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Journal of Ethnopharmacology 117 (2008) 1–27

Review

Psidium guajava: A review of its traditional uses,


phytochemistry and pharmacology
Rosa Martha Pérez Gutiérrez a,∗ , Sylvia Mitchell b , Rosario Vargas Solis c
a
Laboratorio de Investigación de Productos Naturales, Escuela Superior de Ingenierı́a Quı́mica e Industrias extractivas IPN,
Punto Fijo 16, Col. Torres Lindavista C.P. 07708 México, D.F., Mexico
b Medicinal Plant Research Group, Biotechnology Centre, 2 St. John’s Close, University of the West Indies, Kingston 7, Jamaica
c Laboratorio de Investigación de Fitofarmacologı́a, Universidad Autónoma Metropolitana-Xochimilco A.P. 23-181 México, D.F., Mexico

Received 18 August 2007; received in revised form 26 January 2008; accepted 29 January 2008
Available online 3 February 2008

Abstract
Psidium guajava, is an important food crop and medicinal plant in tropical and subtropical countries is widely used like food and in folk medicine
around of the world. This aims a comprehensive of the chemical constituents, pharmacological, and clinical uses. Different pharmacological
experiments in a number of in vitro and in vivo models have been carried out. Also have been identified the medicinally important phyto-constituents.
A number of metabolites in good yield and some have been shown to possess useful biological activities belonging mainly to phenolic, flavonoid,
carotenoid, terpenoid and triterpene. Extracts and metabolites of this plant, particularly those from leaves and fruits possess useful pharmacological
activities. A survey of the literature shows P. guajava is mainly known for its antispasmodic and antimicrobial properties in the treatment of
diarrhoea and dysentery. Has also been used extensively as a hypoglycaemic agent. 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 activities, supporting its traditional uses. Suggest a wide range of clinical applications
for the treatment of infantile rotaviral enteritis, diarrhoea and diabetes.
© 2008 Published by Elsevier Ireland Ltd.

Keywords: Psidium guajava; Myrtaceae; Clinical; Complementary medicine; Phytochemical constituents; Pharmacological actions

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
1.1. Use in traditional medicine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
2. Phytochemistry. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
2.1. Fruits . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
2.2. Fruit skins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
2.3. Leaves . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
3. Biological activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
3.1. Anti-diarrhoeal . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
3.2. Antimicrobial . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
3.3. Acne lesions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
3.4. Effect on dental plaque . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
3.5. Antimalarial effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
3.6. Antitussive effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
3.7. Hepatoprotective effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

∗ Corresponding author at: Punto Fijo No. 16, Col. Torres de Lindavista, C.P. 07708 Mexico, D.F., Mexico.
E-mail address: rmpg@prodigy.net.mx (R.M.P. Gutiérrez).

0378-8741/$ – see front matter © 2008 Published by Elsevier Ireland Ltd.


doi:10.1016/j.jep.2008.01.025
2 R.M.P. Gutiérrez et al. / Journal of Ethnopharmacology 117 (2008) 1–27

3.8. Antioxidant, free radical scavenger and radioprotective activities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7


3.9. Antigenotoxic and antimutagenic effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
3.10. Anti-allergic effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
3.11. Anticancer/antitumour effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
3.12. Cardiovascular, hypotensive effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
3.13. Anti-hyperglycemic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
3.14. Effect on muscular system . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
3.15. Anti-inflammatory/analgesic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
3.16. Antinociceptive effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
3.17. Wound healing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
4. Toxicology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
5. Clinical trials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
5.1. Infantile rotaviral enteritis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
5.2. Infectious gastroenteritis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
5.3. Cardiovascular effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
5.4. Dysmenorrhea . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
5.5. Hypoglycaemic effect . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
6. Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
7. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
Appendix A. Constituents of Psidium guayava . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24

1. Introduction of a number of diseases, e.g. as an anti-inflammatory, for dia-


betes, hypertension, caries, wounds, pain relief and reducing
Psidium guajava, which is considered a native to Mexico fever (Table 1). Some of the countries with a long history of tra-
(Rios et al., 1977) extends throughout the South America, ditional medicinal use of guava include Mexico and other Central
European, Africa and Asia. Based on archaeological evidence. American countries including the Caribbean, Africa and Asia.
It has been used widely and known in Peru since pre-Columbian Some of these uses will be outlined here.
times. It grows in all the tropical and subtropical areas of the Medicinal plants are an important element of the indigenous
world, adapts to different climatic conditions but prefers dry medical systems in Mexico (Lara and Marquez, 1996). These
climates (Stone, 1970). The main traditional use known is as resources are part of their traditional knowledge. The Popoluca
an anti-diarrhoeal. Other reported uses include gastroenteritis, Indians of Veracruz rely on medicinal plants for their health care.
dysentery, stomach, antibacterial colic pathogenic germs of the They appear to have developed a system whereby they select
intestine. and continue to use plants that they find the most effective for
Its medicinal usage has been reported in indigenous system health care purposes. The folk use of guava has been documented
of medicines in America more than elsewhere. Psidium guajava in the indigenous groups of Mexican Indians, Maya, Nahuatl,
Linn. (family Myrtaceae), is commonly called guave, goyave or Zapotec and Popoluca. A decoction of the leaves is used to cure
goyavier in French; guave, Guavenbaum, Guayave in German; cough. According to communities of Nahuatl and Maya origin
banjiro in Japanese; goiaba, goiabeiro in Portugal; araçá-goiaba, and Popoluca of the region of the Tuxtlas, Veracruz, they use a
araçá-guaçú, guaiaba in Brazil; guayaba, guayabo in Español guava leaf decoction to treat digestive suffering associated with
and guava in English (Killion, 2000). Psidium guajava is a small severe diarrhoea. This is a frequent disease in rainy weather
tree which is 10 m high with thin, smooth, patchy, peeling bark. (Heinrich et al., 1998).
Leaves are opposite, short-petiolate, the blade oval with promi- P guajava (Myrtaceae) is widely used in Mexico to treat
nent pinnate veins, 5–15 cm long. Flowers are somewhat showy, gastrointestinal and respiratory disturbances and is used as an
petals whitish up to 2 cm long, stamens numerous (Stone, 1970). anti-inflammatory medicine (Aguilar et al., 1994). Commonly
Fruit are fleshy yellow globose to ovoid berry about 5 cm in roots, bark, leaves and immature fruits, are used in the treatment
diameter with an edible pink mesocarp containing numerous of gastroenteritis, diarrhoea and dysentery. Leaves are applied
small hard white seeds. There has been a tremendous interest on wounds, ulcers and for rheumatic pain, while they are chewed
in this plant as evidenced by the voluminous work. Therefore, to relieve toothache (Heinrich et al., 1998). A decoction of the
we aimed to compile an up to date and comprehensive review new shoots is taken as a febrifuge. A combined decoction of
of Psidium guajava that covers its traditional and folk medicine leaves and bark is given to expel the placenta after childbirth
uses, phytochemistry and pharmacology. (Martı́nez and Barajas, 1991). A water leaf extract is used to
reduce blood glucose level in diabetics. This hot tea was very
1.1. Use in traditional medicine common among the local people of Veracruz (Aguilar et al.,
1994).
More recent ethnopharmacological studies show that Psid- The leaf of Psidium guajava is used traditionally in South
ium guajava is used in many parts of the world for the treatment African folk medicine to manage, control, and/or treat a plethora
R.M.P. Gutiérrez et al. / Journal of Ethnopharmacology 117 (2008) 1–27 3

Table 1
Ethnomedical uses of Psidium guajava
Place, country Part(s) used Ethno medical uses Preparation(s) Reference(s)

