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    Major MangoPolyphenols and

    Their PotentialSignificance to

    Human HealthMartin Masibo and Qian He

     ABSTRACT: The mango is a rich source of various polyphenolic compounds. The major polyphenols in the mangoin terms of antioxidative capacity and/or quantity are: mangiferin, catechins, quercetin, kaempferol, rhamnetin,anthocyanins, gallic and ellagic acids, propyl and methyl gallate, benzoic acid, and protocatechuic acid. The nu-traceutical and pharmaceutical significance of mangiferin, which is a special polyphenol in the mango has beenextensively demonstrated and continues to attract muchattention especially in its potential to combat degenerativediseases like heart diseases and cancer. The amounts of the different polyphenolic compounds in the mango vary from part to part (pulp, peel, seed, bark, leaf, and flower) with most polyphenols being found in all the parts. Mangopolyphenols, like other polyphenolic compounds, work mainly as antioxidants, a property that enables them toprotect human cells against damage due to oxidative stress leading to lipid peroxidation, DNA damage, and many degenerative diseases. Use of pure isolated compounds has been found to be less effective than the use of crude mix-tures from the particular mango part suggesting that synergism of the various mango polyphenols is important formaximum antioxidative activity. In this article, we review the major mango polyphenols, looking at their proposedantioxidative activity, estimated amounts in the different parts, their structures, suggested modes of action, andrelated significance to human health, with great emphasis on mangiferin.

    IntroductionIn the past few years, there has been increasing interest in the

    study of mango phenolics from mango fruits, peels, seeds, leaves,flowers, and stem bark due to their antioxidative and health-promoting properties that make consumption of mangoes andderived products a healthy habit. Bioactive compounds foundin the mangos, among other plants and herbs have been shownto have possible health benefits with antioxidative, anticarcino-genic, antiatherosclerotic, antimutagenic, and angiogenesis in-hibitory activities (Cao and Cao 1999). Interestingly, many herbs,fruits, and vegetables are known to contain large amounts of phe-nolic antioxidants other than the well-known vitamins C, E, andcarotenoids.

    Polyphenolsare secondary metabolites of plants and arewidely

    distributed in beverages and plant-derived foods. Human con-sumption studies indicate 1 g of total polyphenols is frequentlyconsumed per day and it is not anticipated that any acute orlethal toxicity would be observed through the oral intake route(Scalbert and Williamson 2000). Phenolic compounds have thecapacities to quench lipid peroxidation, prevent DNA oxidative

    MS 20080164 Submitted 3/4/2008, Accepted 6/14/2008 . Authors Masibo andHe are with School of Food Science and Technology, Jiangnan Univ., FoodSafety and Quality Control Laboratory, Wuxi -214122, Jiangsu Province, P.R.China. Author Masibo is also with Food and Agricultural Products Laboratory,Kenya Bureau of Standards (KEBS)-54974, Nairobi, Kenya. Direct inquiries toauthor Masibo (E-mail: [email protected]).

    damage, scavenge free radicals (Cao and Cao 1999), and pre-vent inhibition of cell communication (Sigler and Ruch 1993),all of which are precursors to degenerative diseases. Free radi-cals cause depletion of the immune system antioxidants, changein gene expression, and induce abnormal proteins resulting indegenerative diseases and aging.

    Antioxidant nutrients and phytonutrients inhibit the oxidationof living cells by free radicals by protecting the lipids of the cellmembranes through free radical scavenging, blocking the initia-tors of free radical attack, neutralizing or converting free radicalsinto less active, stable products thus breaking the chain reactionand assisting in salvaging oxidized antioxidants enabling them tocontinue to be of benefit (Halliwell and others 1992). There are 2main antioxidant defense mechanisms developed by living organ-

    isms: enzymatic and nonenzymatic components defense systems.An array of small molecules including polyphenols fall underthe later system (Shahidi and others 1992; Rice-Evans and oth-ers 1997). Polyphenols have the ability to scavenge free radicalsvia hydrogen donation or electron donation (Shahidi and oth-ers 1992). A phenolic molecule is often characteristic of a plantspecies or even of a particular organ or tissue of that plant. Theantioxidant activity of polyphenols is governed by the number,reactivity, and location of their aromatic hydroxyl groups (Chenand others 1996).

    The main classes of polyphenols are defined according to thenature of their carbon skeleton and they are: phenolic acids,flavonoids, stilbenes, and lignans (Lee and others 2003). Otherdietary polyphenols are not well-defined chemical entities and

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    result from the oxidative polymerization of flavonoids and phe-nolic acids (Santos-Buelga and Scalbert 2000). The means of ex-tracting polyphenols from plants is crucial as some polyphenolscan be denatured by heat and lost by some solvents. Besides,some solvents are toxic and render the extracts unsafe for humanconsumption. Decoction is an extraction method of choice due to

    the absence of any organic solvent, as is the case with the indus-trial production of (Vimang ), a mango stem bark extract in Cuba.Specific polyphenolic compounds can be determined and quan-tified by chromatographic techniques, while total phenols canbe estimated by reduction of the Folin– Ciocalteu reagent (Single-ton and Rossi 1965). Besides these, antioxidative capacity assaysof plant extracts can also be used to predict their polyphenolicquantity and/or activity.

    Polyphenolic compositionPolyphenolic composition of mango pulp.   Mangiferin, gallic

    acids (m-digallic and  m-trigallic acids), gallotannins, quercetin,isoquercetin, ellagic acid, and   β-glucogallin are among thepolyphenolic compounds already identified in the mango pulp

    (Schieber and others 2000). Gallic acid has been identified asthe major polyphenol present in mango fruits, followed by 6 hy-drolysable tannins and 4 minor compounds, p -OH-benzoic acid,m-coumaric acid,  p - coumaric acid, and ferulic acid (Kim andothers 2007). Schieber and others (2000) found 6.9 mg/kg of gal-licacid and 4.4 mg/kg of mangiferin in mango pulp. In a polyphe-nol screening of 20 mango varieties, Saleh and El-Ansari (1975)reported the co-occurrence of mangiferin, isomangiferin, and ho-momangiferin in mango fruit pulp. Mangiferin has been shownelsewhere to be the main compound of leaves and stem bark withgreat medicinal values. It has been reported that phenolic com-pounds and their associated antioxidant capacity decrease as fruitripens (Kim and others 2007). Gallotannins represent the majorcomponents of unripe fruits and seeds. According to Prabha andPatwardhan (1986) gallic acid is the substrate of polyphenol ox-

    idase in the fruit pulp, whereas ellagic acid is the predominantsubstrate in mango peel.Polyphenolic composition of mango peel.   During mango fruit

