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    A review on the medicinal plantPsidium guajava Linn. (Myrtaceae)

    Sunita Sajjekhan1 and Shruthi SD2*

    1P.G. Department of Studies and Research in Biotechnology and Bioinformatics, Kuvempu

    University, Shankaraghatta 577 451, Karnataka, India

    2P.G. Department of Biotechnology, The Oxford College of Science,

    Bangalore 560 102, Karnataka, India

    Corresponding author*: [email protected]

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    Abstract

    Psidium guajava is an important food crop and medicinal plant available in tropical and

    subtropical countries, widely used in food and folk medicines around the world. It contains

    important phytoconstituents such as tannins, triterpenes, flavonoid: quercetin, pentacyclic

    triterpenoid: guajanoic acid, saponins, carotenoids, lectins, leucocyanidin, ellagic acid, amritoside,

    beta-sitosterol, uvaol, oleanolic acid and ursolic acid. In view of the immense medicinal

    importance of the plant, this review is an effort to compile all the information reported on its

    ethanobotanical, phytochemical and pharmacological activities. The present work attempts to

    generate interest among the masses regarding its potential in preventing and treating several

    common diseases. Many pharmacological studies have demonstrated the ability of this plant to

    exhibit antioxidant, hepatoprotection, anti-allergy, antimicrobial, antigenotoxic, antiplasmodial,

    cytotoxic, antispasmodic, cardioactive, anticough, antidiabetic, antiinflamatory and antinociceptive

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    activities, supporting its traditional uses. Suggesting a wide range of clinical applications for the

    treatment of infantile rotaviral enteritis, diarrhoea and diabetes.

    Key words: ethanobotany, myrtaceae, pharmacology, physicochemical, phytochemical, Psidium

    guajava

    Introduction

    Psidium guajava L. known as Guava is a medicinal plant belonging to the family Myrtaceae.

    P. guajava is a well known traditional medicinal plant used in various indigenous systems of

    medicine. It is widely distributed throughout India (Mital and Sumitra, 2011). The leaves and bark

    ofP. guajava tree have long history of medicinal uses, that is still employed today (Nulinyi et al.,

    2008). It is a native of Central America but is now widely cultivated, distributed and the fruits

    enrich the diets of millions of people in the tropics of the world (Rathish and Sumitra, 2007; El-

    Mahmood, 2009). It is a genus of about 133 genera and more than 3,800 species of tropical shrubs

    and a small tree of about 10m high with spreading branches that thrives on all kinds of soils. It is

    one of the most gregarious fruit trees and is widely known by its common English name (guava).

    In Nigeria, it is called guava (Hausa), gurfa (Yoruba) and Gwaibwa (Igbo) (El-Mahmood, 2009).

    P. guajava also known as the poor mans apple of the tropics has a long history of traditional use,

    and a good proportion of which have been validated by scientific research (Burkil, 1994). The

    ethno-medicinal uses include the crushing of the leaves and the application of the extract on

    wounds, boils, skin and soft tissue infectious sites (Bala, 2006). Extracts of roots, bark and leaves

    are also used to treat gastro-enteritis, vomiting, toothaches, coughs, sore throat, oral ulcers,

    inflamed gums, leucorrhea, stomach ache, epilepsy, convulsions and upper respiratory tract

    infections (Lozoya et al., 2002).

    Nutritional value of guavas are often included among superfruits, being rich in dietary fiber,vitamins A and C, folic acid; and the dietary minerals, potassium, copper and manganese. Having a

    generally broad, low calorie profile of essential nutrients, a single common guava fruit contains

    about four times the amount of vitamin C as an orange (Hassimotto et al., 2005). The food value

    and contents of guava fruit is listed in the Table 1. However, nutrient content varies across guava

    cultivars. Although the strawberry guava (P. littoralevar, cattleianum), notably containing 90 mg

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    of vitamin C per serving, has about 25% of the amount found in more common varieties, its total

    vitamin C content in one serving still provides 100% of the Dietary Reference Intake for adult

    males (Healthaliciousness, 2008). Guavas contain both carotenoids and polyphenols the major

    classes of antioxidant pigments giving them relatively high potential antioxidant value among

    plant foods (Jimenez et al., 2001). As these pigments produce the fruit skin and flesh color, guavas

    that are red-orange have more pigment content as polyphenol, carotenoid and pro-vitamin A,

    retinoid sources than yellow-green ones (Linda et al., 2004).

    Table 1: Nutrient value of guava fruit (Kamanth et al., 2008)

    Nutrients Content

    Moisture 2.8-5.5g

    Crude fiber 0.9-1.0gProtein 0.1-0.5mg

    Fat 0.43-0.7mg

    Ash 9.5-10mg

    Carbohydrate 9.1-17mg

    Calcium 17.8-30mg

    Phosphorous 0.30-0.70mg

    Iron 200-400 I.U.

    Carotene (Vitamin A) 0.046mg

    Thiamin 0.03-0.04mg

    Riboflavin 0.6-1.068mg

    Niacin 40 I.U.

