Koleen Yap Vincent Cabalar 12-Locke

Althea Sayawan Jayson Mauricio

ANTIBACTERIAL PROPERTIES OF JACKFRUIT (ARTOCARPUS HETEROPHYLLUS)

LEAF EXTRACT AGAINST THE BACTERIA STAPHYLOCOCCUS AUREUS

REVIEW OF RELATED LITERATURE AND STUDIES

Staphylococcus aureus is a major human pathogen that causes a wide range of clinical

infections. It is a leading cause of bacteremia and infective endocarditis as well as osteoarticular,

skin and soft tissue, pleuropulmonary, and device-related infections. This review

comprehensively covers the epidemiology, pathophysiology, clinical manifestations, and

management of each of these clinical entities. The past 2 decades have witnessed two clear shifts

in the epidemiology of S. aureus infections: first, a growing number of health care-associated

infections, particularly seen in infective endocarditis and prosthetic device infections, and

second, an epidemic of community-associated skin and soft tissue infections driven by strains

with certain virulence factors and resistance to -lactam antibiotics. In reviewing the literature to

support management strategies for these clinical manifestations, we also highlight the paucity of

high-quality evidence for many key clinical questions. (Tong et al 2015)

In another article, it was discussed how infectious diseases are primary cause of high

risks of being unwell and of mortality. These infections are also the reason for the various

changes in human behavior. By that, it was also given how Staphylococcus aureus and

Escherichia coli are the major cause of many infections such as skin infections, surgical site

infections, bone and joint infections, etc. Moreover, it was said how the need for antibiotic
resistant staphylococci are major public health worry particularly in hospitals as it is a bacteria

that can easily be transported in our environment. (Di ko maopen link

http://www.microbiology5.org/microbiology5/book/637-648.pdf)

Staphylococcus aureus is an important opportunistic pathogen and persistently colonizes

about 20% of the human population. Its surface is 'decorated' with proteins that are covalently

anchored to the cell wall peptidoglycan. Structural and functional analysis has identified four

distinct classes of surface proteins, of which microbial surface component recognizing adhesive

matrix molecules (MSCRAMMs) are the largest class. These surface proteins have numerous

functions, including adhesion to and invasion of host cells and tissues, evasion of immune

responses and biofilm formation. Thus, cell wall-anchored proteins are essential virulence factors

for the survival of S. aureus in the commensal state and during invasive infections, and targeting

them with vaccines could combat S. aureus infections. (Foster et al 2013)

A large number of the known methicillin-resistant Staphylococcus aureus (MRSA) were

confined to hospitals and long-term facilities and are emerging drastically in the community. The

changing epidemiology of methicillin-resistant Staphylococcus aureus bears striking similarity to

the emergence of penicillinase-mediated resistance in S. aureus decades ago. Even though the

origin of the emerging MRSA strains is not known, whether it be from hospitals or in the

community, the prevalence of these strains in the community seems likely to increase

substantially. (Chambers 2001)

The horizontal transmission of methicillin resistance to Staphylococcus aureus (MRSA)

in hospital and community settings, and growing prevalence of these strains, presents a

significant clinical challenge to the management of serious infections worldwide. While infection

control initiatives have stemmed the rising prevalence, MRSA remains a significant pathogen.
More recently, evidence that MRSA is becoming resistant to glycopeptides and newer therapies

raises concern about the use of these therapies in clinical practice. Vancomycin resistance has

become evident in select clinical settings through rising MICs, growing awareness of

heteroresistance, and emergence of intermediate-resistant and fully resistant strains. While

resistance to linezolid and daptomycin remains low overall, point mutations leading to resistance

have been described for linezolid, and horizontal transmission of cfr-mediated resistance to

linezolid has been reported in clinical isolates. These resistance trends for newer therapies

highlight the ongoing need for new and more potent antimicrobial therapies. (Stryjewski et al

2014)

Artocarpus heterophyllus Lam, commonly known as the jackfruit tree, belongs to the

family Moraceae. It is an exotic tree originally native to the Western Ghats of India. The fruits

are of dietary use and are an important source of carbohydrate, protein, fat, minerals and

vitamins. The heart wood is a very durable timber and is used in the preparation of furniture. The

bark, roots, leaves, and fruit are attributed with diverse medicinal properties and are used in the

various traditional and folk systems of medicine to treat a range of ailments. Preclinical studies

have shown that jackfruit possesses antioxidant, anti-inflammatory, antibacterial, anticariogenic,

antifungal, antineoplastic, hypoglycemic, wound healing effects and causes a transient decrease

in the sexual activity. Clinical studies have also shown that the decoction of the leaves possesses

hypoglycemic effects in both healthy individuals and non-insulin-dependent diabetic patients.