Colombia, Mexico Leaves Gastroenteritis, diarrhoea, dysentery, rheumatic Decoction and poultice Heinrich et al. (1998),
pain, wounds, ulcers, and toothache Aguilar et al. (1994)
Indigenous Maya, Leaves Cough, diarrhoea Decoction or infusion Heinrich et al. (1998), Leonti
Nahuatl, Zapotec and et al. (2001)
Popoluca of the region
Tuxtlas, Veracruz,
Mexico
Latin America, Leaves Diarrhoea, stomach ache Infusion or decoction Pontikis (1996)
Mozambique
Mexico Shoots, leaves, bark Febrifuge, expel the placenta after childbirth, Decoction, poultice Martı́nez and Barajas (1991),
and leaves mixed, rip cold, cough hypoglycaemic, affections of the Argueta et al. (1994), Linares
fruits skin, caries, vaginal haemorrhage, wounds, and Bye (1990), Leonti et al.
fever, dehydration, respiratory disturbances (2001), Heinrich et al. (1998)
Panama, Cuba, Costa Leaves Antiinflamatory Externally applied hot on Pardo (1999), Jansen and
Rica, México, inflammations Méndez (1990), Valdizán and
Nicaragua, Panamá, Maldonado (1972)
Perú, Venezuela,
Mozambique,
Guatemala, Argentina
South Africa Leaves Diabetes mellitus, hypertension Infusion or decoction Oh et al. (2005), Ojewole
(2005)
Caribbean Leaves Diabetes mellitus Infusion or decoction Mejı́a and Rengifo (2000)
China Leaves Diarrhoea, antiseptic, Diabetes mellitus Infusion or decoction Teixeira et al. (2003)
Philippines Leaf, bark, unripe Astringent, ulcers, wounds, diarrhoea Decoction and poultice Smith and Nigel (1992)
fruit, roots
India Leaves, Febrifuge, antispasmodic, rheumatism, Decoction or infusion Hernandez
Ghana shoots convulsions, astringent (1971)
Peru Flower buds, leaves Heart and constipation, conjunctivitis, cough, Infusion or decoction Cabieses (1993)
diarrhoea, digestive problems, dysentery,
oedema, gout, haemorrhages, gastroenteritis,
gastritis, lung problems, shock, vaginal
discharge, vertigo, vomiting, worms
Kinshasa, Congo Leaves, bark Diarrhoea, antiamoebic Infusion or decoction, Tona et al. (1999)
tisane
Senegal Shoots, roots Diarrhoea, dysentery Infusion or decoction Tona et al. (1999)
Uruguay Leaves Vaginal and uterine wash, especially in Infusion or decoction Conway (2002)
leucorrhoea
Fiji Leaves, roots, ripe Diarrhoea, coughs, stomach-ache, dysentery, Juice, the leaves are Word Health Organization
fruit toothaches, indigestion, constipation pounded, squeezed in salt (1998)
water
Tahiti, Samoa Whole plant, shoots Skin tonic, painful menstruation, miscarriages, Infusion or decoction, Word Health Organization
uterine bleeding, premature labour in women, paste (1998)
wounds
New Guinea, Samoa, Leaves Itchy rashes caused by scabies Boiled preparation Word Health Organization
Tonga, Niue, Futuna, (1998)
Tahiti
Cook Islands Leaves Sores, boils, cuts, sprains Infusion or decoction Word Health Organization
(1998)
Trinidad Leaves Bacterial infections, blood cleansing, diarrhoea, Infusion or decoction Word Health Organization
dysentery (1998)
Latin America, Central Leaves Gargle for sore throats, laryngitis and swelling Decoction Mejı́a and Rengifo (2000)
and West Africa, and of the mouth, and it is used externally for skin
Southeast Asia ulcers, vaginal irritation and discharge
Panama, Bolivia and Bark and leaves Dysentery, astringent, used as a bath to treat skin Decoction Conway (2002)
Venezuela ailments
Brazil Ripe fruit, flowers, Anorexia, cholera, diarrhoea, digestive Mashed, Decoction Holetz et al. (2002), Cybele et
and leaves problems, dysentery, gastric insufficiency, al. (1995)
inflamed mucous membranes, laryngitis, mouth
(swelling), skin problems, sore throat, ulcers,
vaginal discharge
USA Leaf Antibiotic and diarrhoea Decoction Smith and Nigel (1992)
4 R.M.P. Gutiérrez et al. / Journal of Ethnopharmacology 117 (2008) 1–27

of human ailments, including diabetes mellitus and hypertension and Rengifo, 2000). In Mozambique, the decoction of leaves
(Ojewole, 2005; Oh et al., 2005). is mixed with the leaves of Abacateira cajueiro, to alleviate
Guava has been used widely in the traditional medicine of the flu, cough and pressed chest. In Mozambique, Argentina,
Latin America and the Caribbean in the treatment of diarrhoea Mexico and Nicaragua, guava leaves are applied externally for
and stomach-aches due to indigestion (Mejı́a and Rengifo, 2000; inflammatory diseases (Jansen and Méndez, 1990).
Mitchell and Ahmad, 2006a,b). Treatment usually involves a The use of medicinal plants by the general Chinese population
decoction of the leaves, roots, and bark of the plant. It also is an old and still widespread practice. Psidium guajava leaves
has been used for dysentery in Panama and as an astringent in are example of the plant commonly used as popular medicine
Venezuela. A decoction of the bark and leaves is also reported to for diarrhoea which is also used as an antiseptic (Teixeira et al.,
be used as a bath to treat skin ailments. In Uruguay, a decoction 2003).
of the leaves is used as a vaginal and uterine wash, especially in In Brazil the fruit and leaves are considered for anorexia,
leucorrhoea (Conway, 2002). In Costa Rica, a decoction of the cholera, diarrhoea, digestive problems, dysentery, gastric
flower buds is considered an effective anti-inflammatory remedy insufficiency, inflamed mucous membranes, laryngitis, mouth
(Pardo, 1999). (swelling), skin problems, sore throat, ulcers, vaginal discharge
In Peru, it is used for gastroenteritis, dysentery, stomach pain (Holetz et al., 2002). In USA guava leaf extracts that are used in
(by acting on the pathogenic microorganisms of the intestine), various herbal formulas for a myriad of purposes; from herbal
indigestion, inflammations of the mouth and throat in the form antibiotic and diarrhoea formulas to bowel health and weight
of gargles (Cabieses, 1993). In some tribes of the forest (Tipis), loss formulas (Smith and Nigel, 1992).
the tender leaves are chewed to control toothaches by their Besides the medicinal uses Psidium guayava is employed as
weak sedative effect. Tikuna Indians use the decocted leaves food, in carpentry, in construction of houses and in the manu-
or bark of guava for diseases of the gastrointestinal tract. It is facture of toys (Table 2).
also employed by the Indians of the Amazons for dysentery,
sore throats, vomiting, stomach upsets, vertigo, and to regulate 2. Phytochemistry
menstrual periods, mouth sores, bleeding gums, or used as a
douche for vaginal discharge and to tighten and tone vaginal 2.1. Fruits
walls after childbirth. Flowers are also mashed and applied to
painful eye conditions such as sun strain, conjunctivitis or eye These are characterized by a low content of carbohydrates
injuries (Smith and Nigel, 1992). Guava jelly is tonic to the (13.2%), fats (0.53%), and proteins (0.88%) and by a high-
heart and constipation (Conway, 2002). water content (84.9%), (Medina and Pagano, 2003). Food
In the Philippines the astringent unripe fruit, the leaves, the value per 100 g is: Calories 36–50 kcal, moisture 77–86 g,
cortex of the bark and the roots are used for washing ulcers and crude fibre 2.8–5.5 g, ash 0.43–0.7 g, calcium 9.1–17 mg, phos-
wounds, as an astringent, vulnerary, and for diarrhoea. Leaves phorus (Conway, 2002), 17.8–30 mg, iron 0.30–0.70 mg (Iwu,
and shoots are used by West Indians in febrifuge and antispas- 1993), vitamin A 200–400 I.U., thiamine 0.046 mg, riboflavin
modic baths; the dust of the leaves is used in the treatment of 0.03–0.04 mg, niacin 0.6–1.068 mg, ascorbic acid 100 mg, vita-
rheumatism, epilepsy and cholera; and guava leaves tincture is min B3 40 I.U. (Fujita et al., 1985; Hernandez, 1971; Conway,
given to children suffering from convulsions (Morton, 1987). 2002). Manganese is also present in the plant in combina-
In Latin America, Central and West Africa, and Southeast tion with phosphoric, oxalic and malic acids (Nadkarni and
Asia, guava is considered an astringent, drying agent and a Nadkarni, 1999).
diuretic. A decoction is also recommended as a gargle for sore Hexanal (65.9%), ␥-butyrolactone (7.6%), (E)-2-hexenal
throats, laryngitis and swelling of the mouth, and it is used exter- (7.4%), (E,E)-2,4-hexadienal (2.2%), (Z)-3-hexenal (2%), (Z)-
nally for skin ulcers, vaginal irritation and discharge (Mejı́a 2-hexenal (1%), (Z)-3-hexenyl acetate (1.3%) and phenol

Table 2
Commercial applications of Psidium guajava
Fruit Food: juice, jelly nectar, concentrated, stuffed of candies, gelatines, All the countries Jimenez-Escrig et al. (2001)
pastes, tinned products, confectionery, etc.
Wood and leaves Carpentry and turnery use the leaves to make a black dye for silk Malaya Rodarte (1994)
Wood Engravings India Rodarte (1994)
Wood Spinning tops Guatemala Morton (1987)
Wood Hair combs El Salvador Morton (1987)
Wood Construction of houses Nigeria Lucas et al. (2006)
Leaves Employed to give a black colour to cotton Southeast Asia Rodarte (1994)
Leaves Serve to dye matting Indonesia Rodarte (1994)
Bark Dyes, stains, inks, tattoos and mordants Africa Burkill (1985)
Wood flowers The tree may be parasitized by the mistletoe, Psittacanthus calyculatus Mexico Argueta et al. (1994)
Don, producing the rosette-like malformations called “wood flowers”
which are sold as ornamental curiosities. Also the tree is seeded to give
shade to the coffee and its wood is used in the construction
R.M.P. Gutiérrez et al. / Journal of Ethnopharmacology 117 (2008) 1–27 5

