle and muscle tissue [26, 27]. The bioaccumulation of trace metals in bivalve tissues is dependent on different metabolic processes occurring within specific cell types in target tissues. Metallothioneins (MTs), the low-molecular-weight proteins present in organisms including bivalves are involved in the intracellular regulation of metals such as Cu, Zn, and Cd [28]. Epithelial cells of gill and mantle can synthesize MT and sequester metals into the lysosomes for further transport in circulating hemocytes [29].
\nSentinel organisms accumulate contaminants in their tissues without any harmful effects and can be measured in a sensitive manner the amount of contaminants that are biologically available [30]. Several comprehensive reviews have been published on the use of bivalve molluscs as sentinel organisms and as biomonitors of metal pollution [5, 12, 20, 31–35]. These reviews and studies provide an in-depth discussion on metal bioaccumulation and metal bioavailability, highlighting the historical usage of bivalves in environmental studies.
\nMost of the bivalves such as clams, mussels, and oysters, fulfill the criteria required for a typical sentinel organisms and being successfully used as spatial and temporal trend indicators of contaminants in monitoring program from several parts of the world [3, 7, 12, 14–16, 36–39]. The tissue concentrations of various toxic trace metals in wild mussel species from various regions worldwide are summarized in Table 1. The tissue concentrations ranged from low to high values depending upon the environmental status of the study area.
\nCountry | \nMussel Species | \nAg | \nAl | \nAs | \nCd | \nCr | \nCo | \nCu | \nFe | \nHg | \nNi | \nPb | \nZn | \nTi | \nSe | \nV | \nSr | \nBa | \nMn | \nRef. | \n
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
San Francisco Bay, USA | \nMytilus edulis mg/kg dry wt | \n\n | \n | \n | 6.9 | \n4.05 | \n\n | \n | \n | \n | \n | \n | 92 | \n\n | 4.6 | \n\n | \n | \n | \n | [97, 98] | \n
Claisebrook Cove, Western Australia | \nXenostrobus sp. mg/kg wet wt | \n\n | 12–61 | \n0.46–0.75 | \n0.21–0.27 | \n0.05–0.17 | \n0.06–0.16 | \n1.7–2.2 | \n\n | <0.01 | \n0.22–85 | \n0.08–0.52 | \n6–9.6 | \n\n | 0.34–0.57 | \n\n | \n | \n | 3.3–28 | \n[99] | \n
South Island New Zealand | \nPerna canaliculatus mg/kg dry wt | \n\n | \n | 5.35–27.48 | \n0.14–1.67 | \n\n | \n | 2.19–18.25 | \n\n | \n | 0.08–5.83 | \n0.13–1.53 | \n45.31–147.18 | \n\n | \n | \n | \n | \n | \n | [100] | \n
Offshore South China Sea | \nBathymodiolus platifrons mg/kg dry wt | \n2.6–25.13 | \n2.16–6.73 | \n5.89–10.03 | \n0.78–4.35 | \n0.81–1.72 | \n0.1–0.45 | \n5.53–42.31 | \n14.28–56.07 | \n\n | 0.42–1.25 | \n4.41–4.8 | \n33.76–79.04 | \n\n | \n | \n | 17.98–45.78 | \n2.69–4.06 | \n4.5–8.01 | \n[101] | \n
East coast of China | \nPerna viridis mg/kg dry wt | \n0.01–0.14 | \n\n | 12.64–20.95 | \n0.48–5.31 | \n1.51–10.93 | \n\n | 1.45–28.55 | \n96.62–1002 | \n\n | 1.3–4.78 | \n0.44–2.93 | \n66.05–231 | \n\n | \n | \n | \n | \n | \n | [102] | \n
East Adriatic Sea, Croatia | \nMytilus galloprovincialis mg/kg dry wt | \n\n | \n | 4–30 | \n\n | 1–2.9 | \n\n | 3.7–11.1 | \n53.4–719 | \n\n | 0.8–5 | \n2–7 | \n59.1–273 | \n\n | \n | \n | \n | \n | 2–13 | \n[103] | \n
Adriatic Sea (Montenegro coasts) | \nMytilus galloprovincialis mg/kg dry wt | \n\n | \n | \n | \n | \n | \n | 4.6–17.2 | \n128–603 | \n\n | \n | \n | 132–345 | \n\n | \n | \n | \n | \n | 7.3–85.0 | \n[104] | \n
Tyrrhenian Sea (Gulf of Gaeta) | \nMytilus galloprovincialis mg/kg dry wt | \n\n | \n | \n | \n | \n | \n | 5.5–11.5 | \n\n | \n | \n | \n | 123–180 | \n\n | \n | \n | \n | \n | \n | [105] | \n
Marmara Sea (NW coasts) | \nMytilus galloprovincialis mg/kg dry wt | \n\n | \n | \n | \n | \n | \n | 6.7–9.5 | \n120–415 | \n\n | \n | \n | 208–320 | \n\n | \n | \n | \n | \n | 4.5–11.7 | \n[106] | \n
Aegean Sea | \nMytilus galloprovincialis mg/kg dry wt | \n\n | \n | \n | \n | \n | \n | 3.5–5.3 | \n48.6–49.9 | \n\n | \n | \n | 17.8–28.5 | \n\n | \n | \n | \n | \n | 2.6–4.7 | \n[107] | \n
N Atlantic (Spanish Gallician coasts) | \nMytilus galloprovincialis mg/kg dry wt | \n\n | \n | \n | \n | \n | \n | 3.9–9.7 | \n\n | \n | \n | \n | 159–351 | \n\n | \n | \n | \n | \n | \n | [108] | \n
Island of Gossa (W coast of Norway) | \nMytilus galloprovincialis mg/kg dry wt | \n\n | \n | \n | \n | \n | \n | 1.3–1.8 | \n11.0–11.7 | \n\n | \n | \n | 13.3–15.2 | \n\n | \n | \n | \n | \n | \n | [109] | \n
Spain Cantabrian Coast | \nMytilus galloprovincialis mg/kg dry weight | \n\n | \n | 14.6–31.5 | \n0.4–2.3 | \n2.6–5.7 | \n0.4–69.3 | \n9.1–34.8 | \n\n | \n | 1.5–15.4 | \n1.1–13.3 | \n202.7–300.8 | \n\n | 5.8–8.7 | \n1.7–7.1 | \n\n | \n | 5.6–55.3 | \n[110] | \n
N Aegean Sea (Strait of Canakkale) | \nMytilus galloprovincialis mg/kg dry wt | \n\n | \n | \n | \n | \n | \n | 0.7–12.9 | \n24.3–82.0 | \n\n | \n | \n | 43.8–133.5 | \n\n | \n | \n | \n | \n | 0.4–4.8 | \n[111] | \n
Trinidad | \nPerna viridis mg/kg wet weight | \n\n | \n | \n | 0.01–0.61 | \n0.06–0.2 | \n\n | 1.02–1.98 | \n\n | 0.03–0.07 | \n0.3–0.75 | \n\n | 11.3–40.37 | \n\n | \n | \n | \n | \n | \n | [112] | \n
Venezuela | \nPerna viridis mg/kg wet weight | \n\n | \n | \n | 0.02–0.05 | \n0.12–0.16 | \n\n | 1.42–3.43 | \n\n | 0.02–0.08 | \n0.22–1.3 | \n\n | 8.75–16.38 | \n\n | \n | \n | \n | \n | \n | [112] | \n
Italy Tyrrhenian coastal areas | \nMytilus galloprovincialis mg/kg dry weight | \n\n | \n | \n | 0.33–0.49 | \n0.46–1.31 | \n\n | 5.51–11.5 | \n\n | \n | \n | 1.67–2.49 | \n123–180 | \n\n | \n | \n | \n | \n | \n | [105] | \n
Black Sea (Turkish coasts) | \nMytilus galloprovincialis mg/kg dry wt | \n\n | \n | \n | \n | \n | \n | 11.7–23.3 | \n\n | \n | \n | \n | 312–396 | \n\n | \n | \n | \n | \n | 46.9–73.0 | \n[113] | \n
Turkey Eastern Aegean Sea | \nMytilus galloprovincialis mg/kg dry weight | \n\n | \n | \n | 0.24–0.49 | \n0.32–7.27 | \n\n | 2.44–5.49 | \n\n | 0.11–0.15 | \n\n | 0.84–2.41 | \n75.9–201 | \n\n | \n | \n | \n | \n | \n | [114] | \n
Italy Venice Lagoon | \nMytilus galloprovincialis mg/kg dry weight | \n\n | \n | \n | 1.16–6.59 | \n0.16–2.75 | \n\n | 3.55–10.8 | \n\n | \n | \n | 1.08–4.27 | \n135–400 | \n\n | \n | \n | \n | \n | \n | [115] | \n
Brazil | \nMytella guyanensis mg/kg dry weight | \n\n | 778–2458 | \n1.44–23.1 | \nBdl–1.42 | \nBdl–3.13 | \nBdl–611 | \n6.03–102 | \nBdl–1820 | \nBdl–0.35 | \n\n | Bdl–19.4 | \n50.8–141 | \n\n | Bdl–49.6 | \nBdl–6.93 | \n35.5–95.8 | \nBdl–88.7 | \n30.7–3520 | \n[116] | \n
India | \nPerna viridis mg/kg wet weight | \n\n | \n | \n | 0.24–3.49 | \nBdl–0.46 | \n\n | Bdl–1.84 | \nBdl–235.6 | \n\n | Bdl–2.89 | \nBdl–1.95 | \nBdl–17.36 | \n\n | \n | \n | \n | \n | 1.91–8.77 | \n[15] | \n
Selected trace metal concentrations in the soft tissue of wild mussel species from various regions worldwide.