    Vitamin 36-50mg

    TaxonomyKingdom : Plantae

    Order : Myrtales

    Family : Myrtaceae

    Subfamily : Myrtoideae

    Genus :Psidium

    Species : Guajava

    Binomial name :Psidium guajava Linn.

    http://www.scialert.net/asci/result.php?searchin=Keywords&cat=&ascicat=ALL&Submit=Search&keyword=Psidium+guajavahttp://www.scialert.net/asci/result.php?searchin=Keywords&cat=&ascicat=ALL&Submit=Search&keyword=Psidium+guajava
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    Distribution

    P. guajava has a long history of medicinal use in many tropical American and Southeast Asian

    populations (Deguchi et al., 2010); being considered native to Mexico (Rios et al., 1977), it is

    widespread throughout South America, Europe, Africa and Asia although reported in indigenous

    systems of medicine in the Americas more than elsewhere. Based on archaeological evidence, this

    plant has been known and used widely in Peru since pre-Columbian times. It grows in all tropical

    and subtropical areas and adapts to different climatic conditions, although dry climates are

    preferred (Stone, 1970).Guava is native to tropical America, probably from southern Mexico south

    to South America, but its range has been dramatically increased via cultivation. It is now cultivated

    in southern Florida, Bermuda, and throughout the West Indies from the Bahamas and Cuba to

    Trinidad, and south to Brazil. It is also cultivated and naturalized in much of the Old World tropicsand subtropics. (Little and Wadsworth, 1964) It was first recorded from the Pacific Islands

    (Hawaii) by the early 1800s (Whistler, 1995).

    Habitat

    In the Pacific Islands, Guava is common in dry to wet disturbed areas such as pastures, waste

    places, and scrub forest up to 1200 meters elevation (Whistler, 1995). In Puerto Rico, it forms

    thickets and spreads in pastures, especially on the coastal plains but also in the lower mountain

    regions (Little and Wadsworth, 1964). In southern Florida, it grows wild along roadsides, in old

    fields, and in hardwood hammocks (Elias, 1980).

    Ethanobotany

    P. guajava has a long history of traditional use, a good proportion of which have been validated by

    scientific research (Burkil, 1994). The ethno-medicinal uses include the crushing of the leaves and

    the application of the extract on wounds, boils, skin and soft tissue infectious site (Bala, 2006).

    Extracts of roots, bark and leaves are also used to treat gastro-enteritis, vomiting, toothaches,

    coughs, sore throat, oral ulcers, inflamed gums, leucorrhea, stomach ache, epilepsy, convulsions

    and upper respiratory tract infections (Lozoya et al., 2002). Stem, bark and root-bark are astringent.

    Unripe fruit is indigestible, causes vomiting and feverish. Bark is astringent, febrifuge, antiseptic. Fruit

    is laxative, leaves are astringent (Nadkarni and Nadkarni 1991). Locally, decoction of the leaves is with

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    much benefit to the prolapsus ani of children (Nadkarni and Nadkarni, 1991); ache upsets and for

    vertigo. Extracts from leaves, bark, roots and buds have been used in folk medicine (Little and

    Wadsworth, 1964). Guava leaves are often boiled into a tea to treat diarrhea on many of the Pacific

    Islands (Whistler, 1995). The leaves and bark ofP. Guajava tree have a long history of medicinal

    uses that has still employed today (Nulinyi et al., 2008). It is a native of Central America but is

    now widely cultivated, distributed and the fruits enrich the diets of millions of people in the tropics

    of the world (Rathish and Sumitra, 2007; El-Mahmood, 2009). P. Guajava is very rich in

    antioxidants and vitamins and also high in luctin zeaxanthine and lycopene (Tee et al., 1997;

    Hobert and Tietze, 1998). P. guajava leaf has a long history of folk medicinal uses in Egypt and

    worldwide as a cough sedative, an anti-diarrheic, in the management of hypertension, obesity and

    in the control of diabetes mellitus (Tanaka et al., 1992; Lozoya et al., 1994; Ishihara et al., 1997;

    Karawya et al., 1999; Abdelrahim et al., 2002; Begum et al., 2004; Sunagawa et al., 2004). P.

    guajava leaf is a phytotherapic used in folk medicine to treat gastrointestinal and respiratory

    disturbances and is used as anti-inflammatory medicine. In some cultures, a decoction of the leaves

    is drunk for regulation of menstrual periods, expulsion of the placenta after child birth, tightening

    of vaginal walls after childbirth as well as a douche for vaginal discharges (Burkil, 1994; Lozoya

    et al., 2002). Its anti-amoebic and antimalarial effects have also been documented (Morton, 1987;

    Tona et al., 1998). Guava fruit paste and cheese are popular dishes in Florida, the West Indies and

    parts of South America (Datta, 1988). The plant Psidium guajava Linn. has an ethanomedical

    history as it has various activities especially functionally against the hyperglycemia. It is believed

    that the study of such medicinal plants might offer a natural key to unlock a Diabetologist

    pharmacy in future (Kamala et al., 1999).

    Since the 1950s, guava leaves have been the subject for diverse research on their constituents,

    pharmacological properties and history in folk medicine (Gutierrez, 2008). Most research,

    however, has been conducted on apple guava (P. guajava), with other species remaining unstudied.

