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Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Mangiferin
  5. Flavonoids
  6. Phenolic Acids
  7. Conclusions
  8. References

ABSTRACT:  The mango is a rich source of various polyphenolic compounds. The major polyphenols in the mango in 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 nutraceutical and pharmaceutical significance of mangiferin, which is a special polyphenol in the mango has been extensively demonstrated and continues to attract much attention especially in its potential to combat degenerative diseases 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. Mango polyphenols, like other polyphenolic compounds, work mainly as antioxidants, a property that enables them to protect 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 mixtures from the particular mango part suggesting that synergism of the various mango polyphenols is important for maximum antioxidative activity. In this article, we review the major mango polyphenols, looking at their proposed antioxidative activity, estimated amounts in the different parts, their structures, suggested modes of action, and related significance to human health, with great emphasis on mangiferin.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Mangiferin
  5. Flavonoids
  6. Phenolic Acids
  7. Conclusions
  8. References

In 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 and derived products a healthy habit. Bioactive compounds found in the mangos, among other plants and herbs have been shown to have possible health benefits with antioxidative, anticarcinogenic, antiatherosclerotic, antimutagenic, and angiogenesis inhibitory activities (Cao and Cao 1999). Interestingly, many herbs, fruits, and vegetables are known to contain large amounts of phenolic antioxidants other than the well-known vitamins C, E, and carotenoids.

Polyphenols are secondary metabolites of plants and are widely distributed in beverages and plant-derived foods. Human consumption studies indicate 1 g of total polyphenols is frequently consumed per day and it is not anticipated that any acute or lethal toxicity would be observed through the oral intake route (Scalbert and Williamson 2000). Phenolic compounds have the capacities to quench lipid peroxidation, prevent DNA oxidative damage, scavenge free radicals (Cao and Cao 1999), and prevent inhibition of cell communication (Sigler and Ruch 1993), all of which are precursors to degenerative diseases. Free radicals cause depletion of the immune system antioxidants, change in gene expression, and induce abnormal proteins resulting in degenerative diseases and aging.

Antioxidant nutrients and phytonutrients inhibit the oxidation of living cells by free radicals by protecting the lipids of the cell membranes through free radical scavenging, blocking the initiators of free radical attack, neutralizing or converting free radicals into less active, stable products thus breaking the chain reaction and assisting in salvaging oxidized antioxidants enabling them to continue to be of benefit (Halliwell and others 1992). There are 2 main antioxidant defense mechanisms developed by living organisms: enzymatic and nonenzymatic components defense systems. An array of small molecules including polyphenols fall under the later system (Shahidi and others 1992; Rice-Evans and others 1997). Polyphenols have the ability to scavenge free radicals via hydrogen donation or electron donation (Shahidi and others 1992). A phenolic molecule is often characteristic of a plant species or even of a particular organ or tissue of that plant. The antioxidant activity of polyphenols is governed by the number, reactivity, and location of their aromatic hydroxyl groups (Chen and others 1996).

The main classes of polyphenols are defined according to the nature of their carbon skeleton and they are: phenolic acids, flavonoids, stilbenes, and lignans (Lee and others 2003). Other dietary polyphenols are not well-defined chemical entities and result from the oxidative polymerization of flavonoids and phenolic acids (Santos-Buelga and Scalbert 2000). The means of extracting polyphenols from plants is crucial as some polyphenols can be denatured by heat and lost by some solvents. Besides, some solvents are toxic and render the extracts unsafe for human consumption. Decoction is an extraction method of choice due to the absence of any organic solvent, as is the case with the industrial production of (Vimang), a mango stem bark extract in Cuba. Specific polyphenolic compounds can be determined and quantified by chromatographic techniques, while total phenols can be estimated by reduction of the Folin–Ciocalteu reagent (Singleton and Rossi 1965). Besides these, antioxidative capacity assays of plant extracts can also be used to predict their polyphenolic quantity and/or activity.

Polyphenolic composition

Polyphenolic composition of mango pulp Mangiferin, gallic acids (m-digallic and m-trigallic acids), gallotannins, quercetin, isoquercetin, ellagic acid, and β-glucogallin are among the polyphenolic compounds already identified in the mango pulp (Schieber and others 2000). Gallic acid has been identified as the major polyphenol present in mango fruits, followed by 6 hydrolysable tannins and 4 minor compounds, p-OH-benzoic acid, m-coumaric acid, p- coumaric acid, and ferulic acid (Kim and others 2007). Schieber and others (2000) found 6.9 mg/kg of gallic acid and 4.4 mg/kg of mangiferin in mango pulp. In a polyphenol screening of 20 mango varieties, Saleh and El-Ansari (1975) reported the co-occurrence of mangiferin, isomangiferin, and homomangiferin in mango fruit pulp. Mangiferin has been shown elsewhere to be the main compound of leaves and stem bark with great medicinal values. It has been reported that phenolic compounds and their associated antioxidant capacity decrease as fruit ripens (Kim and others 2007). Gallotannins represent the major components of unripe fruits and seeds. According to Prabha and Patwardhan (1986) gallic acid is the substrate of polyphenol oxidase in the fruit pulp, whereas ellagic acid is the predominant substrate in mango peel.