    development, the total phenols have been found to be higher inthe peel than in the flesh at all stages (Lakshminarayana and oth-ers 1970), with an estimated total polyphenol content in mangopeel of 4066 mg (GAE)/kg (dry matter) (Berardini and others2005b). Generally, ripe peels contain higher total polyphenolsthan raw peels (Ajila and others 2007). The polyphenolic con-stituents of mango peel include mangiferin, quercetin, rhamnetin,ellagic acid, kaempferol, and their related conjugates as shown inTable 1 where it can be seen that the2 main polyphenols in mangopeel are mangiferin and quercetin 3-0-galactoside. Berardini andothers (2005b) found that, while mangiferin contents slightly de-creased at elevated temperatures, the contents of the other xan-thone derivatives significantly increased. The observed changesmay be attributed to the formation of xanthones from benzophe-none derivatives, which were recently identified in mango peels(Berardini and others 2004) and which are considered precursorsof xanthone C-glycosides (Larrauri 1999). Anthocyanins have alsobeen identified in the mango peel and estimated to range from203 to 565 mg/100 g (dry matter) depending on variety and stageof maturity (Berardini and others 2005b). In their study on theantioxidative activity of mango peel extract, Berardini and others(2005b) established that the antioxidative capacity of the extractwas higher than that of standard mangiferin and quercetin 3-O-glucoside, thus indicating that the antioxidative capacity of thepeel extract cannot be attributed to a single component but to thesynergistic effect of all the compounds present.

    Table 1 --- Phenolic compounds in mango peel (mg/kg) on

    dry matter basis.

    Compound Amount (mg/kg)

    Mangiferin 1690.4Mangiferin gallate 321.9

    Isomangiferin 134.5Isomangiferin gallate 82.0Quercetin 3-O-galactoside 651.2Quercetin 3-O-glucoside 557.7Quercetin 3-O-xyloside 207.3Quercetin 3-O-arabinopyranoside 101.5Quercetin 3-O-arabinofuranoside 103.6Quercetin 3-O-rhamnoside 20.1Kaempferol 3-O-glucoside 36.1Rhamnetin 3-O galactoside/glucoside 94.4Quercetin 65.3Total phenolics 4066.0

    Source: Berardini and others (2005a).

    Polyphenolic composition of mango seed kernels.   Besides thepulp and the peel, mango seed kernels are equally rich inpolyphenols with potent antioxidative activity, but ironically theseeds are always discarded as waste during processing and con-sumption of the mango fruit. As an example, in India about300000 metric tons of mango seed kernels are discarded everyyear (Char and Azeemoddin 1989). Ahmed and others (2007)identified and quantified various polyphenolic compounds in themango seed kernel: tannin 20.7 mg/100 g, gallic acid 6.0 mg/ 100 g,coumarin 12.6 mg/100 g, caffeic acid 7.7 mg/100 g,vanillin 20.2 mg/100 g, mangiferin 4.2 mg/100 g, ferulic acid10.4 mg/100 g, cinnamic acid 11.2 mg/100 g, and unknowncompounds 7.1 mg/100 g. The total polyphenolic content of themango seed kernel extract was estimated to be 112 mg (GAE)/ 100 g (Ahmed and others 2007). Soong and Barlow (2004) as-

    sayed the antioxidant activity of a variety of fruit seeds, namely,mango, jackfruit, longan, avocado, and tamarind and found thatthe antioxidant activity of the mango seed kernel was the highest,a fact attributed to its high polyphenolic content. These point to areason to industrially utilize the mango seed kernel as a functionalfood ingredient.

    Polyphenolic composition of mango leaves and stem bark.   Gal-loyl, hydroxy benzoyl esters, and epicatechin have been identi-fied in mango leaves. Chemical studies performed with a standardaqueous extract of the stem bark from  M. indica , which has beenused in nutraceutical formulations in Cuba under the brand namevimang , have enabled the isolation and identification of pheno-lic acids (gallic acid, 3,4 dihydroxy benzoic acid, benzoic acid),phenolic esters (gallic acid methyl ester, gallic acid propyl ester,benzoic acid propyl ester), flavan-3-ols (catechin and epicate-chin), and the xanthone mangiferin, which is the predominantcomponent of this extract (10%) (Sanchez and others 2000). Thetotal polyphenolic content of mango stem bark extract was foundto be 10.61 g (GAE)/100 g of dry weight by the HPLC methodand 9.4 g (GAE)/100 g dry weight by the Folin– Ciocalteu method.Thus, no significant difference was found between the 2 methods.

    At this juncture, it is worth pointing out that environmental anddevelopmental factors have been reported to affect the accumu-lation and eventual concentration of polyphenols in plant parts.Saleh and El-Ansari (1975) reported on the polyphenolic compo-sition of mango leaves, twigs, bark, fruits, and seeds. Mangiferinwas the major component of the leaves, twigs, and bark, withthe bark having the highest content, while the gallotannins werethe major components of the unripe fruits and their seeds besides

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    Major mango polyphenols . . .

    being detected in all parts of the mango, isomangiferin, and ho-momangiferin were mainly present in the leaves and twigs, theformer was also detected in fruits of some varieties. Fisetin washigh in twigs,as wasquercetin in thefruits. Quercetin-3-glucosideand kaempferol-3- glucoside were mainly found in the leaves.Gallic acid was found throughout all parts of the mango and so

    was ellagic acid; however, the latter was found in higher con-centration in twigs, fruits, and seeds as compared to the leaves.m-Digallic acid was high in unripe fruits, as was  β-glucogallin inthe seeds.

    Mango extracts from leaves, fruit, seed kernel, fruit pulp, roots,and stem bark for medicinal purposes in many countries havebeen widely documented in the Napralet database. The eth-nomedical use of the mango stem bark extract in Cuba has beenextensively researched for over 10 y on more than 7000 patientsand has been found effective against cancer, diabetes, asthma, in-fertility, lupus, prostatitis, prostatic hyperplasia, gastric disorders,arthralgies, mouth sores, among others (Nunez-Selles 2005). Thevarious research studies on mango antioxidative bioactivity un-derscore that mango polyphenols are the active compounds inthe extracts.

    The different parts of the mango (fruit pulp, peel, seed kernel,leaves, and stem bark) are a rich source of various polyphenolswith quantities of the different polyphenols varying in the differentparts or missing totally in some parts. Significant research workhas been done on mangoes and many articles have been pub-lished, but most of them have discussed mango polyphenols from1 part only and none has discussed polyphenols in the mango as awhole. In this article, we review forthe 1st time the variousmangopolyphenoliccompounds fromthe different parts and their relatedantioxidative and medical significance to human health payingspecial attention to mangiferin.