(1.6%) were reported from fresh white-flesh guayaba fruit oil. acid, asiatic acid, ilelatifol d and ␤-sitosterol-3-O-␤-d-
3-caryophyllene (24.1%), nerolidol (17.3%), 3-phenylpropyl glucopyranoside, have been isolated from the leaves of
acetate (5.3%) and caryophyllene oxide (5.1%) were isolated Psidium guajava. guajavolide (2a-,3␤-6␤-,23-tetrahydroxyurs-
from essential oil extracted from the fruits (Paniandy et al., 12-en-28,20␤-olide, and guavenoic acid, were isolated from
2000). Subsequently, the active aromatic constituents in pink fresh leaves of Psidium guajava.
guava fruit the 3-penten-2-ol and 2-butenyl acetate were isolated
(Jordan et al., 2003). The fruit also contains glykosen 4.14%, Bark: It contains 12–30% of tannin (Burkill, 1997), resin and
saccharose 1.62%, and protein 0.3% (Dweck, 2001; Hwang et crystals of calcium oxalate (Nadkarni and Nadkarni, 1999).
al., 2002). Roots: They contain tannins, leukocyanidins, sterols, gallic
The unripe fruit is indigestible, causes vomiting and fever- acid, carbohydrates and salts. Root, stem-bark and all leaves
ishness. It changes in chemical composition and the activities of contain a large percentage of tannic acid (Quisumbing, 1978).
hydrolytic enzymes (the activities of ␣-amylase and ␤-amylase Seeds: They contain 14% oil, dry weight, with 15% proteins and
decreased significantly with ripening), chlorophyll, cellulose, 13% starch (Burkill, 1997), phenolic and flavonoid compounds
hemicellulose, and lignin content increased while carotenoid including quercetin-3-O-␤-d-(2 -O-galloyl-glucoside)-4 -O-
content decreased. The unripe fruit is high in tannins, is astrin- vinylpropionate (Michael et al., 2002). Some isolated
gent and has a tendency to cause constipation, but it is sometimes compounds are cytotoxic (Salib and Michael, 2004).
employed in diarrhoea (Jain et al., 2003). Floral bud: Buds have the highest concentrations of
myricetin (256 mg kg−1 ), quercetin (3605 mg kg−1 ), lute-
2.2. Fruit skins olin (229 mg kg−1 ), kaempferol (229 mg kg−1 ) and apigenin
(252 mg kg−1 ) (Vargas et al., 2006).
Ascorbic acid is the main constituent of the skin, secondly in Twigs: Contain calcium (0.30–1.00%), magnesium
the firm flesh, and a little content in the central pulp varies from (0.06–0.30%), phosphorous (0.10–0.38%), potassium
56 mg to 600 mg and may range between 350 mg and 450 mg (0.21–0.39%), and sodium (0.03–0.20%). The concentra-
in nearly ripe fruit (Charles et al., 2006). Canning or other tion of fluoride ranged from 0.02 ppm to 0.11 ppm, copper
heat processing destroys about 50% of the ascorbic acid. The (0.02–0.14 ppm), iron (2.86–5.14 ppm), zinc (0.31–0.57 ppm),
strong odour of the fruit is attributed to its carbonyl compounds manganese (0.00–0.26 ppm), and lead (0.00–0.11 ppm)
(Dweck, 2001). (Okwu and Ekeke, 2003). Contains Flavonoid, sesqui-terpenes
alcohols and acids triterpenoids (Hegnauer, 1969).
2.3. Leaves
3. Biological activity
Leaves contain essential oil with the main components
being ␣-pinene, ␤-pinene, limonene, menthol, terpenyl acetate,
Scientific investigations on the medicinal properties of guava
isopropyl alcohol, longicyclene, caryophyllene, ␤-bisabolene,
dates back to the 1940s. A summary of the findings of these
cineol, caryophyllene oxide, ␤-copanene, farnesene, humu-
studies performed is presented below.
lene, selinene, cardinene and curcumene (Zakaria and Mohd,
1994; Li et al., 1999). Flavonoids, and saponins combined with
oleanolic acid have been isolated from the leaves (Arima and 3.1. Anti-diarrhoeal
Danno, 2002). Nerolidiol, ␤-sitosterol, ursolic, crategolic, and
guayavolic acids have also been identified (Iwu, 1993). In addi- Diarrhoea has long been recognized as one of the most
tion, the leaves contain triterpenic acids as well as flavonoids; important health problems faced globally particularly by the
avicularin and its 3-l-4-pyranoside with strong antibacterial population of developing countries. Each year diarrhoea is esti-
action (Oliver-Bever, 1986), fixed oil 6%, 3.15% resin, and mated to kill about 2.2 million people globally, the majority
8.5% tannin, and a number of other fixed substances, fat, cel- of whom are infants and children below the age of 5 years
lulose, tannin, chlorophyll and mineral salts (Nadkarni and (Venkatesan et al., 2005). Ethanol and aqueous extracts of
Nadkarni, 1999). Also have been isolated from the leaves Psidium guajava at a concentration of 80 ␮g/ml in an organ
of Psidium guajava guavanoic acid, guavacoumaric acid, bath, exhibited more than 70% inhibition of acetylcholine
2␣-hydroxyursolic acid, jacoumaric acid, isoneriucoumaric and/or KCl solution-induced contractions of isolated guinea-
acid, asiatic acid, ilelatifol d and ␤-sitosterol-3-O-␤-d- pig ileum. The rates of propulsion in the small intestine in male
glucopyranoside (Begum et al., 2002a,b). In mature leaves, Sprague–Dawley rats as a means of assessing antidiarrhoeal
the greatest concentrations of flavonoids were found in July: activity of aqueous extracts of the leaf of Psidium guajava using
Myricetin (208.44 mg kg−1 ), quercetin (2883.08 mg kg−1 ), morphine as the standard drug of reference measured (Tona
luteolin (51.22 mg kg−1 ) and kaempferol (97.25 mg kg−1 ) et al., 1999; Lutterodt, 1992). A dose of 0.2 ml/kg fresh leaf
(Vargas et al., 2006). Two triterpenoids, 20␤-acetoxy- extract produced 65% inhibition of propulsion. This dose is equi-
2␣,3␤-dihydroxyurs-12-en-28-oic acid (guavanoic acid), and table with 0.2 mg/kg of morphine sulphate. The antidiarrhoeal
2␣,3␤-dihydroxy-24-p-z-coumaroyloxyurs-12-en-28-oic acid action of the extract may be due, in part, to the inhibition of the
(guavacoumaric acid), along with six known compounds increased watery secretions that occur commonly in all acute
2␣-hydroxyursolic acid, jacoumaric acid, isoneriucoumaric diarrhoeal diseases and cholera.
6 R.M.P. Gutiérrez et al. / Journal of Ethnopharmacology 117 (2008) 1–27

