INTRODUCTION:

Indonesia has rich sources of natural medicines and traditional medicine preparations that have been used by most of the population for generations^1,2,3. A direct advantage of traditional medicine formulations to the community is the ease of obtaining them⁴. The demand for plants used as traditional medicine formulations by the community is also increasing because plant-derived medicines have proven to be healthier and do not cause as many side effects as those derived from chemicals. However, a problem with traditional medicine formulations is the lack of adequate knowledge and information about the various types of plants commonly used as ingredients and their methods of use⁵.

Muntingia calabura L., also known as kersen, belongs to the family Muntingiaceae and is a fast-growing plant that is widely found worldwide⁶. M. calabura L. leaves have been considered by the population to be a medicinal plant and have properties including antidiabetic, anti-gout, antihypertensive, laxative, antiseptic, anti-seizure, gastroprotective, antioxidant, and anti-inflammatory activities as well as activity against productive cough, the flu, headache, and fever^7,8,9. Furthermore, M. calabura L. leaves contain chemical compounds such as flavonoids, triterpenoids, tannins, saponins, and glycosides^10,11.

The phytoconstituents of M. calabura stem bark consist of amino acids, flavonoids, saponins, proteins, triterpenoids, sterols, steroids, alkaloids, phenolic compounds, tannins, glycosides, and carbohydrates¹². The nutritional value of M. calabura L. per gram of the leaves consists of 204.0±3.46mg carbohydrates, 002.04±0.15mg protein, and 001.41±0.07mg amino acids, whereas, that per gram of the fruit consists of 75.33±4.61mg carbohydrate, 06.44±0.15mg protein, and 00.88±0.07mg amino acids¹³. In addition, the pericarp of M. calabura also has many important health benefits⁸.

TAXONOMY:

The cherry plant has the Latin name M. Calabura L and in systematic taxonomy is classified as follows: kingdom, Plant; subkingdom: Tracheobionta; division: Spermatophyta; class: Dicotyledonae; subclass: Dialypetalae; order: Malvales; genus: Muntingia; species: Muntingia calabura L.¹⁴

PLANT DESCRIPTION:

M. calabura L. plants are shrubs that reach a height of 3-12m, with lined leaves and branches that hang down. The leaves are characteristically lanceolate with a smooth feathered surface, pointed tips, asymmetrical blunt base, jagged edges, and are 1.0-6.5cm wide and 2.5-15cm long. The flowers are white with a peculiar smell and slightly small. The fruit is initially green, turns bright red when it ripens, and its contents are runny with thousands of small yellow seeds with a diameter of 0.5 mm that are fully spread inside while the ripe fruit tastes sweet¹⁵.

GEOGRAPHICAL DISTRIBUTION:

Cherry plants (M. calabura L.) are fast growing with slender proportions and are often found flourishing on the side of the road. This plant is native to the Americas and is widely cultivated throughout Southeast Asia¹⁵. This plant has other names such as Jamaica cherry in the US, China cherry or Japan cherry in India, cherry chettu (Telugu)¹⁶, and Calabura in Brazil¹⁵.

ETHNOPHARMACOLOGY:

M. calabura L. is an herbal medicinal plant that is used to treat various health problems worldwide. The leaf is the main plant part of M. calabura L. commonly used to treat various diseases¹⁴.

PHYTOCHEMICAL COMPOSITION:

Table 1. Phytocomponents of Muntingia calabura L.

S. No.	Compound Name	Ref
1	(2S)-50-hydroxy-7,8,30,40-tetramethoxyflavan	17
2	Cabreuvin	17
3	7-hydroxyisoflavone	17
4	Isoliquiritigenin	17
5	20,40-dihydroxychalcone	17
6	5-hydroxy-3,7,8,40-tetramethoxyflavone	17
7	dihydroxy-3,7,8-trimethoxyflavone	17
8	5-hydroxy-3,7,8-trimethoxyflavone	17
9	Gnaphaliin	17
10	Ermanin	17
11	3,8-dimethoxy-5,7,40-trihydroxyflavone	17
12	Pinocembrin	17
13	8-methoxy-3,5,7-trihydroxyflavone	17
14	Chrysin	17
15	3,30-dimethoxy-5,7,40-trihydroxyflavone	17
16	7-hydroxyflavone	17
17	(2S)-7-hydroxyflavanone	17
18	Pinostrobin	17
19	Isokaemferide	17
20	Pinobanksin	17

BIOACTIVITIES:

Antibacterial Activity:

The study by Zakaria et al. (2006)¹⁸ showed that the aqueous extract of M. calabura L. leaves at 100.000ppm has antibacterial activity against Salmonella enteritidis, Citrobacter freundii, P. aeruginosa, Klebsiella pneumoniae, Vibrio cholerae, Pseudomonas aeruginosa, and Salmonella typhi bacteria. The study by Sibi et al. (2012)¹⁹ showed that the aqueous bark extract of this plant has antibacterial activity against P. aeruginosa, Bacillus cereus, and Micrococcus luteus. Furthermore, the aqueous leaf extract has antibacterial activity against M. luteus and P. aeruginosa while the aqueous fruit extract has antibacterial activity against M. luteus.

