INTRODUCTION:

Natural products have been used by humans in the world to treat various diseases. Plants that are generally used by humans as an alternative to primary medicine are widespread, which have characteristics in each region. Some of the reasons most people in developing countries use plant extracts as therapeutic agents are because they are cheaper and easily available. Recently, the natural antimicrobial and antioxidant activity of plant origin has been the subject of the most attention in medicine. The presence of biologically active compounds found in medicinal plants makes plants widely used as alternative medicine for several diseases¹.

Recently, research on antibacterial and antioxidant has increased because generally, plants that have antioxidant activity also have antibacterial activity. The presence of phenolic compounds is the basis for this research to continue to be developed^2,3. Phenolic compounds have activity against several microorganisms which are the result of reactions among this compounds with cell membrane of microorganisms or through the process of destroying cell walls⁴.

Phenolic compounds have also been shown to have the capability as antioxidant which play a role in protecting cells from the effects of reactive oxygen species (ROS) ^5,6,7,8,9. ROS and free radicals like superoxide anions, hydrogen peroxide also hydroxy radicals can trigger degenerative processes associated with aging, cancer and atherosclerosis, by inducing oxidative damage to cell membranes, DNA and proteins¹⁰. Several studies have also mention a direct relationship among total phenol and free radical scavenging plants^11,12,13. Bacteria, fungi and virus are pathogens that can cause severe disease and infections that can cause death in humans. Exploration of natural materials derived from plants can provide a source of new drugs that have the potential to have antimicrobial activity with novel mechanisms of action¹⁴.

Artocarpus is a genus of the Moraceae, a genus known to be widespread in the plains of Asia, especially South Asia and Southeast Asia. Plants of Artocarpus distributed from South Asia, Southeast Asia, Solomon Islands, India, Pacific Islands, North Australia to Central America. There are about 60 genera and 1000 species in the Artocarpus genus. In traditional medicine and food sources, most of these species are widely used. Artocarpus species are edible plants and have high nutritional content, the characteristic of the fruit is its large size^15,16. Artocarpus in Indonesia particularly in Sumatra, Java, Kalimantan, and Sulawesi is known for its tall tree with white sap all over the plant, fleshy fruit with many seeds and hard wood. The leaf sheets of the Artocarpus have a slightly hard texture with fine hairs, especially on the underside with varying leaf sizes^17,18. Traditionally, Artocarpus plants have long been used as medicine^19,20 then researched and proven has pharmacology activity including antimicrobial, anti-inflammatory, antihyperglycemic, antioxidant, antiglycation, anthelmintic, overcoming fever, dysentery, and malaria, diarrhea, ulcers, fever, sores, and skin diseases^21,22.

Artocarpus have been used as traditional folk medicine especially in South-East Asia was mentioned in Table 1.

Profile of Phytochemical Constituent:

The phytochemical profile of Artocarpus is similar with main content in the form of phenolic compounds including flavonoids, stilbenoids, arylbenzofurons, and neolignans which are distributed in fruit, leaves, flowers, bark and roots. The uniqueness can be found in the presence of prenylated and geranylated flavonoid compounds such as 2-geranil 2',3,4,4'-tetrahydroxy dihydrochalcone. These phenolic compounds have relatively strong antioxidant abilities in several test models and have the potential to be developed as antioxidant agents, especially for diseases that involve free radical mechanisms in their pathophysiology¹⁷. The extract of Artocarpus heterophyllus’s leaves reported the presence of flavonoids, anthocyanin, tannins, and proanthocyanidin that can be used in the theraphy of diabetic patients²⁶. Compound isolated from Artocarpus integer such as artocarpanone, cudraflavone, artocarpin, tephrosin, norartocarpin²⁷, from Artocarpus heterophyllus such as artocarpin and artocarpanone²⁸, form Artocarpus lacucha such as Lakoochins A, Lakoochins B and oxyresveratrol^29,30.

Antioxidant Activity of Artocarpus:

Antioxidant activity of Artocarpus was shown in Table 2.

