The ethnobotanical, phytochemistry and pharmacological activities of Psidium guajava L.

Eziuche Amadike Ugbogu; Okezie Emmanuel; Miracle Ebubechi Uche; Emmanuel Dike Dike; Benedict Chukwuebuka Okoro; Chibuike Ibe; Victor Chibueze Ude; Celestine Nwabu Ekweogu; Ositadinma Chinyere Ugbogu

doi:10.1016/j.arabjc.2022.103759

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Review article

05 2022

:15;

103759

doi:

10.1016/j.arabjc.2022.103759

The ethnobotanical, phytochemistry and pharmacological activities of Psidium guajava L.

Eziuche Amadike Ugbogu^{^a,⁎}, Okezie Emmanuel^{^a}, Miracle Ebubechi Uche^{^a}, Emmanuel Dike Dike^{^a}, Benedict Chukwuebuka Okoro^{^a}, Chibuike Ibe^{^b}, Victor Chibueze Ude^{^c}, Celestine Nwabu Ekweogu^{^d}, Ositadinma Chinyere Ugbogu^{^b}

a Department of Biochemistry, Abia State University, PMB 2000, Uturu, Abia State, Nigeria

b Department of Microbiology, Abia State University, Uturu, PMB 2000, Uturu, Abia State, Nigeria

c Department of Medical Biochemistry, College of Medicine Enugu State University of Science and Technology, PMB 01660 Enugu, Nigeria

d Department of Medical Biochemistry, Imo State University, PMB 2000, Owerri, Imo State, Nigeria

⁎Corresponding author at: Department of Biochemistry, Faculty of Biological Sciences, PMB 2000, Abia State University, Uturu, Abia, Nigeria. amasryal@yahoo.com (Eziuche Amadike Ugbogu)

Received: 2021-11-8, Accepted: 2022-1-30,

Disclaimer:
This article was originally published by Elsevier and was migrated to Scientific Scholar after the change of Publisher.

Peer review under responsibility of King Saud University.

Abstract

Psidium guajava L., commonly known as guava is an important tropical food plant with diverse medicinal values. In traditional medicine, it is used in the treatment of various diseases such as diarrhoea, diabetes, rheumatism, ulcers, malaria, cough, and bacterial infections. The aim of this review is to provide up-to-date information on the ethnomedicinal uses, bioactive compounds, and pharmacological activities of P. guajava with greater emphasis on its therapeutic potentials. The bioactive constituents extracted from P. guajava include phytochemicals (gallic acid, casuariin, catechin, chlorogenic acid, rutin, vanillic acid, quercetin, syringic acid, kaempferol, apigenin, cinnamic acid, luteolin, quercetin-3-O-α-L-arabinopyranoside, morin, ellagic acid, guaijaverin, pedunculoside, asiastic acid, ursolic acid, oleanolic acid, methyl gallate and epicatechin) and essential oils (limonene, trans-caryophyllene, α-humulene, γ-muurolene, selinene, caryophyllene oxide, bisabolol, isocaryophyllene, δ-cadinene, α-copaene, α-cedrene, β-eudesmol, α-pinene, β-pinene, β-myrcene, linalool, α-terpineol and eucalyptol). In vitro and in vivo studies demonstrated that P. guajava possesses pharmacological activities such as antidiabetic, antidiarrhoeal, hepatoprotective, anticancer, antioxidant, anti-inflammatory, antiestrogenic, and antibacterial activities which support its traditional uses. The exhibited pharmacological activities reported may be attributed to the numerous bioactive compounds present in different parts of P. guajava. Based on the beneficial effects of P. guajava as well as its bioactive constituents, it can be exploited in the development of pharmaceutical products and functional foods. However, there is a need for comprehensive studies in clinical trials to establish the safe doses and efficacy of P. guajava for the treatment of several diseases.

Keywords

Phytochemistry

Pharmacological

Psidium guajava

Traditional uses

Toxicity Profile

Show Related Articles from PubMed

P. guajava: Psidium guajava
HPLC-ESI-QTOF-MS: High-Performance liquid chromatography coupled to electrospray ionization and quadrupole time-of-flight mass spectrometry
GC-FID: Gas Chromatography/Flame Ionization Detector
GC–MS: Gas chromatography/Mass spectrometry
HPLC: High-Performance liquid chromatography
HPLC-DAD: High-Performance Liquid Chromatography with Diode Array Detection.
UPLC-ESI-QTOF-MS: Ultra-Performance liquid chromatography coupled with electrospray ionization tandem quadrupole time-of-flight mass spectrometry
HPLC: High-Performance Liquid Chromatography
HPLC-PDA: High-Performance liquid chromatography photodiode array detection
MIC: Minimum inhibitory concentration
IC₅₀: Half maximal inhibitory concentration
CCl₄: Carbon tetrachloride
ALT: Alanine aminotransferase
AST: Aspartate aminotransferase
ALP: Alkaline phosphatase
GGT: Gamma glutamyl transferase
DPPH: 2,2-diphenyl-1-picrylhydrazyl
NIST: National Institute of Science and Technology
MCF-7 cell: Michigan Cancer Foundation-7
HCT116: Human Colorectal carcinoma cell line
HT29: Human Colon cancer cell line

1 Introduction

Globally, medicinal plants and its bioactive constituents are used for the treatment of various diseases. It has been reported that over 80% of the world's population uses medicinal plants or its bioactive compounds for the prevention, management, or treatment of several diseases (Joshi, 2013, Pant, 2014; Ugbogu et al., 2021 ). Recently, the uses of medicinal plants or their biologically active compounds have attracted the attention of many scientists/researchers because of their use in drug discovery or discovery of natural constituents for therapeutics (Dimmito et al., 2021, Sinan et al., 2021) and in ethnomedicinal uses for the treatment of life-threatening diseases such as cancer, diabetes, and hypertension (Sofowora et al., 2013, WHO, 2019). Psidium guajava is one of the plants used in traditional medicine for the treatment of various diseases.

Psidium guajava L. is commonly known as guava. It is a tropical shrub tree and food plant that belongs to the Myrtaceae family (Ravi and Divyashree, 2014). It grows up to 10 m and is widely distributed in many countries. Psidium guajava L. is an economically important food plant with diverse medicinal properties. It has a short trunk, patchy, smooth, and peeling bark. The leaves are fleshy dark green with prominent veins (Morais-Braga et al., 2016a; Naseer et al., 2018). It has white flowers, and the fruit contains pulp and small hard seeds (Morais-Braga et al., 2016a) Fig. 1.

Various parts of P. guajava L., chemical constituents, and pharmacological activities.

In ethnomedicine, the various parts of P. guajava – the stem, bark (Beidokhti et al., 2020), fruits, leaves, and roots (Weli et al., 2019) are used in the treatment of diseases such as diarrhea, rheumatism, and diabetes (Gutiérrez et al., 2008, Morais-Braga et al., 2016b, Díaz-de-Cerio et al., 2017 ), digestive problems, laryngitis, ulcers, malaria, cough, and bacterial infections (Ravi and Divyashree, 2014, Díaz-de-Cerio et al., 2017), wound healing and pain relief (Metwally et al., 2010). Many natives consume decoction, infusion, and/or boiled preparations of P. guajava either orally or topically depending on the type of illnesses (Díaz-de-Cerio et al., 2017). For instance, P. guajava leaves can be applied on wounds whereas aqueous leaf extract can be orally consumed to lower the blood glucose level in diabetic patients (Gutierrez et al., 2008).

Psidium guajava consists of important chemical constituents such as flavonoids, tannins, phenols, alkaloids, triterpenes, saponins, carotenoids, lectins, vitamins, carbohydrate, fiber fatty acids, and glycosides (Gutiérrez et al., 2008, Weli et al., 2019). The leaves have a plethora of beneficial phenolic compounds such as guaijaverin, quercetin, kaempferol, apigenin, catechin, chlorogenic acid, hyperin, gallic acid, epicatechin, myricetin, caffeic acid, and epigallocatechin gallate (Kumar et al., 2021).