Phytochemical studies have shown that jackfruit contains useful compounds like the flavonoids,

sterols and prenylflavones which may have been responsible for the various pharmacological

properties. The present paper reviews the nutritional value, culinary uses, the phytochemical
compounds, traditional usage and validated pharmacological properties of jackfruit. (Swami et al

2012)

The Artocarpus heterophyllus is a species of tree of the mulberry family ( Moraceae ).

Artocarpus heterophyllus is an integral part of common Indian. It is available in Indian and

nearby continents. Artocarpus heterophyllus possess antibacterial, anti-inflammatory,

antidiabetic, antioxidant and immunomodulatory properties. Artocarpus heterophyllus is an

essential source of compounds which are useful in fever, boils, wounds, skin diseases,

convulsions, diuretic, constipation, ophthalmic disorders and snake bite like morin,

dihydromorin, cynomacurin, artocarpin, isoartocarpin, cyloartocarpin, artocarpesin,

oxydihydroartocarpesin, artocarpetin, norartocarpetin, cycloartinone, betulinic acid,

artocarpanone and heterophylol. The leaves are useful in fever, boils, wounds and skin diseases.

The young fruits are acrid, astringent, and carminative. The ripe fruits are sweet, cooling,

laxative, aphrodisiac and also used as a brain tonic. The seeds are, diuretic, and constipating. The

wood is nervine, antidiabetic, sedative and is useful in convulsions. (Prakash et al 2009)

The jackfruit tree belongs to the family Moraccae. Fruits coming from it are important

source of carbohydrates, protein, fat, minerals, and vitamins. on the other hand, its bark, roots,

and leaves are then related to medicinal properties used in various traditional and folk systems of

medicine to treat a range of ailments. Moreover, jackfruit leaves contain antioxidant, anti-

inflammatory, and antibacterial characteristics intended for wound healing effects. Also, it

contains useful compounds like flavonoids, sterols, and prenylflavones which may have

contributed to its pharmacological properties. (Hindawi 2014)

Jackfruit (Artocarpus heterophyllus Lam.) is an ancient fruit that is widely consumed as a

fresh fruit. The use of jackfruit bulbs and its parts has also been reported since ancient times for
their therapeutic qualities. The beneficial physiological effects may also have preventive

application in a variety of pathologies. The health benefits of jackfruit have been attributed to its

wide range of physicochemical applications. This review presents an overview of the functional,

medicinal, and physiological properties of this fruit. (Veggi et al 2010)

In another related study, the aqueous fractions, total water extract, and ethyl acetate from

the leaves of Artocarpus heterophyllus were assessed for phenolic content, antioxidant, and

antibacterial activities against certain foodborne pathogens such as E. coli, Listeria

monocytogenes, Salmonella typhimurium, Salmonella enterica, Bacillus cereus, Enterococcus

faecalis, and Staphylococcus aureus. The minimum inhibitory concentration (MICs) of extract

and fractions determined by the agar dilution method were ranged from 221.9 g/mL for ethyl

acetate fraction to 488.1 g/mL for total extract. In the agar diffusion method the diameters of

inhibition were 12.2 for the total extract, 10.7 and 11.5 for ethyl acetate and aqueous fractions,

respectively. Artocarpus heterophyllus showed significant antioxidant activity tested in different

in vitro systems which were DPPH, ABTS, FRAP, and Fe2+ chelating activity assay. In

particular, in DPPH assay A. heterophyllus total extract exhibited a strong antiradical activity

with an IC50 value of 73.5 g/mL while aqueous fraction exerted the highest activity in FRAP

assay (IC50 value of 72.0 g/mL). The total phenols content by FolinCiocalteau method was

determined with the purpose of testing its relationship with the antioxidant and antibacterial

activities. According to the research, the leaves of Artocarpus heterophyllus gives a total water

extract, ethyl acetate, and aqueous fractions which were evaluated to be having phenolic content,

antioxidants, and antibacterials against food borne pathogens including Staphylococcus aureus.