    Mangiferin

    Occurrence

    Mangiferin is a xanthone and xanthones are some of the mostpotent antioxidants known; they are thought to be more potentthan both vitamin C or vitamin E and are sometimes unoffi-cially referred to as   “super antioxidants.”   Xanthones are heat-stable molecules. Mangiferin, generally called C-glucosyl xan-thone, is widely distributed in higher plants (Sanchez and others2000) where it provides protection to producer plants against dif-ferent forms of static and dynamic stresses including ingress of pathogenic microorganisms (Muruganandan and others 2002).It is a pharmacologically active phytochemical and a naturalpolyphenolic antioxidant present in the bark, fruits, roots, andleaves of Mangifera indica Linn, and a few other medicinal plantsrecommended in the Indian system of medicine for treatment of anumber of immunodeficiency diseases (Scartezzini and Speroni2000).

    Mangiferin (C 2-   β   – D   – glucopyranosyl-1, 3, 6, 7-tetrahydroxyxanthone) (Figure 1) was first isolated from Mangifera indica   leaves, while from the bark homomangiferin (1,6,7-trihydroxy-3-methoxy-2-C-  β   -D-glucopyranosyl-xanthone) wasisolated. A quantitative estimation on the dried leaf and barkmaterial revealed that the mangiferin content was higher in themango bark (Sissi and Saleh 1965) than in the leaf. Saleh andEl-Ansari (1975) reported on the co-occurrence of the 3 xan-thones (mangiferin, isomangiferin, and homomangiferin). Theyisolated 2 xanthones in the leaves along with a 3rd xanthone, iso-mangiferin (1-, 3-, 6-, 7-tetrahydroxy-4-C-β-D-glucopyranosyl-xanthone), which had been first identified in   Anemarrhena as- phodeloides . Mangiferin content of mango pulp was found tobe about 4.4 mg/kg (Schieber and others 2000), seed kernel

    42 mg/kg (Ahmed and others 2007), whereas in dried mango peelit was 1690 mg/kg (Table 1). In the mango stem bark, mangiferinwas the most abundant phenolic compound, estimated at about71.4 g/kg (Rastraelli and others 2002). From a global point of view, xanthones are only known to have restricted distribution(about 5 families). On the other hand, mangiferin has a wider

    distribution (recorded within 12 families), and within the anac-ardiacae, besides  Mangifera indica  only  Mangifera zeylanica  isrecorded as containing mangiferin.

    Bioactivity of mango mangiferinMany researchers have established mangiferin as the possi-

    ble active principle of mango (Mangifera indica   L.) stem barkand leaf extract and attributed most of the biological activitiesof the extracts to it (Sanchez and others 2000). From the variousstudies done on mangiferin and the extracts from mango leaves,bark, and flowers, it has been found to exhibit a wide range of pharmacological effects: antioxidant, anticancer, antimicrobial,antiatherosclerotic, antiallergenic, anti-inflammatory, analgesic,and immunomodulatory among many others. Mangiferin hasbeen investigated  in vitro  for its antioxidant (Rouillard and oth-

    ers 1998), immuno-stimulating, and antiviral properties (Zhengand Lu 1990), and it was found to protect hepatocytes, lympho-cytes, neutrophils, and macrophages from oxidative stress; reduceatherogenicity in streptozotocin diabetic rats; and to reduce thestreptozotocin-induced oxidative damage to cardiac and renaltissues in rats (Muruganandan and others 2002).

    The iron-complexing ability of mangiferin was reported as aprimary mechanism for protection of liver mitochondria againstFe2+ citrate-induced lipid peroxidation (Halliwell and Gutteridge1986). They also showed that   in vitro   antioxidant activity of mangiferin is related to its iron-chelating properties and notmerely due to the scavenging activity of free radicals. Iron chela-tors such as mangiferin could be an important approach to re-duce iron-induced oxidative damage in pathologies related toabnormal intracellular iron distribution and/or iron overload,

    such as hereditary hemochromatosis, h-thalassemia, Friedreich’sataxia, and sideroblastic anemia (Britton and others 2002). Themetabolism of mangiferin yields noranthyriol after cleavage of the C– C linkage of the glucose moiety, which exhibits a po-tent iron chelating effect, and an inhibitory effect of the inducedrespiratory burst in rat neutrophyls (Andreu and others 2005b).Those effects were thought to have originated from the high scav-enger capacity of mangiferin by singlet oxygen.

    Mangiferin (MF) was found to protect mitochondrial mem-brane against lipid peroxidation hence preserving its integrity.From their study, Halliwell and Gutteridge (1986) suggested thatmangiferin removes iron from the Fe2+ citrate complex and forms

    Figure 1 --- Chemical structure of mangiferin (C 2-   β-D-

    glucopyranosyl-1, 3, 6, 7-tetrahydroxyxanthone).

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    an unstable complex with it, favoring Fe2+ oxidation to Fe3+

    with subsequent formation of a more stable complex with Fe3+,which is not able to initiate and/or propagate mitochondrial lipidperoxidation. This Fe3+ mangiferin complex impairs ferric ironreduction to ferrous iron by endogenous reducers like ascorbate,sparing them and also preventing Fe2+ reloading of the biologi-

    cal system, which can readily participate in reactions involved inOH formation.It has been suggested that oxidation derivatives of mangiferin

    may sensitize mitochondria to calcium-induced permeabilitytransition (Andreu and others 2005c), a process often related toapoptotic/necrotic cell death. In this regard, it was proposed thatthe accumulation of such oxidation products would take placein such cells exposed to an overproduction of reactive oxygenspecies, such as cancer cells, where the occurrence of apoptosisinduced by mitochondria permeability transition may be a cellu-lar defense mechanism against excessive reactive oxygen speciesformation (Nunez-Selles 2005).

    Mangiferin has been found to inhibit colon tumorigenesis inrats. Bhattacharya and others (1972) reported that the mechanismof this compound in the central nervous system is related to itsability to inhibit monoamine oxidase activity. Malignant cell pro-liferation in thecolonicmucosa of male F344 rats was reduced by75% after addition of MF to the diet (0.1%) in a long-term studywhich suggested that MF may act as a naturally occurringchemo-preventive agent in colon cancer (Yoshimia and others 2001).Chemoprevention effect of MF has also been tested on other tu-mors like the ascitic fibrisarcoma (AFS) in Swiss mice where sig-nificant inhibition levels were recorded coupled with increasedsurvival rates (Guha and Chattopadhyav 1996). Alongside thetumor studies on rats treated with mangiferin, Yoshimia and oth-ers (2001) found that mangiferin also inhibited body weight gainin experimental rats. This points at the possible utilization of mangiferin in food products for special dietary needs like withobese people.