Table 1: Artocarpus as traditional folk medicine

Names	Common names	Uses	Reference
Artocarpus altilis (Parkinson) Fosberg	Breadfruit	Leaves used to treat liver cirrhosis, high blood pressure and antihyperglycemic. Fruit pulp tonic for liver.	21
Artocarpus chempeden Spreng./ Artocarpus integer (Thunb.) Merr.	Chempedak	Seeds used to treat diarrhea, roots treat malaria fever, fruit edible.	22
Artocarpus heterophyllus Lam	Jackfruit	The fruit is edible, roots as antidiarrhea and overcoming fever, leaves as antisyphilitic and vermifuge, ulcers and heal wounds, leaves and stem barks used to treat anemia, asthma, dermatitis, diarrhea, cough.	22
Artocarpus lacucha Buch.-Ham.	Monkeyjack, Lakoocha	The bark is commonly used to treat skin desease and anthelmintic. Seed and bark to treat stomach and liver disease.	23 24
Artocarpus odoratissimus		Leaves used to antihypergligemic drug and the ashes of the leaves are to ward off stings or bites of centipedes and scorpions, while the wood and bark were used as antimalarial	25

Table 2: Antioxidant activity of Artocarpus

Species	Organs	Antioxidant activity	Method	Reference
Artocarpus integer (Thunb.) Merr.	Heartwood	IC₅₀ values of artocarpanone (29.88 μg/ml), cudraflavone C (3.35 μg/ml), artocarpin (4.70 μg/ml), tephrosin (55.58 μg/ml), norartocarpetin (2.83 μg/ml)	DPPH	27
Artocarpus heterophyllus Lam.	Fruit pulp	IC ₅₀ methanol extract 0.4 mg/ml	DPPH	31
	Fruit pulp	Reduce Fe³⁺ to Fe²⁺, 1.4 mM TEAC g⁻¹ for water extract and 1.7 mM TEAC g⁻¹ for methanolic extract.	FRAP	31
	Fruit pulp	IC₅₀ were as follows: 3.9 mg/ml for water extract, 3.6 mg/ml for ethanolic extract and 3.43 mg/ml for methanolic extract.	DMPD	31
	Latex	At 100 µg/ml, the DPPH scavenging activity of aqueous extract (18,89%) and trifluoroethanol extract (1,76%)	DPPH	32
Artocarpus camansi Blanco	Leaves	IC₅₀ of ethanol extract: 73.16, ethyl acetate extract: 73.88 µg/ml n-hexane extract: 374.7 µg/ml	DPPH	33
Artocarpus lacucha Buch.-Ham	Leaves	IC₅₀: Hydroalcoholic extract 48,23 µg/ml	ABTS	34
	Leaves	IC₅₀: Ethanol extract 99,23 µg/ml	DPPH	35
Artocarpus lacucha Roxb	Oxyresveratrol was isolated with a yield of 10% from heartwood	IC₅₀ values: 0.1 mg/ml	DPPH	30
	Oxyresveratrol was isolated with a yield of 10% from heartwood	IC₅₀ values: 0.43 mg/ml	TBARS	30
Artocarpus lacucha Buch.-Ham	Artocarpinol A, 3-epi-artocarpinol A, artocarpinol B, and gambircatechol isolated from leaves and stembark	EC₅₀ Artocarpinol A: 9.4 µmol ml^-1, 3-epi-artocarpinol A: 12.2 µmol mL^-1, artocarpinol B: 10.0 µmol ml^-1 and gambircatechol: 19.0 µmol ml^-1	DPPH	36
Artocarpus lacucha Roxb	Pericarp	IC₅₀ of methanol extract: 49.42 µg/ml	DPPH	37
Artocarpus altilis	Fruit from 5 region of country in Congo	Antioxidant capacity in range 5.44 – 14.83 mmol Fe²⁺/kg	FRAP	38
	Pulp	IC₅₀ methanol extract: 55 µg/ml	DPPH	39
	Peel	IC₅₀ methanol extract: 123 µg/ml	DPPH	39
Artocarpus anisophyllus	Stem bark	IC₅₀ n-hexane extract: 127.69 ppm, ethyl acetate extract 28.65 ppm, and methanol extract 79.43 ppm	DPPH	40