Quercetin showed significant anti-diarrhoeal activity on the The bark tincture showed fungicidal activity at different con-
contraction of guinea pig ileum in vitro and the peristaltic centrations but exhibited only fungistatic property in case of
motion of mouse small intestine, and reduced the permeability Candida albicans (Dutta and Das, 2000).
of abdominal capillaries (Heinrich, 1998; Zhang et al., 2003). Ethanolic extract from the shell of ripe fruit presenting activ-
Quercetin and quercetin-3-arabinoside, extracted from the buds ity on Streptococcus mutans and Escherichia coli (Neira and
and leaves of Psidium guajava at concentrations of 1.6 ␮g/ml Ramirez, 2005). Results supported the utilization of Psidium
showed a morphine-like inhibition of acetylcholine release in guajava in traditional medicine for intestinal diseases produced
the coaxially stimulated ileum, together with an initial increase by microorganisms.
in muscular tone, followed by a gradual decrease (Lutterodt,
1989). It is also reported that the asiatic acid, also extracted 3.3. Acne lesions
from the leaves, showed dose-dependent (10–500 ␮g/ml) spas-
molytic activity in spontaneously contracting isolated rabbit Acne vulgaris is a chronic inflammatory disease involving
jejunum preparations (Conde et al., 2003). Methanol extract colonization of Propionibacterium acnes, plus activation of neu-
from leaves (8 ␮g/ml) of Psidium guajava showed activity trophils and lymphocytes. Circumstantial evidence suggests that
against simian (SA-11) rotavirus (93.8% inhibition) (Goncalves antigen-independent and -dependent immune responses against
et al., 2005). In addition, galactose-specific lectin in guayaba Propionibacterium acnes are involved in the pathogenesis of
was shown to bind to Escherichia coli (a common diarrhoea- inflammatory acne. Epidermal keratinocytes are also suggested
causing organism), preventing its adhesion to the intestinal wall to be involved in initiation and progression of cutaneous inflam-
and thus preventing infection resulting diarrhoea (Coutiño et al., mation. Psidium guajava leaf extracts have potent antimicrobial
2001). activities against Propionibacterium acnes and may be benefi-
A methanolic leaf extract (8 ␮g/ml) of Psidium guajava also cial in treating acne especially when they are known to have
showed activity against simian (SA-11) rotavirus (93.8% inhi- anti-inflammatory activities (Qadan et al., 2005).
bition) (Goncalves et al., 2005). In addition, galactose-specific
lectin isolated from guava fruit ripe were shown to bind to
3.4. Effect on dental plaque
Escherichia coli (a common diarrhoea-causing organism), pre-
venting its adhesion to the intestinal wall and thus preventing
The adhesion of early settlers of dental plaque to the tooth
infection resulting diarrhoea (Coutiño et al., 2001).
surface has a role in the initiation of the development of den-
tal plaque. The hydrophobic surface properties of the bacteria
3.2. Antimicrobial
cell wall are indirectly responsible for the adhesion of the bac-
teria cell to the acquired pellicle on the tooth surfaces. Tooth
The inhibitory effects of aqueous and alcoholic extracts of
brushing is considered a superior technique for reducing plaque
the Psidium guajava (root as well as leaves) on the growth
accumulation. Chemical agents may be used to reduce plaque
of Staphylococcus aureus, Streptococcus mutans, Pseudomonas
accumulation on tooth surfaces. The treatment of the early
aeruginosa, Salmonella enteritidis, Bacillus cereus, Proteus
plaque settlers with 1 mg/ml aqueous extract leaf of Psidium
spp., Shigella spp. and Escherichia coli, causal agent of intesti-
guajava reduced the cell-surface hydrophobicity of Staphylo-
nal infections in humans were examined using the in vitro agar
coccus sanguinis, Staphylococcus mitis and Actinomyces sp. by
well diffusion method (Chah et al., 2006).
54.1%, 49.9% and 40.6%, respectively (Razak et al., 2006).
Methanolic root extract was further separated by column
These results provide some scientific rationale for its use in
chromatograph, yielding four antibacterial compounds. Three
the treatment of dental diseases and suggested that guava leaf
antibacterial substances have been detected in the leaves which
extracts may inhibit the caries-inducing properties of Strepto-
are derivatives of quercetin (Prabu et al., 2006; Arima and
coccus and thus may be beneficial for the dental care.
Danno, 2002).
In another study, it was observed that methanolic extract from
fruit ripe have fungicidal action against Arthrinium sacchari 3.5. Antimalarial effects
M001 and Chaetomium funicola M002 strains (Sato et al., 2000).
Aqueous and methanolic extracts of the leaves are effective The parasite lactate dehydrogenase (pLDH) assay method,
inhibitors of growth spore formation, and enterotoxin produc- a recently developed in vitro enzymatic method for evaluating
tion of Clostridium perfringens type A. No enterotoxins were antimalarial compounds, was used to examine the antiplas-
detected when extracts were added to the media at less than the modial activities of the aqueous leaf, stem-bark and fruit
MIC for growth (Garcia et al., 2002). extracts of Psidium guajava. An in vitro antiplasmodial assay
Psidium guajava leaf and bark tinctures were subjected to in carried out using a chloroquine-sensitive strain of malarial
vitro sensitivity tests by serial dilution at concentrations ranging parasite, Plasmodium falciparum D10 showed antigiardiasic
from 5% to 15% against six test dermatophytes, viz., Trichophy- activity with trophozoite mortality (87% ± 1.0); guava stem-
ton tonsurans, Trichophyton rubrum, Trichosporon beigelii, bark extract showed IC50 values of 10–20 ␮g/ml (Ponce et al.,
Microsporum fulvum, Microsporum gypseum and Candida albi- 1994; Nundkumar and Ojewole, 2002). In another study, leaves
cans. Bark tincture exhibited higher efficacy in controlling the and stem bark of Psidium guajava inhibited Entamoeba histolyt-
mycelial growth of dermatophytes than the leaf tincture. ica growth with MAC < 10 ␮g/ml (Tona et al., 1998).
R.M.P. Gutiérrez et al. / Journal of Ethnopharmacology 117 (2008) 1–27 7

3.6. Antitussive effects and caffeic acid (Jimenez et al., 2001). Guava leaf extracts are a
potential source of natural antioxidants (Ojan and Nihorimbere,
In another report, the water infusion from Psidium guajava 2004).
leaves decreased the frequency of coughing induced by capsaicin Other studies show that guava fruits also exert antioxidant
aerosol as compared to the control, within 10 min after injection and radioprotective activity in the assay with technetium-99m
of the extract (Jaiarj et al., 1999). Infusion on isolated rat tracheal [(99m)Tc] (Abreu et al., 2006).
muscle showed one directly stimulated muscle contraction and
also synergized with the stimulatory effect of pilocarpine. This 3.9. Antigenotoxic and antimutagenic effects
effect was antagonized by atropine (Pranee et al., 1999). These
results suggest that guava leaf extract could be recommended as Generation of DNA damage is considered to be an impor-
a cough remedy. tant initial event in carcinogenesis. A considerable battery of
assays exists for the detection of different genotoxic effects
3.7. Hepatoprotective effects of compounds in experimental systems, or for investigations
of exposure to genotoxic agents in environmental or occupa-
The hepatoprotective effect of an aqueous leaf extract of tional settings. Treatment with the aqueous whole plant extracts
Psidium guajava was studied on rat liver damage induced by car- of Psidium guajava afforded protection (anti-genotoxic activ-
bon tetrachloride by monitoring serum transaminase (aspartate ity) against mitomycin C, nalidixic acid and hydrogen peroxide
amino transferase and serum alanine amino transferase), alkaline (three genotoxins) (Bartolome et al., 2006). In another study,
posphatase, serum cholesterol, serum total lipids and histopatho- a pre-treatment with an aqueous guava leaf extract was found
logical alterations. The leaf extract at doses of 500 mg/kg to be effective in inactivating the mutagenicity of direct-acting
produced significant hepatoprotection (Roy et al., 2006). mutagens 4-nitro-o-phenylenediamine and 2-aminofluorene in
Pretreatment with asiatic acid (a triterpenoid extracted from the tester strains of Salmonella typhimurium. Therefore aqueous
Psidium guajava leaves and fruit) at doses of 25 mg/kg, 50 mg/kg leaf extracts of Psidium guajava show promising antigeno-
or 100 mg/kg significantly blocked the LPS (lipopolysaccharide) toxic/antimutagenic activity (Grover and Bala, 1993).
and (d-galactosamine) d-GalN-induced increases in both serum
aspartate aminotransferase and serum alanine aminotransferase 3.10. Anti-allergic effects
levels, showing improved nuclear condensation, ameliorated
proliferation and less lipid deposition (Gao et al., 2006). Sev- Th1 polarization is one of the mechanisms underlying the
eral studies have indicated the ability of guava to reduce several therapeutic effects of herbal medicine. The action of anti-allergic
parameters associated with liver injury. agents from Psidium guajava on T cell immunity in mice was
investigated. Studies were carried out on methanol and aqueous
3.8. Antioxidant, free radical scavenger and extracts of Psidium guajava leaves. These extracts cause potent
radioprotective activities inhibition of histamine release from mast cells, and blocked IL-
10-mediated, in vitro induction of T regulatory (Tr) cells from
Cellular damage or oxidative injury arising from free CD4+ splenocytes of C57BL/6 mice. The extracts also shifted
radicals or reactive oxygen species (ROS) now appears to the Th1/Th2 balance to a Th1 dominant status by directly atten-
be the fundamental mechanism underlying a number of uating Tr cell activity. Psidum guajava leaf extracts showed
human neurodegenerative disorders, diabetes, inflammation, anti-allergic activity on T cell immunity in mice (Seo et al.,
viral infections, autoimmune pathologies and digestive sys- 2005).
tem disorders. Free radicals are generated through normal
metabolism of drugs, environmental chemicals and other xeno- 3.11. Anticancer/antitumour effects
biotics as well as endogenous chemicals, especially stress
hormones (adrenalin and noradrenalin) (Masuda et al., 2003). An aqueous extract of Psidium guajava leaves inhibited (the
Dried leaves of Psidium guajava were extracted with hot viability) of the cancer cell line DU-145 in a dose-dependent
water. The total phenolic content in the extract was deter- manner. At 1.0 mg/ml, the extract reduced the viability of PCa
mined spectrophotometrically according to Folin–Ciocalteu’s DU-145 (the androgen independent PCa cells) to 36.1% and
phenol method and calculated as gallic acid equivalent (GAE). 3.6%, respectively after 48 h and 72 h of incubations (Chen et al.,
A remarkably high total phenolic content 575.3 ± 15.5 were 2007). Essential oil extracted from leaves of Psidium guajava
obtained (Qian and Nihorimbere, 2004). The antioxidant activ- was highly effective in reducing the growth of human mouth
ity of lyophilized leaf extracts was determined using free radical epidermal carcinoma (KB) and murine leukemia (P388) cell
DPPH (2,2-diphenyl-1-picrylhydryzyl) scavenging. The results lines when they were treated with different concentrations of
obtained showed that ascorbic acid was a substantially more the oil ranging from 0.019 mg/ml to 4.962 mg/ml. Guava leaf
powerful antioxidant than the extracts from guava leaf (Qian oil showed the highest anti-proliferative activity with an IC50
and Nihorimbere, 2004; Thaipong et al., 2005). These antiox- value of 0.0379 mg/ml (four times more potent than vincristine)
idant properties are associated with its phenolic compounds on P388 cell lines (Manosroi et al., 2006); an effect mostly
such as protocatechuic acid, ferulic acid, quercetin and guavin attributed to the monoterpenes present in the essential oil (Citó
B (Thaipong et al., 2005), quercetin, ascorbic acid, gallic acid et al., 2003). A chemopreventive effect was also demonstrated
8 R.M.P. Gutiérrez et al. / Journal of Ethnopharmacology 117 (2008) 1–27