    1-Methyl-4-phenyl-pyridine ion (MPP+), the active metabo-lite of 1-methyl-4-phenyl-1-, 2-, 3-, 6-tetrahydropyridine (MPTP)

    has been found to induce a Parkinsonian syndrome in humansand animals, a neurotoxic effect postulated to derive from ox-idative stress (Amazzal and others 2007). Mangiferin has beenfound to protect neuroblastoma cells line N2A against MPP+ in-duced cytotoxicity, to restore the glutathione (GSH) content, andto downregulate both superoxide dismutase 1 (SOD1) and cata-lase (cat  mRNA) expression all being mediated by oxidative stress(Amazzal and others 2007). In Parkinson’s disease, the nigral levelof iron is increased and may contribute to the hyper-productionof reactive oxygen species, leading to oxidation and nitration of proteins, lipids, and DNA, as was observed in postmortem brains(Halliwell 2006). Therefore, mangiferin could be a useful com-pound in therapies for degenerative diseases, including Parkin-son’s disease, in which oxidative stress plays a crucial role.

    Mangiferin, being able to traverse the blood– brain barrier asdemonstrated by Martınez and others (2001) in gerbils, has beenfound to have real potential to ameliorate the oxidative stressobserved in neurodegenerative disorders. Mangiferin has beenshown to reduce the intracellular Ca2+ concentration, an activ-ity that may contribute to its protective effects and reduce ironneurotoxicity in cells. For the immune system, lymphocyte apop-tosis maintains the normal physiology and self-tolerance of thesystem. For peripheral T cells, apoptosis induced by repeatedT-cell receptor (TCR) stimulation, known as activation-inducedcell death (AICD), may be responsible for the peripheral deletionof autoreactive T cells (Green and Ware 1997) and is involvedin terminating the immune response through elimination of ac-tivated lymphocytes. The imbalance in this apoptotic process isdangerous and leads to severe diseases associated with autoim-

    mune phenomena (Rieux-Lancat and others 1995) and immun-odeficiencies (Alimonti and others 2003). CD95 and its ligand(CD95L) play a crucial role in this type of cell death (Devadas andothers 2002). Activation of T cells via T-cell receptor signaling in-creases intracellular reactive oxygen species and Ca2+, leadingto CD95L expression and, consequently, activation-induced cell

    death (Gulow and others 2005). Activation-induced cell deathplays an important role in the maintenance of peripheral lym-phocyte homeostasis. Reactive oxygen species combined with si-multaneous calcium (Ca2+) influx into thecytosol are required forinduction of activation-induced cell death. Mango stem bark ex-tract, whose main active ingredient is mangiferin has been shownto protect T cells from  in vitro  activation-induced cell death dueto its richness in polyphenols which diminished the increase of intracellular reactive oxygen species and free Ca2+ induced byT-cell receptor triggering (Hernandez and others 2007).

    Reduction of the reactive oxygen species has been found toconsume ATP, thus progressively reducing the energy charge of the system. Mangiferin has been shown to be able to scavenge re-active oxygen species, thus inhibiting all those processes leadingto energy charge decrease, red blood cell damage, and mem-brane destabilization. Erythrocytes and erythrocyte membranehave a high ratio of polyunsaturated fatty acids to total lipids, in-dicating susceptibility to lipid peroxidation. Red blood cells arehighly vulnerable to lipid peroxidation due to constant exposureto high oxygen tension and the presence of large iron ion con-centrations (Pawlak and others 1998). After human cell studies,Rodriguez and others (2006) suggested that Mangiferin protectserythrocytes and red blood cells from reactive oxygen speciesproduction thus contributing to integrity and functionality of thesecells.

    The use of dietary ingredients to protect against radiation-induced damage is an attractive proposition, because they arepart of the daily human diet, do not have side effects, will havewide acceptability, and can be safely manipulated for humanuse. The mango fruit is commonly used by humans in variousforms and the principal compound mangiferin has been isolated.

    From their study on cultured human peripheral blood lympho-cytes (HPBLs), Jagetia and Baliga (2005) found that mangiferinprovided protection against radiation-induced sickness and mor-tality. A similar effect of mangiferin was observed for radiation-induced bone marrow deaths (Jagetia and Baliga 2005).

    It has been suggested that mangiferin reduces blood glucoselevels by inhibiting the glucose absorption from the intestine.This hypothesis could be supported by the recent findings thatmangiferin inhibits the glucosidase enzymes sucrase, isomaltase,and maltase from rats (Yoshikawa and others 2001) which areinvolved in the digestion of carbohydrates into simple sugarsin the gut leading to delay or inhibition of carbohydrate break-down and subsequent slower glucose absorption from the intes-tine (Aderibigbe and others 2001). Mangiferin has been suggestedto possess both pancreatic and extrapancreatic mechanisms in itsantidiabetic action and such apparent dual actions of mangiferinenhance its efficiency.

    Mangiferin was found to significantly reduce plasma totalcholesterol, triglycerides, and LDL-C associated with a concomi-tant increase in HDL-C levels and a decrease in atherogenic in-dex in diabetic rats indicating its potential antihyperlipidemicand antiatherogenic activity (Muruganandan and others 2005).The triglyceride-lowering property of mangiferin could indirectlycontribute to the overall antihyperglycemic activity through theglucose– fatty acid cycle mechanism (Randle and others 1963).According to the Randle glucose– fatty acid cycle, an increasedsupply of plasma triglycerides could constitute a source of in-creased free fatty acid availability and oxidation that can impairinsulin action and glucose metabolism and utilization leading

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    Major mango polyphenols . . .

    to development of hyperglycemia. Therefore, the reduction of triglycerides following administration with mangiferin would alsofacilitate glucose oxidation and utilization and, subsequently, re-duction of hyperglycemia (Muruganandan and others 2005).

    It has been demonstrated elsewhere that mangiferin possessesa wide range of antibacterial effects, both with regard to Gram-

    positive and Gram-negative bacteria. The species most sensi-tive to mangiferin among the Gram-positive microorganisms wasBacillus pumilus, whereas among the Gram-negative species themost sensitive to mangiferin was Salmonella agona, though it hasto be noted that higher concentrations of mangiferin were nec-essary (30% to 35%) to achieve the desired effect with regard tothe Gram-negative microorganisms (Stoilova and others 2005).Antifungal effect of mangiferin has also been shown with re-gard to Thermoascus aurantiacus, Saccharomyces cerevisiae, Tri- choderma reesei, and  Aspergillus flavus  (Lova and others 2005).Chakrabarti and Ghosal (1985) found that the fungus  Fusariummoniliforme  var.   subglutinans  transforms mangiferin into poly-merous quinone, possibly due to the phenoloxidase it releases.It is possible that the resistance to mangiferin by various othermycelial fungi is due to this mechanism.

