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Acetogenins from Annona muricata as Antimicrobial Agents

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Gabriela Aguilar-Hernández, Brandon A. López-Romero, Inkar Huerta-Castellanos, Guillermo Tellez-Isaias and Efigenia Montalvo-González

Submitted: 29 January 2024 Reviewed: 06 May 2024 Published: 03 June 2024

DOI: 10.5772/intechopen.115064

Enterococcus - Unveiling the Emergence of a Potent Pathogen IntechOpen
Enterococcus - Unveiling the Emergence of a Potent Pathogen Edited by Guillermo Téllez-Isaías

From the Edited Volume

Enterococcus - Unveiling the Emergence of a Potent Pathogen [Working Title]

Dr. Guillermo Téllez-Isaías, Dr. Danielle Graham and Dr. Saeed El-Ashram

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Abstract

Annona muricata L. is a plant belonging to the Annonaceae family and is highly appreciated for its bioactive compound content; between them are acetogenins. Acetogenins are molecules with aliphatic chains and a lactonic group, and they have been isolated from various parts of the tree (leaves, stem, and root) or fruit (peel, pulp, columella, and seeds). Also, they present different biological activities such as insecticidal, antiviral, and antitumoral. However, has it been demonstrated that acetogenins are antimicrobial. This chapter aims to show the scientific evidence of the antimicrobial effect of crude extracts or acetogenins isolated from Annona muricata on Gram-positive and Gram-negative bacteria and some yeasts.

Keywords

  • Annona muricata
  • acetogenins
  • bioactive compounds
  • mechanism of action
  • antimicrobial activity

1. Introduction

Annona muricata L. (A. muricata) is belonging to the Annonaceae family. It is mainly known in Mexico as guanabana. However, in some countries, it is also known as corossolier (French), graviola (Portuguese), zuurzak (Germany), durian belanda (Malaysian), and munolla (India) [1, 2]. Fruit is highly consumed by exquisite flavor and aroma; stems, leaves, and roots from A. muricata extracts have been used to combat various human ailments such as cancer, diabetes, hypertension, cardiovascular problems, anti-inflammatory, gastrointestinal disorders, and parasitic infections [3, 4, 5]. It is attributed to bioactive compounds between them, phenolic compounds, terpenes, alkaloids, and acetogenins (ACGs) [6].

ACGs are the most studied biological compounds because they are specific to the Annonaceae family. They can inhibit the mitochondria’s complex I and NADH oxidase, causing cellular apoptosis [7, 8]. In addition, ACGs can affect alternative targets in cells, with possible covalent interaction, such as their ability to inhibit metalloproteins, chelate calcium, and modulate the histone H3 phosphorylation. Due to this, they exhibit essential biological activities such as insecticidal, antiviral, antitumor, and antimicrobial [5, 9, 10, 11].

This chapter aims to demonstrate the potential antimicrobial effect of crude extract, acetogenic fractions, or purified ACGs from A. muricata against different bacteria and yeasts, compiling recent scientific information.

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2. Annona muricata

A. muricata L. is native to the tropical regions of Central and South America, Western Africa, and Southeast Asia [1, 5, 12]. Figure 1 shows the A. muricata tree and fruit (edible fraction and seeds). The A. muricata tree has a height ranging from 4 to 10 m, with a diameter between 13 and 83 cm. It grows upright, and the inflorescence appears on the branches. The fruit is dark green with thorn-shaped protuberances on its pericarp, which reach average weights ranging from 300 g to 4 kg, with a diameter of 15 to 20 cm and a height of 17–25 cm. The endocarp has an abundant white fleshy part with a bittersweet flavor, an exotic smell, and abundant black seeds. The number of seeds is proportional to the size of the fruit, with around 100 or more seeds per fruit [5, 12, 13, 14]. A. muricata tree flourishes in altitude conditions below 1200 m above sea level, with high relative humidity (60–80%), 25–28°C temperatures, and abundant annual rainfall (greater than 1500 mm). The tree usually blooms and bears fruit throughout the year; however, there are defined seasons, which will depend on the geographical altitude of the tree [5, 13].

Figure 1.

Tree and fruit (edible fraction and seeds) of Annona muricata grown in Camichin of Jauja, Tepic, Nayarit, Mexico.