Studies have shown the abundance of the following essential oils; β-bisabolene, caryophyllene oxide, β-copanene, farnesene, longicyclene, humlene, selinene, cardinene, curcumene, β-caryophyllene, pinene, caryophyllene oxide, 1,8-cineeole and limonene in the leaves of P. guajava (Begum et al., 2004, Gutiérrez et al., 2008, De Souza et al., 2017, Weli et al., 2019 ) Fig. 1. The fruit is a rich source of dietary fibre (pectin), protein, vitamins (A and C), and minerals (iron, phosphorus, and calcium) (Naseer et al., 2018).

In 2009, P. guajava L. was listed in WHO monographs as one of the selected medicinal plants with supported clinical data; however, they reported that there is no information on its uses in pharmacopoeias and internal index components (WHO, 2009).

Pharmacological studies have demonstrated that P. guajava extracts possess antimutagenic, lipid-lowering, analgesic, anti-hyperglycemic effect, anti-inflammatory (Vasconcelos et al., 2017), adaptogenic, antidiabetics (Khan et al., 2013, Zhu et al., 2020), anticestodal, antidiarrheal (Koriem et al., 2019), anti-angiogenesis, hepato-protective (Vijayakumar et al., 2020), antioxidant (Laily et al., 2015, Flores et al., 2015), anticancer (Lin and Lin, 2020), antimicrobial (Silva et al., 2018), cardioprotective, spermatoprotective, anti-hypertensive, antiparasitic, and anticough activities (Gutiérrez et al., 2008, Ravi and Divyashree, 2014, Kumar et al., 2021 ) Fig. 1. The pharmacological activities exhibited by P. guajava may be attributed to the numerous bioactive compounds present in the plant.

The aim of this study is to comprehensively review past scientific literatures and provide up-to-update information on the ethnomedicinal uses, phytochemical constituents, in vitro and in vivo pharmacological activities of P. guajava.

2 Materials and methods

2.1

2.1 Search strategy and study selection

In the search of materials for this study, the following search queries or keywords were used “Psidium”, “guajava”, “Psidium guajava”, “Psidium guajava pharmacological”, “Psidium guajava toxicity” and other related words in combination with words related to botanical description, taxonomical grouping, ethnopharmacological uses, phytochemical constituents, bioactive constituents, essential oils and pharmacological activities to find relevant peer-reviewed journals on four scientific databases, namely: PubMed (https://pubmed.ncbi.nlm.nih.gov/), ScienceDirect (https://www.sciencedirect.com/), Wiley (https://www.wiley.com/en-us) and Springer (https://www.springer.com/gp). Only papers that were published in English language were used for this study. Chemical structures identified from the plant were searched in NIST Chemistry Webbook, ChemSpider, and PubChem databases. The identified structures were drawn using ChemDraw (version 12.0.2).

3 Botanical description

Psidium guajava is a member of the Myrtaceae family. It is a small tree approximately 10 m high with a characteristic thin, smooth, patchy, and peeling bark (Gutiérrez et al., 2008). Guava trees usually have wide-spreading branches (Flores et al., 2015). The leaves have an elliptical and oval shape with a dark green colour and obtuse-type apex (Kumar et al., 2021). The leaves lie opposite each other and possess a short-petiolate with prominent veins. The plant has numerous stamens and showy, whitish petals. Its flowers are between 4 and 6 white petals and white stamens with yellow anthers (Flores et al., 2015). Guava fruits appear very fleshy. Their shape ranges from a yellowish globose to ovoid berry. Their mesocarp is edible with several small hard white seeds (Gutiérrez et al., 2008). Different cultivars possess varying morphology of the skin of the fruit (Flores et al., 2015).

4 Geographical description and taxonomy

The Guava plant is a tropical plant indigenous to the Colombia, Mexico, Peru and United States of America (Gutiérrez et al., 2008; Hirudkar et al., 2020). It is commonly distributed in the regions like India, Indonesia, Pakistan, Bangladesh (Kumar et al., 2021), Nigeria, South Africa, Malaysia, Bolivia, Cambodia, Cameroon, Philippines, Costa Rica, Senegal, Brazil, Ghana, Haiti, Cuba, Ethiopia, Kenya, Trinidad, Uganda, Namibia, Bangladesh, China and Sri Lanka (Gutierrez et al., 2008; Morais-Braga et al., 2016a; Weli et al., 2019 ). It is also found in Arabic countries such as Egypt, Oman, Saudi Arabia, Palestine, Sudan, Syria, and Tunisia (Abdelrahim et al., 2002; Qabaha, 2013, Weli et al., 2019 ) Fig. 2. Aboriginal peoples of the tropical and subtropical regions across the world cultivate the plant as food. It adapts to varying climatic conditions, although it thrives better in dry climates (Gutiérrez et al., 2008).

Map of worldwide distribution of Psidium guajava L., the blue colour shows the native regions like Colombia, Mexico, Peru and United States of America, whereas the green colour represents the introduced countries such as Australia, Bangladesh, Brunei, Cambodia, Cameroon, China, Costa Rica, Cote d'Ivoire, Cuba, Dominican Republic, Ecuador, Eritrea, Ethiopia, Fiji, Gabon, Gambia, Greece, Guyana, Haiti, India, Indonesia, Israel, Kenya, Laos, Malawi, Malaysia, Myanmar, Nigeria, Pakistan, Panama, Philippines, Puerto Rico, Samoa, Senegal, South Africa, Sri Lanka, Tanzania, Thailand, Togo, Uganda, Venezuela, Vietnam, Egypt, Oman, Saudi Arabia, Palestine, Sudan, Syria and Tunisia.

5 Traditional/ethnomedicinal uses

Different countries have unique applications of the various parts (i.e., roots, leaves, bark, stem, and fruits) of the guava plants for medicinal purposes. These parts have been utilized for treating stomach-related diseases, diabetes, diarrhea, and other forms of disease conditions (Kumar et al., 2021). Asian countries have adopted the use of guava leaves to develop traditional medicines for the treatment of diabetes (Kumar et al., 2021). Indonesians use guava leaves, pulp, and seeds for treating respiratory and gastrointestinal disorders, as well as for increasing blood platelets in dengue fever patients (Laily et al., 2015). Also, guava leaves have been used therapeutically due to their antiamoebic, antispasmodic, antidiarrhoeal antiinflammatory, antihypertension, antiobesity, and antidiabetic properties (Chen and Yen, 2007, Hirudkar et al., 2020).

Digestive disorders can be treated using young leaves of the guava plant. Decoction of the young leaves and shoots of the plant possess febrifuge and spasmolytic properties. Natives employ the flowers to cool the body and treat bronchitis, as well as eye sores. The fruit can also serve as a tonic and laxative. Patients with bleeding gums can also receive treatment with the fruit extract (Begum et al., 2002). South Africans use leaves of P. guajava for treating diabetes and hypertension (Oh et al., 2005). In Madagascar, the bark of the plant is used in addition to the leaves for the treatment of diabetes (Beidokhti et al., 2020). Brazilians use P. guajava for treating dental and oral diseases. The leaves and bark peels are consumed, either swallowed or mashed whilst still hot, as a tea formulation to combat thrush.

Nigerians employ decoction of the plant for treating microbial infections. In Mexico, Brazil, Philippine, and Nigeria, P. guajava is used to prepare a poultice for skin and wound applications (Gutiérrez et al., 2008).

Digestive disorders and severe diarrhoea are treated by natives of Nahuatll and Maya origin, as well as Veracruz, using the leaf decoction. Indigenous people of Veracruz use the water leaf extract as a hot tea preparation to control blood glucose level in diabetes patients. Mexicans also handle gastrointestinal and respiratory disturbances using the plant extract– as well as for the treatment of inflammation (Gutiérrez et al., 2008).

Latin Americans and people of the Caribbean use guava for the treatment of diarrhoea and stomach pains (Gutiérrez et al., 2008). In Panama, the guava plant is used for treating dysentery. In Uruguay, formulations are prepared from the decoction of the leaves as a vaginal and uterine wash, especially for cases of leucorrhoea. In Costa Rica, preparations are made from the decoction of the flower buds as therapeutics for inflammation (Gutiérrez et al., 2008).