Polyphenolic composition of mango peel During mango fruit development, the total phenols have been found to be higher in the peel than in the flesh at all stages (Lakshminarayana and others 1970), with an estimated total polyphenol content in mango peel of 4066 mg (GAE)/kg (dry matter) (Berardini and others 2005b). Generally, ripe peels contain higher total polyphenols than raw peels (Ajila and others 2007). The polyphenolic constituents of mango peel include mangiferin, quercetin, rhamnetin, ellagic acid, kaempferol, and their related conjugates as shown in Table 1 where it can be seen that the 2 main polyphenols in mango peel are mangiferin and quercetin 3-0-galactoside. Berardini and others (2005b) found that, while mangiferin contents slightly decreased at elevated temperatures, the contents of the other xanthone derivatives significantly increased. The observed changes may be attributed to the formation of xanthones from benzophenone derivatives, which were recently identified in mango peels (Berardini and others 2004) and which are considered precursors of xanthone C-glycosides (Larrauri 1999). Anthocyanins have also been identified in the mango peel and estimated to range from 203 to 565 mg/100 g (dry matter) depending on variety and stage of maturity (Berardini and others 2005b). In their study on the antioxidative activity of mango peel extract, Berardini and others (2005b) established that the antioxidative capacity of the extract was higher than that of standard mangiferin and quercetin 3-O-glucoside, thus indicating that the antioxidative capacity of the peel extract cannot be attributed to a single component but to the synergistic effect of all the compounds present.

Table 1—.  Phenolic compounds in mango peel (mg/kg) on dry matter basis.
CompoundAmount (mg/kg)
Mangiferin1690.4
Mangiferin gallate 321.9
Isomangiferin 134.5
Isomangiferin gallate  82.0
Quercetin 3-O-galactoside 651.2
Quercetin 3-O-glucoside 557.7
Quercetin 3-O-xyloside 207.3
Quercetin 3-O-arabinopyranoside 101.5
Quercetin 3-O-arabinofuranoside 103.6
Quercetin 3-O-rhamnoside  20.1
Kaempferol 3-O-glucoside  36.1
Rhamnetin 3-O galactoside/glucoside  94.4
Quercetin  65.3
Total phenolics4066.0

Polyphenolic composition of mango seed kernels Besides the pulp and the peel, mango seed kernels are equally rich in polyphenols with potent antioxidative activity, but ironically the seeds are always discarded as waste during processing and consumption of the mango fruit. As an example, in India about 300000 metric tons of mango seed kernels are discarded every year (Char and Azeemoddin 1989). Ahmed and others (2007) identified and quantified various polyphenolic compounds in the mango 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 acid 10.4 mg/100 g, cinnamic acid 11.2 mg/100 g, and unknown compounds 7.1 mg/100 g. The total polyphenolic content of the mango seed kernel extract was estimated to be 112 mg (GAE)/100 g (Ahmed and others 2007). Soong and Barlow (2004) assayed the antioxidant activity of a variety of fruit seeds, namely, mango, jackfruit, longan, avocado, and tamarind and found that the antioxidant activity of the mango seed kernel was the highest, a fact attributed to its high polyphenolic content. These point to a reason to industrially utilize the mango seed kernel as a functional food ingredient.

Polyphenolic composition of mango leaves and stem bark Galloyl, hydroxy benzoyl esters, and epicatechin have been identified in mango leaves. Chemical studies performed with a standard aqueous extract of the stem bark from M. indica, which has been used in nutraceutical formulations in Cuba under the brand name vimang, have enabled the isolation and identification of phenolic 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 epicatechin), and the xanthone mangiferin, which is the predominant component of this extract (10%) (Sanchez and others 2000). The total polyphenolic content of mango stem bark extract was found to be 10.61 g (GAE)/100 g of dry weight by the HPLC method and 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 and developmental factors have been reported to affect the accumulation and eventual concentration of polyphenols in plant parts. Saleh and El-Ansari (1975) reported on the polyphenolic composition of mango leaves, twigs, bark, fruits, and seeds. Mangiferin was the major component of the leaves, twigs, and bark, with the bark having the highest content, while the gallotannins were the major components of the unripe fruits and their seeds besides being detected in all parts of the mango, isomangiferin, and homomangiferin were mainly present in the leaves and twigs, the former was also detected in fruits of some varieties. Fisetin was high in twigs, as was quercetin in the fruits. Quercetin-3-glucoside and 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 concentration in twigs, fruits, and seeds as compared to the leaves. m-Digallic acid was high in unripe fruits, as was β-glucogallin in the seeds.

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

The different parts of the mango (fruit pulp, peel, seed kernel, leaves, and stem bark) are a rich source of various polyphenols with quantities of the different polyphenols varying in the different parts or missing totally in some parts. Significant research work has been done on mangoes and many articles have been published, but most of them have discussed mango polyphenols from 1 part only and none has discussed polyphenols in the mango as a whole. In this article, we review for the 1st time the various mango polyphenolic compounds from the different parts and their related antioxidative and medical significance to human health paying special attention to mangiferin.

Mangiferin

  1. Top of page
  2. Abstract
  3. Introduction
  4. Mangiferin
  5. Flavonoids
  6. Phenolic Acids
  7. Conclusions
  8. References

Occurrence

Mangiferin is a xanthone and xanthones are some of the most potent antioxidants known; they are thought to be more potent than both vitamin C or vitamin E and are sometimes unofficially referred to as “super antioxidants.” Xanthones are heat-stable molecules. Mangiferin, generally called C-glucosyl xanthone, is widely distributed in higher plants (Sanchez and others 2000) where it provides protection to producer plants against different forms of static and dynamic stresses including ingress of pathogenic microorganisms (Muruganandan and others 2002). It is a pharmacologically active phytochemical and a natural polyphenolic antioxidant present in the bark, fruits, roots, and leaves of Mangifera indica Linn, and a few other medicinal plants recommended in the Indian system of medicine for treatment of a number of immunodeficiency diseases (Scartezzini and Speroni 2000).