On the other hand, the A. muricata plant is rich in acetogenins. It has been demonstrated that these compounds in crude extracts, purified fractions, or purified compounds have in vitro and in vivo biological activities such as anticancer, antiviral, and antimicrobial [5, 15].

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3. Acetogenins from Annona muricata

A. muricata has a significant content of bioactive compounds such as phenolic compounds, glucosinolates, steroids, saponins, glycosides, terpenoids, polyesterols, alkaloids, and mainly ACGs with unique chemical structures. These bioactive compounds have been extracted from the leaves [4, 16, 17, 18, 19, 20, 21, 22], stem [21], root [21], pulp [23, 24], seed [11, 21, 25, 26, 27], and peel [21].

ACGs are molecules distinguished by a long aliphatic chain of 35 to 37 carbon atoms attached to one, two, or three tetrahydrofuran or tetrahydropyran rings in its central region. The chemical structure (Figure 2) of most acetogenins is characterized by four segments: (a) an α-β-unsaturated γ-lactone ring, (b) an alkyl spacer linking the γ-lactone, (c) one to three tetrahydrofuran (THF) rings with flanking OH groups or other groups such as ketone, epoxy and tetrahydropyran, and (d) a long alkyl tail. The presence of two OH and acetyl groups adjacent to the THF ring(s) is a common structural feature of many acetogenins. The type of ACGs (linear, epoxy, mono-, bis-, tri-, and tetrahydrofuran) is determined by the number of central oxygenated groups, mostly tetrahydrofuran (THF) traces, while the subtype is defined by the structure of the lactonic ring (the α, β-unsaturated being subtype 1) [6, 7, 28, 29, 30]. Several types of ACGs have been characterized based on the nature of the present functional groups. ACGs exhibit many biological properties such as cytotoxic, antitumoral, antiparasitic, pesticidal, and antimicrobial activities [7].

Figure 2.

The general structure of an Annonaceous acetogenin shows the 4 segments of which it is made up (x is OH or O group, R1 and R2 are carbon radicals).

According to the literature, more than 120 ACGs are present in aqueous, methanol, ethanol, or other organic solvent extracts prepared from various parts of the A. muricata plant or fruit [29]. In this sense, one of the main isolated ACGs in this species is annonacin, which has been found in greater abundance in leaves [31, 32], fruit [32, 33, 34], seeds [11, 25, 26, 27, 35], peel [36], and roots [37]. Table 1 shows the main types of ACGs isolated from the various parts of the plant or fruit of A. muricata.