    At this point, it is worth mentioning that Mangiferin alone didnot show higher biological activity than the whole extract of eitherthe leaf or bark raw material, and it has been hypothesized that thetotal antioxidant effect of any mango extract is due to the presenceof a combination of several polyphenolic compounds and theirderivatives and not only the single, though potent, compoundmangiferin (Arts and others 2000).

    Mechanism of mangiferin bioactivityThe chemical structure of mangiferin fulfills the 4 requisites that

    have been reported to have high bioavailability by oral adminis-tration: molecular weight below 500 Dalton (C19H18O12); fewer

    Figure 2 --- Mechanism of action of

    mangiferin (Ghosal and Rao 1996).

    than 5 donor functions for hydrogen bonds; fewer than 10 accep-tor functions for hydrogen bonds; and potential log P (calculated)less than + 5 (log Pmangiferin:+ 2.73). These similar properties areshared by most of the other mango polyphenols.

    The mechanism of bioactivities of mangiferin is mainly cen-tered on its capacity to provide cellular protection as an antioxi-

    dant and radical captodative agent. A biologically active antioxi-dant is a substance that, when present even at low concentration,compared to those of an oxidizable substrate such as membranelipid or DNA, significantly delays or inhibits oxidation of thatsubstrate. Mangiferin performs its antioxidant function at differ-ent levels of the oxidative sequence. As far as membrane lipidperoxidation is concerned, it acts by (a) decreasing the localizedO2 concentration and generating mangiferin phenoxy radicals (2)(Figure 2) in concert, (b) binding metal ions (Fe  2+/3+) in the formof a mangiferin– iron complex also called metal ligand complex(3) (Figure 2), which is a stable complex structure that will not al-low the generation of such tissue damaging   ·OH radicals and/oroxo-ferryl groups; (c) regulating polymer chain initiation by in-teraction with the reactive oxygen species to produce feebly-reactive oxo-ferryl radical (caged oxygen radical) (4) (Figure 2).This radical acts as a soft inducer of polymerization of thevinylic monomer methylmethacrylate (MMA). The generated rad-ical complex containing a polar end group (mangiferin – Fe3+-O-)acts as a chain terminator by oxidizing the other end group car-bon radical of the polymer resulting in a low-molecular-weightmangiferin– Fe– PMMA (polymethylmethacrylate)– polymer (5)(Figure 2), (d) scavenging lipid peroxy/alkoxy radicals and therebypreventing continued abstraction of hydrogen fromcellular lipids,and (e) maintaining a cellular oxidation– antioxidant balance (via1↔2) (Figure 2) (Ghosal and Rao 1996).

    The deficiency in the body’s functioning has for long been as-sociated with free radicals, and thus one tends to view oxidants

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    as bad and antioxidants as good. The actual situation is rarelyso simple; an oxidant– antioxidant balance is a realistic depictionof the normal state. Mangiferin (1) (Figure 2) and the resonance-stabilized phenoxy radicals (2) (Figure 2) in conjugated formswould assist to maintain the desired oxidant↔antioxidant bal-ance in vivo  via such systems as 3 and 4 (Figure 2). These 2 sys-

    tems were found to contribute to the formation of the complexsystem mangiferin– Fe– PMMA– polymer (5) (Figure 2) (Ghosal andRan 1996). Also formed during the activity of mangiferin are low-molecular-weight mangiferin complexes as shown by 6 and 7 inFigure 2 (Ghosal and Rao 1996).

    FlavonoidsFlavonoids are the most abundant polyphenols in our diets.

    Once thought to be vitamins, flavonoids were given such namesas vitamin P and vitamin C2. They can be divided into severalclasses according to the degree of oxidation of the oxygen het-erocycle: flavones, isoflavones, flavanones, flavonols, flavanols,anthocyanins, and proanthocyanidins. The occurrence of someof these flavonoids is restricted to a few foodstuffs. Quercetin,the main flavonol in our diet, is present in many fruits and

    vegetables, while flavones are less common (Hertog and oth-ers 1992) and occur in foods as O-glycosides with sugars boundat the C3  position. Flavonoids with a diphenylpropane skeleton(C6– C3– C6) are known to have antioxidative properties as wellas, antimutagenic, anticarcinogenic, anti-inflammatory, and anti-allergic effects (Hollman and others 1996). The main flavanols arecatechins, whereas proanthocyanidins are polymeric flavanolspresent in plants as complex mixtures of polymers with an aver-age degree of polymerization between 4 and 11, are responsiblefor the astringency of food, and are usually present in associationwith flavanol catechin (Santos-Buelga and Scalbert 2000). On theother hand, anthocyanins are pigments of red fruits (Frankel andothers 1995).

    Flavonoid composition of the mangoThe flavonoids found in mango include catechin, epicatechin,

    quercetin, isoquercetin (quercetin-3-glucoside), fisetin, and as-tragalin (kaempferol-3-glucoside). The flavonoid glucosides arepresent in the mango leaves and are common flavonoids,whereasfisetin is confined to the twigs (Harborne 1994). Quercetin hasbeen identified in unripe mango fruits, but it is interesting to notethat quercetin has been previously identified in the tender fruitsand is also found in mature fruits along with its glucosides, butboth disappear on ripening (El-ansari and others 1969). The skinof mango variety Haden (from Florida) is reported to containpeonidin-3-galactoside. Some mango fruits/varieties have beenknown to have a reddish tint, this could be due to the presence of anthocyanins, a group of phenolic compounds with good antiox-idant properties higher than that of phenolic acids (Rice-Evansand others 1997). Anthocyanin changes during growth of mangoleaf or epidermal cells, where the polyphenols are mainly accu-

    mulated, as reported by Rozema and others (2002).(++)-Catechins.   (+)-Catechin is a flavonoid from the groupof catechins including (– )-epicatechin, (– )-epigallocatechin, (– )-epicatechingallate, and (+)-gallocatechin. The polyphenolic frac-tion of  Mangifera indica  extract, which represents the largest partof the constituents (around 50%), is rich mainly in mangiferin, cat-echin, and epicatechin (Scartezzini and Speroni 2000). Severalepidemiological and in vitro  studies suggest that catechins havebeneficial effects on human health due to their free radical scav-enging and antioxidant activities (Augustyniak and others 2005)serving to protect against congestive heart failure (Ishikawa andothers 1997), cancer (Yamanaka and others 1997), myoglobin-uric acute renal failure (Chander and others 2003), to reduce theincidence of myocardial ischemia, and to support anti-aging.