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) was isolated. A quantitative estimation on the dried leaf and bark material revealed that the mangiferin content was higher in the mango bark (Sissi and Saleh 1965) than in the leaf. Saleh and El-Ansari (1975) reported on the co-occurrence of the 3 xanthones (mangiferin, isomangiferin, and homomangiferin). They isolated 2 xanthones in the leaves along with a 3rd xanthone, isomangiferin (1-, 3-, 6-, 7-tetrahydroxy-4-C-β-D-glucopyranosyl-xanthone), which had been first identified in Anemarrhena asphodeloides. Mangiferin content of mango pulp was found to be about 4.4 mg/kg (Schieber and others 2000), seed kernel 42 mg/kg (Ahmed and others 2007), whereas in dried mango peel it was 1690 mg/kg (Table 1). In the mango stem bark, mangiferin was the most abundant phenolic compound, estimated at about 71.4 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 anacardiacae, besides Mangifera indica only Mangifera zeylanica is recorded as containing mangiferin.

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Figure 1—. Chemical structure of mangiferin (C 2- β-D-glucopyranosyl-1, 3, 6, 7-tetrahydroxyxanthone).

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Bioactivity of mango mangiferin

Many researchers have established mangiferin as the possible active principle of mango (Mangifera indica L.) stem bark and leaf extract and attributed most of the biological activities of the extracts to it (Sanchez and others 2000). From the various studies 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 has been investigated in vitro for its antioxidant (Rouillard and others 1998), immuno-stimulating, and antiviral properties (Zheng and Lu 1990), and it was found to protect hepatocytes, lymphocytes, neutrophils, and macrophages from oxidative stress; reduce atherogenicity in streptozotocin diabetic rats; and to reduce the streptozotocin-induced oxidative damage to cardiac and renal tissues in rats (Muruganandan and others 2002).

The iron-complexing ability of mangiferin was reported as a primary mechanism for protection of liver mitochondria against Fe2+ citrate-induced lipid peroxidation (Halliwell and Gutteridge 1986). They also showed that in vitro antioxidant activity of mangiferin is related to its iron-chelating properties and not merely due to the scavenging activity of free radicals. Iron chelators such as mangiferin could be an important approach to reduce iron-induced oxidative damage in pathologies related to abnormal intracellular iron distribution and/or iron overload, such as hereditary hemochromatosis, h-thalassemia, Friedreich's ataxia, and sideroblastic anemia (Britton and others 2002). The metabolism of mangiferin yields noranthyriol after cleavage of the C–C linkage of the glucose moiety, which exhibits a potent iron chelating effect, and an inhibitory effect of the induced respiratory burst in rat neutrophyls (Andreu and others 2005b). Those effects were thought to have originated from the high scavenger capacity of mangiferin by singlet oxygen.

Mangiferin (MF) was found to protect mitochondrial membrane against lipid peroxidation hence preserving its integrity. From their study, Halliwell and Gutteridge (1986) suggested that mangiferin removes iron from the Fe2+ citrate complex and forms 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 lipid peroxidation. This Fe3+ mangiferin complex impairs ferric iron reduction to ferrous iron by endogenous reducers like ascorbate, sparing them and also preventing Fe2+ reloading of the biological system, which can readily participate in reactions involved in OH formation.

It has been suggested that oxidation derivatives of mangiferin may sensitize mitochondria to calcium-induced permeability transition (Andreu and others 2005c), a process often related to apoptotic/necrotic cell death. In this regard, it was proposed that the accumulation of such oxidation products would take place in such cells exposed to an overproduction of reactive oxygen species, such as cancer cells, where the occurrence of apoptosis induced by mitochondria permeability transition may be a cellular defense mechanism against excessive reactive oxygen species formation (Nunez-Selles 2005).

Mangiferin has been found to inhibit colon tumorigenesis in rats. Bhattacharya and others (1972) reported that the mechanism of this compound in the central nervous system is related to its ability to inhibit monoamine oxidase activity. Malignant cell proliferation in the colonic mucosa of male F344 rats was reduced by 75% after addition of MF to the diet (0.1%) in a long-term study which suggested that MF may act as a naturally occurring chemopreventive agent in colon cancer (Yoshimia and others 2001). Chemoprevention effect of MF has also been tested on other tumors like the ascitic fibrisarcoma (AFS) in Swiss mice where significant inhibition levels were recorded coupled with increased survival rates (Guha and Chattopadhyav 1996). Alongside the tumor studies on rats treated with mangiferin, Yoshimia and others (2001) found that mangiferin also inhibited body weight gain in experimental rats. This points at the possible utilization of mangiferin in food products for special dietary needs like with obese people.

1-Methyl-4-phenyl-pyridine ion (MPP+), the active metabolite of 1-methyl-4-phenyl-1-, 2-, 3-, 6-tetrahydropyridine (MPTP) has been found to induce a Parkinsonian syndrome in humans and animals, a neurotoxic effect postulated to derive from oxidative stress (Amazzal and others 2007). Mangiferin has been found to protect neuroblastoma cells line N2A against MPP+ induced cytotoxicity, to restore the glutathione (GSH) content, and to downregulate both superoxide dismutase 1 (SOD1) and catalase (cat mRNA) expression all being mediated by oxidative stress (Amazzal and others 2007). In Parkinson's disease, the nigral level of iron is increased and may contribute to the hyper-production of 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 compound in therapies for degenerative diseases, including Parkinson's disease, in which oxidative stress plays a crucial role.