Mussels and other marine bivalves are widely used as sentinel organisms in “mussel watch” programs for indicating levels of pollutants in the coastal marine environment due to their ability to bioaccumulate organic or toxic elements [40]. Under mussel watch program, environmental contaminants (trace metals, hydrocarbons, pesticides, etc.) accumulated in the soft tissue of natural, cultured, or deployed bivalves (clams, mussels, and oysters) collected from a set of defined geographical locations over a time-span of several years are systematically and repeatedly measured for assessing and comparing the coastal water quality [5, 40–42]. A prominent example is the US Mussel Watch Program originally started in 1976 [3, 43] and established as the Mussel Watch component of National Oceanic and Atmospheric Administration’s (NOAA) National Status and Trends (NST) program during 1986–2012 [44, 45, 46]. In spite of the criticisms and limitations [47], the US mussel watch results made valuable contributions to our understanding of trace metal contamination and its biogeochemistry in coastal ecosystems [5].
\nLater, the contaminant monitoring programs similar to mussel watch were implemented throughout the world either for monitoring long-term spatial and temporal pollution trends covering large marine region containing multiple monitoring stations and several anthropogenic contamination sources [36–38, 48–51] or for monitoring and solving local pollution problems covering a small geographical areas [7, 8, 15, 32, 52–58].
\nThe mussel watch program initiated in USA has led to the formation of the International Mussel Watch (IMW) Projects [5]. It was initiated by the International Oceanographic Commission (IOC) in collaboration with the United Nations Environment Program (UNEP) and the US NOAA. Table 2 summarizes the details of the international mussel watch program conducted from different geographical locations. Recently, the advantages and limitations of the mussel watch concept were discussed 40 years after its inception [5].
\nProject phase and year | \nStudy areas | \nBivalve species | \nList of contaminants | \nReferences | \n
---|---|---|---|---|
IMW Phase I (Initial Implementation): 1991–1993 | \nSouth America, Central America, Mexico and Caribbean | \nBlue mussels (Mytilus sp.) 134 stations Oysters (Crassostrea sp.)–18 stations Other bivalves–24 stations | \nTotal Polychlorinated biphenyls (PCBs), total Chlordane (CHLs), and total HCHs | \n[5, 117] | \n
IMW Phase II 1997–1999 | \nAsia Pacific Region (Japan, South Korea, Russia, China, the Philippines, Vietnam, Malaysia, Cambodia, Thailand, Indonesia and India) | \nBlue mussel, (M. edulis), and the green mussel (Perna viridis). | \nTotal PCBs, dichloro diphenyl trichloroethane and its metabolites (DDTs), CHLs, hexachlorocyclohexane isomers (HCHs) and hexachlorobenzene (HCB), polychlorinated dibenzo-p-dioxins and furans (PCDDs/Fs), coplanar PCBs (Co-PCBs), Butyltins (BTs) and some heavy metals | \n[38, 118–121] | \n
IMW Pilot Study—Black Sea. 1996–1997 | \nSix Black Sea Countries (Bulgaria, Georgia, Romania, Russia, Turkey and Ukraine). | \nBlue mussels (M. galloprovincialis)- 5–13 sites | \nPAHs, PCBs, DDTs | \n[122] | \n
Western Mediterranean Basin and the International Mediterranean Commission (CISEM) Mussel Watch program. 2002–2006 | \nThe coasts of the Western Mediterranean Basin (Spain, France, Italy, North Tunisia, Algeria and Morocco) | \nCaged mussels (Mytilus sp.) deployed at 122 sites | \nHeavy metals, chlorinated pesticides and PCBs and PAHs | \n[123–125] | \n
Details of the International Mussel Watch (IMW) program conducted from various parts of the globe [5].
Chemical analyses of bivalve tissue samples measure the contaminants present but do not necessarily reveal potential biological effects on bivalves. Therefore, biomarkers were developed to assess the health status of the marine organisms, especially bivalves. Biomarkers are the early warning signals about the health status of bivalves exposed to toxic contaminants, because a toxic effect or response will be apparent at the molecular or cellular level before it is noticeable at higher biological levels. The concept of biomarker is borrowed from medical science, which describes a measurable indicator such as blood cholesterol profile connected to relevant clinical endpoints like atherosclerosis and heart attack. The biochemical biomarkers (acetylcholinesterase inhibition for exposure to neurotoxic compounds, cytochrome P450 for detoxification of polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs), and the different methods to detect genotoxicity), which are used in marine environmental monitoring are still used in humans [59–61].
\nDuring the last decade, several biomarkers sensitive to contaminant exposure and/or impact have been developed as tools for use in marine environmental monitoring and impact assessment [7, 8, 62]. During the same time, various monitoring agencies began to focus on locating the source of contamination and fates as well as the impact as contaminants are usually discharged into the coastal waters, especially estuaries, where effects have been most significantly detected. The European Union’s Water Framework Directive (WFD) also stressed the requirement of monitoring programs to assess the achievement of good chemical and ecological status for all water bodies by 2015 [63]. In the past 30–40 years, numerous biomarkers have been developed on bivalve mollusks, especially mussels (see Table 3) with the objective to apply them for environmental biomonitoring. Biomarkers based on responses at physiological level, cellular/tissue level, and molecular level of bivalve molluscs are developed and recommended as tools for studying the effects of contaminants on field and laboratory exposed bivalves, especially mussels [6, 64–66]. Research into the development and application of accurate biomarker-based monitoring tools for the environmental contaminants has been intensified in several developed countries, and they are using several biomarkers based in marine bivalves to monitor the environmental quality of coastal and estuarine waters [20].
\nGroup | \nBiomarker name | \nDescription | \nReferences | \n
---|---|---|---|
Bivalve Physiology | \nBody Condition Index (BCI) | \nAssessment of tissue weight in comparison with shell cavity volume or shell length | \n[7, 59, 126] | \n
Stress on stress response (SOS) | \nAssessment of survival rate during aerial exposure | \n[71] | \n|
Scope for growth (SFG) | \nMeasurement of physiological energy balance | \n[59, 76] | \n|
Metal-binding cysteine-rich proteins | \nMetallothioneins (MTs) | \nMeasurement of metal binding proteins in tissue samples. Compensatory mechanism during exposure to heavy metals (Cd, Fe, Hg, Zn, As) | \n[28] | \n
Cellular Responses | \nLysosomal membrane stability (LMS); lipofuscin and neutral lipids accumulation | \nAssessment of the condition of lysosomes and the related cell injury | \n[7, 8, 61] | \n
DNA integrity markers | \nMicronuclei | \nAssessment of toxic impact on chromosomes | \n[91, 92, 127] | \n
DNA adducts | \nDNA damage assessment | \n[91, 92, 128] | \n|
Comet assay | \nSingle cell DNA damage assessment | \n[91, 92, 128] | \n
List of biomarkers routinely used for monitoring the coastal waters quality using marine bivalves.