    From preliminary medical research in laboratory models, extractsfrom apple guava leaves or bark

    are implicated in therapeutic mechanisms against cancer, bacterial infections, inflammation and

    pain (Ojewole 2006; Chen et al., 2007; Mahfuzul et al., 2007). Guava leaves are used in folk

    medicine as a remedy fordiarrhea(Kaljee et al., 2004) and bark for their supposed antimicrobial

    http://en.wikipedia.org/wiki/Leaveshttp://en.wikipedia.org/wiki/Pharmacologicalhttp://en.wikipedia.org/wiki/Folk_medicinehttp://en.wikipedia.org/wiki/Psidium_guajavahttp://en.wikipedia.org/wiki/Extracthttp://en.wikipedia.org/wiki/Extracthttp://en.wikipedia.org/wiki/Cancerhttp://en.wikipedia.org/wiki/Bacteriahttp://en.wikipedia.org/wiki/Inflammationhttp://en.wikipedia.org/wiki/Inflammationhttp://en.wikipedia.org/wiki/Painhttp://en.wikipedia.org/wiki/Folk_medicinehttp://en.wikipedia.org/wiki/Folk_medicinehttp://en.wikipedia.org/wiki/Diarrheahttp://en.wikipedia.org/wiki/Antimicrobialhttp://en.wikipedia.org/wiki/Leaveshttp://en.wikipedia.org/wiki/Pharmacologicalhttp://en.wikipedia.org/wiki/Folk_medicinehttp://en.wikipedia.org/wiki/Psidium_guajavahttp://en.wikipedia.org/wiki/Extracthttp://en.wikipedia.org/wiki/Cancerhttp://en.wikipedia.org/wiki/Bacteriahttp://en.wikipedia.org/wiki/Inflammationhttp://en.wikipedia.org/wiki/Painhttp://en.wikipedia.org/wiki/Folk_medicinehttp://en.wikipedia.org/wiki/Folk_medicinehttp://en.wikipedia.org/wiki/Diarrheahttp://en.wikipedia.org/wiki/Antimicrobial
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    properties and as an astringent. In Trinidad, it is the southernmost island in the Caribbean a tea

    made from young leaves is used for diarrhea, dysentery and fever (Mendes, 1986).

    Table 2: Showing worldwide ethanomedical uses of Guava (Kamanth et al., 2008)

    Amazonia for diarrhea, dysentery, menstrual disorders, stomachache, vertigo

    Brazil for anorexia, cholera, diarrhea, digestive problems, dysentery, gastric

    insufficiency, inflamed mucous membranes, laryngitis, mouth(swelling), skin

    problems, sore throat, ulcers, vaginal discharge

    Cuba for colds, dysentery, dyspepsia

    Ghana coughs, diarrhea, dysentery, toothache

    Haiti for dysentery, diarrhea, epilepsy, itch, piles, scabies, skin sores, sore throat,

    stomachache, wounds and as an antiseptic and astringent

    India for anorexia, cerebral ailments, childbirth, chorea, convulsions, epilepsy,

    nephritis

    Malaya for dermatosis, diarrhea, epilepsy, hysteria, menstrual disorders

    Mexico for deafness, diarrhea, itch, scabies, stomachache, swelling, ulcer, worms,

    wounds

    Peru for conjunctivitis, cough, diarrhea, digestive problems, dysentery, edema, gout,hemorrhages, gastroenteritis, gastritis, lung problems, PMS, shock, vaginal

    discharge, vertigo, vomiting, worms

    Philippines for sores, wounds and as an astringent

    Trinidad bacterial infections, blood cleansing, diarrhea, dysentery

    Elsewhere for anorexia, aches, bacterial infections, boils, bowel disorders, bronchitis,

    catarrh, cholera, chorea, colds, colic, convulsions, coughs, diarrhea, dysentery,dyspepsia, edema, epilepsy, fever, gingivitis, hemorrhoids, itch, jaundice,

    menstrual problems, nausea, nephritis, respiratory problems, rheumatism,

    scabies, sore throat, spasms, sprains, stomach problems, swelling, tonic,toothache, ulcers, worms, wounds and as an antiseptic and astringent

    The infusion made from its leaves is indicated as an analgesic, antispasmodic, digestive, diuretic,

    antiseptic, astringent, emollient and healing agent, as well as for hemorrhoid treatment (Silva et al.,

    1995). It is one of such plants in folk medicine that has been used for the management of various

    disease conditions and is believed to be active. Various parts of the plant has been used in

    traditional medicine to manage conditions like malaria, gastroenteritis, vomiting, diarrhoea,

    http://en.wikipedia.org/wiki/Astringenthttp://en.wikipedia.org/wiki/Trinidadhttp://en.wikipedia.org/wiki/Caribbeanhttp://en.wikipedia.org/wiki/Dysenteryhttp://en.wikipedia.org/wiki/Astringenthttp://en.wikipedia.org/wiki/Trinidadhttp://en.wikipedia.org/wiki/Caribbeanhttp://en.wikipedia.org/wiki/Dysentery
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    dysentery, wounds, ulcers, toothache, coughs, sore throat, inflamed gums and a number of other

    conditions (Jaiarj et al., 1999; Abdelrahim et al., 2002; Lutterodt, 1989). It has a long history of

    folk medicinal uses in Egypt and worldwide as a cough sedative, an anti-diarrheic, in the

    management of hypertension, obesity and in the control of diabetes mellitus (Tanaka et al., 1992;

    Morales et al., 1994; Karawya et al., 1999; Abdelrahim et al., 2002; Begum et al., 2004;

    Sunagawa et al., 2004). More recent ethno pharmacological studies showed thatP. guajava is used

    in many parts of the world for the treatment of a number of diseases such as anti-inflammatory, for

    diabetes, hypertension, carries wounds, analgesic and antipyretic effects (Gutierrez et al., 2008).