Mangiferin, being able to traverse the blood–brain barrier as demonstrated by Martınez and others (2001) in gerbils, has been found to have real potential to ameliorate the oxidative stress observed in neurodegenerative disorders. Mangiferin has been shown to reduce the intracellular Ca2+ concentration, an activity that may contribute to its protective effects and reduce iron neurotoxicity in cells. For the immune system, lymphocyte apoptosis maintains the normal physiology and self-tolerance of the system. For peripheral T cells, apoptosis induced by repeated T-cell receptor (TCR) stimulation, known as activation-induced cell death (AICD), may be responsible for the peripheral deletion of autoreactive T cells (Green and Ware 1997) and is involved in terminating the immune response through elimination of activated lymphocytes. The imbalance in this apoptotic process is dangerous and leads to severe diseases associated with autoimmune phenomena (Rieux-Lancat and others 1995) and immunodeficiencies (Alimonti and others 2003). CD95 and its ligand (CD95L) play a crucial role in this type of cell death (Devadas and others 2002). Activation of T cells via T-cell receptor signaling increases intracellular reactive oxygen species and Ca2+, leading to CD95L expression and, consequently, activation-induced cell death (Gulow and others 2005). Activation-induced cell death plays an important role in the maintenance of peripheral lymphocyte homeostasis. Reactive oxygen species combined with simultaneous calcium (Ca2+) influx into the cytosol are required for induction of activation-induced cell death. Mango stem bark extract, whose main active ingredient is mangiferin has been shown to protect T cells from in vitro activation-induced cell death due to its richness in polyphenols which diminished the increase of intracellular reactive oxygen species and free Ca2+ induced by T-cell receptor triggering (Hernandez and others 2007).

Reduction of the reactive oxygen species has been found to consume ATP, thus progressively reducing the energy charge of the system. Mangiferin has been shown to be able to scavenge reactive oxygen species, thus inhibiting all those processes leading to energy charge decrease, red blood cell damage, and membrane destabilization. Erythrocytes and erythrocyte membrane have a high ratio of polyunsaturated fatty acids to total lipids, indicating susceptibility to lipid peroxidation. Red blood cells are highly vulnerable to lipid peroxidation due to constant exposure to high oxygen tension and the presence of large iron ion concentrations (Pawlak and others 1998). After human cell studies, Rodriguez and others (2006) suggested that Mangiferin protects erythrocytes and red blood cells from reactive oxygen species production thus contributing to integrity and functionality of these cells.

The use of dietary ingredients to protect against radiation-induced damage is an attractive proposition, because they are part of the daily human diet, do not have side effects, will have wide acceptability, and can be safely manipulated for human use. The mango fruit is commonly used by humans in various forms and the principal compound mangiferin has been isolated. From their study on cultured human peripheral blood lymphocytes (HPBLs), Jagetia and Baliga (2005) found that mangiferin provided protection against radiation-induced sickness and mortality. 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 glucose levels by inhibiting the glucose absorption from the intestine. This hypothesis could be supported by the recent findings that mangiferin inhibits the glucosidase enzymes sucrase, isomaltase, and maltase from rats (Yoshikawa and others 2001) which are involved in the digestion of carbohydrates into simple sugars in the gut leading to delay or inhibition of carbohydrate breakdown and subsequent slower glucose absorption from the intestine (Aderibigbe and others 2001). Mangiferin has been suggested to possess both pancreatic and extrapancreatic mechanisms in its antidiabetic action and such apparent dual actions of mangiferin enhance its efficiency.

Mangiferin was found to significantly reduce plasma total cholesterol, triglycerides, and LDL-C associated with a concomitant increase in HDL-C levels and a decrease in atherogenic index in diabetic rats indicating its potential antihyperlipidemic and antiatherogenic activity (Muruganandan and others 2005). The triglyceride-lowering property of mangiferin could indirectly contribute to the overall antihyperglycemic activity through the glucose–fatty acid cycle mechanism (Randle and others 1963). According to the Randle glucose–fatty acid cycle, an increased supply of plasma triglycerides could constitute a source of increased free fatty acid availability and oxidation that can impair insulin action and glucose metabolism and utilization leading to development of hyperglycemia. Therefore, the reduction of triglycerides following administration with mangiferin would also facilitate glucose oxidation and utilization and, subsequently, reduction of hyperglycemia (Muruganandan and others 2005).

It has been demonstrated elsewhere that mangiferin possesses a wide range of antibacterial effects, both with regard to Gram-positive and Gram-negative bacteria. The species most sensitive to mangiferin among the Gram-positive microorganisms was Bacillus pumilus, whereas among the Gram-negative species the most sensitive to mangiferin was Salmonella agona, though it has to be noted that higher concentrations of mangiferin were necessary (30% to 35%) to achieve the desired effect with regard to the Gram-negative microorganisms (Stoilova and others 2005). Antifungal effect of mangiferin has also been shown with regard to Thermoascus aurantiacus, Saccharomyces cerevisiae, Trichoderma reesei, and Aspergillus flavus (Lova and others 2005). Chakrabarti and Ghosal (1985) found that the fungus Fusarium moniliforme var. subglutinans transforms mangiferin into polymerous quinone, possibly due to the phenoloxidase it releases. It is possible that the resistance to mangiferin by various other mycelial fungi is due to this mechanism.

At this point, it is worth mentioning that Mangiferin alone did not show higher biological activity than the whole extract of either the leaf or bark raw material, and it has been hypothesized that the total antioxidant effect of any mango extract is due to the presence of a combination of several polyphenolic compounds and their derivatives and not only the single, though potent, compound mangiferin (Arts and others 2000).

Mechanism of mangiferin bioactivity

The chemical structure of mangiferin fulfills the 4 requisites that have been reported to have high bioavailability by oral administration: molecular weight below 500 Dalton (C19H18O12); fewer than 5 donor functions for hydrogen bonds; fewer than 10 acceptor functions for hydrogen bonds; and potential log P (calculated) less than + 5 (log Pmangiferin : + 2.73). These similar properties are shared by most of the other mango polyphenols.