The biological indicators of health in bivalves such as Body Condition Index (BCI), stress on stress response (SOS), and scope for growth (SCF) have been recommended as broad markers of stress caused by either environmental changes or contaminants [59, 64, 67–70]. The stress on stress response is a simple test, which measures the mortality rate (time to kill 50% of the sample) of bivalves when exposed to air [70, 71]. The SOS test examines whether stress caused by environmental changes or contaminants have altered the capacity of bivalves to survive under adverse conditions such as aerial exposure. The body condition index (ratio between soft tissue dry/wet weights to its overall size) is a general indicator of favorable growth conditions as well as the overall biological status. The body condition index is routinely used in aquaculture and environmental monitoring studies to assess the health condition of mussels [7, 25, 72].
\nThe growth, reproduction, and survival of bivalves depend on the availability of sufficient energy reserve in their body. Exposure to contaminants negatively affects the energy balance of bivalves due to the high-energy demand for maintaining homeostasis at the expense of growth, storage, defense, and reproduction [73]. Fitness of an individual organism can be measured in terms of Scope for Growth (SfG), which is the measurement of physiological energy balance and it ranges from optimal (positive values) to stressed conditions (negative values) when the organism is exposed to contaminants or unfavorable environmental conditions [74, 75]. The SFG has been widely used in field monitoring studies [76, 77]. The SFG and the growth rates of mussels were drastically reduced when mussels from uncontaminated sites were transplanted along known pollution gradients or placed in the most contaminated areas [78, 79].
\nThe digestive gland cells in bivalves play a key role in digestive and absorptive processes and also in the detoxification and excretion of contaminants [80]. The lysosomal system in the digestive cells was identified as the main target site for the toxic effects of most of the environmental contaminants including trace metals [81]. Lysosomal responses to cell injury due to contaminant exposure or stress caused by environmental changes fall into three categories: (1) changes in lysosomal contents, (2) changes in fusion events, and (3) changes in membrane permeability [81].
\nChanges in lysosomal membrane permeability of bivalves can be measured using the lysosomal membrane stability (LMS) test [82–84]. The LMS test can be conducted by using two different methodologies: (i) a cytochemical method using cryostat sections of digestive gland tissue and (ii) an in vivo cytochemical method using hemolymph cells. Biomarkers such as LMS, accumulation of lipofuscin and neutral lipids in bivalves were successfully used for coastal pollution monitoring studies [7, 8, 69, 70, 82–84]. Subsequently, different regional conventions have recommended the use of LMS as a general stress biomarker of chemical pollution within the framework of the pollution biomonitoring programs [67, 68, 85]. The proposed integrated assessment approach of contaminants and their effects in the NE Atlantic Baltic Sea Action Plan and in the Mediterranean Ecosystem Approach (EcAp) have included the LMS in mussels as one of the core biomarkers [86–88].
\nIt has been demonstrated that metallothioneins (inducible low molecular, sulfhydryl proteins) levels in the digestive cells of bivalves will be induced after exposure to trace metals such as Cd, Cu, and Zn [89]. The induction of metallothioneins (MT) in bivalves has been proposed as biomarkers of trace metal stress, and it has been recommended to use in coastal pollution monitoring studies [67, 68, 85, 90].
\nA wide variety of chemical contaminants capable of directly or indirectly damaging the DNA of marine organisms are being discharged into the marine environment. These genotoxic chemicals are capable of inducing some changes in the molecular and cellular levels of marine bivalves [91, 92]. Two well-known tests, micronucleus assay and comet assay, are being widely used to assess the genotoxic effects of environmental contaminants on marine bivalves [91, 92]. The micronucleus assay is used to detect the structural and numerical chromosomal changes while the comet assay (single-cell gel electrophoresis) is used to detect DNA strand breaks in marine bivalves.
\nThe biomarkers in marine bivalves based on sub-lethal effects of contaminants are ecologically relevant and can be used to give subtle signals of response to contaminants before damage becomes irreversible. The water quality in European coastal sites was classified ranging from class 1 (clean areas) to class 5 (highly polluted areas), based on global biomarker index for Baltic mussels [93]. The Marine Strategy Framework Directive (Directive 2008/56/EC) since 2008 emphasized on the importance of assessing key biological responses for evaluating the health of organisms and linking the observed changes to potential contaminant effects [94].
\nThe studies conducted prior to 1990s from Puget Sound, Washington, reported high concentrations of toxic metals, polycyclic aromatic hydrocarbons (PAHs) and PCBs in sediments and toxicant-induced, adverse effects in benthic fish samples collected from the urban associated sites [95]. As an example of how biomarker-based indices can be integrated into environmental monitoring of Puget Sound, biomonitoring study using mussels was conducted in 1992 [7]. Blue mussels (Mytilus edulis) were collected from their natural beds from nine sites in Puget Sound (Figure 2). Sites included the minimally contaminated reference areas of Oak Bay, Coupeville, and Double Bluff, in central and north Puget Sound, and Saltwater Park of south Puget Sound. Urban sites that were sampled for mussels included Eagle Harbor, Seacrest and Four Mile Rock in Elliott Bay, City Waterway in Commencement Bay, and Sinclair Inlet.
\nMap showing the mussel sampling sites in Puget Sound, Washington [7].
Relatively high tissue concentrations of contaminants including toxic trace metals were observed in mussels tissue samples from the urban-associated sites compared to the minimally contaminated (reference) sites (Figure 3). Mussels from contaminated sites showed low LMS, enhanced lipofuscin deposition, and increased accumulation of lysosomal and cytoplasmic unsaturated neutral lipids (Figure 3). Mussels from the contaminated sites were smaller in size together with lower somatic tissue weight relative to shell length [7]. Highly significant correlations were observed between tissue concentrations of selected toxic elements (measures of anthropogenic exposure) and LMS [7]. The study showed that biomarkers in mussels have the potential to be used as sensitive, accurate, and rapid techniques for assessing the biological impact of environmental contaminants in the coastal waters. The study results were in agreement with the previous study results, which showed an association between metabolites of aromatic compounds in bile and the occurrence of hepatic lesions in English sole (Parophrys vetulus) from Puget Sound [96].
\nRelationship between lysosomal membrane stability (LMS) and tissue concentration of heavy metals (mercury and lead) of mussels from urban-associated and reference sites in Puget Sound [7].
Commercially and ecologically important marine bivalves (clams, mussels, and oysters) are widely used for monitoring levels of trace metals in the marine environment from several parts of the world. Trace metal monitoring using bivalves has several advantages compared to using seawater or sediment samples for the same purpose. Bivalves such as mussels are having global distribution from the polar to the tropical region and being successfully used for temporal and spatial trend monitoring of trace metals in the coastal waters across the globe. Recently several biomarkers, the biological responses of bivalves to contaminants including trace metals, are being developed and tested to assess the coastal water quality. The biomarkers of stress in bivalves give early warning signal about the presence of toxic trace metals in the marine environment.
\nWe thank the Center for Environment and Water, Research Institute, King Fahd University of Petroleum and Minerals, Dhahran, Saudi Arabia, for providing research facilities. We acknowledge the research funding (# T.K. 11-0629) of the King Abdulaziz City for Science and Technology (KACST). We also thank our colleagues and students who helped us to prepare this manuscript.
\nBerries with a high antioxidant activity have drawn the attention of scientists due to their potential antioxidant, anticancer, anti-inflammatory, and neuroprotective-related effects, identified in in vivo studies [1]. It is well established that many species of berries, for example, strawberries (Fragaria ananassa), blueberries (Vaccinium corymbosum), raspberries (Rubus idaeus), and blackberries (Rubus fruticosus), are rich in bioactive compounds such as flavonoids, polyphenols, and anthocyanins. These compounds could be a supplementation alternative because they are able to cross the blood-brain barrier and accumulate in various structures [2, 3] related to learning, memory, cognition process, and modification of behavior. In addition, their anti-neurodegenerative properties have been observed in diseases such as anxiety associated with stressful events [4] and reduction of depression, AD, and PD symptoms. Additionally, an association has been observed between the consumption of berries and increase in dendritic spine density in some brain structures and hippocampal neurogenesis [5]. In this way, the berry consumption and their bioactive compounds (i.e., polyphenols and anthocyanins) might be an excellent alternative for human nutrition when consumed fresh. They can be consumed as yogurt, juice, jam, or like dietary supplements that can be used as functional and nutraceutical foods.
\nFood is considered as a functional food if, in addition to its basic nutritional, it generates a beneficial effect in the physiological processes in the organism [6]. In the same way, a nutraceutical is a food or part of a food that produces health benefits besides its nutritional content [7, 8]. In the present chapter, we discuss the potential beneficial effects of berries and their derivatives on some central nervous system diseases.