    The parts of the plant mostly used are the leaves, fruits, bark and the roots. However, the plant as a

    whole is sometimes used for various medicinal purposes (Geidam et al., 2007).

    Leaves: The decoction or infusion of the leaves is used as febrifuge, antispasmodic and forrheumatism in India (Hernandez, 1971). It is also used to treat diarrhea and stomach ache in

    Columbia, Mexico, Maya, Nahuatl, Zapotec, USA and Mozambique. The leaves are used in USA

    as an antibiotic in the form of poultice or decoction for wounds, ulcers and tooth ache (Heinrich,

    1998; Leonti et al., 2001). In South Africa and Caribbean, extract of the leaves is used in

    management of diabetes and hypertension. Latin America, Central and West Africa and South East

    Asia use decoction of the leaves as gargle for sore throats, swelling of the mouth, laryngitis,

    external ulcers on the skin and vaginal irritations (Ojewole, 2005; Rouseffet al., 2008; Yang et al.,

    2007; Idstein and Schreier, 1985; Nagar and Rao, 1981). The leaves are used for bacterial

    infections, diarrhea, blood cleansing and dysentery in Trinidad while in New Guinea, Samoa,

    Tonga, Niue, Futuna and Tahiti are used in the form of boiled preparation for itchy rashes caused

    by scabies. It is also used as an astringent and in lung problems (Yang et al., 2007).P. guajava

    leaves are applied externally on inflammations in Panama, Cuba, Costa Rica, Mexico, Nicaragua,

    Venezuela Mozambique, Guatemala and Argentina. In Uruguay, a decoction of the leaves is used

    as a douche in vagina and uterus especially in leucorrhoea (Conway, 2001;Geidam et al., 2007;

    Gutierrez et al., 2008). In Nigeria, South Africa, Ghana and Kenya the leaves are used in treatment

    of conditions such as malaria, gastroenteritis, vomiting, diarrhoea, dysentery wounds, ulcers,

    toothache, coughs, sore throat, inflamed gums and a number of other conditions (Jaiarj et al., 1999;

    Abdelrahim et al., 2002; Lutterodt, 1989). Bronchitis, asthma attacks, cough, pulmonary diseases

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    could be also treated with guava teas (Batick, 1984; Khan and Ahmad, 1985) and could also be

    useful as anti-inflammatory and hemostatic agent (Liu, 1988).

    Bark and root: The bark in the form of decoction and poultice is used as an astringent in the

    treatment of ulcers wounds and diarrhea in Philippines while in Panama, Bolivia and Venezuela,

    the bark is used in treatment of dysentery and skin ailments (Conway, 2001). In Kinshasa and

    Congo the bark is used as antiamoebic as an infusion or decoction (Geidam et al., 2007). In the

    form of decoction and poultice, it is used to expel the placenta after childbirth and in infections of

    the skin, vaginal hemorrhage wounds, fever, dehydration and respiratory disturbances (Gutierrez et

    al., 2008). The root is used in West Africa as a decoction to relieve diarrhea, coughs, stomachache,

    dysentery, toothaches, indigestion and constipation; while in Philippines, Fiji and South Africa, the

    roots are used in the form of decoction and poultice as an astringent in ulcers wounds and intreatment of diarrhea (Gutierrez et al., 2008).

    Whole plant: In general, the whole plant or it shoots are used in the form of infusion, decoction

    and paste as skin tonic in Tahiti and Samoa and as analgesia in painful menstruation, miscarriages,

    uterine bleeding, premature labor and wounds (Gutierrez et al., 2008).

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    Fig 1:Whole plant ofPsidium guajava L. (A) along with leaves (B); fruit (C) and flower(D)

    Pharmacognosy

    Macroscopy

    P. guajava is a large dicotyledonous shrub, or small evergreen tree, generally 3-10 m high with

    many branches (Luckyet al., 2010). Guava is a large tropical evergreen shrub or small shade tree

    of 6 to 25 feet high (Baby Joseph, 2011). The stems are crooked and the bark is light to reddish

    brown, thin, smooth and continuously flaking. Root system is generally superficial and very

    extensive, frequently extending well beyond the canopy. Each has some deep roots but no distinct

    taproot (Gutierrez et al., 2008). The leaves are opposite and simple; stipules are absent, petiole

    short, 3-10 mm long; blade oblong to elliptic, 5-15 x 4-6 cm, apex obtuse to bluntly acuminate,

    base rounded to subcuneate, margins entire, somewhat thick and leathery, dull grey to yellow-

    green above, slightly downy below, veins prominent, gland dotted (Lucky et al., 2010). The

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    flowers are white, incurved petals, 2 or 3 in the leaf axils; they are fragrant, with four to six petals

    and yellow anthers. The fruit is small, 3 to 6 cm long, pear-shaped, reddish-yellow when ripe

    (Little and Wadsworth, 1964; Whistler, 1995; Baby Joseph, 2011). It is native to and widely

    distributed in Mexico and Central America. Generally, guava plant has spread widely throughout

    the tropics because it thrives in a variety of soils, propagates easily and bears fruit relatively

    quickly. The guava berry is an important tropical fruit that is mostly consumed fresh. The fruit

    contains several small seeds and consists of a fleshy pericarp and seed cavity with pulp (Jimenez-

    Escrig et al., 2001; Lozoya et al., 2002; Lapiket al., 2005).