in another study of a methanol leaf extract on mice-induced can- of Psidium guajava was significantly enhanced in the presence of
cer inoculated with B16 melanoma cells. A significant decrease phentolamine suggesting that the effect of Psidium guajava was
in the incidence and average number of animals with cancer to a large extent mediated by activation of an alpha-adrenoceptor
was found compared to the control group (Fernandes et al., and to a lesser extent by acting via calcium ion channel (Olatunji
1995). These findings suggest that Psidium guajava aqueous et al., 2007). A guava leaf extract may therefore be benefi-
leaf extracts are efficacious for the prevention of tumour devel- cial for the prevention of cardiovascular diseases, also since its
opment by depressing Tr cells and subsequently shifting to Th1 traditional use in hypertension is well established.
cells (Seo et al., 2005).
Furthermore, jacoumaric acid (isolated from guava seeds) 3.13. Anti-hyperglycemic
was evaluated for its antitumour effect; it was found to signifi-
cantly reduce the incidence of tumours (Numata et al., 1989). The rapidly increasing diabetes mellitus is becoming a seri-
Phytochemical investigations of the acetone extract of Psidium ous threat to human health in all parts of the world. The control
guajava seeds has led to the isolation of phenyl-ethanoid and treatment of diabetes and its complications mainly depend
glycosides (1-O-3,4-dimethoxy-phenylethyl-4-O-3,4- on the chemical or biochemical agents, but the fact is that it
dimethoxy cinnamoyl-6-O-cinnamoyl-beta-d-glucopyranose has never been reported that someone had recovered totally
and 1-O-3,4-dimethoxyphenylethyl-4-O-3,4-dimethoxy from diabetes. With the distinctive traditional medical opinions
cinnamoyl-beta-d-glucopyranose) which showed cytotoxic and natural medicines mainly originated in herbs, traditional
activities in vitro against Ehrlich ascites cells (EAC) and medicine offers good clinical opportunities and shows a bright
leukaemia P3888 cells (Salib and Michael, 2004). These future in the therapy of diabetes mellitus and its complications.
finding suggested that Psidium guaijava extracts have the The effect of Psidium guajava bark, leaves and fruit as anti-
potential to be developed as new chemotherapeutic agents to diabetic agents has been studied by several authors. Mukhtar et
prevent or to inhibit the growth of tumours and cancers. al. (2006) evaluated anti-hyperglycaemic activity of the ethanol
extract obtained from the stem bark of Psidium guajava on
3.12. Cardiovascular, hypotensive effects blood glucose levels of normal, alloxan-induced hyperglycaemic
rats and normal glucose loaded rats. The results showed that
The effect of an aqueous leaf extract of Psidium guajava on ethanol stem bark extract exhibited statistically significant hypo-
myocardial injury was studied in the model of global ischemia glycaemic activity in alloxan-induced, hyperglycaemic rats but
followed by reperfusion. High-energy phosphates and malon- was devoid of significant hypoglycaemic effect in normal and
dialdehyde in the reperfused hearts were significantly reduced normal glucose loaded rats.
with the plant extract (Conde et al., 2003). In another study, In another study, a decoction of Psidium guajava leaves
aqueous leaf extract of Psidium guajava exhibited cardiopro- was screened for hypoglycaemic activity on alloxan-induced
tective effects against myocardial ischemia-reperfusion injury in diabetic rats. In both acute and sub-acute tests, the water
isolated rat hearts. Augmentation of endogenous antioxidants, extract, at an oral dose of 250 mg/kg, showed statistically
maintenance of the myocardial antioxidant status and significant significant hypoglycaemic activity (Mukhtar et al., 2004).
restoration of most of the altered hemodynamic parameters may The treatment with Psidium guajava aqueous leaf extract
have contributed to its cardioprotective effect (Yamashiro et al., (0.01–0.625 mg/ml) showed significant inhibition on LDL
2003). The cardio-inhibitory actions in rats and guinea pigs of glycation in a dose-dependent manner. Tannins, flavonoids, pen-
the aqueous leaf extract of Psidium guajava also appeared to tacyclic triterpenoids, guiajaverin, quercetin, and other chemical
be due to cholinergic involvement in the mechanism of action. compounds present in the plant are speculated to account for
Ojewole (2005) showed that the aqueous leaf extract caused the observed hypoglycaemic and hypotensive effects of the leaf
hypotension in the experimental animal model used via cholin- extract (Ojewole, 2005; Wang et al., 2005).
ergic mechanisms. Moreover, acute intravenous administrations Psidium guajava is an excellent anti-LDL glycative agent
of the leaf extract (50–800 mg/kg i.v.) produced dose-dependent, whose potential therapeutic uses can be extended to the pre-
significant reductions in systemic arterial blood pressures and vention of a variety of cardiovascular and neurodegenerative
heart rates of hypertensive, Dahl salt-sensitive rats. Although diseases associated with glycations (Hsieh et al., 2007). Oh et
the exact mechanisms of action of the extract remain specula- al. (2005) demonstrated that the methanol extract from Psidium
tive at present, it is unlikely that the extract causes hypotension guajava leaves exhibited significant inhibitory effect on PTP1B
in the mammalian experimental animal model used via cholin- (protein tyrosine phosphatase 1B) in Lepr[db/Lepr[db] mice
ergic mechanisms since its cardiodepressant effects are resistant homozygous for the diabetes spontaneous mutation (Leprdb )
to atropine pre-treatment (Ojewole, 2005). become identifiably obese around 3–4 weeks of age. These
Belemtougri et al. (2006) found that aqueous and ethanolic homozygous mutant mice are polyphagic, polydipsic, and
leaf extracts of Psidium guajava inhibits intracellular calcium polyuric. Blood glucose lowering effect of the methanol extract
release (Chiesi and Schwaller, 1994; Apisariyakul et al., 1999). was observed after i.p. dose of 10 mg/kg, with an antidiabetic
Aqueous leaf extract of Psidium guajava significantly and dose- effect via the inhibition of PTP1B.
dependently (0.25–2 mg/ml) contracted the aorta rings. The In one study, oral administrations of 100 mg/kg, 150 mg/kg
effect was evaluated also in the presence of nifedipine and phen- and 250 mg/kg of juice from ripe guava fruit caused significant
tolamine. The sensitivity of the aortic rings to cumulative doses hypoglycemia in normoglycemic and STZ-treated, diabetic rats
R.M.P. Gutiérrez et al. / Journal of Ethnopharmacology 117 (2008) 1–27 9