The extract was used to compare the inhibition of bacteria before and after it was tested. (Loizzo

et al 2010)
 Jackfruit leaves (Artocarpus heterophyllus) are rich in phenolic compounds, which give

them powerful antioxidant, anti-inflammatory and antibacterial properties; however, there are

few literature data available on jackfruit leaves extraction. Adding value to raw materials using

ecologically correct technologies is ideal to increase income without degrading the environment.

An alternative to fulfill those requirements is the extraction of volatile oils and oleoresins using

supercritical technology. In spite of being a well-known clean technology, there is still no

industrial unit operating with it in South America, because of the high investment costs. Low

pressure solvent extraction (LPSE) still is the most used technology in industries for recovery of

oleoresins; however, this process usually extracts complex crude mixtures, so that the steps of

solvent removal and purification can elevate the final product cost. On the other hand, recent

studies have shown that supercritical fluid extraction (SFE) may be economically viable to

obtain extracts from vegetable matrices, presenting very low operational cost. The use of

simulation softwares allows substantial cost, labor and time reduction in the studying of

industrial processes. (Baliga 2011)

Fruits, vegetable nuts, seeds, and honey often contain Flavonoids that are ubiquitous in

pphotosynthesizing cells. For a very long time, its compounds were used to treat human diseases.

Furthermore, products and researches relating to anti-infectives, flavonoids are becoming the

subject. Tests were made to determine the structures of flavonoids possessing anti fungal,

antiviral, and antibacterial activities. (Cushnie & Lamb 2005)

 The flavonoid compound was successfully isolated from jackfruit leaves (Artocarpus

heterophyllus Lamk.). Extraction was done by maceration with methanol-water (9:1), followed

by methanol-water (1:1) as a solvent. Hydrolyzed extract was obtained by adding of 2NHCl, then

extracted with ethyl acetate and monitored by thin layer chromatography (TLC) with nhexane-

ethyl acetate (3:5) as a mobile phase. Separation was performed by column chromatography,

followed by preparativethin layer chromatography. Purity of isolates was determined by 2-

dimensional thin layer chromatography. Characterization of isolate were carried out by

ultraviolet-visible spectrophotometry and infrared spectrophotometry. The result showed a

maximum absorbance of bands I at 328.4 nm and 271 nm for bands II. Characterization of isolate

by infrared spectrophotometry showed the presence of functional groups OH, CH, C = C, C = O,

CC, and CO. Based on the data, the isolate identified as a flavonoid compound. Antioxidant

activity of ethyl acetate fraction and column fraction by 1,1-diphenyl-2-picryl-hydrazyl (DPPH)

assay showed EC50 at 60.53 mg/mL and 35.27 g/mL respectively. (Riyanti et al 2013)

Flavonoids are hat have antioxidant, anti-inflammatory, anti-viral, anti-cancer, anti-tumor

and anti-diarrheal properties. The study focused on the formulation and characterization of syrup

dosage form prepared with the extracted flavonoids from ripe jackfruit (Artocarpus

heterophyllus) fruit. The fruit extract was obtained by maceration using 95% ethanol as solvent

and separated from solvent by rotary evaporation. The gathered extract was tested for the

presence of flavonoids. All three trials showed yellow solution when the extract was reacted with

diluted NaOH and turned to colorless solution when reacted with diluted HCl, which implies the

presence of flavonoids in the extract. The extract was formulated into a syrup and characterized

by determining its color, odor, taste, pH and viscosity. The formulated syrup has a dark

yellowish- brown color, sweet taste and odor, which resemble the physical properties of a
medicated syrup. The pH of three syrups conforms to the specified range which is greater than

5.4 but not less than 6.9. The researchers determined the viscosities of syrups in three trials. The

viscosity of plain syrup was also determined for comparison. The formulated syrup 1, 2 and 3

took an average of 60.51 centipoise, 67.48 centipoise and 65.06 centipoise to flow respectively,

while the plain syrup took only an average of 37.98 centipoise to flow. It shows that formulated

syrup containing ripe jackfruit (Artocarpus heterophyllus) fruit crude extract is more viscous

than the plain syrup. The statistical test proved that there is an existing significant difference on

the viscosity values of prepared syrup, which means that the four types of syrup significantly

differ in viscosity. Post Hoc using Tukeys HSD Multiple Comparison Test was conducted and

results revealed that of the four types of syrup, syrup 2 showed the highest viscosity value

compared with syrup 1, 3 and plain syrup. This suggests that syrup 2 may have higher soluble

matters of the extract present than syrups 1 and 3. (Bacayo et al 2007)

