GUAVA

 GUAVA

Guava (Psidium guajava  L.) is  one of the famous fruit plant which contain a great number of bioactive compounds having beneficial role to human health. Due to its multidirectional health benefits the fruit is often called as “super food”. It has been valued as a food and medicinal plant since ancient time. Over a long period the fruit is only consumed by the people of tropical and subtropical region (Deguchi et al. 2010). Guava is a familiar fruit in the daily life of most parts of world because of its characteristic flavour, availabity throught the year and less expensive price. Since past few decades the fruit has gained high demand due to its health benefits. It is believed to have originated from Mexico or Central America and is now very popular in Asian countries and is also increasingly available in other countries, particularly after the exposure of information about its health benefits (Uzzaman et al. 2018). Due to its high demand it is abundantly cultivated in many parts of  tropical and subtropical countries. It is commercially cultivated for fruits. Major producer of  guava are India, China, Thailand, Pakistan, Mexico, Indonesia, Brazil, South Africa, Bangladesh, Philippines and Nigeria (Mitra et al. 2012). Most of the countries produce guava for domestic consumption but some countries like India, Pakistan and Brazil  are the larger exporters of  guava. There are many varieties of guava planted in various places of tropical and subtropical regions. The common types of guava include apple guava, yellow fruited cherry guava, strawberry guava, and red apple guava. Since recent few decades the fruit is utilized in processing of  jams, jellies, pickles, wines and many ready to serve beverages (Mitra et al. 2019). In different ancient document guava plant is considered as a source of various medicines and drugs. The pharmacological and medicinal attributes of the plant  have been confirmed by various experiments performed by recent researchers.

 

Botanical Characteristics:

Psidium guajava L.  is  a kind of evergreen perennial fruit tree with small to medium size which reaches to the height of 6 to 25 ft. Taxonomically it belongs to family Myrtaceae. The plant has a wide spreading network of branches which display opposite leaves. Leaves are stalked and petioles  are 3 to 16 cm in lenghth. The lamina are wide and clear green in color and have prominent veins (Rouseff et al. 2008). The plant is easy to recognize because of its smooth, thin, copper-colored bark that flakes off. The roots are very extensive and superficial. The plant produces white flowers with incurved petals having a nice fragrant. Every flower has 4-5 green sepals (6-15 mm long) that are fused together at the base and also 4-5 petals (10-20 mm long). There are  a large numbers (200- 250) of small white stamens (6-10 mm long) and a style (6-12 mm long) topped with a stigma (Uzzaman et al. 2018). Flowers are pollinated by insects (Naseer et al. 2018). Shape of the fruits are extremely variable. It may be round, ovoid, or pear-shaped and with an average diameter and weight ranging from 4-10cm and 100-400g respectively (Ngbolua et al. 2018). The skin of fruit is dark green in young stage and becomes light green in mature stage and turns yellow-green on ripening. After ripening the fruit has a musky special odour which is strong but pleasant. The pulp is fleshy, of varying thickness, and the color may be white, yellow, red or pink depending on the variety. The seeds are numerous, yellowish, bony and reniform (Jaiswal et al. 2005).

 

Bioactive Compounds:

Since ancient times plants are considered as the important sources nurtrionally and medicinally valuable bioactive compounds. Till date a huge number of novel pharmacologically active compounds with many famous drurgs were derived directly or indirectly from plants. Recently rese Since ancient time guava has been widely acknowledged as nutritionally and medicinally valuable plant. The plant has also attracted the attention of researchers  as the plant  is a rich source of various  secondary metabolites with pharmacological activities. The major bioactive compounds of guava are vitamins, tannins, flavonoids, phenolic compounds, essential oils, sesquiterpene alcohols and triterpenoid acids (Smith et al. 1975; Barbalho et al. 2012; Silva et al,2019). Such chemical compounds have been found in measurable amount from fruits, leaves, bark and root of the plant. Generally, such active compounds  do not play vital role in the metabolism of plants, so it is often referred to as secondary metabolites (Stepp et al. 2001). But they have been used to treat many human ailments by acting as antioxidant, antidiabetic, anti-inflammatory, anti-diarrhoea, hypolipidaemia, and anticancer. Fruits of  P. guajava contains 80-90% water and 10-20% solid substances and having calorific value of  42-64 cal/ 100g edible part (Chafer et al. 2003). Their density, specific heat and thermal conductivity are 1050 kg/m³, 3.97 kJ/kg°C and 0.56 W/m°C, respectively (Chen et al. 2006; Arevalo-Pinedo et al. 2007). Among the fruits guava has high amounts of  nutrients, antioxidants and other bioactive compounds having health benefits. The fruit is an outstanding source of  antioxidants like ascorbic acid (Vitamin C), carotenoids, and polyphenols. Depending on variety the amount of ascorbic acid ranges between 60-1000mg/100g. As per the information it has the second highest concentration of ascorbic acid after acerola cherries (Malpighia emarginata DC). The most important carotenoids which provide oxidative protection are α-carotene, β-carotene, lutein, lycopene, zeaxanthin, and β-cryptoxanthin (VERIS. 2000). Guava was  also found to contain alpha tocopherol (vitamin E) at nearly 1.7 mg/100g (Ching et al. 2001), which is an important fat-soluble dietary antioxidant. Among the tropical fruits guava is the top in repect of total phenolic compound. Guava are somewhat unusual in their flavonoid polyphenolic content as well, with significant levels of myricetin (55 mg/100g) and apigenin (58 mg/100g) present in edible tissues, but do not contain the more commonly found flavonoids quercetin and kaempferol (Miean et al. 2001) that are abundant in other fruits and vegetables. In addition it also contain significant levels of citric acid, essential oils, oleanolic acid, lyxopyranoside, arabopyranoside, guaijavarin, quercetin, phenols, triterpenes, flavonoids, saponins, lectins, fiber and fatty acids as well as pectin (Arima et al. 2002; Kamath et al. 2008; Das et al. 2011; Rana et al. 2015). In addition the fruits have considerable levels of minerals including phosphorus, calcium, iron and vitamins such as niacin, pantothenic acid, thiamin, riboflavin and vitamin A (Das et al. 2011) . Manganese is also present in the plant in combination with phosphoric, oxalic and malic acids (Nadkarni et al.1999) .The fruits are completely free of sodium (Chafer et al. 2003). All the bioactive compounds have  significant health benefits.