(Cheng and Yang, 1983). Although effective duration of guava is against thermally and chemically induced nociceptive pain in
less potent than chlorpropamide and metformin. Moreover, acute mice (Ojewole, 2006).
intravenous administrations of the fruit’s juice produced signif- The anti-inflammatory and analgesic activities of 70%
icant reductions in systemic arterial blood pressures and heart ethanolic extract of leaves of Psidium guajava were also inves-
rates of hypertensive patients. Some investigators suggested that tigated in rats using the carrageenan induced hind paw oedema
the hypoglycaemic components in guava fruits might involve model. Extracts which exhibited anti-inflammatory activity
ursolic acid, oleanolic acid, arjunolic acid and glucuronic acid were screened for analgesic activity using the Randall–Selitto
(Chang, 1982). method in rats. The extracts were administered at a dose of
Anti-LDL (low density lipoprotein) glycative agents were 300 mg/kg, p.o. Aspirin (300 mg/kg, p.o.) was employed as the
investigated using aqueous decoctions of Psidium guajava reference drug. Psidium guajava leaves showed significant anti-
fruit ripe at concentrations of 0.01–0.625 mg/ml (Hsieh et inflammatory activity with an inhibition of 58% (Muruganandan
al., 2005). The results have revealed that guava fruits exhibit et al., 2001).
excellent antiglycation effect, being a rather powerful and effec- The essential oil, steam-distilled from leaves of Psidium
tive inhibitor of LDL glycation in both glucose and glyoxal guajava, was given orally to rats to study its effects on the
induced models. The antiglycation activities of guava fruit exudative and proliferative phases of the inflammatory reaction
were relevantly and directly related to its polyphenolic con- (carrageenan induced paw oedema and cotton pellet induced
tent (extractable polyphenols 2.62–7.79%), yet it seemed to us granuloma models). The essential oil (0.8 mg/kg) significantly
that Psidium guajava fruit also possesses a rather specific and reduced oedema formation induced by carrageenan while at
somewhat different degree of free-radical scavenging ability, 0.4 mg/kg and 0.8 mg/kg the oil also significantly reduced gran-
thus it was speculated that the reaction mechanism of guava uloma formation induced by cotton pellets (Kavimani et al.,
might have occurred in the initiation rather than the propagation 1997).
phase, a mechanism being quite different from the conventional
free-radical scavenging by the polyphenolics. This problem is 3.16. Antinociceptive effects
indeed worth exploring in further studies.
The hexane, ethyl acetate and methanol extracts of Psidium
3.14. Effect on muscular system guajava leaves showed activity on the central nervous system in
mice. The three extracts exhibited mostly antinociceptive effects
Degenerative muscular diseases, such as muscular dystrophy, in chemical and thermal tests of analgesia. The extracts also pro-
have been the target of regenerative cell therapy. Although satel- duced dose-dependent prolongation of pentobarbitone-induced
lite cells play central roles in skeletal muscle regeneration that sleeping time (Shaheen et al., 2000). Shortly after intraperitoneal
intrinsically occurs after muscle injury, their application to cell administration of this methanol extract, typical narcotic-like
therapy is confronted with difficulties (Endo, 2007). Water and effects were observed including catalepsy, analgesia, straub tail,
methanolic leaf extracts from Psidium guajava showed antag- shallow respiratory movements and exophthalmos. Doses of
onistic effects on caffeine induced calcium release from the 3.3–6.6 mg/kg i.p. depressed spontaneous locomotor activity
sarcoplasmic reticulum of rat skeletal muscle cells in a dose- and tunnel running was curtailed. Higher doses abolished the
dependent-manner showing a clear calcium-antagonistic effect spontaneous locomotor reflex action (Lutterodt and Maleque,
(Belemtougri et al., 2006). Aqueous leaf infusions of Psidium 1988).
guajava could block the L-type calcium membrane channels These results lend pharmacological credence to the uses of
(Conde et al., 2003). Guava may therefore be beneficial for the plant in the management and/or control of painful, arthritic
patients with muscular dystrophy (Lamb, 2000). and other inflammatory conditions.
It was also reported in another study that the antinocicep-
3.15. Anti-inflammatory/analgesic tive effect of leaf essential oil from Psidium guajava and its
constituent, ␣-pinene produced a significant antinociceptive
A decoction of Psidium guajava leaves is used worldwide effect in the formalin test probably mediated by endoge-
for the treatment of various inflammatory ailments including nously released adenosine (Santos et al., 1998). Hexane, ethyl
rheumatism. The numerous polyphenolic compounds, triter- acetate and methanol extracts of Psidium guajava leaves on
penoids and other chemical compounds present in the plant the central nervous system in mice exhibited mostly dose-
may account for the observed anti-inflammatory and analgesic dependent antinociceptive effects in chemical and thermal tests
effects of the leaf extracts. The anti-inflammatory property of of analgesia. The extracts also produced dose-dependent pro-
the aqueous leaf extract was investigated in rats, using fresh longation of pentobarbitone-induced sleeping time. However,
egg albumin induced pedal (paw) oedema, while the analgesic they had variable and mostly non-significant effects on loco-
effect of the plant extract was evaluated by the hot-plate and motor coordination, locomotor activity or exploration (Shaheen
acetic acid test models of pain in mice. Psidium guajava aque- et al., 2000). A bio-guided fractionation of the hexane extract
ous extract (50–800 mg/kg, i.p.) produced dose-dependent and obtained from Psidium guajava leaves led to the isolation of
significant inhibition of fresh egg albumin-induced acute inflam- sesquiterpenes with depressant activities on the central ner-
mation (oedema) in rats. The leaf extract (50–800 mg/kg, i.p.) vous system. The relaxant properties of the Psidium guajava
also produced dose-dependent and significant analgesic effects hexane extract are largely due to the presence of terpenes,
10 R.M.P. Gutiérrez et al. / Journal of Ethnopharmacology 117 (2008) 1–27

especially caryophyllene-oxide and ␤-selinene, which potenti- diarrhoeal of the treated group (25.1 ± 9.5 h) was significantly
ated pentobarbital sleeping time and the latency of convulsions shorter than that of the control group (38.7 ± 15.2 h, P < 0.01).
induced by leptazol in mice. Calcium concentration–response The content of Na+ and glucose in stool was reduced obviously
curves showed a rightward displacement when hexane extract in the treated group, while the reduction in the control group was
was added to isolated guinea-pig ileum depolarized with K+ insignificant; the treated group was significantly superior to the
(60 mm) and cumulative concentrations of CaCl2 , suggesting control group. The rate of negative conversion of HRV in faeces
that caryophyllene-oxide, a known Ca2+ antagonist agent could of the treated group was 87.1%, significantly better than that of
be responsible for the blockade of extracellular Ca2+ (Meckes the control (58.1%). The treatment with PG has good curative
et al., 1996). effect on infantile rotaviral enteritis (Wei et al., 2000).

3.17. Wound healing 5.2. Infectious gastroenteritis

The wound healing properties of a methanolic leaf extract In the Laboratory of Medicinal Plants Research Unit of Neu-
of Psidium guajava were determined using the excision wound rological Diseases, Mexico, a randomized double-blind trial
model. More than 90% wound healing was observed after 14 examined the efficacy of a standardized aqueous leaf extract
days post-surgery, whereas 72% healing was observed in the Psidium guajava ([QG-5] estimated at quercetin-equivalent
distilled water treated group (Chah et al., 2006). 1 mg per 500 mg capsule) versus placebo in 100 patients
with infectious gastroenteritis. The experimental group (n = 50)
4. Toxicology received 1 capsule of QG-5 orally every 8 h for 3 days, while the
control group (n = 50) received the same regimen with match-
This toxicologic study was conducted using dry leaves of ing placebo capsules. Conventional oral rehydration therapy
Psidium guajava L. In this plant material, acute toxicologic was initiated in both groups. Outcome measures included num-
study by the following methods: mean lethal dose LD50 test ber of daily stools, consistency, presence of mucus, degree of
in Swiss mice and alternative toxicology (acute toxic classes) abdominal pain, number of spasms in 24 h, fever, and number of
in Wistar rats. We also made the genotoxic of 2 extracts, one vomiting episodes. Results indicated a significant difference in
of aqueous type, and the other of henaxic type in an in vitro outcome measures favouring the experimental group, mostly due
system of short-term somatic segregation induction assay in the to an antispasmolytic effect, which helped reduce the number of
Aspergillus nidulans fungus and an in vivo assay of the dry drug episodes of abdominal pain. No adverse effects were reported
in mouse bone marrow micronuclei induction test. No deaths for patients treated with QG-5 (Lozoya et al., 2002). Besides
were observed in the toxicological results of the two experi- constipation, no serious adverse reactions have been reported in
mental models in the dose range using up to 2 g/kg/b.w. Acute patients taking QG-5. Guava is commercially available in cap-
toxicity tests in rats and mice have proven the LD50 of guava leaf sules, liquids, powders, and tablets in a standardized form for
extracts to be more than 5 g/kg. In vitro genotoxicity and muta- gastroenteritis.
genicity tests on Psidium guajava in human peripheral blood In Cuba, a longitudinal randomized double blind study was
lymphocytes found no disturbances in cell division (Jaiarj et al., carried out among 100 adult patients with acute diarrhoea. The
1999; Manosroi et al., 2006). The histological results did not effect of an oral treatment with 10 ml tincture from Psidium
suggest any damage attributable to toxicity of the studied plant guajava dissolved in water, every 8 h, on the treatment of diar-
material. In the in vitro study with Aspergillus nidulans D-30, rhoea was determined. The results revealed that this 20% leaf
results indicated a lack of genotoxic effect of these extracts, tincture significantly reduced the time to ceasing diarrhoea and
as well as in the mouse bone marrow micronucelus induction no adverse reactions were detected (Echemendia and Moron,
system (Martinez et al., 2001). 2004). Guava offers an effective and safe alternative treatment
for patient with diarrhoea disease.
5. Clinical trials
5.3. Cardiovascular effects
5.1. Infantile rotaviral enteritis
Evidence from a randomized, single-blind, clinical trial sug-
A pilot study was carried out at the Nanfang Hospital, First gests that by adding moderate amounts of guava fruit to the diet,
Military Medical University, and Guangzhou on Psidium gua- changes in dietary fatty acids and carbohydrates may decrease
java (PG) leaf decoction for treating infantile rotaviral enteritis. lipoprotein metabolism and blood pressure. Two groups of
Sixty-two patients of rotaviral enteritis were randomly divided patients (N = 120) were assessed over 12 weeks; each group
into the verum group treated with PG and the control group received ripe guava fruit, preferably before meals. At the end of
treated with Gegen Qinlian decoction. The time for ceasing diar- the period, approximately half of the patients had a net decrease
rhoeal, the content of Na+ in blood, the content of Na+ and in serum total cholesterol (9.9%), triglycerides (7.7%), and
glucose in stool, and the rate of negative conversion of human blood pressure (9/8 mm Hg), with a net increase in high-density
rotavirus (HRV) antigen were observed. The rate of recovery lipoprotein (HDL) cholesterol (8%) (Singh et al., 1992).
in 3 days for the treated group was 87.1%, significantly higher A single-blind, randomized, controlled trial of 145 hyperten-
than that of the control group (58.1%). The time of ceasing sive patients found similar results. Patients received a fibre and
R.M.P. Gutiérrez et al. / Journal of Ethnopharmacology 117 (2008) 1–27 11