\nEnhanced consumption of fruits and vegetables is highly recommended in dietary guidelines. Specially, the consumption of berries is recommended due to their antioxidant properties [1]. Berries, in botanical terms, are defined as fleshy fruits that emerge from the plant ovary that encloses the seeds; due to this, berries include grapes, blueberries, black currants, and coffee beans [9].
\nIn this chapter we will focus on strawberries, blueberries, raspberries, chokeberries, black currants, and blackberries, among other endemic fruits. We selected these fruits because, in addition to being rich in polyphenols and anthocyanins, they are the most consumed in human diet; therefore, more studies related to their supplementation and chemical composition have been published.
\nBerries (i.e., blackberry, black raspberry, blueberry, cranberry, red raspberry, and strawberry) are popularly consumed either fresh, frozen, or processed as yogurts, beverages, jam and jellies, as well as dried or canned. Furthermore, berry extracts have been used as a functional food or dietary supplement [1].
\nBerries (blueberry, strawberry, blackberry, and Brazilian berries {Eugenia uniflora L.}) are considered an important group within functional foods, since multiple investigations have shown that their consumption produces beneficial health effects ranging from the mitigation of adverse physiological processes related to cardiovascular diseases and metabolic disorders to the amelioration of cognitive brain functions [10]. This highlights their ability to modulate neuroinflammation [11], glucoregulation [12], brain vascular function [13], and hippocampal neurogenesis [5]. These effects have been linked to their chemical compounds, specifically, to the presence of phenolic compounds in these fruits [14]. Table 1 shows specifically most consumed berries, their effect produced, and metabolite involved.
\nBerry | \nEffect | \nMetabolite involved | \nRef | \n
---|---|---|---|
Blueberry (Vaccinium Virgatum A.)\n | \nAntioxidant | \nAnthocyanins (1202 mg) | \n[9] | \n
Strawberry (Fragaria ananassa Duch.)\n | \nAntioxidant | \nPolyphenols (13550 mg) | \n[9] | \n
Blackberry (Rubus sp.)\n | \nAntioxidant | \nAnthocyanins (870 mg) | \n[9] | \n
Blueberry (*NS)\n | \nModulate neuroinflammation | \nFlavonoids: various concentrations of blueberry (50-500 μg) | \n[10] | \n
Blueberry Highbush (Vaccinium corymbosum)\n | \nGlucoregulation | \nAnthocyanins-flavonols (220 mg) | \n[11] | \n
Blueberry (Vaccinium corybosum)\n | \nSynaptic plasticity | \nAnthocyanins (10.2 mg)/ Total phenolics (33 mg) | \n[12] | \n
Blueberry (*NS)\n | \nHippocampal neurogenesis | \nBlueberry extract diet (20 g) (*NS anthocyanins or polyphenols) | \n[5] | \n
Rasperry (Rubus idaeus)\n | \nAnti-cancer | \nAnthocyanins (314 mg) | \n[14] | \n
Strawberry Beverage (*NS)\n | \nAnti-inflamatory/ hypoglycemic | \nTotal phenols (94.7 mg)/ Anthocyanins (39 mg) | \n[15] | \n
Grape (*NS) | \nGenoprotective | \nAnthocyanins (1576.5 mg)/ Total phenolics (2750.4 mg) | \n[16] | \n
Blueberry Highbush (Vaccinium corymbosum)\n | \nNeuroprotection/Proneurogenesis | \nAnthocyanins (4968·3 ng) | \n[17] | \n
Cranberry (Vaccinium oxycoccus)\n | \nVascular | \nPolyphenols (835 mg)/ Anthocyanins (94 mg) | \n[18] | \n
Rabbiteye Blueberry (Vacciniumn ashei)\n | \nMotor and cognitive function Anxiolytic Genoprotective | \nAnthocyanins (2.6-3.2 mg) | \n[19] | \n
Berries: effects and metabolites involved.
NS: not specified; Ref: reference
Even though the composition and the content of these compounds are dependent on the plant species, production status, agricultural processing, and storage, berries are an excellent source of polyphenols, flavonoids, and anthocyanins [20, 21], which have been related to their potential beneficial effects on health.
\nBerries are rich in phytochemicals such as minerals, vitamins, fatty acids, and dietary fibers and specifically contain provitamin A, minerals, vitamin C, and B complex vitamins. Additionally, fruits contain soluble solids, fructose, and chemopreventive agents as A, C, and E vitamins, folic acid, calcium, and selenium. Carotene and lutein are present in berries as well as phytosterols such as sitosterol and stigmasterol and also contain triterpene esters, and there is an excellent source of phenolic molecules such as flavonols, flavanols, proanthocyanidins, ellagitannins, phenolic acids, and anthocyanins specially cyanidin-3-glucoside, gallic acid, pelargonidin, delphinidin, peonidin, and malvidin, among others [22].
\nThe metabolism, bioavailability, and biological effects attributed to berries depend specifically on the type of chemical structure contained in its phenolic compounds that individually or synergistically exert protection against several health disorders [23]. Table 2 shows the main phytochemical compounds present in berries and their representative chemical structures.
\nTotal polyphenols, anthocyanins and characteristic structure content of berries.
Chemical structure was determined according to berry bioactive compound. TP: total polyphenols; TF: total flavonoids; TA: total anthocyanins; FW: fresh weight; DW: dry weight.
Polyphenols or phenolic compounds are phytochemicals that result from the secondary metabolism of plants coming from the metabolic pathway of shikimic acid and acetate-malonate. They are composed of various chemical structures characterized by an aromatic nucleus of benzene substituted by a hydroxyl group called phenol [21]. Differences between subclasses are given by the number of phenolic rings and the elements attached to them, thus creating several families of compounds, such as flavonoids, anthocyanins, flavones, tannins, and coumarins, among others [21, 27, 28, 29].
\nPolyphenols are present in fruits, vegetables, leaves, nuts, seeds, flowers, and barks [30] and act as inhibitors or activators for a wide variety of mammalian enzyme systems and as metal chelators and oxygen free radical scavengers [31, 32]. Moreover, it has been reported that some flavonoids rise ion chlorine flow at the GABAA receptor in male rats [33, 34]. They can act as positive or negative modulators by direct actions on the effect of GABA [35, 36]. Considerable scientific evidence has shown that flavonoids are able to cross into the brain and influence brain function [37, 38]. They have a variety of effects like relief of anxiety, antidepressant actions, and neuroprotective [29] and sedative actions [39].
\nThe ability of polyphenols to modulate the activity of different enzymes and consequently interfere in signaling mechanisms and different cellular processes may be due, in part, to the physicochemical characteristics of these compounds, which allow them to participate in different oxide-reduction cellular metabolic reactions [40].
\nA diet rich in polyphenols has been shown to augment health [41]. It is best known for its biological effects in humans as anti-inflammatory [42] and anticarcinogenic [43]; in vitro as antiviral [44]; and in animals as gastroprotector [45] and antibacterial [46]; among others. More than 8000 phenolic compounds are known in nature [47], which according to their chemical composition are divided into 2 groups: phenolic acids (benzoic and cinnamic) and flavonoids (flavonoids, anthocyanins, and tannins) [48]. For the purposes of this chapter, we will focus on describing flavonoids in a general sense and anthocyanins in a particular manner.
\nTheir name derives from the Latin flavus, which means “yellow,” and constitutes the most abundant subclass of polyphenols within the vegetable kingdom [49]. They are low molecular weight compounds sharing a common diphenylpyrane skeleton (C6-C3-C6′), composed by two phenyl rings (A and B) bound through a heterocyclic pyran C ring. All flavonoids are hydroxylated structures in their aromatic rings and are therefore polyphenolic structures [41].
\nThe main subgroups of flavonoid include flavonols, flavones, flavanones (dihydroflavones), isoflavones, and anthocyanins [50]. The flavonoid quercetin (4 mg/day) produces antineoplastic effects [51] and cholesterol-lowering effects in Japanese women aged 29–79 years old (9.3 ± 7.4 mg/day) [52], and at preclinical research in rats, quercetin (25 and 50 mg/kg) produces antithrombotic effects [53], while a hepatic regenerative effect was detected with supplementations of silymarin (100 mg/kg/day) [54].