In Peru, gargles are formulated from the plant for treating gastroenteritis, dysentery, stomach pain, indigestion, inflammations of the mouth and throat. Leaf and bark decoctions of guava plants are also used by Tikuna Indians for treatment of gastrointestinal tract diseases (Gutiérrez et al., 2008). The Indians of the Amazons use decoctions of the plant leaves and bark for treating dysentery, sore throats, vomiting, stomach upsets, vertigo, mouth sores, as well as for regulating menstrual periods (Gutiérrez et al., 2008). West Indians use the leaves and shoots in febrifuge and antispasmodic baths. The Chinese use guava leaves as an antiseptic and anti-diarrhoea agent. Brazilians consume preparations of the plant fruit and leaves for treating anorexia, cholera, diarrhoea, digestive problems, dysentery, gastric insufficiency, inflamed mucous membranes, laryngitis, mouth (swelling), skin problems, sore throat, ulcers, and vaginal discharge (Holetz et al., 2002).

6 Phytochemistry

The study of Díaz-de-cerio et al. (2016) reported the presence of 72 phenolic constituents in guava leaves using high-performance liquid chromatography coupled to electrospray ionization and quadrupole time-of-flight mass spectrometry (HPLC-ESI-QTOF-MS). De Araújo et al., (2014) quantified the polyphenolic content (gallic acid and catechin) of P. guajava leaves using high-performance liquid chromatography (HPLC). Results of the study showed the presence of condensed tannins (catechins) and hydrolysable tannins (gallic acid) in P. guajava leaves (Table 1). Phytochemical studies of P. guajava leaves by Bhagavathy et al. (2018) using gas chromatography and mass spectrometry (GC–MS) confirmed the presence of carotenoids, flavonoids, alkaloids, polyphenols, saponins, tannins, glycosides and sterols. Babatola and Oboh (2021) characterized and quantified the phenolic constituent of guava leaves using HPLC-DAD, the major compounds identified include: chlorogenic acid, rutin, vanillic acid, quercetin, and p-hydroxyl benzoic acid, syringic acid, kaempferol, myricetin, isoquercetin, and apigenin. Bezerra et al. (2018, 2020) analyzed the chemical constituents of two fractions, viz. flavonoid and tannic fractions extracted from P. guajava leaves using UPLC-ESI-QTOF-MS. In the flavonoids fraction, reynoutrina (quercetin-3-O-β-D-xylopyranoside), guajaverina (quercetin-3-O-α-L-arabinopyranoside) and Morin), a condensed tannin (Catechin), and two hydrolysable tannins (ellagic acid and guavinoside B), an acetophenone (myrciaphenone B) were identified, whereas in the tannic fraction two flavonoids (quercetin and 2,6-dihydroxy-3-methyl-4-O-(6″-O-galloyl-β-D-glucopyranosyl)-benzophenone), a condensed tannin (catechin), a hydrolysable tannin (guayinoside C), and an elagotonine (vescalagin/Castalagin isomer, (1S*,5S*)-2,2-bis(biphenyl-4-yl)-5- indian-1-yltetrahydrofuran (IV-81)). Hseih et al. (2007) reported the presence of the following phenolic compounds; gallic acid, ferulic acid, and quercetin, in P. guajava leaves. Eidenberger et al. (2013) demonstrated that ethanolic extract of guava leaves contain seven main flavonol-glycosides through semipreparative HPLC analysis. They include; peltatoside quercetin-3-O-arabinoglucoside, hyperoside, quercetin-3-β-O-arabinoglucoside, isoquercetrin, quercetin-3-O-β-glucoside, guaijaverin, and quercetin-3-O-α-L-arabinopyranoside (Table 1). Flores et al. (2015) identified the following chemical compounds; delphinidin-3-O-glucoside and cyanidin-3-O-glucoside, myricetin-3-O-arabinoside, myricetin-3-O-xyloside, isorhamnetin-3-O-galactopyranoside, myricetin-3-O-glucoside, gallocatechin-(4α-8)-gallocatechol, gallocatechin-(4α-8)-catechin, abscisic acid, turpinionoside A, pinfaensin, pedunculoside, guavenoic acid, madecassiac acid and asiastic acid from guava cultivars (Table 1).

The chemical constituents present in the essential oil of P. guajava include; α-pinene, β-pinene, β-myrcene, linalool, α-terpineol, δ-3-carene, limonene, eucalyptol, trans-caryophyllene, α-humulene, γ-muurolene, β-selinene, α-selinene, α-bisabolene β-bisabolene, trans-nerolidol, epi-β-cubenol, epi-α-cadinol, hinesol, 14-hydroxy-9-epi-(e)-caryophyllene, β-bisabolol, α-bisabolol, iso-caryophyllene, veridiflorene, β-caryophyllene, farnesene, dl-limonene, δ-cadinene, α-copaene, β-copaene, aromadendene, elemol, scadinol, 1,8-cineole, trans-calamenene, junipene, α-gurjunene, cis-ocimene, β-ocimene, aromadendene, α-muurolene, δ-cadinol, β-eudesmol, γ-eudesmol, α-cedrene, Ɗ-Limoene, globulol, viridiflorol, cubenol, tau-muurolol, cis-lanceol, α-acorenol, epiglobulol, spathulenol, ledol and caryophyllene oxide (De Souza et al., 2018; Weli et al., 2019; Hassan et al., 2020 ) (Table 2).

7 Pharmacological activities of P. guajava

7.1

7.1 Antidiabetic activity

Several researchers have investigated the antidiabetic potential of P. guajava (Huang et al., 2011, Khan et al., 2013, Luo et al., 2019, Zhu et al., 2020; Uuh-Narvaez et al., 2021 ). Rai et al. (2009, 2010) reported that raw fruit peels and aqueous unripe fruit peels extracts of P. guajava exhibited hypoglycaemic effect in streptozotocin-induced diabetic rats. Supplementation of 125 and 250 mg/kg of guava fruit for 4 weeks in streptozotocin (STZ)-induced diabetic rats reduced blood glucose levels (Huang et al., 2011). Ojewole (2005) observed that the aqueous P. guajava leaf extracts have a hypoglycaemic effect in diabetic rats (Table 3). Rajpat and Kumar (2021) revealed that 200 mg/kg ethanolic extract of P. guajava leaves extract reduced blood glucose levels in diabetic mice. Shen et al. (2008) posited that guava leaf aqueous extract reduces blood glucose level and accelerates plasma insulin level. Oral administration of 300 mg/kg body weight/day of P. guajava leaf extract for 30 days to STZ-induced diabetes rats decreased blood glucose levels (Subramanian et al., 2009).

Table 3 Pharmacological activities of Psidium guajava plant.