 

Ascorbic acid is actively involved in neutralizing free radicals and protects from oxidative damage. Ascorbic acid and Citric acid are found to have anti-mutagenic activity (Grover et al.1993). The wonder pigment Carotenoids have demonstrated many beneficial health effects related to their antioxidant properties (Wilberg et al.1995) . Beneficial health effects of carotenoids includes cancer inhibition, immuno-enhacement, and prevention of cardiovascular diseases (Wilberg et al.1995) . Lycopene, an important carotenoid of guava, has reported a superior antioxidant activity in relation to lutein or β-carotene, due to its conjugated double bonds (Lin et al.2003) . The strong pleasant smell of fruit is credited to the carbonyl compounds (Chen et al.2010). There are 41 hydrocarbons 25 esters, 13 alcohols and 9 aromatic compounds in guava  (Vernin et al.1991). Among  them major constituents are hydrocarbon (α-pinene, β-caryophellene), alcohol (hexanol, terpineol, cis-3-hexenol) and ester (ethyl acetate, cis-hexenyl acetate) and similar compounds (Pino et al.2001) . Titratable acid and the total soluble solids are also present in fruit (Reyes et al.1995). The fruit contains 4.14-4.30% ‘glycosen’, 1.62% - 3.40% saccharose, 0.3% proteins (Begum et al.2004) .

 

Leaves of P. guajava are used as astringent, anodyne, febrifuge, antispasmodic and tonic (Anjaria et al.2002). From the ancient time guava leaves  has been used as medicines by traditional medicine practitioners. The guava leaves are used in the treatment of colic, diarrhoea, diabetes, cough, pain,  high cholesterol, heart disease, pain, weight loss, and cancer (Rana et al. 2020). Leaves of the plant contain various compounds namely menthol, α-pinene, β-bisabolene, β-pinene, β-copanene, limonene, terpenyl acetate, isopropyl alcohol, caryophyllene, longicyclene, cineol, euginol, avicularin, quercetin, longicyclene, caryophyllene oxide, humulene, farnesene, selinene, curcumene and cardinene (Oliver-Bever,1986; Lin et al. 2003). Oleanolic acid is also found in the guava leaves (Begum et al.2004) . Leaves have high content of limonene about 42.1% and caryophyllene about 21.3%  (Ogunwande et al.,2003). Leaves of guava have a lot of volatile compounds. Among the essential oil of leaves, 6% is fixed oil , 0.365% is volatile oil is  (Taylor et al. 2001), 3.15% is resin  and 8.5% is tannin. In addition a number of other fixed substances  like cellulose, fats, chlorophylls, mineral salts are also found in leaves (Nadkarni et al.1999) .

 

The bark includes 12–30% of tannin and one source declares that it includes tannin 27.4%, or polyphenols, resin and the crystals of calcium oxalate. It has a huge content of antimicrobial and antibacterial compounds (Rahim et al. 2010). The roots are also rich in tannin (Quisumbing 1978). The plant also contains leukocyanadins  sterols, and gallic acid in the roots (Michael et al. 2002) . There is a high percentage of carbohydrates and salts. Root, stem-bark and leaves contain a large percentage of tannic acid. The seeds which are very small but abundant in the fruit and have been reported to  contain 14% oil on dry weight, with 15% proteins and 13% starch (Burkill 1997). Ten phenolic and flavonoid compounds including one new acylated flavonol glycosidewere isolated. In addition to such compound the twigs of the plant contain significant amount of calcium [0.30-1.00%], magnesium [0.06-0.30%], phosphorous [0.10-0.38%], potassium [0.21-0.39%], sodium [0.03-0.20%], copper [0.02-0.14 ppm], iron [2.86-5.14 ppm] zinc [0.31-0.57 ppm], manganese [0.00-0.26 ppm], lead [0.00-0.11 ppm]   and  fluoride [0.02-0.11ppm] (Okwu et al. 2003) .