\nAmong the most reported effects of flavonoids on the central nervous system are their participation in learning and memory mechanisms in Sprague Dawley rats supplemented with nobiletin (725 mg; extracted from Citrus depressa peels) [55]; in vitro aid in the treatment of AD by inhibiting the formation of plaques related to memory loss (myricetin, 1 mM) [56] and their neuroprotective role in PD (quercetin, 0.1 μM, or sesamin, 1 pM) [57]; and in male Swiss mice, antidepressant effect supplemented with Schinus molle L. (0.3–3 mg/kg) [58] and anxiolytic activities in Wistar rats (1 mg/kg of chrysin i.p.) and zebra fish (1 98 μL/0.1 g b.w.) [59].
\nAnthocyanins are an important group of water-soluble flavonoid compounds responsible for the red, purple, and blue colors in flowers, fruits, and other parts of plants that are not toxic for human consumption [48]. Their name derives from the Greek ανθός (anthos) meaning “flower” and κυανός (kyáneos) meaning “blue” [60].
\nThey are polyhydroxy- or polymethoxy-glycosides derived from the basic structure, 2-phenyl benzopyryllium [61]. They consist of structures known as anthocyanidins or aglycones, which consist of an aromatic ring attached to a heterocyclic ring containing oxygen which, in turn, is linked to a third aromatic ring. When anthocyanidins are found in glucosylated form, they are then known as anthocyanins and are mainly accompanied by glucose, rhamnose, galactose, arabinose, xylose, and other disaccharides and trisaccharides [62]. These carbohydrates are always bound to anthocyanidin position 3, and glucose is often found additionally in position 5 and, less commonly, in positions 7, 3′, and 4′ [63].
\nAnthocyanins are less water-soluble than when they are found in glucosinolates and rarely exist in free form in food. Today, about 19 natural anthocyanidins are known, although the most commonly found in foods are six: pelargonidin, delphinidin, cyanidin, petunidin, peonidin, and malvidin [64], names derived from the plant source from which they were first isolated. In the same sense, a measure of the antioxidant capacity of anthocyanin pigments revealed that cyanidin-3-glucoside and delphinidin-3-glucoside have the highest antioxidant activity [65] and have been identified in fruits coming from the berry family [66], specifically in blackberries [67, 68].
\nIt is important to mention that anthocyanins resist passage through the digestive tract of mammals and are absorbed in the stomach and in the middle portion of the small intestine, reaching the bloodstream almost intact [69]; they reach organs such as the liver, eyes, and brain, thus accumulating in them [14, 70].
\nThe biological functions of anthocyanins can be classified into two types: those related to their antioxidant capacity and those involved in the modulation of cell signaling pathways [71]. In general, they are attributed with effects such as the prevention and/or reduction of atherosclerosis [72]; reduction in the incidence of cardiovascular disease [73]; anticancer [74] and anti-inflammatory activity [75]; hypoglycemic effects [76]; and augmented visual acuity [77] and cognition [78].
\nSpecifically, anthocyanins cross the blood-brain barrier and accumulate in brain regions related to learning and memory, such as the hippocampus and cerebral cortex, modifying behavior [2]. It has been observed in in vitro studies that consumption of these compounds inhibits the enzyme monoamine oxidase (MAO), in which increased activity is related to AD and other neurological disorders [79]. In addition, they display antioxidant capabilities, such as decreasing free radicals and stress signals controlling calcium homeostasis in the brain [80, 81], as well as the presence of hydrogen peroxide (H2O2) and radicals peroxide (ROO) and superoxide (O2) [82, 83]. They also exert protective effects against oxidative stress in cellular models of PD [84] and promote optimal neurotransmission, primarily in advanced age [21].
\nIt has also been observed that anthocyanins ameliorate anti-ocular-inflammatory in male Lewis rats supplemented with crude aronia extract (Aronia melanocarpa) in doses of 100 mg/kg, an effect similar to that found in ophthalmic prednisolone in a dose of 10 mg; this effect is evidenced by the direct blockage of the expression of the iNOS and COX-2 enzymes leading to suppression of NO, PGE2, and TNF-α production [85]. Another study in female Wistar rats ovariectomized and supplemented with anthocyanin (200 mg/kg, 7 days of treatment) showed an augment in learning and memory in rats with estrogen deficiency caused by ovariectomy, showing lower errors and latency times in shuttle box test [86].
\nThe recent increase in life expectancy worldwide has augmented the incidence of age-related diseases, particularly neurodegenerative diseases and psychiatric disorders.
\nBelow, we will describe the effects of berry consumption and the relationship between diseases such as anxiety, depression, Alzheimer’s and Pasrkinson’s diseases, as well as human cognition, because those are the most common mental illness and neurodegenerative diseases [5].
\nIn addition, you will find in Table 3 the most recent research carried out related with supplementation in humans and in animal models and, additionally, study design and summarized findings.
\nTopic | \nAuthor/location | \nStudy design | \nIntervention | \nSummarized findings | \n
---|---|---|---|---|
Anxiety | \nFernández-Demeneghi et al., 2019 [4]/Mexico | \nn=45, 21 days treatment, Wistar male rats (200- 250 g) | \nFive groups were used: Veh (control group administered with 8.7 ml/kg), BL (low dose group of blackberry juice, 2.6 mg/kg of anthocyanins, 14.57 mg/kg of polyphenols) BM (medium dose group of blackberry juice, 5.83 mg/kg anthocyanins, 27.10 mg/kg polyphenols) BH (high-dose blackberry juice group 10.57 mg/kg anthocyanins, 38.4 mg/kg polyphenols) DZP (diazepam group administered 2 mg/kg). | \nThe intermediate dose of blackberry juice (5.83 mg/kg of anthocyanins, 27.10 mg / kg of polyphenols) had an anxiolytic effect similar to DZP, improving coping strategies at the behavioral level. These results were supplemented by the forced swim test, where medium and high doses improved the response to acute stress. | \n
Depression | \nChang et al., 2016 [85]/USA-UK | \nn=82643 women. Prospectively, the study examined the associations between the estimated usual intake of flavonoids in the diet and the risk of depression. Semiquantitative food frequency questionnaire was applied (FFQ). | \nTwo samples were used: Nurses\' Health Study (NHSI) (from 1976 nurses aged 30-55) and NHSII (from 1989 nurses aged 25-42). | \nHigher flavonoid intakes may be associated with lower depression risk, particularly among older women. | \n
Khalid et al., 2017 [86]/United Kingdom | \nn=21 university students (18-21 years)/The Positive and Negative Affect Schedule-NOW (PANAS-NOW) was used to assess current mood. | \nTwo groups were used: The flavonoid-rich wild blueberry (WBB), which administered 253 mg of anthocyanins, a combination of 30 g of lyophilized WBB, 30 ml of Rocks Orange Squash and 220 ml of water), placebo (4 mg of WBB, 30 ml of Rocks Orange Squash and 220 ml of water were combined). | \nIn both studies, an increase in positive affection was observed after 2 hours of consumption of the WBB drink. Flavonoid supplementation can play a key role in promoting positive mood and are a possible way to prevent dysphoria and depression. | \n|
n=50 children (7-10)/child version of the Positive and Negative Affect Scale (PANAS-C). | \nTwo groups were used: The flavonoid-rich wild blueberry (WBB) 253 mg anthocyanins, combination of 30 g lyophilized WBB, 30 ml Rocks Orange Squash and 170 ml water); placebo (4 mg WBB, 30 ml Rocks Orange Squash and 170 ml water were combined). | \n|||
Nabavi et al., 2018 [87]/Iran | \nn=40, 7 days treatment, balb/c strain mice (5 weeks old, 20-25 g). | \nFour groups were used: control (healthy group), BCCAO (group with bilateral occlusion of the common carotid artery) 10 mg/kg (group with lesion + 10 mg/kg of aqueous extract of red berries of H. Androsaemum (WE) 30 mg/kg (group with lesion + 30 mg/kg of WE). | \nThe protective effects of WE in post-stroke depression in a mouse model were demonstrated in vivo, both groups administered with WE reduced immobility time in forced swim and tail suspension tests. These findings are correlated with the antioxidant capacity of its bioactive constituents. | \n|