    Rastraelli and others (2002) found both (+) catechin and (– )epicatechin (Figure 3 and 4) in mango stem bark extract, the rawmaterial for the formulationof a Cuban foodsupplement (Vimang )at concentrations of 1308 mg and 807.4 mg/100 g dry matter,respectively. This high concentration points to the contributionof catechins to the potency of mango stem bark extract as an

    antioxidant with great medicinal use.Catechin (C), epicatechin (EC), and mangiferin (MF) may re-act with H2O2  directly or prevent the Fenton reaction betweenFe2+ and H2O2   to form hydroxyl radicals (Sanchez and others2000; Andreu and others 2005a) reducing H2O2  induced by T-cell receptor activation and thus controlling the reactive oxygenspecies-pathway against activation-induced cell death (Hernan-dez and others 2007) resulting in the protection of human T lym-phocytes from   in vitro  activation-induced cell death (AICD) ina concentration-dependent manner. The effects of these 3 majorpolyphenols are not equivalent; the decreased order in protectiveeffects was classified as C  > EC  > MF at a constant concentra-tion (Hernandez and others 2007). However, C and EC compriseconsiderably less content of the whole mango stem bark/leaf ex-tract compared with MF, whose prevalence in the extract deter-mines its predominant action. Although the major polyphenols inthe mango extracts (mangiferin and catechin) inhibit activation-induced cell death, none of them singly could reach the inhibitorylevel achieved by the whole extract at equivalent concentration(Hernandez and others 2007).

    Andreu and others (2006) evaluated the ability of membranepermeability transition (MPT) induction in rat liver mitochondriaby the most representative compounds in mango stem bark ex-tract besides mangiferin, namely, gallic acid, benzoic acid, andcatechin. All showed some MPT-inducing ability with benzoicacid being the most effective. This compound, however, togetherwith its derivatives, comprises only around 2% of the whole ex-tract, considerably less than mangiferin’s 16% content in mangostem bark extract; gallic acid, a poor MPT inducer, makes uparound 5% and catechin, the 2nd major component, togetherwith epicatechin, comprises approximately 11%. The bioactiv-

    ity of catechin and epicatechin polyphenolic components of themango owes its power to their strong antioxidative capacities thathave given them good medicinal properties.

    Figure 3 --- Chemical structure of (++)-catechin.

    Figure 4 --- Chemical structure of (–)-epicatechin.

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    Major mango polyphenols . . .

    Quercetin.   Quercetins, among other flavonoids, are largelyresponsible for the colors of many fruits, flowers, and vegeta-bles. They often occur in plants as glycosides, such as rutin(quercetin rutinoside). Schieber and others (2000) demonstratedthe presence of quercetin (Figure 5) and related glycosides inmango pulp, with the predominant flavonol glycoside being

    quercetin 3-galactoside amounting to 22.1 mg/kg, followed byquercetin 3-glucoside (16.0 mg/kg) and quercetin 3-arabinoside(5.0 mg/kg). The amount of the quercetin aglycon was 3.5 mg/kg.Other flavonol glycosides (kaempferol) were only present in traceamounts. In a separate study on mango peel, Berardini and oth-ers (2005b) found higher quantities of quercetin and its relatedglycosides as illustrated in Table 1.

    Roberts-Thomson and others (2008) evaluated the abilities of the mango components quercetin and mangiferin and the agly-cone derivative of mangiferin, norathyriol, to modulate the trans-activation of peroxisome proliferator-activated receptors (PPARs)throughthe use of a gene reporter assay. They found that quercetininhibited the activation of all 3 isoforms of PPAR (PPARγ   IC50  =56.3 µM; PPARα IC50 = 59.6 µM, and PPARβ IC50 = 76.9 µM)asdid norathyriol (PPARγ  IC 50= 153.5 µM; PPARα IC50= 92.8µM,and PPARβ IC50 = 102.4µM), whereas mangiferin did not inhibitthe transactivation of any isoform. PPARs are nuclear receptorsthat control many cellular and metabolic processes. Three iso-types: PPARα, PPARβ, and PPARγ   have been identified in lowervertebrates and mammals with each subtype fulfilling specificfunctions. However, all the 3 PPARs affect energy homoeostasisand inflammatory responses. Their activity can be modulated bydrugs such as the hypolipidemic fibrates and the insulin sensi-tizing thiazolidinediones. Thus, identifying small molecule mod-ulators of the PPARs is an active area of research and may im-pact chronic diseases such as diabetes, obesity, heart disease, andatherosclerosis. The study of Roberts-Thomson and others (2008)concluded that mango components and metabolites may altertranscription and could contribute to positive health benefits.

    Some conjugates of quercetin such as quercetin rhamnosides,quercetin xylosides, and quercetin galactosides are not easily hy-

    drolyzed by the enzyme lactase phlorizin hydrolase, and mostlikely are not readily absorbed by small intestinal cells. In com-parison, the quercetin in the form of quercetin glucosides and freequercetin are easily hydrolyzed making them more bioavailableto small intestinal cells as demonstrated in cell and in vitro studiesby Boyer and Liu (2004). On absorption, quercetin is metabolizedmainly to isorhamnetin, tamarixetin, and kaempferol.

    Quercetin downregulates expression of mutant breast cancercells, arrests human leukemic T cells, inhibits tyrosine kinase,and inhibits heat shock proteins (Lamson and Brignall 2001).Quercetin protects Caco-2 cells from lipid peroxidation inducedby hydrogen peroxide and Fe2+ (Peng and Kuo 2003). In mouseliver, quercetin decreases lipid oxidation and increases glu-tathione, thus protecting the liver from oxidative damage (Molinaand others 2003). Elsewhere it has been found that high doses of 

    Figure 5 --- Chemical structure of quercetin.

    quercetin inhibit cell proliferation in colon carcinoma cell linesand in mammary adenocarcinoma cell lines, but at low dosesquercetin increases cell proliferation in colon and breast can-cer cells (Woude and others 2003), inhibits cell proliferation inMol-4 human leukemia cells, induces apoptosis (Mertens-Talcottand others 2003), and inhibits platelet aggregation, calcium

    mobilization, and tyrosine protein phosphorylation in platelets(Hubbard and others 2003). Modulation of platelet activity mayhelp prevent cardiovascular disease. Quercetin has also beenfound to exhibit antihistamine and antinflammatory effect associ-ated with various forms of arthritis. Quercetin works mainly as anantioxidant.