OrganAcetogeninsMolecular formulaTypeReference
SeedsDiepomuricanin-AbC35 H62 O4ACGs without THF (Bis-epoxy)Leprevote et al. [38]
Corepoxylone (CO,10)C35 H62 O5Gromek et al. [39]
SolaminC35 H64 O5Mono-THF α, α´ dihidroxylatedMyint et al. [40]
15-palmitoylsolaminC51 H94 O6Gleye et al. [41]
15-oleylsolaminC53 H96 O6Gleye et al. [41]
CorossolinC35 H64 O6Mono-THF α, α´ dihidroxylated (Trihidroxylated and dihidroxylated ketonic)Cortes et al. [42]
Corossolone (CO,10)C35 H62 O6Cortes et al. [42]
Cis-goniothalamicinC35 H62 O7Mono-THF α, α´ dihidroxylated (Tetrahidroxylated and tri hydroxylated ketonic)Rieser et al. [43]
Arianacin + javoricinC35 H62 O7
Rollinecin-A + BC35 H64 O7
Cis-corossolone (CO-10)C35 H62 O6Liaw et al. [31]
Cis-annonacinone (CO,10)C35 H62 O7Rieser et al. [43]
Cis-annomontatacinC37 H68 O7Liaw et al. [44]
Muricin-G (or annomocherin)C35 H62 O7Kim et al. [45, 46]
Muricatin-C (CO,10)C35 H62 O8Mono-THF α, α´ dihidroxylated (Polyhidroxylated and tetrahidroxylated ketonic)Li et al. [47]
Muricatatin-C (CO,10)C35 H66 O8
MuricatalinC35 H64 O8Mono-THF α- or α´ monohydroxylated (With OH at C4)Ghi et al. [48]
Muricatin-BC35 H64 O8Li et al. [47]
Annopentocin-A + BC35 H64 O8Zeng et al. [49, 50, 51]
Annopentocin-CC35 H64 O8Zeng et al. [49, 50, 51]
Muricin-AC35 H62 O7Chang and Wu, [52]
Muricin-Bd
Muricin-C
Muricin-D
Muricin-E
Muricin-F
AnnocatalinC35 H64 O7Mono-THF α- or α´ monohydroxylated (Without OH at C4)Liaw et al. [31]
Muricin-HC35 H64 O6
Muricin-IC35 H66 O6
Annomuricinone-DC35 H64 O8Mono-THF iso-ACGsZeng et al. [49, 50, 51]
Annocatacin-AC35 H62 O6Adjacent bis-THF α-monohydroxylated γ-lactoneChang et al. [53]
Annocatacin-B
RobustecinC35 H62 O5Gleye et al. [54, 55]
BullatacinC37 H66 O7Adjacent bis-THF α, α´-dihidroxylated (Trihydroxylated and tetrahydroxylated)López-Romero et al. [25]
Squamostatin-DC37 H66 O7Non-adjacent bis-THF
PseudoanonacinC35 H67 O7Mono-THF α, α´ dihidroxylated (Tetrahihydroxylated and trihydroxylated ketonic)
AnnonacinC35 H64 O7
SquamocinC37 H66 O7Adjacent bis-THF α, α´-dihidroxylated (Trihydroxylated, dihidroxylated ketonic, tetrahydroxylated and pentahydroxylated)
IsodesacetyluvaricinC37 H66 O6Adjacent bis-THF α, α´-dihydroxylated (dehydroxylated)
DesacetyluvaricinC37 H66 O6
LeavesAnnomutacinC37 H68 O7Mono-THF α, α´-dihydroxylated (Tetrahydroxylated and trihydroxylated ketonic)Wu et al. [56]
Cis-corossolone (CO-10)C35 H62 O6Liaw et al. [31]
Annomuricin-AC35 H64 O8Mono-THF α, α´-dihydroxylated (Polyhidroxylated and tetrahidroxylated ketonic)Wu et al. [57]
Annomuricin-BC35 H64 O8
Muricatocin-AC37 H66 O7Wu et al. [58]
Muricatocin-BC35 H67 O7
Muricatocin-CC35 H64 O7Wu et al. [59]
Annomuricin-CC37 H66 O7
AnnohexocinC37 H66 O7Zeng et al. [60]
Annomuricin-EC35 H64 O8Kim et al. [61, 62]
MuricapentocinC35 H64 O8
Murihexocin-A + BC35 H64 O9Mono-THF α- or α´-monohydroxylated (THF α -monodydroxylated)Zeng et al. [49, 50, 51]
Annopentocin -A + BC35 H64 O8
Annopentocin-CC35 H64 O8
Annomuricinone-DC35 H67 O7Mono-THF (Mono-THF iso)
MuricoreacinC35 H64 O9Mono-THF α- or α´-monohydroxylated (THF a-monodydroxylated)Kim et al. [61, 62]
Murihexocin-CC35 H64 O7
MuricatalicinC35 H64 O8Mono-THF α, α´-dihydroxylated (Polyhidroxylated and tetrahidroxylated ketonic)Gui and Yu [63]
Annonacinone-AC35 H64 O7Mono-THF (Mono-THF-iso)Wu et al. [56, 57, 58, 59]
RootMontecristinC37 H66 O4Vicinal dihidroxylated and olefinic linearGleye et al. [64, 65]
Cohibin-AC35 H66 O6
Cohibin-BC35 H64 O4
Muriedienin-1C35 H62 O2Olefinic and acetylenic linearGleye et al. [66, 67]
Muriedienin-2C37 H66 O2
Chatenaytrienin-1 + 2C35 H60 O2
Chatenaytrienin-3 + 4C37 H64 O2
MuricadieninC35 H62 O2
Muricadienin-3 + 4C37 H66 O2
SabadelinC35 H62 O3ACGs without THF rings; epoxy ACGsGleye et al. [68]
CoroninC37 H64 O4ACGs without THF rings (Bis-epoxy ACGs)Gleye et al. [69]
Cis-solaminC35 H64 O5Mono-THF α, α´ dihidroxylated (Dihydroxylated)Gleye et al. [67]
Cis panatellinC35 H64 O5
Cis-uvariamicin-IVC37 H68 O5
Cis-uvariamicin-IC37 H68 O5
Cis-reticulacinC35 H62 O5
Cis-reticulatacin-10-oneC37 H68 O6Mono-THF α, α´ dihidroxylated (Trihidroxylated and dihidroxylated ketonic)
Ripe FruitEpomurinin-AC35 H62 O3ACGs without THF rings; epoxy ACGsMelot et al. [70]
Epomurinin-BC35 H62 O3
Stem barkEpoxymurin-AC35 H62 O3Hisham et al. [71]
Epoxymurin-BC35 H62 O3Roblot et al. [72]
Epomuricenin-AC35 H62 O3Hisham et al. [71]
Epomuricenin-AC35 H62 O3Roblot et al. [72]
PulpAnnonamuricin-BC35 H64 O7Mono-THF α, α´-dihydroxylated (Tetrahydroxylated and trihydroxylated ketonic with OH at C4)Sun et al. [73]
Annonamuricin-CC35 H64 O7
Annonamuricin-DC35 H64 O7
Muricin-NC35 H64 O7Sun et al. [74]
muriceninC35 H66 O3
Muricin-JC35 H64 O7Sun et al. [75]
Muricin-KC35 H64 O7
Annonamuricin-AC35 H64 O7Mono-THF α- or α´-monohydroxylated (with OH at C4)Sun et al. [73]
Muricin-MC35 H64 O7Sun et al. [74]
Muricin-OC35 H64 O7Sun et al. [75]
PeelAnnonacinC35 H64 O7Mono-THF α, α´ dihidroxylated (Tetrahihydroxylated and trihydroxylated ketonic)Jaramillo et al. [36]
Annonacin AC35 H64 O7
Annomuricin AC35 H64 O8Mono-THF α, α´-dihydroxylated (Polyhidroxylated and tetrahidroxylated ketonic)