Di Lorenzo et al, 2019 [88]/Italy | \nn=50, 7 days treatment i.p., balb/c strain mice (2 weeks old, 20-25 g). | \nFive groups were used: 1) control: healthy group, 2) BCCAO (group with stroke common carotid artery bilateral occlusion), 3) 25 mg/kg (lesion + 25 mg/kg Maqui berry extract (MBE)), 4) 50 mg/kg (lesion + 50 mg/kg MBE), 5) 100 mg/kg (lesion + 100 mg/kg MBE). | \nThe results showed that the antidepressant-like activity provided by the extract, which was found to restore normal mouse behavior in both despair swimming and tail suspension tests, could be linked to its antioxidant activity, leading to the conclusion that maqui berries might be useful for supporting pharmacological therapy of Post-stroke depression by modulating oxidative stress. | \n|
Alzheimer’s disease | \nGutierres et al., 2014 [89]/Brazil | \nMale Wistar rats (3-months-1-year-old, 350-400g), 7 days of treatment with 200 mg/kg anthocyanin (ANT) the rats were injected with intracerebroventricular streptozotocin (3 mg/kg) (STZ), and four days later the behavior parameters were performed. | \nFour different groups: control (CTRL), anthocyanin (ANT), streptozotocin (STZ) and streptozotocin + anthocyanin (STZ + ANT). | \nA memory deficit was found in the STZ group, but ANT treatment showed that it prevents this impairment of memory. This work demonstrated that anthocyanin is able to regulate ion pump activity and cholinergic neurotransmission, as well as being able to enhance memory and act as an anxiolytic compound in animals with sporadic dementia of Alzheimer\'s type. | \n
McNamara et al, 2018 [90]/USA | \nn=76, 24 weeks treatment, study conducted in men and women aged 62-80 with cognitive impairment. They used the Dysexecutive Questionnaire. | \nFour groups were used: FO (fish oil + placebo powder), BB (blueberry [Vaccinium sp] powder + placebo oil), FO+BB (fish oil + cranberry powder), PL (oil + placebo powder). Fish oil (400 mg EPA (1.6 g) and 200 mg DHA (0.8 g)) and cranberry powder (phenolic concentration (20.4±0.31), anthocyanins (14.5±0.04)). | \nIt was demonstrated that supplementation with FO and BB showed a reduction of self-reported inefficiencies in daily operation, by the BB group showed less interference in memory. | \n|
Parkinson’s Disease | \nFan et al., 2018 [91]/New Zealand | \nn= 11 male patients with Parkinson’s disease and older than 40 years old. 2 sessions where samples of plasma and cerebrospinal fluid (CSF) were taken (in both sessions a 12-hour low anthocyanin diet was requested before taking the samples). | \nStudy of pre and post treatment samples, where patients were supplemented with 300 mg blackcurrant capsules (35% anthocyanins, Super Currantex® 20) twice daily for four weeks. | \nThe neuropeptide cyclic glycine protein (cGP), a natural BCA nutrient, was shown to be effectively absorbed in the brain after supplementation. The increase of cyclic glycine proline (cGP) in plasma and cephalorachidian fluid in Parkison patients is mainly due to central uptake of the neuropeptide in plasma. Thus, the role of insulin-like growth factor 1 (IGF-1) improves in patients with Parkinson’s disease. | \n
Qian et al., 2019 [92]/China | \nn=45, 3 weeks treatment, 6-week old male C57BL/6 mice (18-22 g). This study was designed to investigate the effects of the ANC rich blueberry extracts (BBE) on behavior and oxidative stress in the mouse model of PD induced by 1- methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP). | \nFive groups were used: 1) control (received i.p. saline), 2) MPTP (received i.p. MPTP 30 mg/kg for 5 days and saline, 3)BBE 50 mg/kg (received i.p. MPTP 30 mg/kg for 5 days and 50 mg/kg blueberry extract (BBE), 4) BBE 100 mg/kg (received i.p. MPTP 30 mg/kg for 5 days and 100 mg/kg of BBE) and 5) i.p MPTP and fed daily with levodopa and benserazide (10 mg/kg/day). | \nBBE improved motor function in MPTP- induced Parkinson\'s mice through a possible mechanism of their antioxidant capacity to eliminate free radicals and reduce oxidative damage to neurons. | \n|
Other effects | \nDevore et al., 2012 [93]/USA | \nn=16,010 women, aged ≥70; follow-up assessments were conducted twice, at two-year intervals. | \nFollow-up questionnaire on eating habits (2-year period) and assessment of congenital impairment. Six cognitive tests were administered: Telephone Interview of Cognitive Status, a telephone adaptation of the Mini-Mental State Examination; East Boston Memory Test – immediate and delayed recalls; category fluency; delayed recall of the Telephone Interview of Cognitive Status 10- word list; and backwards digit span. | \nIncreased consumption of berries and anthocyanidins, as well as total flavonoids, was shown to be associated with slower progression of cognitive impairment in older women. | \n
Watson et al., 2015 [94]/New Zealand | \nn=36 healthy, young participants (18-35 years). The battery used was formed: digit vigilance, stroop, rapid visual information processing (RVIP) and logical reasoning. | \nThree intervention drinks were used: 1. control (containing 0 mg polyphenols), 2. Blackadder (7.78 mg/kg anthocyanins from an extract of Ribes nigrum). 3. DelCyan (trademark) (8.05 mg/kg anthocyanins from a blackcurrant extract). | \nIt was demonstrated that the consumption of drinks supplemented with blackcurrants produce a cognitive benefit in healthy young people, evidenced by greater accuracy in the RIVP test; likewise, Blackadder improved reaction times in the task of monitoring digits. Clinically significant inhibition of monoamine oxidase-B and monoamine oxidase-A was identified using a commonly consumed fruit. | \n|
Whyte & Williams (2015) [95]/United Kingdom | \nn=16 children (8-10 years), 7 days of treatment. Two hours after consumption, the children completed a battery of five cognitive tests comprising the Go-NoGo, Stroop, Rey’s Auditory Verbal Learning Task, Object Location Task, and a Visual N-back. | \nTwo intervention drinks were used: 1. blueberry (prepared by mixing 200 g of Star variety blueberries with 100 ml, which contained 143 mg of anthocyanins). Control (combined with blueberry drink for sugars and vitamin C by adding 0.02 g of vitamin C powder, 8.22 g of sucrose, 9.76 g of glucose and 9.94 g of fructose to 100 ml of semi-skimmed milk). | \nIt was identified that anthocyanins (143 mg) present in blueberry juice have memory benefits in children aged 8 to 10 years, however, little evidence in attention, visuospatial, working memory were observed. | \n
Recent research in humans and animal models related to supplementation with berries.
Anxiety is a common and chronic psychiatric disorder that is a source of suffering and impairment [96]. In 2017, the World Health Organization reported that more than 260 million people suffer from an anxiety disorder [97]. Its pharmacological treatment is based on the use of benzodiazepine drugs, as well as some antidepressants with anxiolytic activity [98]. Unfortunately, these drugs are accompanied by severe side effects such as sedation, pharmacological tolerance, and drug dependence [99, 100]; in this sense, some patients complement their therapies with natural compounds coming from plants.
\nThe study of the potential effect of berries on anxiety, due to their high content of polyphenols and anthocyanins associated with anxiolytic activity at the preclinical level, has attracted important interest [101, 102]. It has been observed that these compounds, present in blueberries, have shown anxiolytic effects in animal models and their possible mechanisms of action are related to the antioxidant properties of anthocyanins [103] which inhibit the enzyme monoamine oxidases (MAOs), decreasing its activity and providing neuroprotection [77, 104].
\nSupplementation with blueberries in mice for 30 days has shown to increase the time spent in the open arms (anxiolytic effect) in the elevated plus maze test (EPM); in addition, it is shown to reduce oxidative damage to neural DNA, and this antioxidant neural protection has been proposed as a mechanism for the anxiolytic property of berries [19].
\nOne of the most studied berries for anxiety at the preclinical level is the black chokeberry (Aronia melanocarpa) belonging to the Rosacea family [105], for example, in male Wistar rats, the acute administration of the juice at doses of 5 and 10 ml/kg exerts dose-dependent anxiolytic activity in the social interaction test in a manner comparable to diazepam [102]. While, subchronic administration of Aronia melanocarpa fruit juice (10 ml/kg, orally) in male Wistar rats induces a time-dependent anxiolytic effect [106]. Furthermore, the month-long unlimited consumption of black chokeberry juice (>20 ml/kg b.w daily) exerts reduction of anxiety-like behavior associated with MAO-A/MAO-B inhibitions [104], which is probably due to the high antioxidant activity that black chokeberry has shown to have [107].