Doses	Experimental models	Observation	Effects	References
Psidium guajava dissolved in 125 μL tryptic soy broth	Streptococcus salivarius, Streptococcus mutans, Streptococcus mitis, Streptococcus sanguinis and Streptococcus sobrinus	Inhibitory activity (500–100 μg/mL) against all Streptococcus species used.	Antibacterial activity	Silva et al. (2018)
1000, 500, 250 and 125 μg/ml of essential oils extracted from Psidium guajava	Enterococcus faecalis, S. aureus, Streptococcus aureus, E. coli, Haemophilus influenzae and P. aeruginosa	Inhibitory activity against Enterococcus faecalis and Streptococcus aureus.	Antibacterial activity	Weli et al. (2019)
25, 50, 100 and 150 μgml⁻¹	E. coli, Klebsiella pneumoniae and Salmonella typhimurium	40 μgml⁻1 induced a 90% inhibition of Klebsiella spp. and 30% inhibition of Proteus spp.	Antibacterial activity	Pelegrini et al. (2008)
1024 μg/mL of Psidium guajava extracts	E. coli, P. aeruginosa and S. aureus	Extract produced an MIC value of 256 μg/mL against S. aureus	Antibacterial activity	Morais-Braga et al. (2016a,b)
Chemical constituents isolated from Psidium guajava	S. aureus, S. epidermidis, and Mycobacterium Smegmatis	Psidinone extracted showed inhibitory activity with MIC values of 16, 8, and 0.5 μM respectively.	Antibacterial activity	Huang et al. (2021)
Dilutions of methanol, chloroform and hexane extracts of Psidium guajava	Agrobacterium tumefaciens	IC₅₀ values; 65.02 μg/mL, 160.7 μg/mL and 337.4 μg/mL for hexane, chloroform and methanol extracts	Antitumor activity	Ashraf et al. (2016)
0.5 mL dilutions of methanol, chloroform and hexane extracts ofPsidium guajava	Brine shrimp; Artemia salina nauplii	IC₅₀ values of 32.18 μg/mL, 41.05 μg/mL 63.81 μg/mL for hexane, chloroform and methanol extracts	Anticancer activity	Ashraf et al. (2016)
16,384 μg/mL of Psidium guajava	Fungal strains of C. albicans and C. tropicals	IC₅₀ value of 3235.94 μg/mL	Antifungal activity	Morais-Braga et al. (2015)
1000 to 5 μg mL⁻¹ of concentrated Psidium guajava	C. albicans, C. krusei, C. glabrata	Antifungal activity against C. glabrata with MIC value of 80 μg/mL	Antifungal activity	Fernandes et al. (2014)
250, 500 and 1000 μg/mL of Psidium guajava	3 × 10⁴ per millilitre of Trypanosoma cruzi epimastigote	Hydroethanolic extract of Psidium guajava led to death of mammalian cells at 76.30%	Antiparasitic activity	Machado et al. (2018)
75 mg/kg of ethanolic extract of Psidium guajava	2x10⁵ Giardia lamblia cysts /0.1 mL intraesophageally in rats	Extract produced a percentage reduction in trophozoite count	Antiparasitic activity	Khedr et al. (2021)
8, 40 and 200 μg/ml of guava seed polysaccharides	2 × 10⁵ cells/ml of MCF-7 cells	Extracts at the concentration (40 and 200 μg/mL) inhibited MCF-7 cell viability.	Anticancer activity	Lin and Lin (2020)
800 to 6.25 μg/mL of lycopene extracted from Psidium guajava.	2 × 10⁵ cells/ml of MCF-7 cells	Extract at the concentration (5.964 μg/mL) inhibited MCF-7 cell viability.	Anticancer activity	dos Santos et al. (2017)
20 to 100 μM of compounds separated from Psidium guajava	HCT116 and HT29 cells	After 72 h of administration compound extracted inhibited growth of cells at 81.4% with IC₅₀ value of 60 μM	Anticancer activity	Zhu et al. (2020)
10 to 100 mg/mL of methanol, hexane and chloroform of Psidium guajava extracts	KBM5, SCC4 and U266	Hexane extract showed maximum inhibitory activity against cancer cells with IC₅₀ value less than 30 mg/mL	Anticancer activity	Ashraf et al. (2016)
50 mg/kg of water and fractionated extracts of Psidium guajava	0.3 mol L⁻¹ of Citric acid aerosol in cognizant guinea pigs	After 30mins of administration antitussive activity becomes prominent with suppression of cough	Antitussive activity	Khawas et al. (2018)
1,2,5 g/kg of Psidium guajava leaf extract	30 μmol of capsaicin induced in rats and guinea pigs	Doses suppressed cough by 16%, 35% and 54% respectively after 10 mins	Anticough activity	Jaiarj et al. (1999)
12.5, 25 and 50 mg/kg of extracts fractionated from P. guajava	0.3 mg/kg of 17 β-estradiol in female Wistar rats	Administration of extracts inhibited the proliferative effect of 17 β-estradiol on the uterus.	Anti-estrogenic activity	Bazioli et al. (2020)
125 and 250 mg/kg of P. guajava	55 mg/kg of STZ in male Sprague–Dawley rats	Reduction of blood glucose levels and amelioration of STZ-induced weight loss	Anti-diabetic activity	Huang et al. (2011)
300 mg/kg of P. guajava extracts	50 mg/kg of STZ in rats	Increase in levels of glycosylated hemoglobin, insulin, glucose and restoration of normal hexokinase activity	Anti-diabetic activity	Khan et al. (2013)
Doses of flavonoids extracted from guava leaves	40 mg/kg of STZ in rats	Regulation of fasting blood glucose levels	Anti-diabetic activity	Zhu et al. (2020)
25, 50 mg/kg of P. guajava extract	55 mg/kg of STZ in female Sprague–Dawley rats	Reduction of blood glucose levels	Anti-diabetic activity	Soman et al. (2013)
200 mg/kg of P. guajava extract	70 mg/kg of STZ in rats	Reduction of blood glucose levels	Anti-diabetic activity	Rajpat and Kumar (2021)
1.00, 0.50 and 0.75 g/kg of ethanolic P. guajava extract	100 mg/kg of alloxan tetrahydrate in Wistar rats	Reduction of blood glucose levels	Anti-diabetic activity	Mazumdar et al. (2015)
200 mg/kg of guava leaf extracts	40 mg/kg of STZ in rats	Increase in levels of antioxidants and insulin signalling genes	Anti-diabetic activity	Jayachandran et al. (2020)
300 mg/kg of ethanolic extract of P. guajava	1.5 mL/kg of carbon tetrachloride (CCl₄)	Decrease in serum levels of ALT, AST, and ALP	Hepatoprotective activity	Vijayakumar et al. (2020)
250 and 500 mg/kg of Psidium guajava and P. cattleianum extracts	Single dose of paracetamol (600 mg/kg)	Decrease in serum levels of AST, ALT, and ALP	Hepatoprotective activity	Saber et al. (2018)
0.2 mL of guava leaf solution	1 mL of 0.2mM 2,2-diphenyl-1-picrylhydrazyl (DPPH) ethanolic solution	Production of an antioxidant content value of 201.71 mg BHA eqv · g⁻¹	Antioxidant activity	Laily et al. (2015)
50 μL aliquot of P. guajava sample	150 μL of 400μM DPPH	High antioxidant activity in DPPH and ABTS assays	Antioxidant activity	Flores et al. (2015)
1 mL of chloroform, methanolic and hexane extracts of P. guajava	4 mL of 0.1 mM DPPH	High antioxidative activity of methanolic extract	Antioxidant activity	Ashraf et al. (2016)
200 μL of essential oils derived from P. guajava	50 μL of 1 mM DPPH	Reduction of DPPH radical.	Antioxidant activity	Lee et al. (2012)
100 μL of solution silver nanoparticles from P. guajava	200 μL of 100 μM DPPH methanol solution	Antioxidant activity increased in dose dependent manner	Antioxidant activity	Wang et al. (2018)
100 μL guava extract solution	100 μL of 0.5 mmo1/L DPPH solution	Presence of poly phenols induced good antioxidant activity	Antioxidant activity	Tan et al. (2020)
90 μL of 1000–50 μg/mL P. guajavaextracts and fractions	2.7 mL of Ferric reducing antioxidant power (FRAP) reagent	Flavonoid fraction showed highest antioxidant with lowest EC₅₀ value	Antioxidant activity	Sobral-Souza et al. (2018)
50 μL of P. guajava leaf fractions	1 mL of 0.1 mM DPPH	Methanolic extract showed the most antioxidant activity	Antioxidant activity	Zahin et al. (2017)
Water extract (WE-PGL) and sulfate polysaccharide (PS-PGL) fraction of P. guajava	DPPH radicals	PS-PGL produced IC₅₀ value of 0.02 mg/mL whilst WE-PGL produced 0.11 mg/mL against hydroxyl radical	Antioxidant activity	Kim et al. (2016)
25, 50 and 100 mg/kg of lycopene extracted from guava leaves	50 μL of a Carrageenan suspension in Swiss mice	Extract at high doses inhibited formation of edema	Anti-inflammatory activity	Vasconcelos et al. (2017)
50–200 mg/kg of P. guajava extract	0.1 mL of a carrageenan suspension in rats	Inhibition of edema	Anti-inflammatory activity	Olajide et al. (1999)
50 and 100 mg/kg of P. guajava extracts	Lactose containing diet in mice	Reversal of abnormalities in serum electrolytes and urine levels	Antidiarrheal activity	Koriem et al. (2019)
100, 200, 400 mg/kg of P. guajava extracts	1 mL of 3.29 × 10⁹ CFU/ml of Escherichia coli in rats	Reduction in number and weight of stools	Antidiarrheal activity	Hirudkar et al. (2020)
250 mg/kg, 500 mg/kg and 750 mg/kg of P. guajava extracts	2 mL of castor oil in rats	Reduced number of wetted feaces and drop in frequency of stooling	Antidiarrheal activity	Mazumdar et al. (2015)

Uuh-Narvaez et al. (2021) posited that 10 mg/kg of edible parts P. guajava administered to diabetic rodents demonstrated high antihyperglycemic activity. Mazumdar et al. (2015) showed that ethanolic extracts of P. guajava administered to alloxan-induced diabetic rats reduced the blood glucose concentration. Jayachandran et al. (2020) investigated the activity of 200 mg/kg b.w of P. guajava extract against the insulin signalling proteins of streptozotocin-induced diabetic rats and reported antidiabetic activity of P. guajava because of its regulation of insulin signalling pathway genes.