The mechanism of bioactivities of mangiferin is mainly centered on its capacity to provide cellular protection as an antioxidant and radical captodative agent. A biologically active antioxidant is a substance that, when present even at low concentration, compared to those of an oxidizable substrate such as membrane lipid or DNA, significantly delays or inhibits oxidation of that substrate. Mangiferin performs its antioxidant function at different levels of the oxidative sequence. As far as membrane lipid peroxidation is concerned, it acts by (a) decreasing the localized O2 concentration and generating mangiferin phenoxy radicals (2) (Figure 2) in concert, (b) binding metal ions (Fe 2+/3+) in the form of a mangiferin–iron complex also called metal ligand complex (3) (Figure 2), which is a stable complex structure that will not allow the generation of such tissue damaging ·OH radicals and/or oxo-ferryl groups; (c) regulating polymer chain initiation by interaction 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 the vinylic monomer methylmethacrylate (MMA). The generated radical complex containing a polar end group (mangiferin –Fe3+-O-) acts as a chain terminator by oxidizing the other end group carbon radical of the polymer resulting in a low-molecular-weight mangiferin–Fe–PMMA (polymethylmethacrylate)–polymer (5) (Figure 2), (d) scavenging lipid peroxy/alkoxy radicals and thereby preventing continued abstraction of hydrogen from cellular lipids, and (e) maintaining a cellular oxidation–antioxidant balance (via 1[LEFT RIGHT ARROW]2) (Figure 2) (Ghosal and Rao 1996).

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Figure 2—. Mechanism of action of mangiferin (Ghosal and Rao 1996).

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The deficiency in the body's functioning has for long been associated with free radicals, and thus one tends to view oxidants as bad and antioxidants as good. The actual situation is rarely so simple; an oxidant–antioxidant balance is a realistic depiction of the normal state. Mangiferin (1) (Figure 2) and the resonance-stabilized phenoxy radicals (2) (Figure 2) in conjugated forms would assist to maintain the desired oxidant[LEFT RIGHT ARROW]antioxidant balance in vivo via such systems as 3 and 4 (Figure 2). These 2 systems were found to contribute to the formation of the complex system mangiferin–Fe–PMMA–polymer (5) (Figure 2) (Ghosal and Ran 1996). Also formed during the activity of mangiferin are low-molecular-weight mangiferin complexes as shown by 6 and 7 in Figure 2 (Ghosal and Rao 1996).

Flavonoids

  1. Top of page
  2. Abstract
  3. Introduction
  4. Mangiferin
  5. Flavonoids
  6. Phenolic Acids
  7. Conclusions
  8. References

Flavonoids are the most abundant polyphenols in our diets. Once thought to be vitamins, flavonoids were given such names as vitamin P and vitamin C2. They can be divided into several classes according to the degree of oxidation of the oxygen heterocycle: flavones, isoflavones, flavanones, flavonols, flavanols, anthocyanins, and proanthocyanidins. The occurrence of some of 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 others 1992) and occur in foods as O-glycosides with sugars bound at the C3 position. Flavonoids with a diphenylpropane skeleton (C6–C3–C6) are known to have antioxidative properties as well as, antimutagenic, anticarcinogenic, anti-inflammatory, and anti-allergic effects (Hollman and others 1996). The main flavanols are catechins, whereas proanthocyanidins are polymeric flavanols present in plants as complex mixtures of polymers with an average degree of polymerization between 4 and 11, are responsible for the astringency of food, and are usually present in association with flavanol catechin (Santos-Buelga and Scalbert 2000). On the other hand, anthocyanins are pigments of red fruits (Frankel and others 1995).

Flavonoid composition of the mango

The flavonoids found in mango include catechin, epicatechin, quercetin, isoquercetin (quercetin-3-glucoside), fisetin, and astragalin (kaempferol-3-glucoside). The flavonoid glucosides are present in the mango leaves and are common flavonoids, whereas fisetin is confined to the twigs (Harborne 1994). Quercetin has been identified in unripe mango fruits, but it is interesting to note that quercetin has been previously identified in the tender fruits and is also found in mature fruits along with its glucosides, but both disappear on ripening (El-ansari and others 1969). The skin of mango variety Haden (from Florida) is reported to contain peonidin-3-galactoside. Some mango fruits/varieties have been known to have a reddish tint, this could be due to the presence of anthocyanins, a group of phenolic compounds with good antioxidant properties higher than that of phenolic acids (Rice-Evans and others 1997). Anthocyanin changes during growth of mango leaf or epidermal cells, where the polyphenols are mainly accumulated, as reported by Rozema and others (2002).

(+)-Catechins (+)-Catechin is a flavonoid from the group of catechins including (–)-epicatechin, (–)-epigallocatechin, (–)-epicatechingallate, and (+)-gallocatechin. The polyphenolic fraction of Mangifera indica extract, which represents the largest part of the constituents (around 50%), is rich mainly in mangiferin, catechin, and epicatechin (Scartezzini and Speroni 2000). Several epidemiological and in vitro studies suggest that catechins have beneficial effects on human health due to their free radical scavenging and antioxidant activities (Augustyniak and others 2005) serving to protect against congestive heart failure (Ishikawa and others 1997), cancer (Yamanaka and others 1997), myoglobinuric acute renal failure (Chander and others 2003), to reduce the incidence 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 raw material for the formulation of a Cuban food supplement (Vimang) at concentrations of 1308 mg and 807.4 mg/100 g dry matter, respectively. This high concentration points to the contribution of catechins to the potency of mango stem bark extract as an antioxidant with great medicinal use.