\nOn the other hand, this berry fruit has been evaluated in different concentrations and behavioral tests such as the EPM and the social interaction test [102]. Likewise, a methanolic extract of blackberry (Rubus fruticosus) was used and reported an anxiolytic effect (100, 200, and 300 mg/kg, orally) in the hole-board test in a dose-dependent response [108]; also, the effect of Rubus brasiliensis fruits in Wistar rats has been studied, reporting an anxiolytic effect in EPM, in a dose of 2.5 mg/kg administered per gavage [109]. In turn, an anxiety-related effect has been reported in treated male Swiss mice through supplemented water (2.6–3.2 mg/kg) per day of anthocyanins present in blueberry (Vaccinium ashei) [19].
\nOur working group [4] recently reported the anxiolytic effect from blackberry juice (doses intermediate: 5.83 mg/kg anthocyanins, 27.10 mg/kg polyphenols) on EPM in male Wistar rats, and the design was accompanied by the forced swim test (6 min). A decrease in the anxiety index was observed, without alterations in locomotor activity. This was similar to the group administered with the anxiolytic drug diazepam. Results revealed a better response to behavioral stress in the rats treated with blackberry juice, reinforcing the effects previously reported in EPM (Table 3).
\nThe anxiolytic effect of some flavonoids and anthocyanins has been identified by affinity to GABAA receptors [89, 110]. However, its antioxidant capacity is still considered the main mechanism of action [106], since oxidative stress has been proposed as an important contributor to anxiety generation [79].
\nDepression is the most prevalent psychiatric disorder; according to the World Health Organization, it affects 300 million people worldwide [97]. Depressive disorders are characterized by the presence of a sad and irritable mood accompanied by somatic and cognitive changes that negatively impact everyday life function [97] and result in high financial costs [111]. A great variety of drugs exist for its treatment [112], in which therapeutic effects are driven by actions on diverse neurotransmission systems (serotonergic, dopaminergic, and noradrenergic), exerting long-term changes which can restore neuronal function, for example, restoration of basal levels of neurotransmitters mainly serotonin, increase in neurotrophic factors (brain-derived neurotrophic factor and nerve growth factor) that can indirectly modify neuronal microarchitecture, reduction of oxidative stress, as well as neuroinflammation processes in structures related to the pathophysiology of depression which can impact at the affective level exerting favorable effects on the quality of life of the subjects. These drugs include tricyclic antidepressants (i.e., imipramine), selective serotonin recapture inhibitors (i.e., fluoxetine), monoamine oxidase inhibitors (phenelzine), and dual antidrepressant drugs (venlafaxine), among others [113]. Most of these drugs have a late onset and are often accompanied by side effects when taken for prolonged periods. This has encouraged a search for new substances with potential antidepressant effects and, most importantly, the use of possible natural alternatives.
\nAn association between the role the hippocampus and the etiology of depression has been suggested, given that a reduction in hippocampal neurogenesis has been observed in depressed patients with respect to the non-depressed control group, which is accompanied by a decrease in the hippocampal volume [114]. In this sense, antidepressants such as fluoxetine have been shown to ameliorate neurogenesis in the hippocampus [115].
\nAt the preclinical level, the administration of Aronia melanocarpa juice showed a decrease in total immobility time in the forced swimming test [107], similar to animals treated with imipramine. In addition, the study was supplemented with in vitro testing, where inhibition of the enzyme monoamine oxidase was observed, both in its A form and to a lesser extent in its B form [104]. MAO-A and MAO-B inhibitors are used clinically for the treatment of psychiatric and neurological disorders, respectively [116]. This activity has been proposed as another mechanism for the action of berries in mental disorders, as it is related to increased levels of serotonin, dopamine, and noradrenaline.
\nIn addition, human studies related to blueberry and red berry supplementation have shown that a higher intake of these foods is associated with a lower risk of depression [85, 86]. Similarly, studies in mice have shown similar effects with the consumption of red berries, observing a reduction in depressive-like behaviors [87, 88] (Table 3).
\nAlzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive memory loss, as well as cognitive decline [117] in which prevalence augments with age [118]. The neuropathologic changes underlying AD include senile plaques formed by the peptide β-amyloid and neurofibrillary tangles composed of hyperphosphorylated Tau protein that promotes synaptic dysfunction and neuronal death early and consistently [119].
\nOxidative stress has been associated with the onset and progression of AD [120]. This is supported by the high vulnerability of neurons to reactive oxygen species (ROS) [121]. Oxidative stress can induce damage to membrane lipids, changes in glial and neuronal function, structural damage to DNA, synaptic dysfunction, and apoptosis [122].
\nSeveral studies have demonstrated the potential protective effect of blackberry fruits (Rubus L. subgenus Rubus Watson), in the prevention of age-related neurodegenerative disorders [123], specifically with PD. Berry fruits such as blackberry, black raspberry, blueberry, and strawberry are good sources of phytochemicals that provide protection against neurological disorders [93].
\nExtracts of black currant have been shown to inhibit the formation and spread of β-amyloid [124] and ROS fibrils. Supplementation of blackberry in in vitro studies has been reported to exhibit potent anti-inflammatory and antiproliferative properties [125, 126]; also, the consumption of blueberries is related to neuronal augment in the hippocampus [5].
\nRecently a neuroprotective effect of anthocyanins has been observed in a model of AD induced by streptozotocin that resulted in a cognitive deficit (in short-term memory and spatial memory), as well as dysfunction in the activity of the enzyme acetylcholinesterase, while inducing lipid peroxidation and a decrease in antioxidant enzymes in the cerebral cortex [127]. These alterations were attenuated in the group administered with anthocyanins. Similarly, it has been observed that blueberry powder (Vaccinium sp.) supplementation in patients with Alzheimer’s disease and cognitive decline reduces the self-reported inefficiencies in daily functioning [90] (Table 3).
\nParkinson’s disease (PD) is characterized by tremors, stiffness, and akinesia. It is caused by the progressive degeneration of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies. Many Parkinson’s risks and preventive factors have been investigated. The onset of this disorder has been associated with exposure to certain pesticides and heavy metals [128], tobacco consumption [129], and coffee consumption [130], among other environmental factors. While current treatments have shown effectiveness in early management of the motor symptoms of the disease [131] and both surgery and deep brain stimulation are useful, PD is currently not yet curable [132]. A diet enriched in phenolic compounds has been shown to have some efficacy in relieving Parkinson’s symptoms [133]. Most of the studies related to fruit consumption and disease focus on supplementation with blueberries, strawberries, black currant, and grapes, due to their powerful antioxidant effects related to their high content of polyphenols and anthocyanins [134].
\nCell models have reinforced studies of neurodegenerative disorders, recently demonstrating that anthocyanins from grape seed, blueberry, and mulberry enhance mitochondrial function [135] and suppressed dopaminergic cell death caused by rotenone (insecticide and pesticide) in mitochondrial respiration. This has suggested that anthocyanins may alleviate neurodegeneration in PD by improving mitochondrial function. In addition, polyphenols are able to ameliorate inflammatory responses associated with glial activation [136]. Phenolic compounds are known for their ability to eliminate reactive oxygen species (ROS) due to their antioxidant action; however, since their concentrations in the brain are lower than those of endogenous antioxidants, it has begun to be seen that they also exert their neuroprotective effects through additional mechanisms [137, 138], highlighting the inhibition of MAO, in its two forms, A and B [77, 104]. At the preclinical level, one of the most widely used models in PD research is the administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a neurotoxin that causes a severe Parkinson’s-like syndrome in humans, monkeys, and mice [139, 140, 141, 142]. It has been observed that daily administration of resveratrol (red wine polyphenol) in male mice C57BL/6 prevented a decrease in striatal dopamine and maintained striatal tyrosine hydroxylase levels. In addition, mice that received resveratrol as pretreatment showed a greater number of immunopositive tyrosine hydroxylase neurons, indicating the protective role of resveratrol over nigral neurons [143]. In the same disease model, it was observed that blueberry extract attenuated behavioral impairment (motor coordination) as well as decreased levels of malondialdehyde in the brains of mice [92]. These data reveal the ability of resveratrol and polyphenols present in blueberry extract to counteract the toxic effects of MPTP administration and in the near future may be used as a complementary neuroprotective therapy (Table 3). Current PD therapies act by controlling the disease’s symptoms, but do not slow the underlying neurodegeneration in the brains of PD in patients [135]; this is an opportunity to use functional foods as adjuvant therapy in the presence of disease.