Beidokhti et al. (2020) stated that leaf and bark extracts of P. guajava effectively improved glucose uptake in muscle cells and inhibited α-amylase, respectively. Yang et al. (2020) reported that guava leaf extract reduced fasting plasma glucose, fasting insulin, and insulin resistance in KK-Ay diabetic mice. P guajava leaves extract decreased fasting blood glucose, lipid level, and altered glucose metabolism in STZ-induced diabetic rats (Khan et al., 2013, Xu et al., 2020) (Table 3).

Supplementation of flavonoids extracted from P. guajava markedly reduced fasting plasma glucose, glucose tolerance, and insulin resistance in diabetic mice (Zhu et al., 2020). Luo et al. (2019) opined that polysaccharide from guava leave exhibited anti-diabetic effects in STZ-induced diabetic mice. Shabbir et al. (2020) reported blood glucose level reduction potential of polyphenol extracted from guava pulp, seeds, and leaves in diabetic mice. These antidiabetic activities could be due to the ability of P. guajava to increase levels of glycogen synthase and decrease in the activity of the enzyme; glycogen phosphorylase (Tella et al., 2019).

7.2

7.2 Hepatoprotective activity

Vijayakumar et al. (2020) assessed the hepatoprotective effect of P. guajava against carbon tetrachloride-induced damage in rats. Hepatotoxicity was induced in the liver by the administration of 1.5 mL/kg of carbon tetrachloride (CCl₄) in rats. Daily oral administration of the extract for 21 days decreased the CCl₄ induced increase in serum levels of liver biomarkers (ALT, AST, ALP, and GGT). A similar result was observed by Roy and Das (2010). Saber et al. (2018) studied the effects of P. guajava in combination with P. cattleianum against paracetamol-induced toxicity in rats. The pre-administration of the extract at 250 and 500 mg/kg reduced elevated levels of liver enzymes ameliorating hepatotoxicity. The hepatoprotective effects of aqueous unripe P. guajava fruit peel extract in STZ-induced diabetic rats were evaluated by Rai et al. (2010). They observed a significant decrease in ALP, AST, ALT, indicating hepatoprotective effects of unripe P. guajava fruit peel. P. guajava extract treatment at the doses of 100, 200, and 300 mg/kg, bw and 20 mg/kg of quercetin fraction decreased lipid metabolism in CCl₄-induced hepatotoxic rats (Vijayakumar et al., 2018). Li et al. (2021) reported that triterpenoid-enriched guava leaf extract reduced serum ALT and AST levels, and hepatic ROS and MDA in acetaminophen-exposed C57BL/6 male mice. Li et al. (2020) posited that 100 mg/kg/day of Guavinoside B extracted from guava fruit markedly improved serum and hepatic biochemical parameters in acetaminophen-induced liver injury in mice (Table 3).

7.3

7.3 Antioxidant activity

Scientific studies have reported the antioxidant activities of P. guajava (Laily et al., 2015, Flores et al., 2015, Li et al., 2015; Ashraf et al., 2016 ). Tan et al., (2020) investigated the antioxidative properties of extracts derived from red and white P. guajava fruits through different drying processes. Findings from this study revealed maximum antioxidant activity in red P. guajava powders extracted by vacuum drying compared to other drying methods. Sobral-Souza et al. (2018) reported the antioxidative ability of flavonoids extracted from extracts of P. guajava.

Luo et al. (2019) opined that polysaccharide from guava leaves exhibited antioxidant activities by increasing the total antioxidant activity and superoxide dismutase (SOD) enzyme and lower MDA activities in STZ-induced diabetic mice. Methanolic leaf extract of P. guajava fraction showed antioxidant activity (Khedr et al., 2021).

Zahin et al. (2017) revealed that P. guajava fractionated in methanol possesses maximum antioxidant activity compared to other solvents; petrol, benzene, acetone, and ethyl acetate. Kim et al. (2016) evaluated the antioxidative properties of polysaccharides extracted from P. guajava using hydroxyl radical and 2,2-diphenyl-1-picrylhydrazyl (DPPH). Results from the study of Kim et al. (2016) showed that the extract possesses strong antioxidant activity against hydroxyl radicals. Wang et al. (2018) observed strong antioxidant ability of silver nanoparticles extracted from P. guajava. Lee et al. (2012) reported moderate antioxidant activities of essential oil (EO) extracted from guava leaves. Feng et al. (2015) examined the antioxidative effects of compounds isolated from P. guajava. Results from this study revealed guavinoside C, guavinoside F, quercetin, quercetin-3-O-a-L-arabinofuranoside and quercetin-3-O-a-L-arabinopyranoside showed strong antioxidant activity using DPPH assay. The antioxidant activity of P. guajava extracts might be due to the presence of high phenolic compounds (Hartati et al., 2020) (Table 3).

7.4

7.4 Anti-inflammatory activity

Vasconcelos et al. (2017) investigated the anti-inflammatory activity of lycopene extracted from guava and lycopene purified from guava against carrageenan-induced paw edema. Edema in experimental rats was induced using a single injection of 50 μL of a carrageenan suspension. 25, 50, and 100 mg/kg of lycopene extracted from guava were administered alongside indomethacin. Findings from this study revealed the inhibition of edema by extract at a high dose (50 mg/kg). Olajide et al. (1999) evaluated the anti-inflammatory activity of rats against Carrageenan-induced rat paw edema. Rats were pre-administered P. guajava extracts at doses between 50 and 200 mg/kg. Results revealed the significant inhibitory activity of P. guajava on edema formation processes (Table 3).

7.5

7.5 Antidiarrhoeal activity

Koriem et al. (2019) assessed the antidiarrhoeal activity of P. guajava extracts against lactose-containing diet-induced osmotic diarrhoea in rats (Table 3). Rats in treatment groups were administered 50 and 100 mg/kg of P. guajava extracts daily for 1 month. Desmopressin was used as the standard drug. Administration of extract revealed a return to normal volume of urine excretion and serum electrolytes. Lipid peroxidation was reduced, emphasizing the extract’s antidiarrheal activity. Hirudkar et al. (2020) evaluated the antidiarrhoeal effect of P. guajava extracts against enteropathogenic Escherichia coli in rats. Diarrhoea was induced in rats by administration of 1 mL of 3.29 × 10⁹ CFU/ml of enteropathogenic Escherichia coli. Findings from this study revealed the administration of the extract at 100, 200, 400 mg/kg induced a reduction in the total number of diarrhoeal stools, a decline in the weight of stools, and reduced mean defecation rate of stools in treatment groups. A reversal in declined values of WBC, Hb, and platelets also indicated the antidiarrhoeal ability of the extract. Mazumdar et al. (2015) examined the effect of ethanolic extract of P. guajava on castor oil-induced diarrhoea in rats. Doses of 250 mg/kg, 500 mg/kg, and 750 mg/kg of the plant’s extract were administered and 2 mg/kg of loperamide was used as a standard drug. Mazumdar et al. (2015) reported that the administration of extract induced a reduction in defecation frequency and the number of wetted faeces. Lutterodt (1992) assessed the propulsion rates in the small intestine of microlax induced diarrhoea in rats. Leaf extract of P. guajava at doses ranging from 50 to 400 mg/kg p.o. produced anti-diarrhoeal effect against castor oil-induced diarrhoea in rats and mice (Ojewole et al., 2008). P. guajava exhibited anti-inflammatory activity (Jang et al., 2014). El-Ahmady et al. (2013) reported that P. guajava leaf oil has anti-inflammatory activity. Results showed the extract exhibits a similar inhibition rate compared to the standard drug, morphine sulphate injection used (Table 3).