 

Medicinal importance:

Psidium guajava L. is an important fruit crop with high therapeutic value of its biochemical constituents. Various parts of the plant have been used as folk medicines for long time in different countries and civilizations. With the increase of popularity of  folk medicine and alternative medicine many parts of developed countries consider such plant parts as medicines. From ancient literature it is well known that the plant is used for the cure of different sickness like diarrhea, dysntry, vomiting, gastroenteritis,wounds, ulcers, toothache, malaria, coughs, fever, sorethroat, inflamed gums, diabetes, sterility, cadiac problems, cancers etc ((Lutterodt 1992; Jaiarj et al. 1999; Abdelrahim et al. 2002). Though the plant is used traditionally for a number of ailments since a long time but scientific investigations on the medicinal properties of plant products date back to the 1940s (Daswani et al. 2017). Till then laboratory studies and clinical trials provide a strong scientific evidence in support of  ethnobotanical and ethnopharma-cological properties of guava plant.

 

Antioxidant activity:

Almost all parts of  guava plant contains high amount of anti-oxidants, which are essential to control the free radical activities in human body. Antioxidants refers the natural and semi-synthetic substances which retard the oxidation process. Antioxidant compounds reduce or inhibit oxidation reaction by terminating free radicals which damage cells in  various ways. Such damages are responsible for several metabolic diseases and physiological abnormality in humans. A majority  of complex diseases and disorders are the consequence of  imbalance in the pro-oxidation and anti-oxidation reaction occurring in the living system (Chakraborty et al. 2019). Ascorbic acid found in fruits and leaves is the well known antioxidant having multitudinous health benefits (Fleuriet et al. 2003;  Soman et al. 2010; Manikandan et al. 2015) Several experiments found that the plants also contain some flavonoides having antioxidant activity (Fleuriet et al. 2003). Such antioxidants have both preventive and curative activity on human health. Some workers claimed  that higher amount of antioxidants in guava fruit is very beneficial to infertile male because antioxidants can improve  the quality and quantity of sperm (Akinola et al. 2007).S ome studies revealed that guava has radio-protective ability with antioxidant activity (He et al. 2004). In some study it is found that guava has some remarkable antioxidant contents which can significantly increase percentage of neutrophils (Ulvie et al. 2014). Leaves of guava has a  strong antioxidant - Quercetin, which play a pivotal role in balancing of  radical (Soman et al. 2010) . The antioxidative potential the plant has rendered a new therapeutic route against the various complications and diseases. Presently investigators are involved in  further research to find the actual mechanism involved in antioxidant activity and their probable side effect if any.

 

Antimicrobial activity:

From last few decades scientists and doctors face the problem of growing resistance against the doses of useful antimicrobial drugs. Thus the outlook of such drugs in the near future is still uncertain. It is also fact that high doses of such antimicrobial drugs are also harmful to organs of human body  as well as to the  beneficial microorganisms within  human body. Thus there is an increase demand for complementary and alternative medicines. In many ancient documents of   folk medicine  it  is considered that the bioactive compounds in fruits and leaf extract of guava help to treat and manage various microbial diseases. Morais Braga et al. (2016), in their recent review have stated that guava has efficacy against 34 bacterial species, 19 fungal species, 6 protozoal species, and 4 types of viruses (Morais Braga et al. 2016). Many antibacterial compounds were isolated from the leaves of P. guajava. Flavonoids extracted from guava leaves were found to be active against the several strains of spoilage and food borne pathogenic microbes  like fungi and bacteria (Akangi et al..2009). The antibacterial activity of guava is high against gram positive bacteria and moderate against the gram negative bacterial strains (Nair et al..2007). Guava leaf extract has high antibacterial activity that can inhibits the growth of Staphylococcus  aureus significantly (Naseer et al. 2018). Methanolic extracts of  leaf and bark of the plant have high antimicrobial activity against some bacterial species belonging to genus  Bacillus and Salmonella (Joseph et al. 2007). Methanol and acetone extract of  leaves also exhibited antibacterial activity against several Gram positive and Gram negative bacteria such as Staphylococcus spp, Bacillus subtilis, Micrococcus flavus, Pseudomonas spp., and Escherichia coli (Nair et al..2007). The flavonoid compounds and their derivatives in guava  inhibit the multiplication of bacteria in the human body and also prevent the adherence of bacteria to the healthy cells of the body (Arima et al. 2002; Prabu et al. 2006; Metwally et al. 2011). Aqueous extract of leaves  shows moderate antimicrobial activity against Propionibacterium acnes due to presence of terpinene and pinene (Pandey et al. 2018). It is also found that extracts of the leaves are effective inhibitors of growth, sporulation and enterotoxin production of some bacterial strain like Clostridum prefringens type A (Garcia et al. 2002).Some researchers claimed that the aqueous extracts were more potent in inhibiting the growth of pathogenic  bacteria like Proteus mirabilis, Streptococcus pyogenes, Escherichia coli, Staphylococcus aureus and Pseudomonas aeroginosa than the organic extracts (Abdelrahim et al. 2002; Abubakar 2009)