    Microscopy

    The microscopy reveals the presence of abundant unicellular trichome, paracytic stomata, xylem

    vessels, calcium crystals and few crystal sheath (Laddha, 1992; Kokate, 1994, Rahul et al., 2011).

    A comparative study to understand the differences in pharmacognostical parameters of young and

    mature leaves forms the basis of study (Laddha, 1992). The average stomatal index on upper

    epidermis is more than on lower epidermis for mature leaf and found opposite in case of young leaf

    (Kokate, 1994). It is obvious from the mature leaves contain more vein islet and vein termination

    number than young one; in fact, young leaves contain more moisture, moreover, water and alcohol

    soluble compounds are present nearly in same amount in both young and mature leaves. The TS of

    midribs show gutter shaped xylem and phloem and beneath the phloem pericycle present, which

    contain collenchymatous cells (Rahul et al., 2011, Sunita et al., 2011).

    Physico-chemical and phytochemical studies

    The proximate analysis of powdered sample ofP. guajava leaves showed low moisture content of

    1.0% and low ash value of 2.80%. The ash value indicates the quantity of inorganic components of

    the plant; hence a low value indicates that the powdered leaves ofP. guajava contain more of

    organic components. There is also low quantity of protein and fat but an abundance of

    carbohydrate which makes it a source of energy. The metal analysis of powdered sample ofP.

    guajava showed the presence of all the metals screened for which include; magnesium,

    manganese, zinc, calcium, iron, sodium and potassium. The quantity of these metals revealed that

    they were well below tolerable upper intake level and within the recommended daily intake in

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    healthy individuals established by the Dietary Reference Intakes (Pearson, 1976; Lucky et al.,

    2010).

    The Phytochemical screening revealed that the leaf extract contains an appreciable amount of

    flavonoids and tannins. The leaf extract also contains resins, glycosides, alkaloids and saponins

    (Odebiyi and Sofawora, 1978). Phytochemical screening done by Buvaneswari et al., (2011)

    showed that it contains alkaloids, flavanoids, phenols and tannin. The plant extracts were also

    screened for the presence of bio-active components in the leaves and roots (Evans, 1989;

    Sofowora, 1993; Akinjogunla et al., 2009). The results of phytochemical analysis showed that the

    crude hydro-ethanolic leaf extract of Psidium guajava have different classes of bioactive

    constituents such as saponins, alkaloids, tannins, cardiac-glycosides, terpenes, flavonoids and

    sterols. The results showed that saponins, tannins and alkaloids are present in high concentrations,

    followed by terpenes, flavonoids and sterols while small concentration of cardiac-glycosides

    (Akinjogunla et al., 2011).

    Phytochemistry

    Guava contains broad spectrum of phytochemicals including polysaccharides, vitamins, essential

    oils (Smith and Siwatibau, 1975; Macleod and Troconis, 1975), minerals, enzymes, proteins (Deo

    and Shastri, 2003), sesquiterpenoid alcohols and triterpenoid acids (Smith et al., 1975; Wilson and

    Shaw, 1978; Begum et al., 2002), alkaloids, glycosides, steroids, flavanoids, tannins, saponins

    (Cho etal., 2003; Narayana et al., 2001; Geidam et al., 2007). Guava is very rich in antioxidants

    and vitamins and also high in lutein, zeaxanthine and lycopene (Tee et al., 1997; Hobert and

    Tietze, 1998). The guava leaves contain several chemical constituents such as -pinene, -pinene,

    limonene, menthol, terpenyl acetate, isopropyl alcohol, longicyclene, caryophyllene, -bisabolene,

    caryophyllene oxide, -copanene, farnesene, humulene, selinene, cardinene and curcumene, mallic

    acids, nerolidiol, -sitosterol, ursolic, crategolic, and guayavolic acids, cineol, quercetin, 3-L-4-4-

    arabinofuranoside (avicularin) and its 3-L-4-pyranoside (essential oil), resin, tannin, eugenol,

    caryophyllene (1a -, 4a -, 7 -, 7a -, 7b - )]-decahydro-1H-cycloprop[e] azulene, Guajavolide

    (2 -,3 -,6 -,23-tetrahydroxyurs-12-en-28,20 -olide; 1) and guavenoic acid (2 -,3 -,6 -,23-

    tetrahydroxyurs- 12,20(30)-dien-28-oic acid, triterpene oleanolic acid, triterpenoids, flavinone-2

    2-ene, prenol, dihydrobenzophenanthridine and cryptonine (Zakaria et al., 1994, Iwu 1993,

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    Nadkarni and Nadkarni, 1999; Oliver- Bever, 1986; Begum et al., 2002; Wyket al., 1997, Joseph

    et al., 2010). Guavas contain both carotenoids and polyphenols, the major classes of antioxidant

    pigments giving them relatively high potential antioxidant value among plant foods (Jimenez-

    Escrig et al., 2001). As these pigments produce the fruit skin and flesh color, guavas that are red-

    orange have more pigment content as polyphenol, carotenoid and pro-vitamin A, retinoid sources

    than yellow-green ones (Linda et al., 2004).