potassium enriched diet containing 0.5–1 kg of guava daily or sules containing 500 mg of Psidium guajava fruit in 40 patients
their usual diet; alcohol, caffeine, cholesterol, fat, and salt intake showed a reduction in blood glucose level in weeks 3, 4 and 5
were similar in both groups. After 4 weeks, systolic and diastolic with changes in glucose level of −12.3%, −24.79% and −7.9%
pressures improved, decreases occurred in serum total choles- respectively as compared with the diabetic control group. This
terol and triglycerides, and there was a mild increase in the ratio study showed that supplementation of 0.517 g/day could reduce
of total cholesterol/HDL-cholesterol in the guava group (Singh fasting blood glucose level but the mean was not significant
et al., 1993). (Yusof and Said, 2004).
In another trial conducted for a 9-week period in “Institut
Kemahiran Belia Negara”, Hulu Langat, Selangor, Malaysia, 6. Summary
a randomized double-blind study of 122 people examined the
effects of consuming 400 g/day of guava fruit on total antiox- Psidium guajava is a well-known medicinal plant that is fre-
idant status and lipid profile (total cholesterol, triglycerides, quently prescribed in various indigenous systems of medicine
low-density lipoprotein [LDL] and HDL cholesterol). Consump- especially those of Central America and Africa. Guava extracts,
tion of guava fruit reduced oxidative stress and blood cholesterol traditionally prepared (infusions, decoctions, tinctures of the
levels. Thus, it could reduce the risk of disease caused by free barks and leaves and ripe fruit) by many widely separated
radical activities and high cholesterol in the blood (Rahmat et cultures for eons of time for various uses (Table 1) have, as sum-
al., 2004). marised in this review, been shown by the application of modern
scientific methods to indeed possess multiple disease ameliorat-
5.4. Dysmenorrhea ing properties. Such properties have been further explained by
several studies detailing the specific bioactivity of individual
A double-blinded randomized clinical trial was conducted phytochemicals extracted from guava and on clinical studies.
in 197 women with primary dysmenorrhea. Four interven- Extracts and phytochemicals isolated from Psidium guajava
tion groups were defined: two leaf extract doses (3 mg/day leaves have been shown to have multiple disease ameliorat-
and 6 mg/day); ibuprofen (1200 mg/day); placebo (3 mg/day). ing effects caused by microbial pathogens (Table 1). Its most
Participants were followed up individually for 4 months. The widespread traditional use has been for the treatment of diar-
main outcome variable was abdominal pain intensity measured rhoea. Leaf extracts of Psidium guajava, as reviewed here, have
according to a visual analogue scale (VAS). The average age of been found to have antimicrobial activity against several bacte-
participants was 19 years; menarche occurred around 12 years ria, fungi, viruses and parasites, with proven ability to ameliorate
of age. Participants had menstrual cycles of 28 or 29 days, with diarrhoeal, and also gastroenteritis, dental plaque, acne, infantile
menstruation lasting 5 days and pain intensity mean of 8.2 on rotaviral enteritis and even malaria suggesting wide antimicro-
the VAS. During each successive treatment cycle, participants bial activity. The activity guided purification resulted in the
experienced a lower pain intensity score. Multiple regression isolation of quercetin, quercetin-3-arabinoside, and asiatic acid
analysis, after adjusting each cycle for baseline pain, treat- which showed significant anti-diarrhoeal activity.
ment compliance and other variables, showed that the group Another traditional use of guava has been in the treatment
receiving 6 mg/day leaf extract had significantly reduced pain of coughs; experimental data presented here show that guava
intensity (p < 0.001). This effect was maintained in cycles 2 and leaf extract do indeed exert an inhibitory effect on frequency of
3, although the reduction in the mean of pain intensity was lower. coughing.
The group receiving the 3 mg/day extract did not show a con- Research summarised here also indicates that guava leaves
sistent effect throughout the three cycles. The guava leaf extract provide antioxidant and other effects providing beneficial pro-
standardized to 6 mg flavonol/day, reduced menstrual pain sig- tective properties to the heart and liver with an improvement in
nificantly compared with conventional treatment and placebo myocardial and muscular function. In other animal studies guava
(Vladislavovna et al., 2007; Svetlana et al., 2007). leaf extracts showed anti-allergic, anti-inflammatory, analgesic,
sedative, and central nervous system (CNS) depressant activity.
5.5. Hypoglycaemic effect While these are not known folk uses per se, they help to explain
such folk recipes as the use of leaf extracts for rheumatic pain,
In China, a multicentric randomized controlled trial was con- convulsions, vomiting and menstrual pain. The effect on diar-
ducted to evaluate the efficacy of guava in the management of rhoeal, for example seems to be due to its antimicrobial activity,
diabetes. The mean age of participants was 59.6-year-old and but also in other ways as discussed in Section 3.1.
average duration of diabetes was 5.4 years. Oral administration Leaves are the part of the plant that is most frequently used
capsules containing 500 mg of aqueous leaf extract from Psid- in the forms of decoction. The studies performed by the authors
ium guajava to 50 diabetic patients showed hypoglycaemic less have been discussed. Most of the pharmacological and chemi-
potent than chlorpropamide and metformin. Thus, it is suggested cal work has been carried out on the leaf, reveals the connection
that guava may be employed to improve and/or prevent diabetes between medicinal herbs and cultural beliefs toward healing.
mellitus (Cheng and Yang, 1983). Guava leaves contain tannins as well as ␤-sitosterol, flavonoids,
Guava is a tropical fruit that contains high levels of dietary triterpenoids, volatile oil. The main traditional use is for the treat-
fibre and could have health potential in the management of blood ment of the gastrointestinal disorders (diarrhoea, stomach pain,
glucose level in diabetic subjects. Oral administration of cap- gastroenteritis, indigestion, and dysentery) and dermatologic
12 R.M.P. Gutiérrez et al. / Journal of Ethnopharmacology 117 (2008) 1–27

conditions (boils, skin, infection, and ulcers). The recommended 7. Conclusion


dosage for acute diarrhoea is 0.5–1.0 cup of decoction (take a
handful of leaves to make a decoction with 1 l of water) 3–5 The pharmacological studies conducted on Psidium guajava
times daily. indicate the immense potential of this plant in the treat-
The ripe guava fruit, on the other hand, has been shown here ment of conditions such as diarrhoeal, gastroenteritis and
and in other reviews (Hwang et al., 2002) to be a very use- rotavirus enteritis, wounds, acne, dental plaque, malaria, aller-
ful nutraceutical with important properties that can affect the gies, coughs, diabetes, cardiovascular disorder, degenerative
maintenance of health and prevention of many diseases. All muscular diseases, inflammatory ailments including rheumatism
parts of the fruit can be eaten, with the skin actually possess- and menstrual pain, liver diseases, cancer, etc. Not surprisingly,
ing the highest vitamin C level. The fruit and its juice have guava also exhibits antioxidant and anti-inflammatory effects as
been documented to lower blood sugar levels in normal and dia- oxidative injury underlies many of these diseases. However, the
betic animals and humans, ameliorate rheumatism (analgesic diverse pharmacological activities of guava extracts and isolated
and anti-inflammatory effects), while reducing blood pressure, phytochemicals have only been assayed in in vitro tests using
triglycerides and cholesterol levels. Interestingly, guava bark and laboratory animals, and the results obtained may not necessarily
leaves have also been shown to have important antioxidant and be portable to the situation in humans. While there are gaps in
anti-diabetic properties with the bark being more active. This the studies conducted so far, which need to be bridged in order to
lends pharmacological credence to the folkloric, ethnomedical exploit the full medicinal potential of guava, it is still very clear
uses of the plant in the management or control of adult-onset, that this is a plant with tremendous widespread use now and also
type 2 diabetes mellitus and hypertension in some rural commu- with extraordinary potential for the future. On the basis of the low
nities. toxicity of guava extracts and derived phytochemicals and their
As well as the traditional preparations, individual chemicals use as nutraceutical (fruit) and medicinal (leaves, bark, seeds,
have been shown to exhibit previously unknown properties. The roots) agents, backed by proven activity of both the traditional
inherent cytotoxicity of triterpenes in the seeds and leaf is the formulations (infusions, decoctions, tinctures) and their derived
most promising and should be better explored in the search for phytochemicals (phenolics, flavonoids, carotenoids, triterpenes,
new antineoplastic agents because the leaf oil has been shown essential oil constituents and others), further research, clinical
to be four times more potent than vincristine. trials and product development can only cement Psidium gua-
Most importantly, Psidium guajava has been used for a long java as a very important part of our biodiversity to respect and
period of time with no serious adverse effects reported or docu- sustainably use for generations to come.
mented.
Appendix A. Constituents of Psidium guayava

Structure Source Activities

Phenolic compounds isolated from Psidium guajava

Leaf and roots, Okuda et al. (1984), Cardioprotective effects against


Quisumbing (1978) ischemia-reperfusion. Antioxidant, Yamashiro et al.
(2003).