 

Methanolic extract of guava root has antifungal activity and most of the researchers believed that quercetin is key compound for fungicidal properties (Prabu et al. 2006). Flakes of bark also showed antifungal property however it exhibited only fungistatic property against Candida albicans, Candida parasilosis  and Candida neoformans (Abdelrahim 2002; Dutta et al. 2000; Chanda et al. 2011). Leaf extract of the plant is also effective against some harmful fungi. Different concentrations (20% -100%) of essential oil extracted from guava leaves were found to inhibit dermatophytes  like Microsporium canis, Trichophytom ruburum, Trichophyton verrucosum, Trichophyton tonsurans  (Bhushan et al. 2014). Hot water extract and the methanol extract of leaves also show antifungal activity against Arthrinium sacchari and Chaetomium funicola strains (Sato et al. 2010). It has been reported that these oils and extracts penetrate the lipid bilayer of the cell membrane, rendering it more permeable, leading to the leakage of vital cellular contents (Juven et al. 1994; Burt 2014).

 

Guava fruits probably contain some antiviral agents and probably such antiviral components have the ability to degrade essential proteins of viruses (Banu et al. 2012). It is widely believed that guava fruit  can prevent infections of influenza virus and allied virues (Jaiarj et al. 1999) . Some study claimed that few phytoconstituents of  guava can inhibit viral hemagglutination and neuraminidase activity (Sriwilaijaroen et al. 2012) and thus protect human from the viral diseases. In an experiment the purified guava flavonoid glycosides (GFGs) showed to have competitive inhibitory activity against IAV virus replication via early regulation of IL-1β and IL-8, as well as with P53 gene expression (Khalil et al. 2018). The leaves of P. guajava were also  reported to possess retroviral reverse transcriptase inhibitor activity (Suthienkul et al. 1993; Metwally et al. 2011). In addition to antiviral activity the leaves also possesses antiamoebic activity which is concentrated in the polyphenolic fraction (Tona et al. 2000). The aqueous leaf, stem bark and fruit extracts of P. guajava L. were used to examine anti-plasmodial acivity (Patwardhan et al. 2005). In another study, it was found that leaves and stem bark of P. guajava inhibit the growth of  Entamoeba histolytica (Nundkumar et al. 2002). The leaf extracts also have trypanocidal activity which may be attributed mainly due to the broad antimicrobial property of the flavonoids and the iron chelating property of tannins (Adeyemi et al. 2009).

 

Antidiarrhoeal activity

Diarrhoea is one of most common and worldwide well recognized  health problem. Mostly it is caused by an infection in gastrointestinal tract but some time it is caused due impaired nutrient absorption, impaired digestive function, endocrinal imbalance, drugs or laxative intake etc. It is very common even in developed countries. Most recent evidences have shown that, the disorder affects almost 3–5 billion people every year and accounts for about 5-6 million deaths among children younger than 5 years of age (Hirudkar et al. 2020).  Several experiments on diarrhoea model  revealed that fruits and leaves of guava have excellent antidiarrhoeal activity. Since a long time peoples of various regions use guava leaves in various ways to treat diarrhoea.Various investigations on  chemical induced diarrhoea model showed thatit the leaves of the P. guajava consist significant antidiarrhoeal property (Ojewole et al. 2008; Lin et al. 2002). Some workers opined that the antidiarrhoeal property is due to its inhibitory effect on few pathogens responsible for diarrhea i.e., Escherichia coli, S. aureus etc (Vieira et al. 2001). Further research reported that  flavonoids and tannins are the active compound that exhibit the antidiarrhoeal activity through denaturing protein hence forming interaction protein-tannates which reduce the intestinal mucosal permeability (Ezekwesili et al. 2010). Quercetin of leaf is also thought  to have  antidiarrhoeal activity as it can repressed intestinal contraction encouraged by enhanced absorption of calcium and also facilitate ileum for its spasmolytic activity (Teixeira et al. 2010; Zhang et al. 2003; Mazumdar et al. 2015). Quercetin-3-arabinoside  has also been reported to  decrease spontaneous contraction of intestinal muscle by inhibition of  release of acetylcholine together with an initial increase in the muscle tone (Lutterodt et al. 1989). Some researchers found  that Lectin, which is a specific galactose of guava leaf, is an effective  inhibitor of the development of Escherichia coli, an agent that causes diarrhoea in organisms by preventing its adhesion to the gut wall (Coutino et al. 2001).The plants also contain some other phytoconstituents having beneficial activities against some gastro-intestinal disorders related to diarrhoea. Newer tender leaves are particularly rich in fiber and roughage which is crucial for the prevention and treatment of constipation and hemorrhoids. The alkaline nature of guava leaf gives very good response against hyperacidity of the stomach and subsequent ulceration of the stomach.