Table 1.

Main acetogenins isolated from the different parts of the plant or fruit of A. muricata.

THF: Tetrahidrofuranic; ACGs: acetogenins.

The most isolated ACGs are from the A. muricata seeds, leaves, and roots. Also, this table shows that the primary type of ACGs reported in this genus are mono-THF type. Thus, the following section will address the mechanism of action of ACGs as antimicrobials.

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4. Mechanism of action of acetogenins as antimicrobials

It has been demonstrated that the biological activities are dependent on the ACGS chemical structure, the presence of either of the two OH groups adjacent to the THF ring is sufficient to maintain potent activity, and only when the γ-lactone and THF ring molecules are directly linked by an alkyl spacer (the optimal length of which is about 13 carbon atoms), ACGs act as a potent inhibitor [76, 77]. Shimada et al. [78, 79] demonstrated that a robust interaction could occur between the THF rings and the polar terminals of phospholipids within liposome membranes. They proposed that these THF rings serve as a hydrophilic anchor to the membrane, enhancing the alignment and configuration of the functional groups of ACG. The terminal lactone is considered a component of the domain spacer, which is the segment of the molecule expected to directly engage with the active site of the enzyme in mitochondrial complex I. This interaction is facilitated through lateral diffusion within the inner mitochondrial membrane.

There are different proposed mechanisms of ACGs as antimicrobials. The established first (Figure 3A) was that they are the most potent inhibitors of NADH ubiquinone oxide reductase (located in complex I) of the mitochondrial respiratory chain in eucaryotic and procaryotic cells, and NADH oxidase located in the plasma membrane of bacteria, which reduces the production of ATP in the cells causing apoptosis [7]. By inhibiting these enzymes, ACGs modify the transit of negatively charged ions through the respiratory chain and inhibiting proton cascades that affect cellular respiration and directly inducing apoptosis, autophagy, or cell cycle interruption, causing cell death [4, 77].

Figure 3.

(A) Mechanism of action of acetogenins and their effect on mitochondrial complex I (NADH ubiquinone oxidoreductase). (B) Interaction of acetogenins with calcium ions forming a chelating complex (adapted of Bermejo et al. [7] and Liaw et al. [80]).

