Antimicrobial Activity and Chemical Composition of Momordica Charantia: A Review

Plants are a very rich source of new chemical entities1, so much so that, to date2, new prototypes with various therapeutic potentials are still being sought.3 No stranger to it, bitter melon (Momordica charantia L.) is a plant species that has attracted researchers’ interest in recent years (Figure 1). Chemical and pharmacological studies on the Momordica charantia L. (M. Charantia) plant have been in existence since 1963 and have had a growing interest, deduced by the increase in the amount of research work over the years to the present; since 1993, investigations were initiated on its antibacterial activity and since 1997, on its antifungal activity (Figure 1).


INTRODUCTION
Plants are a very rich source of new chemical entities 1 , so much so that, to date 2 , new prototypes with various therapeutic potentials are still being sought. 3 No stranger to it, bitter melon (Momordica charantia L.) is a plant species that has attracted researchers' interest in recent years ( Figure 1). Chemical and pharmacological studies on the Momordica charantia L. (M. Charantia) plant have been in existence since 1963 and have had a growing interest, deduced by the increase in the amount of research work over the years to the present; since 1993, investigations were initiated on its antibacterial activity and since 1997, on its antifungal activity ( Figure 1).
The fruits of M. Charantia are consumed daily as a food and as a medicinal plant for traditional use in Southeast Asia, Indo-China 4 , as well as in Brazil. 5 M. Charantia is a plant belonging to the Cucurbitaceae family and is widely distributed in tropical and subtropical areas around the world. [5][6][7] Studies have determined that this plant contains a great diversity of primary and secondary metabolites 8,9 with therapeutic potential as antiulcer properties 6,10 , antioxidant [11][12][13][14] , antimicrobial 6,8,12,[15][16][17] , anthelmintic 18,19 , antidiabetic 6,11,20,21 , antiinflammatory 21,22 , antihyperglycemic 6,21,23 and anticancer 4,19,21,24 , and nutritional as antilipolytic. 11,25 Bacterial resistance is one of the main problems around the world, it is thought that by 2050 bacterial resistance will be one of the leading causes of death in the world. [26][27][28] Currently there are bacteria that are resistant to almost all existing antibacterials. 29 That is why the search for new entities with antibacterial potential is a worldwide research focus 30 and M. Charantia is a species with great possibilities. Several studies have demonstrated antifungal and antibacterial activity in M. Charantia 9,31-34 , as well as antimicrobial activity in leaves 8,[35][36][37][38][39][40] , and fruit. 41 In the last two years there has been a significant increase in publications of scientific articles on M. charantia (Figure 1), generating a large amount of information about it and its antimicrobial activity, which is why the organization and selection of this information become necessary and important in order to provide interested researchers with updated information on this species.

Taxonomic classification
M. charantia is an annual or perennial, monoclimber, herbaceous, 3-4 m long plant, which belongs to the Cucurbitaceae family. It contains almost sixty species that grow in tropical and subtropical regions ( Figure 2). 4,42,43 Víctor Eduardo Villarreal-La Torre 1, *, William Sagástegui Guarniz 1 , Carmen Silva-Correa 1 , Lizardo Cruzado-Razco 1 , Raúl Siche 2 charantia is a slender and slightly hairy or hairless plant that can be grown at high altitude. 4,46 A description of each part of the M. charantia is shown in Table 1.

4,42
Fruit Pendular discoid with ovoid shape, 2 to 10 cm in length, covered with broken or continuous longitudinal ridges and warts. The young fruit is white or emerald green that turns orange when ripe, and its white pulp becomes scarlet during ripening.