Leaf and fruit, Okuda et al. (1984). Antioxidant, Thaipong et al. (2005)

Leaf, Liang et al. (2005) Antibacterial activities. Antioxidant, Zhou et al.


(2007)
R.M.P. Gutiérrez et al. / Journal of Ethnopharmacology 117 (2008) 1–27 13

Appendix A (Continued )
Structure Source Activities

Leaf, Zhu et al. (1997) Antioxidant, Misra and Seshadri (1968), Qian and
Nihorimbere (2004)

Leaf, Liang et al. (2005), Qian and Antioxidant, capacity radical scavenging activity,
Nihorimbere (2004) antimutagenic/anticarcinogenic effect, inflammation
inhibiting and endothelial protective properties, Li
and Chang (2005)

Leaf, stem-bark, and roots, Misra and Possesses analgesic and antiinflammatory
Seshadri (1968) properties, Ojewole (2006)
*

Leaf and fruit, Okuda et al. (1984), Zhu Antioxidant, Okuda et al. (1984)
et al. (1997)

Flavonoids isolated from Psidium guajava

Leaf flowers and fruit, Liang et al. (2005) Antidiarrhoea effect, Zhang et al. (2003). Exhibited
antioxidant and spasmolytic effects, Formica and
Regelson (1995), Yamashiro et al. (2003). Also
showed inhibition on skeletal muscles contraction,
Chaichana and Apisariyakul (1996); Induced
reduction of presynaptic molecular activity,
Apisariyakul et al. (1999) Also showed vasodilator
effects, Duarte et al. (1993)
14 R.M.P. Gutiérrez et al. / Journal of Ethnopharmacology 117 (2008) 1–27

Appendix A (Continued )
Structure Source Activities

Leaf, flowers and fruit Nadkarni and


Nadkarni (1999)

Leaf flowers and fruit Liang et al. (2005)

Leaf flowers and fruit Liang et al. (2005)

Acylated flavonol glycoside Seeds, Michael et al. (2002)

Leaf and fruit Liang et al. (2005)

Leaf and fruit Liang et al. (2005)


R.M.P. Gutiérrez et al. / Journal of Ethnopharmacology 117 (2008) 1–27 15

Appendix A (Continued )
Structure Source Activities

Leaf flowers and fruit Liang et al. (2005)

Leaf and fruit, Prabu et al. (2006) Showed antimicrobial activity against Streptococcus
mutans, Prabu et al. (2006)

Leaf and fruit, Arima and Danno (2002) Showed antimicrobial activity against Salmonella
enteritidis and Bacillus cereus, Arima and Danno
(2002)

Leaf and fruit, Arima and Danno (2002) Showed antimicrobial activity against Salmonella
enteritidis and Bacillus cereus, Arima and Danno
(2002)

Leaf and fruit, Liang et al. (2005)


16 R.M.P. Gutiérrez et al. / Journal of Ethnopharmacology 117 (2008) 1–27

Appendix A (Continued )
Structure Source Activities

Leaf and fruit, Liang et al.


(2005)

Carotenoids isolated from Psidium guajava

Leaf and fruit, Acts as a chain-breaking


Mercadante et al. (1999) antioxidant and thus protects
cell against photo-oxidation
Palozza and Krinsky (1992)

Leaf and fruit,


Mercadante et al. (1999)

Leaf and fruit,


Mercadante et al. (1999)

Leaf and fruit,


Mercadante et al. (1999)

Leaf and fruit,


Mercadante et al. (1999)

Leaf and fruit,


Mercadante et al. (1999)

Leaf and fruit Mercadante


et al. (1999)
R.M.P. Gutiérrez et al. / Journal of Ethnopharmacology 117 (2008) 1–27 17

Appendix A (Continued )
Structure Source Activities

Leaf and fruit, Mercadante et al. (1999)

Cytokinins isolated from Psidium guajava

Leaf and fruit, Nagar and Rao (1981)

Zeatin riboside Leaf and fruit, Nagar and Rao (1981)


Zeatin nucleotide Leaf and fruit, Nagar and Rao (1981)
Triterpenes isolated from Psidium guajava

Leaf and fruit, Siddiqui et al. (2002)

Leaf and fruit, Begum et al. (2002a)

Leaf and fruit, Begum et al. (2002a)


18 R.M.P. Gutiérrez et al. / Journal of Ethnopharmacology 117 (2008) 1–27

Appendix A (Continued )
Structure Source Activities

Leaf and fruit, Begum et al. (2004)

Leaf and fruit, (Begum et al., 2002a,b)

Leaf and fruit, (Begum et al., 2002a)

Leaf and fruit, (Begum et al., 2004)

Leaf, (Begum et al., 2002a)


R.M.P. Gutiérrez et al. / Journal of Ethnopharmacology 117 (2008) 1–27 19

Appendix A (Continued )
Structure Source Activities

Leaf and fruit, Begum et al.


(2004)

Leaf and fruit, Begum et al.


(2002a)

Leaf and fruit, Begum et al. Showed spasmolytic, Conde-Garcia et al. (2003),
(2002a,b) antioxidative, anti-inflammatory and
hepatoprotective activities, Gao et al. (2006)

Leaf and fruit, (Begum et al.,


2002a,b)

Leaf and fruit, Begum et al.


(2002a,b)
20 R.M.P. Gutiérrez et al. / Journal of Ethnopharmacology 117 (2008) 1–27

Appendix A (Continued )
Structure Source Activities

Leaf and fruit, Begum et al. (2004)

Seeds, Salib and Michael (2004)

Seeds, Salib and Michael (2004) Showed cytotoxic activities in vitro


against Ehrlich ascites Carcinoma
cells (EAC) and leukaemia P3888
cells Salib and Michael (2004)

Constituents from the essential oil of Psidium guajava

Fruit, Li et al. (1999) Content: 18.81%. Cytotoxic to brine


shrimp larvae, Citó et al. (2003)

Fruit, Li et al. (1999) Content: 11.80%. Antiinflammatory


and inhibition of nitric oxide
production; in vitro antitumour, Siani
et al. (1999)

Leaf, Li et al. (1999 Content 10.27%, Li et al. (1999)


R.M.P. Gutiérrez et al. / Journal of Ethnopharmacology 117 (2008) 1–27 21

Appendix A (Continued )
Structure Source Activities

Leaf, Oliver-Bever (1986) Content 7.36%, Oliver-Bever (1986)

Leaf, (Li et al., 1999) Antiinflammatory and inhibition of


nitric oxide production; in vitro
antitumour (Siani et al., 1999)

Leaf, Kenneth et al. (1970)

Fruit, Kenneth et al. (1970)

Fruit, Kenneth et al. (1970)

Fruit, Kenneth et al. (1970)

Fruit, Kenneth et al. (1970)

Fruit, Kenneth et al. (1970)


22 R.M.P. Gutiérrez et al. / Journal of Ethnopharmacology 117 (2008) 1–27

Appendix A (Continued )
Structure Source Activities

Leaf, Li et al. (1999)

Fruit, Kenneth et al. (1970)

Fruit, Kenneth et al. (1970)

Fruit, Kenneth et al. (1970)

Fruit, Kenneth et al. (1970)

Fruit, (Jordan et al., 2003)

Fruit, Jordan et al. (2003)

Fruit, Jordan et al. (2003))

Fruit, Jordan et al. (2003)


R.M.P. Gutiérrez et al. / Journal of Ethnopharmacology 117 (2008) 1–27 23

Appendix A (Continued )
Structure Source Activities

Micellaneous

Flowers, roots, Jordan et al. (2003)

Leaves, fruit, Fujita et al. (1985)

Leaves, fruit, Fujita et al. (1985)

Leaves, fruit, Radha and Chandrasekaran


(1997)

Leaves, fruit, Radha and Chandrasekaran


(1997)
24 R.M.P. Gutiérrez et al. / Journal of Ethnopharmacology 117 (2008) 1–27

Appendix A (Continued )
Structure Source Activities

Seeds, Salib and Michael (2004) Showed cytotoxic activities in vitro


against Ehrlich ascites Carcinoma
cells (EAC) and leukemia P3888
cells Salib and Michael (2004)

Leaves, fruit, Radha and Chandrasekaran


(1997)

Seeds, Salib and Michael (2004)

Seeds, Salib and Michael (2004) Showed cytotoxic activities in vitro


against Ehrlich ascites Carcinoma
cells (EAC) and leukemia P3888
cells Salib and Michael (2004)

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