Another mechanism that involves the THF segments of ACG and their adjacent hydroxy groups is the independent interactions with bivalent cations, such as Ca2+ and Mg2+. Individual ACG molecules can assume novel secondary structures distinct from their free counterparts. Bivalent cations can form complexes with multiple ACG molecules, allowing THF nuclei and neighboring hydroxy groups to engage with ions and form chelating complexes. The creation of chelating complexes involving ACG and Ca2+ can potentially disrupt intracellular calcium balance by sequestering these ions within the ACG-Ca2+ complexes (Figure 3B). This process facilitates the movement of ions across the mitochondrial membrane, driven by the hydrophobic nature of the complexes. Consequently, this leads to elevated calcium levels within the cell, specifically within the mitochondria, resulting in a decrease in mitochondrial membrane potential and the initiation of proapoptotic signal [80, 81].

On the other hand, other studies suggest that the bioactivity of ACG mixtures also depends on their structure, purity, concentration, and the type of microorganism evaluated [26, 82]. Therefore, in the following section, we will discuss the effect of these compounds as antimicrobials.

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5. Antimicrobial activity of acetogenins

The antimicrobial effect of ACGs has been little explored; however, this review shows all the studies on the antimicrobial effect of ACGs on various Gram-positive and Gram-negative bacteria, some yeasts, and their advantages compared with antibiotics (see Table 2).

Sample typePart of plant or fruitConcentration
(mg/mL)		MicroorganismResultsReferences
Aqueous-methanol ExtractLeaves0.00125–0.4S. aureus, E. faecalis, B. subtilis, C. sporogenes, P. aeruginosa, K. pneumonia, E. coli, and S. marcesensThe MIC values ranged between 0.0313–0.0625 μg/mL. It was most inhibitory against S. typhi, S. aureus, E. faecalis, K. pneumonia, and S. marcescensOyedeji et al. [16]
Aqueous extractsLeaves0.01–0.2S. mutans, S. mitis, P. gingivalis, P. intermedia, and C. albicansShows a bacterial inhibition of 20.8% against S. mutansPai et al. [17]
Aqueous-ethanol-methanol extractLeaves0.0015–2hydrophila, B. subtilis, A. niger, and S. aureusA MIC of 500–1000 μg/mL was determined against B. subtilis, S. aureus, A. hydrophila and A. niger.Ulusola et al. [18]
Methanolic
Extract		Leaves0.0025–5B. cereus, E. faecalis, S. aureus, E. aerogenes, E. cloacae, E. coli, P. aeruginosa, S. Typhimurium, S. Choleraesuis, and S. dysenteriaeBactericidal effect for S. typhimurium, S. aureus, and P. aeruginosa (MIC = 78–625 μg/mL) and bacteriostatic for the other bacteria tested (MIC = 39–1250 μg/mL)Pinto et al. [4]
Fractionated extractsFresh pulp2S. Typhimurium, E. aerogenes, E. faecalis, B. subtillis, R. stolonifer, and C. gloeosporioidesHigher antimicrobial activity of all fractions was observed for E. aerogenes (25.95–41.15%) and C. gloeosporiodes (10–59.90%).León-Fernández et al. [23]
Ethanolic extractsLeaves50–400S. mutansAntibacterial activity was observed at all concentrations tested with 10–80% inhibition.Rodriguez-Perez and Millones-Gomez [19]
Ethanolic extractsLeaves100C. albicansAn inhibition percentage of 96.9% against C. albicans was observed.Rustanti and Fatmawati [20]
Aqueous-ethanol extractLeaf, stem, seed, peel, and root0.25–32Methicillin-resistant S. aureusA synergistic effect of streptomycin and tetracycline was observed with A. muricata extracts, with a 32-fold increase in antibacterial activity against S. aureus (methicillin-resistant).Neglo et al. [21]
Crude extract and isolated ACGsSeeds0.0125–4C. albicans, C. glabrata, C. tropicals, and C. kruseiThe highest inhibition was observed with ACGs isolated at 400 μg/mL against C. albicans (15.50 mm), C. tropicalis (14 mm), and C. krusei (13.50 mm).López-Romero et al. [25]
Crude extract and isolated ACGsSeeds0.0125–4S. mitis, L. monocytogenes, S. aureus, E. faecalis, S. mutans, S. salivaris, A. hydrophila, E. coli, S. cholerasius, B. cenocepacia, S. paratyphi, and K. pneumoniaeThe isolated ACGs show the highest antibacterial effect against E. faecalis (11–15.67 mm), L. monocytogenes (12–18 mm), A. hydrophila (10.33–11.67 mm), B. cenocepacia (11–12 mm), and S. paratiphy (11–15.67 mm) at all concentrations tested, and a MIC 0.009–12.50 μg/mL.Aguilar-Hernández et al. [26]
ACGs-NanosuspensionsSeeds0.0987, 0.177 and 0.32E. faecalis and Listeria monocytogenesThe highest inhibition for E. faecalis (87%) and L. monocytogenes (75%) was observed with up to 12 h of exposure to 320 μg/mLLópez-Romero et al. [27]
ACGs-NanosuspensionsSeeds0.0987, 0.177 and 0.32E. faecalis and Listeria monocytogenesThe highest inhibition for E. faecalis (83%) and L. monocytogenes (86%) was observed with up to 12 h of exposure to 320 μg/mLMontalvo-González et al. [11]