Gastrointestinal nematodiasis causes deleterious effects mainly on the productivity of

goats resulting in profit loss for goat raisers. Gastrointestinal parasites in ruminants cause a

reduction in feed intake, alteration of gastrointestinal motility and digesta flow, causing

inappetence and diarrhea (Holmes, 1987). Gastrointestinal parasitism also causes loss of proteins

into the gastrointestinal tract; changes in host metabolism account for much of the reduced

protein and energy retention by infected animals (Holmes, 1987). Mineral metabolism and water

and electrolyte balance are also frequently disturbed (Holmes, 1987). Chemical dewormers are

being used to decrease these effects but there have been increasing reports of anthelmintic

resistance to these chemical dewormers in Southeast Asia, including Malaysia, Thailand,

Indonesia and the Philippines. In the Philippines, studies in different regions including Luzon,

Visayas and Mindanao confirmed that resistance of different nematodes to different chemicall
dewormers is present among sheep and goats farms with possible widespread distribution

(Venturina, 2003). In view of these reports, farmers resort to inexpensive alternative ways for

controlling gastrointestinal parasitism in their farms. Jackfruit (Artocarpus heterophyllus L.) and

tamarind (Tamarindus indica L.) leaves are being used as alternative anthelminthic in ruminants.

However, their anthelmintic efficacy has not been extensively evaluated against nematodes in

goats. The objective of the study was to evaluate the anthelmintic efficacy of jackfruit and

tamarind leaves decoction against gastrointestinal nematodes of goats in different concentrations

using larval development assay (LDA). (Ducusin et al 2008)

From the next study, it was mentioned that the research was conducted in order to

evaluate antibacterial activities of essential oil obtained from the plant Artocarpus heterophyllus.

The species were this plant belongs was reported to be used in several traditional folk medicine

in the country of Indonesia in treating stomachache, diarrhea, defective urinary secretion and

more. It so happened that this plant are a rich source of phenolic compounds like granulated

flavones. In the process of experimenting, it was found out that that bacterial strains tested were

sensitive to the said essential oil and showed effectiveness in terms of antibacterial activity

resulting to minimum inhibitory region. (Shipra & Srivastava 2013)

Jackfruit (Artocarpus heterophyllus Lam) is popular fruit crop that is widely grown in

Thailand and other tropical areas. The ripe fruit contains well flavored yellow sweet bulbs and

seeds (embedded in the bulb). The edible bulbs of ripe jackfruit are consumed fresh or processed

into canned products. Seeds make-up around 10 to 15% of the total fruit weight and have high

carbohydrate and protein contents (Bobbio et al 1978 and Kumar et al 1988). Seeds are normally

discarded or steamed and eaten as a snack or used in some local dishes. As fresh seeds cannot
kept for a long time, seed flour can be an alternative product, which be used in some food

products. (Tulyathana 2002)

Jackfruit (Artocarpus heterophyllus) root extract, with a bronchodilating agent, is

traditionally used for treating asthma. To provide a scientific basis for such claim, this study was

conducted to evaluate the safety and efficacy of the formulated syrup of such extract by

determining its acute oral toxicity level, approximate effective dose, the significant difference in

the total leukocyte count (TLC), total eosinophil count (TEC) and histopathologic evaluation of

lung tissue. Female Swiss mice were used to determine the toxicity at selected fixed dose levels

of 5, 50, 300 and 2000 mg/kg. Approximate Effective Dose (AED) determination was conducted

using female albino rats with a logarithmic increase by 0.6 intervals. Animals were administered

with alum-ovalbumin and desired dose of root extract, respectively. Blood samples were

collected for leukocyte and eosinophil counts. It was found that acute oral toxicity was at

2000mg/kg and 5000 mg/kg. AED has significant influence on TLC and TEC at dose levels of

15.85, 251.19, 1000 and 3981.07 mg/kg. Analysis of Variance showed a significant difference in

the mean of the decrease in the total leukocyte count due to the formulated syrup of root extract,

Salbutamol (positive control) and plain syrup (negative control). Tukeys multiple comparison

tests, t-test and histopathologic evaluation on the group treated with Salbutamol and root extract

formulation showed no significant difference on the TLC and TEC. Salbutamol was not

significantly different from the formulated syrup. Hence, both treatments were effective as

bronchodilating agents. (Bersabal et al 2007)

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