    Guavas contain bothcarotenoids andpolyphenols like (+)-gallocatechin(Tomoaki Matsuoet et al.,

    1994), guaijaverin, leucocyanidin and amritoside (Seshadri et al.,1965) the major classes of

    antioxidantpigments (Jimnez-Escrig et al., 2001; Hassimotto et al., 2005; Mahattanatawee et al.,

    2006). It was reported that the leaves ofP. guajava contain an essential oil rich in cineol, tannins

    and triterpenes. In addition three flavonoids (quercetin, avicularin, and guaijaverin) have been

    isolated from the leaves (Khadem and Mohammed, 1959). The leaves of guava are rich in

    flavonoids, particularly quercetin. The bark of guava tree contains considerable amounts of tannins

    (11-27%), and hence is used for tanning and dyeing purposes. Leucocyanidin, luectic acid, ellagic

    acid and amritoside have been isolated from the stem bark. Five constituents, including one new

    pentacyclic triterpenoid: guajanoic acid and four known compounds beta-sitosterol, uvaol,

    oleanolic acid and ursolic acid, have been recently isolated from the leaves ofP. guajava by

    Begum et al. (2004). The essential oil contains alpha pinene, caryophyllene, cineol, D-limonene,eugenol, and myrcene. The major constituents of the volatile acids include (E)-cinnamic acid and

    (Z)-3-hexenoic acid (Latza et al., 1996; Conde et al., 2003). The guava fruit has high water content

    with lesser amounts of carbohydrates, proteins and fats. The fruit also contains iron, vitamins A

    and C, thiamine, riboflavin, niacin and manganese. The characteristic fruit odor is attributed to

    carbonyl compounds. Unripe fruits are high in tannins. The major constituent of the fruit skin is

    ascorbic acid, largely destroyed by canning and processing (Gutierrez et al., 2008).

    Active factors ofP. guajava fruits involve ursolic acid, oleanolic acid, arjunolic acid and

    glucuronic acid (Chang, 1982). Saponin combined with oleandolic acid: morin-3-O--L-

    lyxopyranoside and morin-3-O--Larabinopyranoside; pentane-2-thiol; and flavonoids: guaijavarin

    and quercetin (Hermandez, 1971; Bassols and Demole, 1984; Nadkarni and Nadkarni, 1999;

    Pniandy et al., 2000; Dweck, 2001; Hwang, 2002; Jordan et al., 2003; Dweck, 2003; Matsuzaki,

    http://en.wikipedia.org/wiki/Carotenoidhttp://en.wikipedia.org/wiki/Carotenoidhttp://en.wikipedia.org/wiki/Polyphenolhttp://en.wikipedia.org/wiki/(%2B)-gallocatechinhttp://en.wikipedia.org/w/index.php?title=Guaijaverin&action=edit&redlink=1http://en.wikipedia.org/wiki/Leucocyanidinhttp://en.wikipedia.org/w/index.php?title=Amritoside&action=edit&redlink=1http://en.wikipedia.org/wiki/Antioxidanthttp://en.wikipedia.org/wiki/Pigmenthttp://en.wikipedia.org/wiki/Carotenoidhttp://en.wikipedia.org/wiki/Polyphenolhttp://en.wikipedia.org/wiki/(%2B)-gallocatechinhttp://en.wikipedia.org/w/index.php?title=Guaijaverin&action=edit&redlink=1http://en.wikipedia.org/wiki/Leucocyanidinhttp://en.wikipedia.org/w/index.php?title=Amritoside&action=edit&redlink=1http://en.wikipedia.org/wiki/Antioxidanthttp://en.wikipedia.org/wiki/Pigment
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    2010). In comparison, huge amounts of -sitosterol glucoside, brahmic acid, and polyphenolics

    including gallic acid, ferulic acid, and quercetin (Lee, 1986, Peng and Hsieh, 2006); and flavonoids

    (Fujita et al., 1985; Iwu, 1993; Conway, 2002; Medina and Pagano, 2003; Hsieh et al., 2005; Peng

    and Hsieh, 2006), and triterpenoids (Hsieh et al., 2005), exist in guava leaves (Lee, 1986; Hsieh,

    2005; Peng and Hsieh, 2006). Thus, it is clear that P. guajava contains many components reported

    to display efficacy against various diseases.

    Pharmacology

    Pharmacology of extracts:

    Psidium guajava leaves have long been recognized for their antimicrobial activity. They have

    shown to be inhibit gram positive and gram negative bacterial cultures (Buvaneswari et al., 2011).

    The aqueous extract ofPsidium guajava leaves exhibited good antibacterial activity against

    various test cultures. Report says that flavanoids extracted from guava leaves believed to be

    responsible for antibacterial activity (Buvaneswari et al., 2011). The microbicidal activity ofP.

    guajava is also attributable to guajaverine and to psydiolic acid (Berdy et al., 1981). Quercetin has

    several pharmacologic actions; it inhibits the intestinal movement, reduces capillary permeability

    in the abdominal cavity (Zhang et al., 2003) and possesses dose-dependent antioxidant properties

    (Nakamura et al., 2000), anti-inflammatory activity (Havsteen, 1983; Middleton and Drzewieki,

    1984; 1985; Yoshimoto et al., 1983; Pearce et al.,1984; Busse et al., 1984; Amella et al., 1985)antiviral and antitumor activities (Farkas et al., 1982; Guttneret al., 1982; Mucsi and Pragai, 1985;

    Kaul et al., 1985; Murray and Pizzorno, 1999;Kaneuchi et al., 2003). The leaf extract was found

    to possess anticestodal (Tangpu et al., 2006), analgesic, anti-inflammatory properties (Ojewole et

    al., 2006), antimicrobial (Nair et al., 2007), hepatoprotective (Ret et al., 2006) and antioxidant

    activities (Hui-YinChin et al., 2007). In addition, the leaf extract is used in many pharmaceutical

    preparations as a cough sedative (Metwally, 2010). It has demonstrated antibacterial and anti-

    diarrheal effects and is able to relax the intestinal smooth muscle and inhibit bowel contractions.