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

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

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Catechin (C), epicatechin (EC), and mangiferin (MF) may react with H2O2 directly or prevent the Fenton reaction between Fe2+ and H2O2 to form hydroxyl radicals (Sanchez and others 2000; Andreu and others 2005a) reducing H2O2 induced by T-cell receptor activation and thus controlling the reactive oxygen species-pathway against activation-induced cell death (Hernandez and others 2007) resulting in the protection of human T lymphocytes from in vitro activation-induced cell death (AICD) in a concentration-dependent manner. The effects of these 3 major polyphenols are not equivalent; the decreased order in protective effects was classified as C > EC > MF at a constant concentration (Hernandez and others 2007). However, C and EC comprise considerably less content of the whole mango stem bark/leaf extract compared with MF, whose prevalence in the extract determines its predominant action. Although the major polyphenols in the mango extracts (mangiferin and catechin) inhibit activation-induced cell death, none of them singly could reach the inhibitory level achieved by the whole extract at equivalent concentration (Hernandez and others 2007).

Andreu and others (2006) evaluated the ability of membrane permeability transition (MPT) induction in rat liver mitochondria by the most representative compounds in mango stem bark extract besides mangiferin, namely, gallic acid, benzoic acid, and catechin. All showed some MPT-inducing ability with benzoic acid being the most effective. This compound, however, together with its derivatives, comprises only around 2% of the whole extract, considerably less than mangiferin's 16% content in mango stem bark extract; gallic acid, a poor MPT inducer, makes up around 5% and catechin, the 2nd major component, together with epicatechin, comprises approximately 11%. The bioactivity of catechin and epicatechin polyphenolic components of the mango owes its power to their strong antioxidative capacities that have given them good medicinal properties.

Quercetin Quercetins, among other flavonoids, are largely responsible for the colors of many fruits, flowers, and vegetables. They often occur in plants as glycosides, such as rutin (quercetin rutinoside). Schieber and others (2000) demonstrated the presence of quercetin (Figure 5) and related glycosides in mango pulp, with the predominant flavonol glycoside being quercetin 3-galactoside amounting to 22.1 mg/kg, followed by quercetin 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 trace amounts. In a separate study on mango peel, Berardini and others (2005b) found higher quantities of quercetin and its related glycosides as illustrated in Table 1.

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Figure 5—. Chemical structure of quercetin.

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Roberts-Thomson and others (2008) evaluated the abilities of the mango components quercetin and mangiferin and the aglycone derivative of mangiferin, norathyriol, to modulate the transactivation of peroxisome proliferator-activated receptors (PPARs) through the use of a gene reporter assay. They found that quercetin inhibited the activation of all 3 isoforms of PPAR (PPARγ IC50= 56.3 μM; PPARα IC50= 59.6 μM, and PPARβ IC50= 76.9 μM) as did norathyriol (PPARγ IC50= 153.5 μM; PPARα IC50= 92.8 μM, and PPARβ IC50= 102.4 μM), whereas mangiferin did not inhibit the transactivation of any isoform. PPARs are nuclear receptors that control many cellular and metabolic processes. Three isotypes: PPARα, PPARβ, and PPARγ have been identified in lower vertebrates and mammals with each subtype fulfilling specific functions. However, all the 3 PPARs affect energy homoeostasis and inflammatory responses. Their activity can be modulated by drugs such as the hypolipidemic fibrates and the insulin sensitizing thiazolidinediones. Thus, identifying small molecule modulators of the PPARs is an active area of research and may impact chronic diseases such as diabetes, obesity, heart disease, and atherosclerosis. The study of Roberts-Thomson and others (2008) concluded that mango components and metabolites may alter transcription and could contribute to positive health benefits.

Some conjugates of quercetin such as quercetin rhamnosides, quercetin xylosides, and quercetin galactosides are not easily hydrolyzed by the enzyme lactase phlorizin hydrolase, and most likely are not readily absorbed by small intestinal cells. In comparison, the quercetin in the form of quercetin glucosides and free quercetin are easily hydrolyzed making them more bioavailable to small intestinal cells as demonstrated in cell and in vitro studies by Boyer and Liu (2004). On absorption, quercetin is metabolized mainly to isorhamnetin, tamarixetin, and kaempferol.

Quercetin downregulates expression of mutant breast cancer cells, 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 induced by hydrogen peroxide and Fe2+ (Peng and Kuo 2003). In mouse liver, quercetin decreases lipid oxidation and increases glutathione, thus protecting the liver from oxidative damage (Molina and others 2003). Elsewhere it has been found that high doses of quercetin inhibit cell proliferation in colon carcinoma cell lines and in mammary adenocarcinoma cell lines, but at low doses quercetin increases cell proliferation in colon and breast cancer cells (Woude and others 2003), inhibits cell proliferation in Mol-4 human leukemia cells, induces apoptosis (Mertens-Talcott and others 2003), and inhibits platelet aggregation, calcium mobilization, and tyrosine protein phosphorylation in platelets (Hubbard and others 2003). Modulation of platelet activity may help prevent cardiovascular disease. Quercetin has also been found to exhibit antihistamine and antinflammatory effect associated with various forms of arthritis. Quercetin works mainly as an antioxidant.

Kaempferol, rhamnetin, and anthocyanins Little information is available about these flavonoids in the mango. Studies here have centered only on the identification and characterization of these compounds with no studies detailing the effect of mango kaempferol, rhamnetin, or anthocyanins on human or animal health. Kaempferol and its related conjugates are found in almost the same quantities in mango pulp (Schieber and others 2000), while in mango peel Berardini and others (2005b) found 36 mg/kg of kaempferol-3-0 glucoside. In other studies, kaempferol was found to be a strong antioxidant with in vitro studies by Kowalski and others (2005) showing that kaempferol inhibits monocyte chemoattractant protein (MCP-1). MCP-1 plays a role in the initial steps of atherosclerotic plaque formation. Elsewhere kaempferol has been found to help fight cancer in cultured human cancer cell lines by reducing the resistance of cancer cells to anticancer drugs (Ackland and others 2005), induce apoptosis in human glioblastoma cells (Sen and others 2007) besides being found to be absorbed more efficiently than quercetin in humans, even at low oral doses, and excretion is low (Kroon and others 2004). The chemical structure of kaempferol is shown in Figure 6.