Table 3: Antibacterial activity of Artocarpus

Species	Organs	Bacteria	Reference
Artocarpus integer (Thunb.) Merr.	Heartwood	Escherichia coli, Salmonella typhi, Staphylococcus aureus and Streptococcus pneumonia	41
Artocarpus heterophyllus	Bark	S. typhi	42
	Shell	S. aureus, Bacillus subtilis, Bacillus cereus, Listeria monocytogenes and Streptococcus faecalis	43
	Seed	Methicillin-resistant S. aureus, methicillin-susceptible S. aureus, and multidrug-resistant Pseudomonas aeruginosa	44
	Latex	P. aeruginosa, S. aureus, and Bacillus sp.	32
	Artocarpin of Heartwoood	Streptococcus mutans, S. pyogenes, B. subtilis, S. aureus, and S. epidermidis	28
	Artocarpanon of Heartwoood	E. coli	28
	Ethyl acetate extract of heartwood	S. mutans, S. pyogenes, and B. subtilis	28
Artocarpus camansi	Leaves	B. subtilis, E. coli, S. aureus, P. aeruginosa	33
	Leaves	Shigella dysenteriae and B. subtilis	45
Artocarpus lacucha	Bark	Shigella soneii 2, B. subtilis, Bacillus pumillus, E.coli MTCC 1568, E.coli Row, P. mirabilis	23
	Roots	Lakoochins A and Lakoochins B exhibited antimycobacterial	29
Artocarpus altilis	Pulp	S. aureus, B. cereus, S. epidermidis, E. coli, S. typhimurium and K. pneumoniae	39
Artocarpus elasticus	Seed	MDR E. coli	46
Artocarpus lanceipolius	Seed	MDR E. coli	46
Artocarpus edoratissimus	Seed	MDR E. coli	46

Antibacterial activity of Artocarpus:

Antibacterial activity of Artocarpus was exposed in Table 3.

Artocarpus is a genus that contains important compounds as medicine in addition to its fruit which contains many minerals, vitamins, antioxidants and various nutrients so it is good for consumption. The content of antioxidant compounds in Artocarpus functions to scavenging free radicals and ROS which are responsible for a number of health problems in humans ²². In general, plants of the Artocarpus contain phenol compound derivatives and nonphenolic. Artocarpus contains of flavonoids which have diverse biological activities, including antioxidant^47,48,49,50.

There are many research results regarding the genus Artocarpus, but in Indonesia not all of the genus Artocarpus have been studied for their biological and phytochemical activities. Flavonoid compounds, stilbenoids and aryl benzofuran are typical compounds of the genus Artocarpus because they are known to be detected in the species studied. It has been reported about the antimicrobial activity of stilbenes and prenylated flavones isolated from certain species^51,52,53,54.

From the review, it had been known that Artocarpus has scavenging free radicals activity. Phenolic compounds and flavonoids are compounds that are responsible for the antioxidant activity of the extract⁵⁵. Evaluation of antioxidant activity mostly done by DPPH method^{56,57, 58,59,60} although there were some methods used to evaluate antioxidant activity such as ABTS, FRAP, TBARS, and DMPD^61,62. Assessment of the antioxidant activity of plant products cannot be carried out by a single method because the results are less accurate due to the complex nature of the phytochemical constituents. Artocarpus is a natural source that has many phytochemical constituents including phenolic compounds so that it provides opportunities to be developed into value-added products, nutraceutical applications and foods that are beneficial for improving human health²². Natural antioxidants are in great demand because they provide many benefits for human health and their use does not cause potential side effects ^63,64,65.

Antibacterial agents derived from biological sources^66,67and the important role of plants as alternative antimicrobials has been reported by several studies^{68,69, 70}. From the review, it was known that Artocarpus has antibacterial activity for some Gram negative and some Gram positive bacteria.

Antimicrobial activities of flavonoids⁷¹, saponins⁷², and tannins⁷³ have been documented. Phytochemical analysis of Artocarpus extract showed compound content of tannins, flavonoids, saponins and terpenoids. The problem of antibiotic resistance is one of the important reasons for the possible use of plants in the treatment of bacterial infections because most bacterial strains are resistant to various antibiotics currently available^38,39.

CONCLUSION:

The results of this review concluded that Artocarpus has potential to be developed as an antioxidant related to diseases caused by the effect of free radicals and antibacterial to treat infectious diseases.

CONFLICT OF INTEREST:

Declared none

ACKNOWLEDGEMENT:

The authors are thankful to Institut Teknologi Bandung.

FUNDING:

This work was supported by the Education Financing Service Center, Ministry of Education, Culture, Research and Technology and the Educational Fund Management Institution Ministry of Finance of the Republic of Indonesia with the registration number of 202101121470.

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Received on 18.06.2022 Modified on 15.08.2022

Research J. Pharm. and Tech 2023; 16(5):2531-2536.

DOI: 10.52711/0974-360X.2023.00416