    Kaempferol, rhamnetin, and anthocyanins.  Little information isavailable about these flavonoids in the mango. Studies herehave centered only on the identification and characterization of these compounds with no studies detailing the effect of mangokaempferol, rhamnetin, or anthocyanins on human or animalhealth. Kaempferol and its related conjugates are found in almostthe same quantities in mango pulp (Schieber and others 2000),whilein mango peel Berardiniand others (2005b) found 36 mg/kgof kaempferol-3-0 glucoside. In other studies, kaempferol wasfound to be a strong antioxidant with  in vitro  studies by Kowal-ski and others (2005) showing that kaempferol inhibits mono-cyte chemoattractant protein (MCP-1). MCP-1 plays a role inthe initial steps of atherosclerotic plaque formation. Elsewherekaempferol has been found to help fight cancer in cultured hu-man cancer cell lines by reducing the resistance of cancer cellsto anticancer drugs (Ackland and others 2005), induce apopto-sis in human glioblastoma cells (Sen and others 2007) besidesbeing found to be absorbed more efficiently than quercetin inhumans, even at low oral doses, and excretion is low (Kroon andothers 2004). The chemical structure of kaempferol is shown inFigure 6.

    Mango peel extract was found to contain about 94.4 mg/kgof rhamnetin 3-0 galactoside/glucoside (Berardini and others2005b) (Figure 7). In other studies invloving pure compounds,the effect of, rhamnetin, on serum and liver cholesterol concen-

    trations, liver lipoperoxide content, and antioxidative enzymeactivities were studied and it was found that the flavonoid re-duced the total serum cholesterol in rats, and the activities of liver

    Figure 6 --- Chemical structure of kaempferol.

    Figure 7 --- Chemical structure of rhamnetin.

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    superoxide dismutase and catalase were almost unaffected byfeeding these flavonoids (Igarashi and others 2008).

    Today, interest in anthocyanins has intensified because of theirpossible health benefits as dietary antioxidants. Over 300 struc-turally distinct anthocyanins have been identified in nature, witha basic structure as shown in Figure 8. The total anthocyanin

    content in the mango was found to be more in ripe mango peeland ranged from 360 to 565mg/100g as compared to 203 to326mg/100g in raw peels. Elsewhere, a novel anthocyanin 7-O -methylcyanidin 3-O -β-D-galactopyranoside has been identifiedin the mango peel of cv. ”Tommy Atkins”  (Berardini and others2005b). The daily intake in humans of anthocyanins has beenestimated to be approximately up to 200 mg/d (Kuhnau 1976).Anthocyanins have been proposed to exert therapeutic activi-ties on human diseases associated with oxidative stress such ascoronary heart disease, cancer (Duthie and others 2000), protectagainst DNA damage (Lazzè and others 2003), prevent inflam-mation and subsequent blood vessel damage, dampen allergic re-actions (Bertuglia 1995), prevent tyrosine nitration (anthocyaninpelargonidin) and, therefore, help protect against neurologicaldiseases with some researchers reporting reversal of age-relatedneurological deficits in animals (Joseph 1999), fight atheroscle-rosis, relax blood vessels (Andriambeloson 1998), maintain mi-crocapillary integrity (Bertuglia 1995), manage diabetes, preventabnormal protein proliferation (Perossini and others 1987), andimprove eyesight (Nakaishi 2000).

    Phenolic AcidsPhenolic acids are abundant in plant foods. Among

    those already identified in the mango are gallic acid, 3,4-dihydroxybenzoic acid, benzoic acid, gallic acid methyl ester,gallic acid propyl ester, and benzoic acid propyl ester (Rastraelliand others 2002). They are esterified to a polyol, usually glu-cose. The phenolic acids are either gallic acid in gallotannins(mango fruit) or other phenolicacids derived from the oxidation of galloyl residues in ellagitannins (Scalbert and Williamson 2000).

    Hydrolyzable tannins are derivatives of phenolic acids and theiroccurrence is much more limited than that of condensed tan-nins. Major components in this category (hydrolyzable tannins)identified in mango parts (pulp, peel, seed, leaf, and stem barkextracts) include gallic acid, methyl gallate, digallic acid, ellagicacid, β-glucogallin, and α-gallotannin. Although gallotannins arereported to be toxic, their concentration in fruits is rather negligi-ble (El-sissi and others 1971). Gallotannins are generally regardedas safe (GRAS) food additives and ellagic acid has been allowedfor use as a food additive, functioning as an antioxidant in somecountries, including Japan. Hydrolyzable tannins are easily hy-drolyzed in vivo  by the action of acid and/or enzymes, releasinggallic acid or ellagic acid units (Scalbert and Williamson 2000).Tannins have been implicated as the bitter principle present inthe kernel; they are known to form a complex with protein and

    Figure 8 --- Chemical structure of anthocyanins.

    minerals, thereby reducing the biological value of protein-richfoods significantly (Narasinga and others 1982). About 75% of the total tannin content in mango seed kernel has been foundto contain hydrolyzable tannins. These tannins require treatmentduring processing to reduce their  in vivo  toxic effect. The tannintoxic effect can be reduced by water blanching, which lowers

    the rate of tannin formation through enzyme activity with theadditional advantage of the possible leaching of soluble tannicsubstances into the soak water.

    Gallic acid, ellagic acid, and their derivatives.   Gallic acid (3, 4,5-trihydroxybenzoic acid) (Figure 9) and its dimeric derivative,known as ellagic acid, exist either in the free form or bound asgallo-tannins and/or ellagi-tannins, respectively. Since gallic acidhas hydroxyl groups and a carboxylic acid group in the samemolecule, its 2 molecules can react with one another to forman ester, digallic acid. Gallic acid does not combine with proteinand has therefore no astringent taste. Gallic acid was identified asthe major polyphenolic compound present in mangoes, followedby 6 hydrolyzable tannins (Kim and others 2007). The amount of gallic acid in mango seed extract ranged from 23 to 838 mg/100 g(on dry matter basis) depending on the method of extraction(Soong and Barlow 2006). Rastraelli and others (2002) found atotal of 226.2 mg/100 g (of dry matter) of gallic acid in mangostem bark extract. Among the phenolic acids, gallic acid was themajor compound (6.9 mg/kg) found in the mango pulp (Schieberand others 2000).

    Gallic acid and, in general, total hydrolyzable tannins werefound to significantly decrease during mango fruit ripening frommature-green to full ripe stages, but were unaffected by hot watertreatment which is often used to control invasive pests in har-vested mango fruits. Gallic acid concentration was found to de-crease by about 22%, whereas the total hydrolyzable tannins de-creased by an average of 57% (Kim and others 2007). In contrast,Kim and others (2007) reported an increase in hydrolyzable tan-nins in ”Tommy Atkins ”  mangoes during ripening, indicating thatdifferences may occur among fruit varieties under different grow-ing conditions or harvest periods. Several studies have shown

    that polyphenolic compounds generally decrease in climactericfruits like mangoes during ripening (Haard and Chism 1996).Tannic acid, which is simply gallic acid anhydride, when oxidizedis converted into gallic acid. Tannic acid is the more powerful of the two as an astringent, it coagulates albumen and gelatin, im-pairs digestion, stops peristalsis, and causes constipation, whilegallic acid does not. Tannic acid is, however, converted into gallicacid in the stomach before absorption.