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Figure 6—. Chemical structure of kaempferol.

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Mango peel extract was found to contain about 94.4 mg/kg of rhamnetin 3-0 galactoside/glucoside (Berardini and others 2005b) (Figure 7). In other studies invloving pure compounds, the effect of, rhamnetin, on serum and liver cholesterol concentrations, liver lipoperoxide content, and antioxidative enzyme activities were studied and it was found that the flavonoid reduced the total serum cholesterol in rats, and the activities of liver superoxide dismutase and catalase were almost unaffected by feeding these flavonoids (Igarashi and others 2008).

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Figure 7—. Chemical structure of rhamnetin.

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Today, interest in anthocyanins has intensified because of their possible health benefits as dietary antioxidants. Over 300 structurally distinct anthocyanins have been identified in nature, with a basic structure as shown in Figure 8. The total anthocyanin content in the mango was found to be more in ripe mango peel and ranged from 360 to 565 mg/100 g as compared to 203 to 326 mg/100 g in raw peels. Elsewhere, a novel anthocyanin 7-O-methylcyanidin 3-O-β-D-galactopyranoside has been identified in the mango peel of cv. "Tommy Atkins" (Berardini and others 2005b). The daily intake in humans of anthocyanins has been estimated to be approximately up to 200 mg/d (Kuhnau 1976). Anthocyanins have been proposed to exert therapeutic activities on human diseases associated with oxidative stress such as coronary heart disease, cancer (Duthie and others 2000), protect against DNA damage (Lazzè and others 2003), prevent inflammation and subsequent blood vessel damage, dampen allergic reactions (Bertuglia 1995), prevent tyrosine nitration (anthocyanin pelargonidin) and, therefore, help protect against neurological diseases with some researchers reporting reversal of age-related neurological deficits in animals (Joseph 1999), fight atherosclerosis, relax blood vessels (Andriambeloson 1998), maintain microcapillary integrity (Bertuglia 1995), manage diabetes, prevent abnormal protein proliferation (Perossini and others 1987), and improve eyesight (Nakaishi 2000).

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Figure 8—. Chemical structure of anthocyanins.

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Phenolic Acids

  1. Top of page
  2. Abstract
  3. Introduction
  4. Mangiferin
  5. Flavonoids
  6. Phenolic Acids
  7. Conclusions
  8. References

Phenolic 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 (Rastraelli and others 2002). They are esterified to a polyol, usually glucose. The phenolic acids are either gallic acid in gallotannins (mango fruit) or other phenolic acids derived from the oxidation of galloyl residues in ellagitannins (Scalbert and Williamson 2000). Hydrolyzable tannins are derivatives of phenolic acids and their occurrence is much more limited than that of condensed tannins. Major components in this category (hydrolyzable tannins) identified in mango parts (pulp, peel, seed, leaf, and stem bark extracts) include gallic acid, methyl gallate, digallic acid, ellagic acid, β-glucogallin, and α-gallotannin. Although gallotannins are reported to be toxic, their concentration in fruits is rather negligible (El-sissi and others 1971). Gallotannins are generally regarded as safe (GRAS) food additives and ellagic acid has been allowed for use as a food additive, functioning as an antioxidant in some countries, including Japan. Hydrolyzable tannins are easily hydrolyzed in vivo by the action of acid and/or enzymes, releasing gallic acid or ellagic acid units (Scalbert and Williamson 2000). Tannins have been implicated as the bitter principle present in the kernel; they are known to form a complex with protein and minerals, thereby reducing the biological value of protein-rich foods significantly (Narasinga and others 1982). About 75% of the total tannin content in mango seed kernel has been found to contain hydrolyzable tannins. These tannins require treatment during processing to reduce their in vivo toxic effect. The tannin toxic effect can be reduced by water blanching, which lowers the rate of tannin formation through enzyme activity with the additional advantage of the possible leaching of soluble tannic substances 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 as gallo-tannins and/or ellagi-tannins, respectively. Since gallic acid has hydroxyl groups and a carboxylic acid group in the same molecule, its 2 molecules can react with one another to form an ester, digallic acid. Gallic acid does not combine with protein and has therefore no astringent taste. Gallic acid was identified as the major polyphenolic compound present in mangoes, followed by 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 a total of 226.2 mg/100 g (of dry matter) of gallic acid in mango stem bark extract. Among the phenolic acids, gallic acid was the major compound (6.9 mg/kg) found in the mango pulp (Schieber and others 2000).

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Figure 9—. Chemical structure of gallic acid.

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Gallic acid and, in general, total hydrolyzable tannins were found to significantly decrease during mango fruit ripening from mature-green to full ripe stages, but were unaffected by hot water treatment which is often used to control invasive pests in harvested mango fruits. Gallic acid concentration was found to decrease by about 22%, whereas the total hydrolyzable tannins decreased by an average of 57% (Kim and others 2007). In contrast, Kim and others (2007) reported an increase in hydrolyzable tannins in "Tommy Atkins" mangoes during ripening, indicating that differences may occur among fruit varieties under different growing conditions or harvest periods. Several studies have shown that polyphenolic compounds generally decrease in climacteric fruits like mangoes during ripening (Haard and Chism 1996). Tannic acid, which is simply gallic acid anhydride, when oxidized is converted into gallic acid. Tannic acid is the more powerful of the two as an astringent, it coagulates albumen and gelatin, impairs digestion, stops peristalsis, and causes constipation, while gallic acid does not. Tannic acid is, however, converted into gallic acid in the stomach before absorption.