    Guava has antioxidant properties attributed to polyphenols found in its leaves. The presence of the

    metabolites such as cardiac glycosides, saponins, tannins, alkaloids in P. guajava may be

    responsible for its potential use as a drug against pathogenic bacteria (Sofowora, 1986;

    Akinjogunla et al., 2010). According to Ebana et al. (1991) and Cushnie and Lamb, (2005)

    presence of alkaloids and flavonoids in guava are responsible for antimicrobial activities.

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    Alkaloids, flavonoids are phenolics structure containing one carbonyl group complexes with extra

    cellular and soluble protein and with bacterial cell wall (Cowan, 1999), thus exhibits antibacterial

    activity through these complexes.

    In the pharmacological action guava leaf extracts have also been indicated to inhibit disturbances

    of the central nervous system: insomnia, convulsions and epilepsy (Lutterodt and Maleque, 1988;

    Meckes et al., 1996). In addition, anti-rotavirus activity has also been reported to exist in these

    extracts (Goncalves et al., 2005). Bark and leaf extracts were shown to have in vitro toxic action

    against numerous bacteria. Water and chloroform extracts of guava were effective in activating the

    mutagenecity ofSalmonella typhimurium (Groveret al., 1993). It was shown that P.guajava leaf

    extracts might be beneficial in treating acne especially those that have anti-inflammatory activities

    (Qadan et al., 2005). In several studies, guava showed significant antibacterial activity against

    common diarrhea causing bacteria such as Staphylococcus, Shigella, Salmonella,Bacillus,E. coli,

    Clostridium and Pseudomonas, which was concluded that guava has good curative effect on

    infantile rotaviral enteritis (Wei et al., 2000). In a study carried out with leaf extract of the plant,

    inhibition of gastrointestinal release of acetylcholine by quercetin present in extract was suggested

    as a possible mode of action in the treatment of acute diarrheal disease (Lutterodt, 1989; 1992; Lin

    et al, 2002). Guava fruit and leaf showed antioxidant and free radical scavenging capacity (Hui-

    Yin Chen et al., 2007). Its leaf extract possess anticough activity by reducing the frequency of

    cough induced by capsaicin aerosol (Jaiarj et al., 1999). Leaf extract of guava had inotropic effect

    on guinea pig atrium (Conde Garcia et al., 2003). Another study investigated that the

    hypoglycemic and hypotensive effects of P. guajava leaf aqueous extract in rats showed

    hypoglycemic activity. The hypoglycemic effect of plant extract was examined in normal and

    diabetic rats, using streptozotocin (STZ) induced diabetes mellitus model (Ojewole, 2005). In the

    study, i.p. treatment with 1 g/kg guava juice produced a markable hypoglycemic action in normal

    and alloxan-treated diabetic mice (Cheng et al., 1983).

    The anti-stress and adaptogenic activity exhibited by ethanol extract ofP. guajava possess anti-

    stress property. It may be useful in the treatment of several disorders caused by stress by its

    immunostimulating, immunomodulating properties and also by enhancing the homeostatic

    mechanisms (Lakshmi and Sudhakar, 2009). Aqueous extract ofP. guajava budding leaves has

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    been shown to possess anti-prostate cancer activity in a cell line model. Guava leaf essential oil has

    been shown to possess cytotoxic effect on human cervical cancer cell lines (Chen et al., 2010;

    Joseph et al., 2010).

    The leaf extract has an excellent capacity to form coloured complex with iron (Thepanon et al.,

    2005). Iron chelation therapy has been shown to be anti-parasitic especially in African

    trypanosomiasis (Ekanem, 1989). Furthermore, decreasing of free-radicals has antioxidizing effect

    in the body, meaning that polyphenols can prevent arterial sclerosis, thrombosis, cataract and

    inhibit senescence of the body and skin (Okuda et al., 1982). In other animal studies, guava leaf

    extracts have shown central nervous system (CNS) depressant activity (Shaheen, 2000). It can also

    be used as antihypertensive and antidiarrhoeal agents in traditional medicine, by inhibiting

    intracellular calcium release (Belemtougri, 2005). P. guajava is reputed for its medicinal use in

    hyperactive gut disorders. In castor oil-induced diarrheal model, the crude extract ofP. guajava

    provided significant protection. In isolated rabbit jejunum preparations, crude extract was found

    more potent against high K+ than spontaneous pre-contractions, similar to verapamil, suggests

    calcium channel blocking activity, as a possible mode of action. These data indicate that crude

    extract of P. guajava possesses Ca++ antagonist-like constituent(s), which explain its inhibitory

    effect on gut motility (Abdul Jabbar Shah, 2011). In a recent study with guinea pigs Brazilian

    researchers reported that guava leaf extracts have numerous effects on the cardiovascular system

    which might be beneficial in treating irregular beat (arrhythmia). Previous research indicated guava

    leaf provided antioxidant effects beneficial to the heart, heart protective properties, and improved

    myocardial function. Guava leaf extracts decreased spasms associated with induced diarrhea in

    rodents. Reduced defecation, severity of diarrhea and intestinal fluid secretion reductions have also

    been demonstrated (Lutterodt, 1992; Morales et al., 1994; Olajide et al., 1999; Lozoya et al., 2002;

    Zhang et al., 2003; Gutierrez et al., 2008; Ojewole et al., 2008). Activity is generally associated

    with the ability of quercetin and its derivatives to affect smooth muscle fibers via calcium

    antagonism, inhibit intestinal movement and reduce capillary permeability in the abdominal cavity

    (Lozoya et al., 2002; Zhang et al., 2003).