    Gallic acid has been shown through in vivo  and  in vitro  stud-ies to have antioxidant, anti-inflammatory, antimicrobial, antimu-tagenic, anticancer, radical scavenging activities (Madsen andBertelsen 1995), decrease histamine release in rat basophilicleukemia cells (Matsuo and others 1997), and inhibit inflamma-tory allergic reactions (Shin and others 2005).

    Ellagic acid is a fused 4-ring polyphenol (Figure 10) that ispresent in the mango among other plants where it is present in

    Figure 9 --- Chemical structure of gallic acid.

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    Major mango polyphenols . . .

    the form of ellagitannin, (ellagic acid bound to a sugar molecule)which is a more water-soluble compound and easier for an-imals to absorb in their diets. The amount of ellagic acid inmango seed extract has been found to range from 3 to 156mg/100 g (GAE), on dry matter basis, depending on the methodof extraction (Soong and Barlow 2006). Ellagic acid has been

    found to inhibit the DNA binding and the DNA adduct for-mation of N-nitrosobenzylmethylamine (NBMA) in cultured ex-plants of rat esophagus (Mandal and others 1988), prevent N-nitrosodiethylamine-induced lung tumorigenesis in mice (Khan-duja and others 1999), exhibit antimutagenic, antiviral, antiox-idant properties, and stimulate the activities of detoxifying en-zymes (Mandal and others 1988). Elsewhere, 13-cis-retinoic acidhas been found to antagonize the preventive effects of ellagicacid (Daniel and Stoner 1991). Application of small amounts of ellagitannins derived from natural sources has been suggested tobe more effective in the human diet than large doses of purifiedellagic acid.

    Methyl gallate and propyl gallate (Figure 11 and 12) are deriva-tives of gallic acid and both have been found to have strongantioxidative properties. Rastraelli and others (2002) found thatmango stem bark extract contained about 445.2 mg/100 g and476.2 mg/100 g (on dry matter) of methyl gallate and propyl gal-late, respectively. In other studies, methyl and propyl gallate havebeen found to have inhibitory potential against herpes simplexvirus in vitro  (Kane and others 1988), adhesion of human leuko-cytes, adhesionof cancercells with vascular endothelial cells, hu-man collagenase, growth of intestinal bacteria (Chung and others1998), and to decrease the peroxidation of ox brain phospho-

    Figure 10 --- Chemical structure of ellagic acid.

    Figure 11 --- Chemical structure of propyl gallate.

    Figure 12 --- Chemical structure of methyl gallate.

    lipids. Contrary to these antioxidant properties, they (methyl gal-late and propyl gallate) were found   in vitro  and cell studies toaccelerate damage to the sugar deoxyribose in the presence of ferric-EDTA and H2O2 (Aruoma and others 1993).

    Benzoic acid and related conjugates.  Benzoic acid, the simplestaromatic carboxylic acid containing a carboxyl group bonded

    directly to a benzene ring (Figure 13), was found to be presentin mango stem bark extract at about 198.6 mg/100 g, while itsconjugate, benzoic acid propyl ester, was 398.7 mg/100 g in theextract (Rastraelli and others 2002). Benzoic acid and its relatedpolyphenolic derivatives have been found to be among the activecomponents in vimang , a mango stem bark extract used in Cubaas a nutritional supplement. It was found to play a role in inducedmitochondrial permeability transition (MPT) in rat liver mitochon-dria besides other polyphenolic substances (Pardo-Andreua andothers 2005).

    In studies of theconjugation of benzoic acid in man, it was pro-posed that the body has no store of preformed glycine and thatbenzoic acid acts as a stimulus for the synthesis of this aminoacid. Glycine production was found to increase with increasedamounts of benzoic acid up to a certain maximum (Quick 1931).Two urinary metabolites of benzoic acid are known, namely,hippuric acid and benzoyl-glucuronic acid. Conjugation withglycine and glucuronic acid occurs in preference to oxidationbecause benzoic acid strongly inhibits fatty oxidation in the liver.In man, benzoic acid is almost entirely excreted as hippuric acid,whereas dogs excrete more conjugated glucuronic acid than hip-puric acid (Quick 1931).

    Protocatechuic acid (3, 4 dihydroxybenzoic acid) (Figure 14)is one of the several forms of dihydroxybenzoic acid identifiedand quantified in mango stem bark extract at about 226.2 mg/100g of dry matter (Rastraelli and others 2002). Dihydroxybenzoicacids are used as intermediates for pharmaceuticals, especiallyfor antipyetic, analgesic, antirheumatism drugs, and other or-ganically synthesized drugs. Many experiments undertaken onthese phenolic acids and their derivatives have shown that theyexhibit strong pharmacological antimutagenic, anticarcinogenic,

    antifungal, antibacterial, antioxidant, and neuroprotective prop-erties (Wang and others 2007).Besides the previously discussed phenolic acids, other pheno-

    lic acids found in the mango, albeit in small amounts, are: caffeicacid 7.7 mg/kg, ferulic acid 10.4 mg/kg, and cinnamic acid 11.2mg/kg (Ahmed and others 2007), all of which are strong antiox-idative agents in their own right but their low concentrations inthe various mango parts make their nutraceutical and pharma-ceutical contribution insignificant, but not irrelevant.

    Figure 13 --- Chemical structure of benzoic acid.

    Figure 14 --- Chemical structure of protocatechuic acid.

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    ConclusionsThe mango is a potential source of polyphenolic compounds

    with high antioxidative activity that help protect the body againstdamage linked to oxidative stress. The quantities and characteris-tics of different mango phenolics differ in the different plant partsbesides being affected by the geographic locations of the plants.

    Mangiferin, which is mainly concentrated in the bark and leavesof the mango tree, is a unique polyphenol to the mango with highpharmaceutical activity, a potential which has been exploited inmedicine and food supplements. Whole mango extracts are morepotent than pure isolated mangiferin highlighting the synergismbetween mangiferin and other mango polyphenols for enhancedactivity. Being a very popular plant, especially within the tropicsand owing to its uniqueness of all parts (pulp, peel, seed, bark,leaves, and flowers) being utilized domestically or industrially,the mango thus could be a cheap and readily available supplierof dietary polyphenols with great antioxidative potential that willhelp reduce degenerative diseases such as cancer, atherosclero-sis, diabetes, and obesity.

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