 

Anti-inflammatory and Immunostimulatory Activity:

Inflammation refers the complex biological response of vascular tissues occurs when cells and body tissues are injured by biological, chemical, or physical stimuli such as bacteria, trauma, toxins, or heat. In traditional medicine system different parts of the plant Psidium guajava has been used to treat different inflammatory diseases. It has been found that leaves and fruits of  P. guajava  showed immunomodulatory effect on both humoral and cell mediated immunity (Shabbir et al. 2016). Inflamation is a protective attempt by the organism to remove the injurious stimuli in body and it is also an initiation of the healing process for the tissue. All the parameters of immunity and anti-inflammatory activity, viz.,total leukocyte count, neutrophil count, lymphocyte count, monocyte count, RBC count, hemoglobin content, and platelet count etc are positively influenced by the consumption of fruits. The leaf extract is also effective against inflammation and similar responses. It was experimentally proved that different guava leaf extract compositions have different immunostimulatory effects on cell mediated immunity. It has tremendous capability to prevent the cyclophosphamide induced myelo-suppression and acceleration of delayed hypersensitivity (Shabbir et al. 2016). Many workers suggest that regular consumption of guava fruit stimulate macrophage mediated immune response. By stimulating macrophages, it also induces various immune responses. After stimulation macrophages induce the release proinflammatory mediators and proteins (Grip et al. 2003), including interleukin-6 (IL-6), tumor necrosis factor-a (TNF-a), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) (Rao et al. 2015). After inflammation wound healing, revomal of destructed residual etc are initiated. In the absence of inflammation, wounds and infections would never heal and progressive destruction of the tissue would compromise the survival of the organism (Rao et al. 2015). Pharmacological study also showed that whole plant extract is also effective in case of anti-inflamatory activity (Rai et al. 2007) and immunomodulation. Some parts of the plant has the efficiency to reduce autoimmuno disorders.  Guava leaves has been used for the treatment of various autoimmuno disorders including Rheumatoid arthritis (RA) (Gutierrez et al. 2008). Rheumatoid arthritis is an autoimmune disease that attacks the joints of the body and causes chronic inflammation in the synovium (Baroroh et al. 2015). Extensive investigations of various researchers concluded that the anti-inflammatory action of guava is associated with the ability to inhibit prostaglandin, kinin and histamine (Kavimani et al., 1998). However Olajide et al., (1999) concluded that (Olajide et al. 1999) the anti-inflamatory effects of guava leaves is also dependent on the essential oil. The leaves also inhibit histamine production due to insect bite and lessens the effects of allergies (Barbalho et al. 2012) and  thus leaf extract is also used as a useful remedy for insect bite. In addition it is also found that extract of guava in ethyl acetate can stop the germ infection and thymus production. Some molecular biological experiments  reveal that leaf extract can alter the activity of heme oxygenase-1 protein by enhancing the mRNA expression (Jeong et al. 2014). Benzophenone and flavonoids of guava effectively lower the inflammatory resposes by inhibition of  histamine and nitric acid production in human body (Matsuzaki et al. 2010). Guava extract also show anti-nociceptive activity by the production of  acetic acid (Chandra Sekhar et al. 2014). The dose of guava extracts are effective in liver damage inflammation and serum production (Roy et al. 2006).

 