Table 2.

Antimicrobial effect of extracts from different parts of the plant or fruit A. muricata against various microorganisms studied.

MBC = Minimum bactericidal concentration; MIC = Minimum bactericidal concentration; ACGs: acetogenins.

The study developed by Oyedeji et al. [16] demonstrated that an extract from A. muricata leaves (1000 μg/disc) presented similar inhibition to the antibiotic tested (streptomycin at 10 μg/disc) when they were tested against S. Typhi and E. faecalis with inhibition of 28.3 mm and 26.3 mm, respectively. Similarly, streptomycin presented inhibition of 27.3 mm and 28.6 mm, respectively. In addition, these authors found a bactericidal minimum concentration (BMC) of 0.125 μg/mL against S. Typhi and 0.0625 μg/mL for E. faecalis. Another study development by Pinto et al. [4] demonstrated that an A. muricata leaf extract at concentrations of 0.0025–5 mg/mL showed bactericidal effect (MIC =78–625 μg/mL) against Salmonella Typhimurium, Staphylococcus aureus, and Pseudomonas aeruginosa and a bacteriostatic significant impact (MIC = 39–1250 μg/mL) against Bacillus cereus, Enterococcus faecalis, Enterobacter aerogenes, Enterobacter cloacae, Escherichia coli, Salmonella choleraesuis, and Shigella dysenteriae. These authors concluded that the antibacterial action of A. muricata leaf extract varied depending on the type of microorganism. Still, it was effective against both Gram-positive and Gram-negative bacteria. The results could be explained by bioactive compounds that damage the bacterial membrane by increasing membrane permeability and the leakage of nucleotides that inhibit bacterial growth and induce cell death. The authors also mention that damage to the membranes of Gram-negative bacteria may be more significant than in Gram-positive bacteria because Gram-positive bacteria consist of a thick cell wall surrounded by several layers of peptidoglycan and surface glycopolymers, such as teichoic acids; in contrast, Gram-negative bacteria have an outer membrane, lipoproteins, lipopolysaccharides, and a single layer of peptidoglycan. The bacterial membrane limits the entry of drugs or chemicals and serves as an essential barrier to keep intracellular proteins intact. Therefore, Gram-positive bacteria may have reduced permeability to bioactive compounds from A. muricata extracts [4].

On the other hand, the same authors mentioned that the extract inhibited the bacteria more rapidly and with greater potency compared to antibacterial agents with slow elimination kinetics. Thus, another study showed that the A. muricata extract (9.75, 19.5, and 39 μg/mL) had a similar action to chloramphenicol (6.25 and 12.5 μg/mL) in the initial stages of growth of S. aureus, S. Typhimurium, and E. faecalis. However, the extract had better inhibition after the bacterial latency phase, with greater efficacy than chloramphenicol, a bacteriostatic drug [4].

Furthermore, a study conducted by López-Romero et al. [25] found that the crude extract and isolated ACGs from A. muricata seeds showed a significant antifungal effect against Candida albicans, Candida glabrata, Candida tropicalis, and Candida krusei at concentrations of 0.0125–4 mg/mL. However, the most significant impact as an inhibition zone was found when isolated ACGs at concentrations of 0.8 mg/mL against C. albicans (15.50 mm), C. tropicalis (14 mm), C. krusei (13.50 mm), and C. glabrata (8.50 mm). These authors demonstrated that crude and isolated ACGs at all concentrations showed more significant inhibition against C. albicans, C. krusei, and C. tropicalis compared to ketoconazole (500 mg/mL), which only showed inhibition against C. albicans (14.75 mm). It demonstrated the potential of ACGs against this type of yeast. Yeasts and fungi contain NADH dehydrogenase or NADH-ubiquinone-6-oxidoreductase type II enzymes. Because of this, ACGs can block the activity of these enzymes and, as a result, promote cell death; however, this depends on the type of microorganism. Furthermore, isolated or purified bioactive compounds cause microbial inhibition by adherence to the cell surface or diffusion into the fungal cells. The antifungal compounds in an extract can prevent the formation of nucleic acids (DNA and RNA), thus inactivating the ability of the genetic material to function [83].