4,6,42
Seed 8-15 mm long, rectangular squares, corrugated on the margin, sculpted on both sides, but covered with a white pulp when green and red when ripe. 4,42,46  and Colletotrichum musae. 87 An extract of the whole plant has shown antiprotozoal activity against Entamoeba histolytica 88 , Salmonella typhi, Staphylococcus aureus, Streptococcus pyogenes 16 and Mycobacterium tuberculosis 86 , and an extract of isolated proteins from leaves demonstrated an antifungal effect. 36,89 MAP30 is an isolated protein of M. charantia that can be used in combination with chloramphenicol or erythromycin, and be beneficial in terms of reducing the side effects of antibiotics, as lower concentrations of antibiotics are required due to their antibacterial ability. 63 A synergistic effect has also been demonstrated between ethanolic extract and aminoglycosides, chlorpromazine, kanamycin and amikacin, indicating the participation of an efflux system in the resistance to these aminoglycosides. 90 This represents a new weapon against bacterial resistance to antibiotics. In addition, silver nanoparticles have been studied with M. charantia 52,[91][92][93] although studies are still lacking to determine the real biochemical route by which it exerts its antimicrobial effects.
The leaf extract of M. charantia has a potent antimicrobial action against S. typhi with potential for hepato-inflammatory improvement by decreasing the concentrations of total and direct bilirubin, alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase and gamma glutamyl transferase compared to the group control. 38 In addition, photosynthetic pigments and cinnamic acid showed a direct correlation with the antimicrobial potential against Staphylococcus aureus and Pseudomonas aeruginosa, sinaptic acid showed a positive correlation only with Staphylococcus aureus; likewise, cinnamic acid, coumaric acid, syringic acid and quercetin in direct correlation with Pseudomonas aeruginosa. 8 Plumericin (Figure 3), an iridoid lactone isolated from the stem of M. charantia, has shown antibacterial activity against Enterococcus faecalis and Bacillus subtilis with minimal inhibitory concentration values better than cloxacillin. 66 The aqueous seed extract has shown greater antimicrobial capacity by inhibiting the growth of Fusarium solani 19 and Pasteurella multocida, compared to the extracts of methanolic, ethanolic, hexane and ethyl acetate that were effective against S. aureus, Enterococcus and fungi. 33,[94][95][96] Seed oil, with t-nerolidol, c-dihydrocarveol and germacrene ( Figure  3) as its main constituents, has shown antimicrobial activity towards S. aureus, E. coli and C. albicans 75,97 , which makes the development of green antibacterial soaps, without chemical aggregates, feasible. 15 The levels of flavonoids and phenols such as catechin, myricetin, quercetin, gallic acid, chlorogenic acid, gentisic acid and salicylic acid, increase considerably in hair roots in vitro growth compared to unprocessed roots, although metabolites such as ferulic acid, rutin, naringenin and naringin decreased significantly in the hair roots. Due to these metabolic variations, antimicrobial activity increases in hair roots in vitro growth compared to non-transformed roots. 51 Fresh fruits extracts have exhibited similar antibacterial properties against strains of Bacillus subtilis, Pseudomonas aeruginosa and Saccharomyces cerevisiae 60 , also have shown activity against E. coli, Staphylococcus, Pseudomonas, Salmonella and Streptobacillus very similar to the hydrophilic extracts of leaves 6 and Aspergillus Niger. 32 Application of M. charantia fruit powder at wound sites is equally effective in stimulating tissue regeneration and wound healing in rats. 98 Fruit extracts have shown a better activity compared to leaf extracts 41 and seeds 40 , with methanol extracts having the best antibacterial activity. 37 Recombinant α-momorcharin inhibits the growth of F. solani, causing deformation of cells with irregular outbreaks, integrity loss of the cell wall, rupture of the fungal cell membrane, DNA fragmentation, in addition to affecting macromolecular synthesis and organelles functions. 49 RK29, the active lectin isolated from ripe fruit and seed, inhibits HIV-1 viral reverse transcriptase. 6 Cucurbitane triterpenoids (kuguacins F-S), pentanorcucurbitacins, octanorcucurbitacin and trinorcucurbitacins exhibit weak in vitro anti-HIV-1 activities. 99 The triterpene glycosides momordicines I and II are anthelmintic but not antiviral ( Table 2). 82

Current and future challenges
There is a growing interest in investigating the antimicrobial activity of M. charantia (Figure 1) motivated by the search for new sources of chemical entities with therapeutic potential. Antimicrobial activity has been reported in isolation from fruits (Table 3) 100 , so it is recommended to conduct studies of the efficacy of isolated cucurbitane, such as charantin found in almost all parts of the plant (Table 2), in vivo. In addition, cucurbitane are attributed antidiabetic activity 46 , an effect that could enhance treatments against infections in diabetic foot.     On the other hand, studies of its safety and efficacy have been carried out in combination with antimicrobials such as aminoglycosides 90 , with the intention of being able to cope with bacterial resistance as well as a decrease in side effects; Therefore, it is recommended to continue studies on proteins such as α-momorcharin and MAP30 which is located in leaves, stems, fruits and seeds (Table 2), which have demonstrated very good antimicrobial metabolites 49,63 as well as some protein fractions 89 .

Root
Although there are a large number of articles that corroborate the antimicrobial activity, the mechanism of this therapeutic activity is not yet known.

CONCLUSIONS
Although a large number of medicinal plants have been reported with antimicrobial activity, studies that corroborate their efficacy and safety are still needed. The phytochemical analysis and demonstration of the in vivo and in vitro antimicrobial activity of M. charantia, promotes the need to study the probable mechanisms by which bioactive compounds such as charantin, α-momorcharin and MAP30 act.