Gallic acid has been shown through in vivo and in vitro studies to have antioxidant, anti-inflammatory, antimicrobial, antimutagenic, anticancer, radical scavenging activities (Madsen and Bertelsen 1995), decrease histamine release in rat basophilic leukemia cells (Matsuo and others 1997), and inhibit inflammatory allergic reactions (Shin and others 2005).

Ellagic acid is a fused 4-ring polyphenol (Figure 10) that is present in the mango among other plants where it is present in the form of ellagitannin, (ellagic acid bound to a sugar molecule) which is a more water-soluble compound and easier for animals to absorb in their diets. The amount of ellagic acid in mango seed extract has been found to range from 3 to 156 mg/100 g (GAE), on dry matter basis, depending on the method of extraction (Soong and Barlow 2006). Ellagic acid has been found to inhibit the DNA binding and the DNA adduct formation of N-nitrosobenzylmethylamine (NBMA) in cultured explants of rat esophagus (Mandal and others 1988), prevent N-nitrosodiethylamine-induced lung tumorigenesis in mice (Khanduja and others 1999), exhibit antimutagenic, antiviral, antioxidant properties, and stimulate the activities of detoxifying enzymes (Mandal and others 1988). Elsewhere, 13-cis-retinoic acid has been found to antagonize the preventive effects of ellagic acid (Daniel and Stoner 1991). Application of small amounts of ellagitannins derived from natural sources has been suggested to be more effective in the human diet than large doses of purified ellagic acid.

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Figure 10—. Chemical structure of ellagic acid.

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Methyl gallate and propyl gallate (Figure 11 and 12) are derivatives of gallic acid and both have been found to have strong antioxidative properties. Rastraelli and others (2002) found that mango stem bark extract contained about 445.2 mg/100 g and 476.2 mg/100 g (on dry matter) of methyl gallate and propyl gallate, respectively. In other studies, methyl and propyl gallate have been found to have inhibitory potential against herpes simplex virus in vitro (Kane and others 1988), adhesion of human leukocytes, adhesion of cancer cells with vascular endothelial cells, human collagenase, growth of intestinal bacteria (Chung and others 1998), and to decrease the peroxidation of ox brain phospholipids. Contrary to these antioxidant properties, they (methyl gallate and propyl gallate) were found in vitro and cell studies to accelerate damage to the sugar deoxyribose in the presence of ferric-EDTA and H2O2 (Aruoma and others 1993).

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Figure 11—. Chemical structure of propyl gallate.

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Figure 12—. Chemical structure of methyl gallate.

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Benzoic acid and related conjugates Benzoic acid, the simplest aromatic carboxylic acid containing a carboxyl group bonded directly to a benzene ring (Figure 13), was found to be present in mango stem bark extract at about 198.6 mg/100 g, while its conjugate, benzoic acid propyl ester, was 398.7 mg/100 g in the extract (Rastraelli and others 2002). Benzoic acid and its related polyphenolic derivatives have been found to be among the active components in vimang, a mango stem bark extract used in Cuba as a nutritional supplement. It was found to play a role in induced mitochondrial permeability transition (MPT) in rat liver mitochondria besides other polyphenolic substances (Pardo-Andreua and others 2005).

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Figure 13—. Chemical structure of benzoic acid.

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In studies of the conjugation of benzoic acid in man, it was proposed that the body has no store of preformed glycine and that benzoic acid acts as a stimulus for the synthesis of this amino acid. Glycine production was found to increase with increased amounts 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 with glycine and glucuronic acid occurs in preference to oxidation because 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 hippuric acid (Quick 1931).

Protocatechuic acid (3, 4 dihydroxybenzoic acid) (Figure 14) is one of the several forms of dihydroxybenzoic acid identified and quantified in mango stem bark extract at about 226.2 mg/100 g of dry matter (Rastraelli and others 2002). Dihydroxybenzoic acids are used as intermediates for pharmaceuticals, especially for antipyetic, analgesic, antirheumatism drugs, and other organically synthesized drugs. Many experiments undertaken on these phenolic acids and their derivatives have shown that they exhibit strong pharmacological antimutagenic, anticarcinogenic, antifungal, antibacterial, antioxidant, and neuroprotective properties (Wang and others 2007).

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Figure 14—. Chemical structure of protocatechuic acid.

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Besides the previously discussed phenolic acids, other phenolic acids found in the mango, albeit in small amounts, are: caffeic acid 7.7 mg/kg, ferulic acid 10.4 mg/kg, and cinnamic acid 11.2 mg/kg (Ahmed and others 2007), all of which are strong antioxidative agents in their own right but their low concentrations in the various mango parts make their nutraceutical and pharmaceutical contribution insignificant, but not irrelevant.

Conclusions

  1. Top of page
  2. Abstract
  3. Introduction
  4. Mangiferin
  5. Flavonoids
  6. Phenolic Acids
  7. Conclusions
  8. References

The mango is a potential source of polyphenolic compounds with high antioxidative activity that help protect the body against damage linked to oxidative stress. The quantities and characteristics of different mango phenolics differ in the different plant parts besides being affected by the geographic locations of the plants. Mangiferin, which is mainly concentrated in the bark and leaves of the mango tree, is a unique polyphenol to the mango with high pharmaceutical activity, a potential which has been exploited in medicine and food supplements. Whole mango extracts are more potent than pure isolated mangiferin highlighting the synergism between mangiferin and other mango polyphenols for enhanced activity. Being a very popular plant, especially within the tropics and 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 supplier of dietary polyphenols with great antioxidative potential that will help reduce degenerative diseases such as cancer, atherosclerosis, diabetes, and obesity.

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  2. Abstract
  3. Introduction
  4. Mangiferin
  5. Flavonoids
  6. Phenolic Acids
  7. Conclusions
  8. References
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