The methanol extract of M. calabura L. leaves at 100.000ppm has antimicrobial activity against C. freundii, K. pneumoniae, Vibrio cholerae, V. parahaemolyticus, and S. typhi bacteria¹⁸. The study by Sibi et al. (2012)¹⁹ showed that the methanol bark extract has antibacterial activity against B. cereus and M. luteus, the leaf extract had additional activity against P. aeruginosa, and the fruit extract was effective against Serratia marcescens. Furthermore, the study by Buhian et al. (2016)²⁰ showed that the ethanol extracts of leaves and stems of M. calabura L. have antimicrobial activity against B. subtilis, Staphylococcus aureus, S. typhimurium, P. Aeruginosa, and Escherichia coli bacteria.

Antifungal Activity:

The ethanol extracts of M. calabura L. leaf and stem have antifungal activity against Candida albicans²⁰. The methanol, chloroform, and petroleum ether extracts of M. calabura L. roots at a concentration of 100mg/mL have antifungal activity against Phytophthora sp., Colletotrichum sp., Alternaria solani, Pythium sp., Aspergillus niger, Fusarium oxysporum f.sp lycopersici, and Rhizoctonia solani²¹

Antihyperglycemic and Antidiabetic Activities:

Several studies have demonstrated the antihyperglycemic and antidiabetic activities of M. calabura L. For example. Aligita (2018)²² reported that at a dose of 400mg/kg body weight (BW), the aqueous leaf extract effectively reduced the blood glucose level, increased insulin sensitivity, and regenerated pancreatic β cells in a mouse model of type 2 diabetes. While other studies reported by Nugroho (2019)²³ showed that the coadministration of M. calabura L. leaf extract and metformin at 300 and 45mg/kg BW, respectively effectively reduced the blood glucose levels in type 1 diabetic rats. In addition, the study by Sridhar et al. (2011)¹⁶ demonstrated that the methanolic extract of M. calabura L. leaves at a dose of 500mg/kg BW significantly reduced the blood glucose levels of diabetic rats.

Antinociceptive Activity:

Studies by Zakaria et al. (2007)²⁴ showed that the aqueous extract of M. calabura L. leaves exhibited a heat-stable antinociceptive activity, which was partially mediated by an opioid receptor.

Antioxidant Activity:

In the study by Preethi et al. (2010)²⁵, data analysis showed that the fruit extracts had high levels of antioxidant activity.

Anti-inflammatory activity:

The study by Mondal et al. (2013)²⁶ showed that oral administration of 100, 250, and 500mg/kg BW of the ethanol extract of the stem bark showed significant anti-inflammatory activity. Moreover, the study by Gomathi et al. (2013)²⁷ showed that oral administration of 200 and 400mg/kg BW of the polyphenol extracts of M. calabura L. fruit exhibited significant anti-inflammatory activity.

Antipyretic Activity:

Administration of 500mg/kg of M. calabura L. extract significantly decreased fever caused by yeast and this finding supports the view that the extract affects biosynthesis of prostaglandin, which is assumed to control body temperature²⁶.

Anti-severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Activity:

Therapeutic agents that act on the coronavirus can be divided into several categories based on the specific pathways they affect. (1) Some agents act on enzymes or functional proteins that are critical to the virus, preventing viral RNA synthesis and replication. (2) Some agents acting on structural viral proteins to block the virus from binding to human cell receptors or inhibit the viral self-assembly process. (3) Some agents produce virulence factors that restore the host's innate immunity, and (4) some act on the host's specific receptors or enzymes, preventing the virus from entering host cells (Figure 1). On the other hand, Kharisma and Ansori (2020)²⁸ reported the construction of epitope-based peptide vaccine against SARS-CoV-2. Ansori et al. (2020)²⁹characterized SARS-CoV-2 spike glycoprotein genes from Indonesia to investigate their genetic composition and variability.

Fig. 1. Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) genome.

Traditional medicine is widely used worldwide and plants still constitute a large source of novel compounds with different bioactivities including anti-inflammatory, anticancer, antiviral, antibacterial, and cardioprotective. Antioxidants also play a health-promoting role³⁰. However, there are no data on the activity of M. calabura L. against coronaviruses and we suggest that its phytocomponents should be tested via computational study (in silico), in vitro, and in vivo studies including on SARS-CoV-2 (Figure 2).

Fig. 2 Phytomedicinal benefits Muntingia calabura L. and against Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2).

CONCLUSION:

In conclusion, ethnomedicinal and scientific reports on the medicinal properties of M. calabura L. exhibit it as a valuable plant and establish it as a candidate for future drug development against SARS-CoV-2.

ACKNOWLEDGEMENT:

This study was supported by the Directorate General of Higher Education, Ministry of Education and Culture of the Republic of Indonesia. We thank Editage for editing the manuscript.

CONFLICT OF INTEREST:

The authors declare no conflict of interest.

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Received on 01.07.2020 Modified on 17.08.2020

Research J. Pharm. and Tech. 2021; 14(8):4509-4512.

DOI: 10.52711/0974-360X.2021.00784