Anticancer Effects

Cancer is a global health problem with high morbidity and mortality. It is a great economic and psychological challenge of this era. The classic methods of cancer treatments like surgery, radiation, chemotherapy are extremely hazardous for the patient and the success rate of such treatment against cancer is also very less. Therefore, oncologists are still searching for new anticancer drugs with more potent inhibitory and less side effects (Lajimi et al. 2010). There is no doubt that  effective plant-derived bioactive compound might target those molecules which regulate the cell cycle, cellular senescence, and apoptosis (Hsu et al. 2004). Many constituents of guava plant showed cancer suppressive activity when tested on various  cancer cell line of human,  including colon cancer, gastric cancer, liver tumour, pulmonary tumour, prostate cancer,  breast cancer, cervical cancer, glioma, lung fibroblast, leukemia etc. The consumption of guava fruit is reasonably helpful for the inhibition of growth of the cancerous cells and metastasis. Present investigators believed that ascorbic acid, apigenin and lycopene are the key molecules of guava which reduce the probability of cancer (Sato et al. 2010). In addition different composition of leaf extract were also reported to exhibit anticancerous activity. Some findings suggested that leaf extracts  have the potential to prevent or to inhibit the growth of tumors and cancers. An aqueous extract of P. guajava leaves has been reported to inhibit the viability of the cancer cell line DU-145 in a dose dependent manner. Some researchers also concluded that essential oils extracted from leaves of the plant was highly effective in reducing the growth of Pca DU-145 (the androgen independent Pca cells), human mouth epidermal carcinoma (KB) and murine leukemia (P388) (Joseph et al. 2011; Chen et al.2007). Some other workers confirmed that  essential oils of guava leaf has the highest antiproliferative activity with an IC50 value of 0.0379mg/ml on P388 cell lines, which is four times more potent than the widely known anticancerous drug vincristine (Chen et al. 2010;Joseph et al. 2011). It is also found that leaf extract exhibited the potential cytotoxic effect on human cervical cancer cell lines and it may have probable apoptotic activity. In an experiment on mice model it was concluded that leaf extract show chemopreventive effect on B16 melanoma cells.  The compound β-caryophyllene oxide isolated from the essential oil of P. guajava was reported to kill myeloma, prostate and breast cancer cell lines (Kim et al. 2014; Liu et al. 2020). Guava extract is also effective against breast cancer as it has estrogen-like activity and in an experiment guava extract is found useful for treating ER-positive breast cancer cells, such as MCF-7 cells (Rizzo et al. 2014). Some research findings concluded that aqueous extract of guava budding leaves possess anti-prostate cancer activity in a cell line model and concluded they are promising anti-androgen-sensitive prostate cancer agent (Yadav et al. 2010).

 

The Jacoumaric acid of seed extract also has antitumour effect and  it was found to significantly reduce the incidence of tumors (Numata et al. 1989). Phytochemical investigations of an acetone extract of Psidium guajava seeds has led to the isolation of many compounds which showed cytotoxic activities in vitro against Ehrlich Ascites Cells (EAC) and leukaemia P3888 cells (Numata et al. 1989).

 

Cardiovascular System Effects

Psidium guajava  has been reported to have action on the heart and cardiovascular system. Guava fruit is highly useful for the treatment of hypertension, hyperlipidemia and heart disease. It improves heart health, prevents stroke by controlling high blood pressure and lowering cholesterol. Different phytoconstituents of guava help in controlling blood pressure by relaxing blood vessels. According to modern researchers moderate intake of guava fruit in diet may alter the dietary fatty acids and carbohydrates levels which in turn  may decrease blood pressure and alter the lipoprotein metabolism. It lowers the levels of triglycerides along with cholesterol (LDL), which causes the advancement of heart disease but simultaneously improves levels of the good cholesterol i.e., HDL (Kaur et al. 2018). Arjunolic acid and presence of falvonoids  usually keep lipids in in normal range and  acts as cardio protective (Kumari et al. 2013). Guava fruits have high amount of potassium, a most important mineral that decreases the effects of sodium on the hypertension and  also helped in the expansion of the arteries and ensures smooth blood flow all over the body (Vijaya Anand et al. 2020). Moreover, Guava contains a high concentration of pectin which causes a significant reduction in the blood lipids by delaying absorption of the foods and thereby reduces the risk of cardiovascular illnesses (Garcia et al. 2002). In a study of an aqueous leaf extract, P. guajava exhibited cardioprotective effects against myocardial ischaemia-reperfusion injury (Ojewole et al. 2008) showed that an aqueous leaf extract caused hypotension in the experimental animal model used via cholinergic mechanisms. Guava can affect the myocardium inotropism (Coutino et al. 2001; Garcia et al. 2002). The acute intravenous administrations of the leaf extract produced dose dependent, significant reductions in systemic arterial blood pressures and heart rates of hypertensive. It was found that an aqueous and ethanolic leaf extracts of P. guajava L. inhibits intracellular calcium release (Vernin et al. 1993; Apisariyakul et al. 1993; Chiesi et al. 1994). An Aqueous leaf extract of the plant significantly and dose-dependently (0.25-2mg/ml) contracted the aorta rings. The sensitivity of the aortic rings to cumulative doses of Psidium guajava L. was significantly enhanced in the presence of phentolamine suggesting that the effect of Psidium guajava L. was to a large extent mediated by  activation of an alpha-adrenoceptor and to a lesser extent by activating via calcium ion channels (Olatunji et al. 2007). The antihypertensive effect was also observed on the pink guava puree. Moreover, Guava contains a high concentration of pectin which causes a significant reduction in the blood lipids by delaying absorption of the foods and thereby reduces the risk of cardiovascular illnesses (Garcia et al. 2002), incidence of stroke associated with hypertension and hyperlipedimiea (Obarzanek et al. 2001). It is also believed by many investigators that some phytoconstituents of leaves like gallic acid, catechins, epicatechins, rutin, naringenin and kaempferol are responsible for the inhibition of the enzyme, pancreatic cholesterol esterase resulting in lower cholesterol in the blood.