7.6

7.6 Antibacterial activity

Abdelrahim et al. (2002) stated that the aqueous bark and methanolic extracts of P. guajava possess anti-bacterial activity. Dutta et al. (2020) reported that benzyl isocyanate obtained from methanol extract of P. guajava leaves inhibited S. aureus. P. guajava leaves extract reduced virulence of P. aeruginosa, C. violaceum, S. aureus and S. marcescens (Patel et al. 2019) (Table 3). Essential oil of the senescent leaves of P. guajava inhibited human pathogenic bacteria and plant pathogenic fungi, namely C. lunata and F. chlamydosporum (Chaturvedi et al., 2021).

Silva et al. (2018) showed that extracts of P. guajava exhibited antibacterial activity against bacterial species; Streptococcus salivarius, Streptococcus mutans, Streptococcus mitis, Streptococcus sanguinis, and Streptococcus sobrinus. Weli et al. (2019) studied the antibacterial activity of essential oils derived from P. guajava against; Enterococcus faecalis and Staphylococcus aureus. Findings revealed P. guajava possesses significant antibacterial activity at all tested doses; 125, 250, 500 and 1000 μg/ml against tested doses. Pelegrini et al. (2008) revealed that the extracts of P. guajava inhibited the growth of Klebsiella pneumoniae. Morais-Braga et al. (2016b) showed strong activity against Escherichia coli, Pseudomonas aeruginosa, Staphyloccocus aureus. The extract showed strong activity against Staphyloccocus aureus exhibiting a MIC value of 256 μg/mL. Huang et al. (2021) showed that chemical constituents isolated from P. guajava inhibited Staphylococcus aureus, Staphylococcus epidermidis and Mycobacterium Smegmatis (Table 3).

7.7

7.7 Anticough activity

Jaiarj et al. (1999) investigated the anticough mechanism of P. guajava leaf extracts in rats and guinea pigs. A dose of 30 μmol of capsaicin was used to induce cough in rats and guinea pigs (Table 3). Animals in treatment groups were intraperitoneally administered extracts at 1, 2 and 5 g/kg. Findings from this study revealed the suppression of cough in a dose-dependent manner by the extracts. This result emphasizes the therapeutic effect of P. guajava on this disorder.

7.8

7.8 Anticancer activity

Lin and Lin (2020) evaluated the anticancer activity of guava seed polysaccharides on MCF-7 cells. Findings from this study revealed the inhibition of MCF-7 cell viability significantly in a dose-dependent manner. dos Santos et al. (2017) investigated the anticancer activity of extracts obtained from red P. guajava. dos Santos et al. (2017) revealed the inhibitory activity of lycopene-rich extract of P. guajava with IC50 value of 29.85 at 5.964 μg/mL. In another study, Zhu et al. (2019) identified compounds exhibiting anticancer activity against HCT116 and HT29 cells. Ashraf et al. (2016) showed the maximum inhibitory activity of P. guajava against cancer cells with IC₅₀ value of less than 30 mg/mL (Table 3). The anticancer activity of P. guajava might be due to the presence of bioactive components; tetracosane, vitamin E, and g-sitosterol (Ryu et al., 2021) (Table 3).

7.9

7.9 Antiestrogenic activity

Bazioli et al. (2020) investigated the antiestrogenic effects of extracts fractionated from P. guajava. In vitro and in vivo studies were carried out on 17-β-estradiol inoculated in MCF7 BUS cells and female Wistar rats respectively. 1 × 10⁴ cell mL⁻¹ of MCF7 BUS cells in the presence of 10^-9M 17 β-estradiol were treated with 0.3, 0.6, 1.25, and 2.5 μg/mL of fractionated P. guajava extracts. Experimental rats were inoculated with 0.3 mg/kg of 17-β-estradiol and treated with 12.5, 25, and 50 mg/kg of extracts fractionated from P. guajava for 3 days. Results from both in vitro and in vivo assays revealed inhibition of the proliferative activity of 17-β-estradiol upon administration of extracts suggesting its antiproliferative activity (Table 3).

7.10

7.10 Toxicological evaluation

Legba et al. (2019) reported that P. guajava does not have any toxic effect on the liver and kidney of Wistar rats. Manekeng et al. (2019) evaluated the possible toxicological effects of methanolic extracts of P. guajava. Findings from this study revealed no mortality from the administration of extracts at 5000 mg/kg on experimental rats (Table 3). Evaluations of haematological parameters showed no significant differences in levels of white blood cells, lymphocytes, monocytes, granulocytes, haemoglobin, haematocrit, mean corpuscular hemoglobin concentration and mean corpuscular haemoglobin except platelet levels in experimental male rats at 1000 mg/kg. Observation of serum biochemical parameters showed a significant decrease in total protein levels, alanine aminotransferase, aspartate aminotransferase, total cholesterol, and low-density lipoprotein cholesterol levels. Manekeng et al. (2019) also reported no significant injuries observed from histopathological evaluations of kidneys of male experimental rats. Information gathered from this study emphasizes the low-toxic nature of P. guajava.

8 Conclusion

This study revealed that many researchers have conducted in-depth in vivo and in vitro studies to validate the acclaimed use of P. guajava in disease prevention, management, and treatment. In their studies, they reported that P. guajava has antioxidant and heptoprotective activities and can be used in the treatment of plethora of health abnormalities such as cough, cancer, bacterial infection, diarrhoea, inflammation, and diabetes. The health-promoting capacity of P. guajava has been linked to the presence of vital phytochemicals, essential oils, and biological active components present in the plant. Based on the beneficial effects of P. guajava as well as its bioactive constituents, it can be exploited in the development of pharmaceutical products and functional foods. However, there is need for comprehensive studies in clinical trials to establish the safe doses and efficacy of P. guajava for the treatment of several diseases.