    TheP. guajava L. infusion at the higher concentration caused a statistically significant inhibition

    of cellular division in the onion root-tip cells. No statistically significant alterations were found, as

    compared to untreated controls, in either the cell cycle or the number of chromosome alterations,

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    after treatments with either plant, in rat cells or in cultured human lymphocytes. These results

    regarding the cytotoxicity and mutagenicity of these plants provide valuable information about the

    safety of using them as therapeutic agents (Rosangela et al., 2003). During various episodes of

    screening of medicinal plants, extract fromP. guajava leaves exhibited significant inhibitory effect

    on the protein tyrosine phosphatase1B (PTP1B). Significant blood glucose lowering effects of the

    extract were observed after intraperitoneal injection of the extract at a dose of 10 mg/kg in both 1

    and 3 month old mice (Oh et al., 2005).

    In a study including 17 Thai medicinal plants on anti-proliferative effects on human mouth

    epidermal carcinoma and murine leukemia cells using MIT assay, guava leaf showed anti-

    proliferative activity, which was 4.37 times more than vincristine (Manosroi et al., 2006).

    Pharmacology of pure compounds:

    Gallocatechin isolated from the methanol extract of guava leaf showed antimutagenic activity

    against E. coli (Matsuo et al., 1996). The active flavonoid compound quercetin-3-Oalpha-l-

    arabinopyranoside (guaijaverin) extracted from leaves has high potential antiplaque activity by

    inhibiting the growth ofStreptococcus mutans (Limsong et al., 2004). Joseph et al, (2010) reported

    guava leaf essential oil contains more terpenoids and that can strongly inhibit human cervical

    cancer cells. Lectin chemicals inguava were shown to bind to E. coli, preventing itsadhesion to

    the intestinal wall and thuspreventing infection and resulting diarrhea (Rodriguez et al., 2001).

    The effective use of guava in diarrhea, dysentery and gastroenteritis can also be related to guava's

    documented antibacterial properties (Lozoya et al., 1990; 1994; Tona et al., 2000).

    Clinical trials:

    In two randomized human studies, the consumption of guava fruit for 12 weeks was shown to

    reduce blood pressure by an average 8%, decrease total cholesterol level by 9%, decrease

    triglycerides by almost 8% and increase HDL cholesterol by 8%. The effects were attributed to the

    high potassium and soluble fiber content of the fruit. A randomized, single-blind, controlled trial

    was conducted to examine the effects of guava fruit intake on blood pressure and blood lipids in

    patients with essential hypertension. It is possible that an increased consumption of guava fruit can

    cause a substantial reduction in blood pressure and blood lipids without decreasing HDL-

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    cholesterol level (Singh et al., 1992; 1993). A double-blind clinical study of the effects of a

    Phytodrug (QG- 5) developed from guava leaf showed a decrease in duration of abdominal pain,

    which is attributed to antispasmodic effect of quercetin present in leaf extract (Xavier Lozoya et

    al., 2002). The fruit or fruit juice has been documented to lower blood sugar levels in normal and

    diabetic animals and humans. Most of these studies confirm the plant's many uses in tropical herbal

    medicine systems (Conde Garcia et al., 2003). Guava leaf extracts and fruit juice has also been

    clinically studied for infantile diarrhea. In a clinical study with 62 infants with infantile rotaviral

    enteritis, the recovery rate was 3 days in those treated with guava, and diarrhea ceased in a shorter

    period than controls. It was concluded in the study that guava has 'good curative effect on infantile

    rotaviral enteritis' (Wei et al., 2000). Its traditional use against diarrhea, gastroenteritis and other

    digestive complaints has been validated in numerous clinical studies.

    Conclusion

    Psidium guajava (Linn.) is popularly known as 'poor man's apple of the tropics', has a long

    history of traditional use for a wide range of ailments. The fruit as well as its juice is freely

    consumed for its great taste and nutritional benefits. Much of the traditional uses have been

    validated by scientific research. Toxicity studies in mice and other animal models as well as

    controlled human studies show both leaf and fruit are safe without any side effects. The plant has

    been extensively studied in terms of pharmacological activity of its major components, and the

    results indicate potent anti-diarrheal, antihypertensive, hepatoprotective, antioxidant, antimicrobial,

    hypoglycemic and anti-mutagenic activities. A number of chemicals isolated from plants like

    quercetin, guaijaverin, flavonoids and galactose-specific lecithins have shown promising activity in

    many human trials. In recent years, emphasis of research has been on utilizing traditional

    medicines that have a long and proven history of treating various ailments. Quite a significant

    amount of work has been done on the pharmacological and biological activity and possible

    application of chemical compounds from whole part of the plant. Hence extensive investigation onits pharmacodynamics, kinetics, and proper standardization and clinical trials is needed to exploit

    their therapeutic utility to combat various diseases.

    References

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    1.