 

Antidiabetic Activity:

The rapidly increasing diabetes mellitus is becoming a serious threat to human health in all parts of the world. During various episodes of screening of medicinal plant extract from Psidium guajava, it exhibited anti-diabetic effect (Rai et al. 2001). The daily consumption of guava fruit has a positive effect in individuals with diabetes mellitus by regulating blood glucose, improves insulin sensitivity, and reduces insulin resistance (Vijaya Anand et al. 2020). Chang (1982) (Chang 1982) suggested that oleanolic acid, ursolic acid, glucuronic acid, and arjunolic acid may be responsible components in the guava fruit in regulating the blood glucose levels. Kumari et al. (2016) identified a drop in the blood glucose levels after supplementation of guava fruit without peels, which could be due to the high content of dietary fiber i.e., pectins in guava fruit flesh and seed. The fruits also contain high amount of magnesium, which is essential for the entry of glucose in the muscles and cells (Vijaya Anand et al. 2020). Guava skin extract can control level of diabetes after 21 days treatment (Rai et al. 2007). In addition tannins, flavonoids, pentacyclic triterpenoids, guiajaverin, quercetin and other chemical compounds are speculated to account for hypoglycaemic and hypotensive effects of the leaf extract  (Wang et al. 2005). Different experiments on animal model also confirmed antidiabetic effect of guava leaf extract and bark extract (Mukhtar et al. 2004; Cheng et al. 2005; Oh et al. 2005; Mukhtar et al. 2006). Some heteropolysaccharides like guavapoly-saccharide-1, guavapolysaccharide-2, guavapoly-saccharide-3, and guavapolysaccharide-4 have the ability to reduce the levels of fasting blood glucose, HbA1c, insulin, cholesterol, triglycerides, and serum alanine transaminase and maintain homeostasis (Vijaya Anand et al. 2020). The aqueous leaf extract, was reported to possess inhibitory effect against carbohydrate-degrading enzymes and also possess the ability to suppress the postprandial blood glucose level in human  (Yamanobe et al. 1998). The leaf extract is also claimed as inhibitor of lipase (Ngbolua et al. 2018). Quercetin and flavonoid content in guava leaves also has been found to counteract many diseases originating in the gastrointestinal tract (Arima et al. 2002). The alkalinity of fruits and leaves discourages the growth of pathogenic microbes responsible for gastroenteritis.

 

Effect on Muscular System:

Guava plant has many significant role in preventing and curing mascular diseases. Many phytoconstituents of the plant have been used extensively in treatment of various disorders of mascular system. It is very beneficial for the patients suffering from muscular dystrophy  Lamb et al. 2000). Aqueous leaf infusion of Psidium guajava exhibit a positive therapeutic effect on Degenerative muscular diseases like  muscular dystrophy (Endo 2007). Aqueous leaf infusion of Psidium guajava could block the L-type calcium membrane channels and maintain mascular homeostasis. In addition it is also found from the experiment on animal model that water and methanolic leaf extracts showed antagonistic effects on caffeine induced calcium release from the sarcoplasmic reticulum of  skeletal muscle cells in a dose-dependent-manner showed a clear calcium antagonistic effect.

 

Central Nervous System Related Activity

Several experiments reveal that extracts of guava have shown tranquilizing action on nervous system  (Shaheen et al. 2000). Ticzon (1997) showed that leaves of guava tree in decoction is effective in spasms, epilepsy and other cerebral affections. The sesquiterpenes isolated from hexane extract of Psidium guajava leaves were shown to have  depessant activities in mice model (Ticzon 1997). The relaxant properties of the hexane extract of the leaf is largely due to the presence of terpenes, especially caryophylleneoxide and ß-selinene, which influence pentobarbital sleeping time and the latency of convulsions induced by leptazol in mice  (Meckes et al. 1996).

 

Hepatoprotective Activity:

The aqueous extract of leaves of P. guajava possesses hepatoprotective activity. Researches using animal model demonstrated that aqueous leaf extracts have significant hepatoprotective activities (Roy et al. 2006). Pretreatment with asiatic acid (a triterpenoid extracted from Psidium guajava L. leaves and fruit) also induce increase in both serum aspartate aminotransferase and serum alanine aminotransferase levels, and showing improved nuclear condensation, ameliorated proliferation and less lipid deposition (Gao et al. 2006). Hot water extracts showed high hepatoprotective and lower cytotoxic effects than other extracts (Metwally et al. 2011; Hung-Hui et al. 2011). The leaves of P.guajava also contain copper which promotes healthy thyroid functioning, which is an important process in regulating hormone levels  (Alhamdi et al. 2019).