Funding

No specific funding was provided for this work.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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Name of compound	Chemical structure	Method of identification	Pharmacological activity	References
Gallic acid		High-Performance Liquid Chromatography with diode-array detection coupled to electrospray ionization quadrupole time-of-flight mass spectrometry (HPLC-DAD-ESI-QTOF-MS) analysis of phenolic fraction of P. guajava leaves using an ultrasound bath and a mixture of ethanol:water 80/20 (v/v) (Díaz-de-cerio et al., 2016)	Anti-inflammatory, Antifungal activities	Alves et al. (2014); De Araújo et al. (2014)
Pedunculagin		HPLC-DAD-ESI-QTOF-MS analysis of phenolic fraction of P. guajava leaves using an ultrasound bath and a mixture of ethanol:water 80/20 (v/v) (Díaz-de-cerio et al., 2016)	Anti-diabetic activity	Eidenberger et al. (2013)
Casuariin		HPLC-DAD-ESI-QTOF-MS analysis of phenolic fraction of P. guajava leaves using an ultrasound bath and a mixture of ethanol:water 80/20 (v/v) (Díaz-de-cerio et al., 2016)	Anticoagulant, Anti-hypertensive activities	Dong et al. (1998); Xie et al. (2007)
Prodelphinidin dimer isomer		HPLC-DAD-ESI-QTOF-MS analysis of phenolic fraction of P. guajava leaves using an ultrasound bath and a mixture of ethanol:water 80/20 (v/v) (Díaz-de-cerio et al., 2016)	Antioxidant activity	Ma et al. (2019)
Gallocatechin		HPLC-DAD-ESI-QTOF-MS analysis of phenolic fraction of P. guajava leaves using an ultrasound bath and a mixture of ethanol:water 80/20 (v/v) (Díaz-de-cerio et al., 2016)	Anti-aggregation activity	Sohail et al. (2018)
Catechin		HPLC-DAD-ESI-QTOF-MS analysis of phenolic fraction of P. guajava leaves using an ultrasound bath and a mixture of ethanol:water 80/20 (v/v) (Díaz-de-cerio et al., 2016)	Anti-inflammatory, Antifungal activities	De Araújo et al. (2014); Bezerra et al. (2018)
Chlorogenic acid		HPLC-DAD analysis using phenolic fraction of guava leaves (Babatola and Oboh, 2021)	Potential anti-inflammatory activity	Bhandarkar et al. (2019)
Rutin		HPLC-DAD analysis using phenolic fraction of guava leaves (Babatola and Oboh, 2021)	Antitumor, Antimicrobial, Antidiabetic activities	Budzynska et al. (2019); Ghorbani (2017)
Vanillic acid		HPLC-DAD analysis using phenolic fraction of guava leaves (Babatola and Oboh, 2021)	Antioxidative activity	Yao et al. (2020)
Quercetin		HPLC-DAD analysis using phenolic fraction of guava leaves (Babatola and Oboh, 2021)	Anti-hypertensive, Antimicrobial, Antioxidant, Antidiarrhea activities	Alves et al. (2014); Hirudkar et al. (2020); Marunaka et al. (2017)
p-hydroxyl benzoic acid		HPLC-DAD analysis using phenolic fraction of guava leaves (Babatola and Oboh, 2021)	Anti-inflammatory activity	Banti et al. (2021)
Syringic acid		HPLC-DAD analysis using phenolic fraction of guava leaves (Babatola and Oboh, 2021)	Anti-inflammatory, Anti-microbial activities	Liu et al. (2020)
Kaempferol		HPLC-DAD analysis using phenolic fraction of guava leaves (Babatola and Oboh, 2021)	Anti-inflammatory, Antimicrobial, Antioxidant activities	Alam et al. (2020); Bezerra et al. (2018)
Myricetin		HPLC-DAD analysis using phenolic fraction of guava leaves (Babatola and Oboh, 2021)	Cardioprotective activities	Wang et al. (2019)
Isoquercetin		HPLC-DAD analysis using phenolic fraction of guava leaves (Babatola and Oboh, 2021)	Neuroprotective activities	Dai et al. (2018)
Apigenin		HPLC-DAD analysis using phenolic fraction of guava leaves (Babatola and Oboh, 2021)	Anticancer activities	Imran et al. (2020)
Cinnamic acid		HPLC-DAD analysis using phenolic fraction of guava leaves (Babatola and Oboh, 2021)	Anti-inflammatory activities	Karatas et al. (2020)
Luteolin		HPLC-DAD analysis using phenolic fraction of guava leaves (Babatola and Oboh, 2021)	Anti-inflammatory, Antifungal activities	Zhang et al. (2018)
Reynoutrina (quercetin-3-O-β-D-xylopyranoside)	‘	Ultrafine liquid chromatography coupled to quadruple time-of-flight (UPLC-QTOF) analysis flavonoid fraction of guava leaves (Bezerra et al., 2018)	Anti-inflammatory activities	Yang et al. (2021)
Guajaverina (quercetin-3-O-α-L-arabinopyranoside)		UPLC-QTOF analysis flavonoid fraction of guava leaves (Bezerra et al., 2018)	Antifungal, Antibacterial activities	Ukwueze et al. (2015)
Morin		UPLC-QTOF analysis flavonoid fraction of guava leaves (Bezerra et al., 2018)	Anti-mastitis, Antimicrobial, Antioxidant activities	Jiang et al. (2020)
Ellagic acid		UPLC-QTOF analysis flavonoid fraction of guava leaves (Bezerra et al., 2018)	Anti-inflammatory activities	Bensaad et al. (2017)
Guavinoside B		UPLC-QTOF analysis flavonoid fraction of guava leaves (Bezerra et al., 2018)	Hepatoprotective activity	Li et al. (2020)
Myrciaphenone B		UPLC-QTOF analysis flavonoid fraction of guava leaves (Bezerra et al., 2018)	Anti-fungal activities	De Leo et al. (2004)
Vescalagin		UPLC-QTOF analysis flavonoid fraction of guava leaves (Bezerra et al., 2018)	Anticancer activities	Kamada et al. (2018)
Castalagin Isomer		UPLC-QTOF analysis flavonoid fraction of guava leaves (Bezerra et al., 2018)	Anticancer activity	Kamada et al. (2018)
Hyperoside		High-Performance Liquid Chromatography coupled to Ultraviolet light and Mass spectrometry (HPLC/UV/MS) analysis of 80% ethanolic extract of guava leaves (Eidenberger et al., 2013)	Anticancer activity	Qiu et al. (2019)
Quercetin-3-O-β-glucoside		HPLC/UV/MS analysis of 80% ethanolic extract of guava leaves (Eidenberger et al., 2013)	Neuroprotective activities	Magalingam et al. (2016)
Guaijaverin		HPLC/UV/MS analysis of 80% ethanolic extract of guava leaves (Eidenberger et al., 2013)	Antimicrobial activities	Prabu et al. (2006)
Quercetin-3-O-α-L-arabinopyranoside		HPLC/UV/MS analysis of 80% ethanolic extract of guava leaves (Eidenberger et al., 2013)	Anti-inflammatory activity	Kim et al. (2018)
Delphinidin-3-O-glucoside		High-Performance Liquid Chromatography coupled to Photodiode-Array Detection (HPLC-PDA) analysis of guava pulp extracted using CH₃OH/H₂0/formic acid (Flores et al., 2015)	Anticancer activity	Mazewski et al. (2019)
Cyanidin-3-O-glucoside		HPLC-PDA analysis of guava pulp extracted using CH₃OH/H₂0/formic acid (Flores et al., 2015)	Anti-obesity activity	Molonia et al. (2020)
Pedunculoside		HPLC-PDA analysis of guava pulp extracted using CH₃OH/H₂0/formic acid (Flores et al., 2015)	Antihyperlipidemic activities	Liu et al. (2018)
Madecassiac acid		HPLC-PDA analysis of guava pulp extracted using CH₃OH/H₂0/formic acid (Flores et al., 2015)	Anticancer activities	Valdeira et al. (2019)
Asiastic acid		HPLC-PDA analysis of guava pulp extracted using CH₃OH/H₂0/formic acid (Flores et al., 2015)	Anti-inflammatory activities	Hao et al. (2017)
Ursolic acid		Thin layer chromatography (TLC) analysis of fresh ethanol leaf extract of P. guajava (Begum et al., 2004)	Anti-inflammatory, anticancer, antidiabetic, antioxidant, and antibacterial activities	Hsieh et al. (2007); Mlala et al. (2019)
Oleanolic acid		Thin layer chromatography (TLC) analysis of fresh ethanol leaf extract of P. guajava (Begum et al., 2004)	Antitumor, Anti-diabetic, Antimicrobial, Hepatoprotective actiivities	Hsieh et al. (2007); Ayeleso et al. (2017)
Beta-sitosterol glucoside		Thin layer chromatography (TLC) analysis of ethanol leaf extract of P. guajava (Begum et al., 2002)	Anticancer, apoptogenic activity	Vo et al. (2020); Dolai et al. (2016)
Methyl gallate		HPLC-UV analysis of leaf extract of P. guajava (Farag et al., 2020)	Antileishmanial,antioxidant, anti-inflammatory, antimicrobial and anti-tumor activities	Dias et al. (2020); Anzoise et al. (2018)
Epicatechin		HPLC–DAD of hydroethanolic or aqueous extract of P. guajava leaves (Morais-Braga et al., 2017)	Anticoagulant, Pro-fibrinolytic, enzyme-inhibitory activities	Sinegre et al. (2019); Wu et al. (2019)
Procyanidin		HPLC-DAD-ESI-QTOF-MS analysis of phenolic fraction of P. guajava leaves using an ultrasound bath and a mixture of ethanol:water 80/20 (v/v) (Díaz-de-cerio et al., 2016)	Antioxidant activity	Hsieh et al. (2007); Ma et al. (2019)
Protocatechuic acid		LC-HRMS-MS with the OLE Ultra-High-Performance Liquid Chromatography (UHPLC) analysis of P. guajava leaf decoction (Lorena et al., 2022)	Antioxidative, Neuroprotective, Anti-atherosclerotic activities	Krzysztoforska et al. (2019); Zheng et al. (2020)
Caffeic acid		HPLC–DAD of hydroethanolic or aqueous extract of P. guajava leaves (Morais-Braga et al., 2017)	Neuroprotective, enzyme-inhibitory activities	Habtemariam (2017); Zhang et al. (2019); Maruyama et al. (2018)