\nPolyphenols present in berries have also been associated with cognitive amelioration and neuronal function, as is the case with grape juice, which in both young [144] and older adults [145] ameliorate neurocognitive functions of memory, attention, and calmness, compared to the placebo group. In this same regard, in mothers (40–50 years) of preadolescent children, an association of grape juice consumption has been observed (≥30 h/week 355 ml, during 12 weeks) with subtle augment in immediate spatial memory and safer driving behavior in a virtual simulator [146]. At the same time, it was found that, in a double-blind crossover design of children (7 and 10 years old), supplementation of 15 or 30 g freeze-dried wild blueberry powder significantly ameliorates word acquisition and recognition, as well as the ability to overcome the effects of response interference [147].
\nIn a pilot study in healthy young adults in both genders (18–35 years old), it has been observed that the acute administration of black currant juice (500 mg/day of polyphenols, supplemented only 1 day per week, during 31 days) exerts an anxiolytic-like effect, as well as ameliorates alertness, less fatigue, and reaction speed [94].
\nIn a randomized, double-blind placebo-controlled trial, dietary blueberry of 24 g/day for 3 months raised the cognition in tests of executive function in adults between 60 and 75 years old of both sexes by increasing accuracy during task switching and reduced repetition errors during word-list recall [148]. The positive effects on cognition have been related to activation of the prefrontal cortex using functional magnetic resonance imaging [149]; therefore, the administration of blueberry to have the same effects on these tasks could be exercising greater activation of this structure to raise cognition. Another study found that daily consumption of 6 and 9 ml/kg for 12 weeks of blueberry (Vaccinium angustifolium Aiton) juice exerted neurocognitive benefits measured by California Verbal Learning Test-II (CVLT) augmented associate learning and word-list recall in older adults of both sexes who had experienced age-related memory decline [145]. Similarly, randomized controlled trial has shown that dietary berry juice (200 ml/day) for 12 weeks ameliorate memory and cognition in adults (70–80 years old) with cognitive impairment measured using a battery Rey Auditory Verbal Learning Test (RAVLT) [150].
\nFurthermore, a randomized, double-blind, placebo-controlled study showed that the daily administration of two capsules (10o mg) of a purified extract of blueberry (wild blueberry extract) for 3 months raised episodic and working memory in older adults of both sexes [151]. Additionally, a randomized, single-blind, parallel group design showed that the acute consumption of 200 ml of wild blueberry drink (253 mg anthocyanins) in healthy children aged 7–10 years significantly enhanced the memory and attentional aspects of executive function with respect to the placebo group 2 h after consumption; therefore, the consumption of the wild blueberry drink during the critical period of development (as is the case of childhood) could provide acute cognitive benefits [152]. Therefore, a double-blind, counterbalanced, crossover intervention study showed that acute supplementation with haskap berry extract “Lonicera caerulea L.” (200 and 400 mg anthocyanins) raised the episodic memory and exerts benefits in cognitive performance following a single acute dose in older adults compared to placebo [153].
\nThese findings support that the consumption of berries produces beneficial effects on cognition in humans, which are probably related to the effects of the berries on the nervous system. For example, blueberry diets are associated with enhanced working memory which is accompanied by an increase in the neurogenesis of the hippocampus [17]. A randomized, controlled, double-blind, crossover studio showed that the administration of 766 mg total blueberry polyphenols in healthy young men reduced neutrophil NADPH oxidase activity at 1, 2, 4, and 6 h after consumption [154]. In this sense, NADPH oxidase has been shown to play an important role in oxidative stress induction in the brain [155], because it uses oxygen and NADPH to generate superoxide [156]. Therefore, the administration of blueberry could be generating a reduction of superoxide and indirectly preventing oxidative stress events a long term. The mechanisms by which flavonoids and polyphenols exert these actions on cognitive performance are still being studied, including evidence suggesting that they can increase brain blood flow, as well as modulate the activation state of neuronal receptors, signaling proteins, and gene expression [157].
\nAccording to our knowledge, there are some reports relating berry consumption in humans with side effects or toxicity. Data of toxicity in vivo was reported in 1997, in a study of the relation between flavonoid intake and subsequent cancer risk in 9959 Finnish men and women, aged 15–99 years and who are initially cancer free. Food consumption and dietary history method calculated the consumption of lingonberries, blueberries, black currants, raspberries, and gooseberries. People with higher consumption of berries were found to have a high risk of lung cancer. Apparently, the phenolic compounds produce toxicity proliferating cancer cells, but are not toxic in healthy cells [49].
\nAnother study of 5-weeks-old Swiss Webster male mice, supplemented with lyophilized nightshade berries (Solanum dulcamara, 8 g/kg) with two different stages of maturity, showed that immature fruit supplementation produced gastrointestinal lesions; however, this condition was not observed in mice administered with mature lyophilized fruit. The authors concluded that these effects were attributed to the presence of saponin in the immature fruit [158]. In 2015, the first toxicity report by Solanum dulcamara was reported in a dog puppy (Labrador Retriever); the toxicity was attributed to steroidal glycoalkaloid solanine. After causing vomiting to the dog, dried stems and immature berries were observed, and gastric contents were evaluated by a local botanist identifying Solanum dulcamara intake, concluding that dog poisoning was due to the consumption of this fruit [159].
\nAnother report was in 2009, when dozens of dead cedar waxwings in Thomas County, Georgia, USA, were found. In this case report, after evaluating five birds, the investigation group observed pulmonary, mediastinal, and tracheal hemorrhages and also found berries (Nandina domestica Thunb.) intact and partly digested into the gastrointestinal tracts. Due to their voracious feeding behavior, these birds ingested toxic doses of N. domestica and at the same time high concentrations of cyanide present in fruit berry [160]. It is important to note that S. dulcamara and N. domestica species are found wildly and are not consumed by humans.
\nRegarding berries supplementation and synergy, it is recently reported that gallic acid, quercetin, ellagic acid, and cyanidin have a market antioxidant activity [161, 162], due to the synergistic effects between the numbers of aromatic ring mixtures. In addition, polyphenols present in berries can interact between them, improve their antioxidant properties, and, therefore, increase human’s health benefits [162]. According to our knowledge, no studies were found related with pharmacological interactions and berry supplementation. It is necessary to carry out studies involving pharmacological molecules, berries’ activities, and their phenolic compounds in order to generate new therapies and identify the existence of side or toxic effects.
\nAccording to the research reported in this chapter, the supplementation of berries and their bioactive compounds as flavonoids, polyphenols, and anthocyanin suggests a potential health benefit for human nutrition.
\nThe objective of this research is to contribute with knowledge to the development of new strategies for the treatment of diseases such as anxiety, depression, AD, and PD, which includes natural products, particularly berry fruits that work as preventive or coadjuvant therapy in the treatment of these diseases.
\nA further evaluation of fruits berry supplementation in neural processes is required, as well as the identification of the effect of each particular bioactive compound on psychiatric and neurological disorders. More studies will be necessary to identify the mechanisms of action of this substance. It is also important to understand the scope in other neural processes and their application, effectiveness, synergy, pharmacological interaction, and side or toxic effects at clinical and preclinical levels of studies.
\nThe present chapter evidenced a number of investigations in vivo related with the use of different berry fruit supplement doses, not only in humans but also in animal models. These results suggest the potential health effect of berries due to bioactive compounds mainly flavonoids, polyphenols, and anthocyanins, used commonly for its antioxidant capacity. According to our knowledge, the cases reported in the literature by animal toxicity are related with the consumption of wild berries. In humans the relationship between phenol compound consumption and lung cancer has been reported; however, there is no evidence of side or toxic effects related with berry supplementation or their bioactive compounds, and pharmacological interaction related to their consumption due to no dietary intervention studies has been reported.
\nIn addition, berry consumption has shown to be effective in a number of cardiovascular and metabolic diseases, and also recent investigations are proposed for the management of berry fruit supplementation as neuroprotector and the reduction of symptoms in diseases such as anxiety, depression, AD, and PD, among others. The use of this biological berry compounds might promote an alternative for prevention and give excellent opportunities for human nutrition as a functional food and nutraceutical. Future research in this field is necessary, in order to clarify and support the evidence of the effects of flavonoids, polyphenols, and anthocyanins at the brain level, as well as their potential direct and indirect mechanisms of action.
\nThe authors gratefully acknowledge the financial support from CONACyT (Scholarship no. 592714, 628503, 297410, 713495).
\nThe authors declare no conflict of interest.
.
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