 

Effect on Dental Plaque:

Dental problem is very common health complaint of human. Some members of oral microbiome of human are responsible for dental problems. More than 350 cultivable bacterial species have been identified in the oral cavity and molecular analyses suggest that an equal number of non-cultivable flora are also present  (Marcotte et al. 1998). Microbial accumulation on oral surfaces is a major factor in the development of most of the common dental diseases such as dental caries, plaque and periodontal disease  (Vohra et al. 2012). Guava contains good concentration of quercetin which has been shown to exhibit incredible antibacterial activity against such oral microbes like Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Fusobacterium nucleatum, Prevotella intermedia etc. The fermented products and other metabolites of such microorganisms often dissolves the mineral in the tooth enamel leads to decalcification and formation of tooth decay or cavities   (Shaheena et al. 2019). The adhesion of early settlers of dental plaque to the tooth surface has a role in the initiation of the development of dental plaque. Guava extract without disturbing the oral cavity acts against oral plagues  (Kafle et al. 2018). The phytoconstituents of guava  may also fight against oxidative stress and prevent deterioration of oral health  (Shetty et al. 2015). Intake of guava fruit is also effective against bleeding gums (scurvy) and ulcers. Leaves can be chewed directly to get instant relief from toothache. Bad breath can also be controlled with guava leaves owing to folate content in guava. In some regions including Indian subcontinent raw young leaves and tender shoots of guava have been used for toothache and mouth ulcers (Okwu et al. 2003; Pradhan et al. 2008)

 

Anti cough:

Consumption of Guava fruit is very effective against common cold and cough as it contains ascorbic acid in huge amount. In folk treatment guava leaves are frequently used against cough. The leaves have been found to be effective in curing cough it is rich in ascorbic acid and iron. Ascorbic acid acts  against unfriendly microbes of respiratory tract, where as iron reduces lungs congestion  and mucous formation (Jaiarj et al. 1999).The water infusion from Psidium guajava leaves decreased the frequency of coughing induced by capsaicin aerosol as compared to the control, within10 minutes after injection of the extract (Jaiarj et al. 1999) .These results suggest that guava leaf extract could be recommended as a cough remedy.

 

Wound Healing:

From the ancient time guava leaves have been used extensively on wound. The wound healing properties of a methanol leaf extract of Psidium guajava L. were determined using the excision wound model. More than 90% wound healing was observed after 14 days post-surgery, whereas 72% healing was observed in the distilled water treated group (Michael et al. 2002) . Tannins and flavonoids exhibit faster healing of experimental wound when a methanolic extract of guava leaves was applied locally twice daily  (Kafle et al. 2018).

 

Antistress Activity:

Indigenous medicinal  practitioners use leaf extract of guava in treatment of stress and nerve stimulant. An ethanol extract of the Psidium guajava L. were investigated for anoxia stress tolerance test and swimming endurance test in Swiss mice and showed significant adaptogenic activity against the stress models  (Lozoya et al. 2002). A study showed that an ethanol extract of  Psidium guajava were investigated for anoxia stress tolerance stress and swimming endurance test in Swiss mice and showed significant adaptogenic activity against stress model  (Echemendia et al. 2004).

 

Skin Disorders:

The phytoconstituents in the guava fruit help to delay the aging process and also reduce the occurrence of skin disorders. Lycopene and flavonoids help in the cure of cancerous cells and help to prevent skin aging before time  (Vijaya Anand et al. 2016). Several experiments confirmed that the phytoconstituents of guava leaves are effective against different dermatophytes and other microbes associated with skin infections (Dutta et al. 2000; Vijaya Anand et al. 2002; Nair et al. 2007, Chanda et al. 2011).

 

Conclusion

The use of natural therapy in the treatment and prevention of disease is not only safe, but also easily available. Presently physicians or practioners are also looking for alternative treatment of medicine for curing various diseases. It is undoubtedly confirmed by the researchers that the small amount of guava in  daily diet provide huge health benefits. Different parts of this plant species have been used as folk medicine without any side effects. Several reports have dealt with the numerous properties of guava in the forms of fruits, leaf extract, bark, essential oils, phenolic compounds, flavonoids and isolated bioactive components. World Health Organization has also recommended that the daily consumption of  fruits like guava  reduces the risks of many diseases and disorders. In addition bioactive compounds of different parts of the plant protect human health from various pathogens. The present communication revealed that all parts of Psidium guajava L. is a pharmacologically and chemically beneficial for human. Apart from the fruit different parts of the plant contains herbal drugs and phytoconstituents. In present scenario there is a growing trend to use the medicinal plants as the natural resources in order to develop new drugs and in that point of view Guava plant is a bless of nature for the present civilization. However, this information alone is not sufficient to provide evidence for safety and efficacy of a natural product and requires further investigation.

Cited as :

Mazumder M, Sen S and Sarkar AK(2021) Organoprotective Role  and Therapeutic Implication of Psidium guajava L. and its Bio-active compounds. In (Eds.) Lenka C. and Biswas K. “Nutrition and Public Health”. A1 Publication, West Bengal. 97-116.