Name of compound	Method of identification	Pharamacological activity	References
Limonene	Gas chromatography coupled to Flame ionized detector or Gas chromatography coupled to mass spectrometry (GC-FID/GC–MS) of P. guajava leaves hydrolate (De Souza et al., 2018)	Antitumor, antiviral, anti-inflammatory, antibacterial, anticancer activities	De Souza et al. (2017); Mukhtar et al. (2018)
Eucalyptol	GC-FID/GC–MS of P. guajava leaves hydrolate (De Souza et al., 2018)	Retinoprotective activity	Kim et al. (2020); Hassan et al. (2020)
Trans-Caryophyllene	GC-FID/GC–MS) of P. guajava leaves hydrolate (De Souza et al., 2018)	Antileishmanial, antischistosomal, antifungal activities	De Souza et al. (2017)
α-Humulene	GC-FID/GC–MS of P. guajava leaves hydrolate (De Souza et al., 2018)	Antiinflammatory	De Souza et al. (2017); Hassan et al. (2020)
γ-Muurolene	GC-FID/GC–MS of P. guajava leaves hydrolate (De Souza et al., 2018)	Antifungal, antimicrobial, and anticancer activities	Doan et al. (2021)
β-Selinene	GC-FID/GC–MS of P. guajava leaves hydrolate (De Souza et al., 2018)	Trypanocidal activity	De Souza et al. (2017); Fernandes et al. (2021); Hassan et al. (2020)
α-Selinene	GC-FID/GC–MS of P. guajava leaves hydrolate (De Souza et al., 2018)	Antifungal activity	De Souza et al. (2017); Oladeji et al. (2020)
β-Bisabolene	GC-FID/GC–MS of P. guajava leaves hydrolate (De Souza et al., 2018)	Cytotoxic activity	Yeo et al. (2016); Hassan et al. (2020)
Trans-Nerolidol	GC-FID/GC–MS of P. guajava leaves hydrolate (De Souza et al., 2018)	Antifungal activity	De Souza et al. (2017); Hassan et al. (2020)
Caryophyllene oxide	GC-FID/GC–MS of P. guajava leaves hydrolate (De Souza et al., 2018)	Antifungal and antibacterial activity	Policegoudra et al. (2012); Hassan et al. (2020)
Hinesol	GC-FID/GC–MS of P. guajava leaves hydrolate (De Souza et al., 2018)	Antitumor activity	De Souza et al. (2017); Guo et al. (2019)
β-Bisabolol	GC-FID/GC–MS of P. guajava leaves hydrolate (De Souza et al., 2018)	Antimicrobial, antitumor activities	De Souza et al. (2017)
α-Bisabolol	GC-FID/GC–MS of P. guajava leaves hydrolate (De Souza et al., 2018)	Antimicrobial, antitumor activities	De Souza et al. (2017)
Isocaryophyllene	Gas chromatography coupled to mass spectrometry (GC–MS) analysis of P. guajava leaves hydrolate (Weli et al., 2019)	Anticancer	Legault and Pichette (2010)
dl-limonene	GC–MS analysis of P. guajava leaves hydrolate (Weli et al., 2019)	Antiaflatoxigenic activity	Singh et al. (2010)
δ-cadinene	GC–MS analysis of P. guajava leaves hydrolate (Weli et al., 2019)	Larvicidal, Anticancer activities	Govindarajan et al. (2016); Hui et al. (2015);
α-copaene	GC–MS analysis of P. guajava leaves hydrolate (Weli et al., 2019)	Attractant activity	Kendra et al. (2017); Hassan et al. (2020)
Aromadendrene	GC–MS analysis of P. guajava leaves hydrolate (Weli et al., 2019)	Insecticidal activity	Hassan et al. (2020); Giuliani et al. (2020)
δ-cadinol	GC–MS analysis of P. guajava leaves hydrolate (Weli et al., 2019)	Anti-mildew	Su et al. (2015); Hassan et al. (2020)
Elemol	GC-FID/GC–MS of P. guajava hydrolate (De Souza et al., 2018)	Immunosuppressive activity	Yang et al. (2015)
γ-Eudesmol	GC-FID/GC–MS of P. guajava hydrolate (De Souza et al., 2018)	Cytotoxic activity	Britto et al. (2012); Hassan et al. (2020)
α-Bisabolene	GC-FID/GC–MS) of P. guajava hydrolate (De Souza et al., 2018)	Anti-cancer	Yeo et al. (2016)
α-Cedrene	GC-FID/GC–MS) of P. guajava hydrolate (De Souza et al., 2018)	Potential anti-obesity activity	Kim et al. (2015)
β-Eudesmol	GC-FID/GC–MS) of P. guajava hydrolate (De Souza et al., 2018)	Anti-allergic, anticancer, anti-angiogenic activities	Han et al. (2017); Narahara et al. (2020); Acharya et al. (2021)
Copaene	GC–MS analysis of methanolic extract of P. guajava leaves (Bhagavathy et al., 2018)	Cytotoxic activity	Türkez et al. (2014)
α-Pinene	GC–MS analysis of P. guajava leaves hydrolate extracted with hexane (Hassan et al., 2020)	Antioxodant, anti-inflamatory, anticancer, pro-osteogenic activities	Zhao et al. (2018); Min et al. (2020);
β-Myrcene	GC–MS analysis of P. guajava leaves hydrolate extracted with hexane (Hassan et al., 2020)	Anxiolytic, antioxidant, anti-ageing, anti-inflammatory, analgesic, genotoxic activities	Surendran et al. (2021); Orlando et al. (2019)
Linalool	GC–MS analysis of P. guajava leaves hydrolate extracted with hexane (Hassan et al., 2020)	Antibacterial, anti-inflammatory, anticancer, anti-hyperlipidemic, antinoceptive, analgesic, anxiolytic activities	Sabogal-Guáqueta et al. (2019)
α-Terpineol	GC–MS analysis of P. guajava leaves hydrolate extracted with hexane (Hassan et al., 2020)	Cytotoxic, antitumor, antidiarrheal,	Negreiros et al. (2021); Dos Santos Negreiros et al. (2019)
δ-3 carene	GC–MS analysis of P. guajava leaves hydrolate extracted with hexane (Hassan et al., 2020)	Sleep-enhancing, anti-inflammatory, antimicrobial, anxiolytic activities	Woo et al. (2019); Shu et al. (2019)
Ɗ-Limoene	GC–MS analysis of P. guajava leaves hydrolate extracted with hexane (Hassan et al., 2020)	Antioxidant, antidiabetic, anticancer, anti-inflammatory	Anandakumar et al. (2021); Seo et al. (2020)
Epiglobulol	GC–MS analysis of P. guajava leaves hydrolate extracted with hexane (Hassan et al., 2020)	Antimicrobial activity	Kim and Shin (2004)
Spathulenol	GC–MS analysis of P. guajava leaves hydrolate extracted with hexane (Hassan et al., 2020)	Antioxidant, anti-inflammatory, antiproliferative activities	do Nascimento et al. (2018); Ziaei et al. (2011); Lou et al. (2019)
Globulol	GC–MS analysis of P. guajava leaves hydrolate extracted with hexane (Hassan et al., 2020)	Potential antimicrobial activity	Tan et al. (2008)
Viridiflorol	GC–MS analysis of P. guajava leaves hydrolate extracted with hexane (Hassan et al., 2020)	Anti-inflammatory, antioxidant, antibacterial activities	Trevizan et al. (2016)
β-Caryophyllene	GC–MS analysis of P. guajava leaves hydrolate extracted with hexane (Hassan et al., 2020)	Neuroprotective, anticancer, analgesic, anti-inflammatory, wound-healing, antimicrobial activities	Scandiffio et al. (2020); Koyama et al. (2019); Yoo and Jwa (2018)
Ledol	GC–MS analysis of P. guajava leaves hydrolate extracted with hexane (Hassan et al., 2020)	Antitumor activity	Cianfaglione et al. (2017)

The ethnobotanical, phytochemistry and pharmacological activities of Psidium guajava L.

Abstract

Keywords

Phytochemistry

Pharmacological

Psidium guajava

Traditional uses

Toxicity Profile

Abbreviations

1 Introduction

2 Materials and methods

2.1 Search strategy and study selection

3 Botanical description

4 Geographical description and taxonomy

5 Traditional/ethnomedicinal uses

6 Phytochemistry

7 Pharmacological activities of P. guajava

7.1 Antidiabetic activity

7.2 Hepatoprotective activity

7.3 Antioxidant activity

7.4 Anti-inflammatory activity

7.5 Antidiarrhoeal activity

7.6 Antibacterial activity

7.7 Anticough activity

7.8 Anticancer activity

7.9 Antiestrogenic activity

7.10 Toxicological evaluation

8 Conclusion

Funding

Declaration of Competing Interest

References

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