Recently, Aguilar-Hernández et al. [26] concluded that isolated ACGs (0.0125–4 mg/mL) from A. muricata seeds exhibited a significant inhibitory effect (7–18 mm of inhibition zone) against Gram-negative (Streptococcus mitis, Listeria monocytogenes, Staphylococcus aureus, Enterococcus faecalis, Streptococcus mutans, and Streptococcus salivaris), and Gram-positive bacteria (Aeromonas hydrophila, Escherichia coli, Salmonella cholerasius, Burkholderia cenocepacia, Salmonella paratyphi, and Klebsiella pneumoniae). In this study, it was demonstrated that the isolated ACGs showed a similar effect to ampicillin (500 mg/mL) against L. monocytogenes and S. aureus; however, for Gram-negative bacteria (except E. coli and S. paratyphi), this inhibition was more remarkable when compared to ampicillin, which did not show any inhibition against the rest of the bacteria.

On the other hand, although ACGs have a broad antimicrobial spectrum, their high hydrophobicity restricts in vitro and in vivo applications. Therefore, López-Romero et al. [27] and Montalvo-González et al. [11] developed nanosuspensions to carrier isolated ACGs from A. muricata seeds in aqueous media. These nanosuspensions were tested at concentrations of 0.0987, 0.177, and 0.32 mg/mL against Enterococcus faecalis and Listeria monocytogenes. Both authors coincided that the highest bacterial inhibition was observed against E. faecalis (83–87%) and L. monocytogenes (75–86%) at 320 μg/mL. Furthermore, it has been noted that the quantity of unsaturations in the aliphatic chain of ACGs is a structural characteristic that significantly affects their antibacterial action. Additionally, a process of insertion into the cell membrane similar to that of fatty acids affects the viability and functionality of bacteria [84]. Finally, with the studies described in this section, it was possible to demonstrate that ACGs can be potent inhibitors against Gram-positive and Gram-negative bacteria and some yeasts, even under the same conditions as the antibiotics used or at lower doses, and in some cases inhibit antibiotic-resistant microorganisms, such as B. cenocepacia and C. tropicalis.

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6. Conclusions

The fight against pathogenic microorganisms has always been relevant because they cause millions of deaths yearly in humans and food animals worldwide. The studies analyzed in this chapter demonstrated that crude extracts, fractions, and acetogenins isolated from the pulp, leaves, and seeds of A. muricata have a vital potential with a broad spectrum of antimicrobial applications against Gram-positive bacteria (S. aureus, S. mutans, S. mitis, L. monocytogenes, E. faecalis, S. salivaris, S. mitis, and B. subtilis) and Gram-negative bacteria (E. cloacae, V. cholerae, E. coli, P. gingivalis, A. hydrophila, K. pneumoniae, S. paratyphi, S. abatetuba, S. cholerasius, S. Typhimurium, B. cenocepacia, and E. aerogenes), and some yeasts (C. albicans, C. glabrata, C. tropicals, C. krusei, R. stolonifera, and C. gloeosporioides); therefore, although many studies are needed to investigate other types of pathogens, we can suggest that ACGs are very promising bioactive compounds that could be used as a potential alternative against others bacteria (including more enterococci) using in vivo models.

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Acknowledgments

The authors thank CONAHCYT-Mexico for the postdoctoral granted to Gabriela Aguilar-Hernández (No. 590664) and the scholarship (No. 794251) awarded to Brandon A. López-Romero.

To USDA-NIFA Sustainable Agriculture Systems with the “Empowering US Broiler Production for Transformation and Sustainability” project. Grant No. 2019-69012-29905.

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Conflict of interest

The authors declare that they have no financial interests or personal relationships that could influence the work presented in this research.

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Written By

Gabriela Aguilar-Hernández, Brandon A. López-Romero, Inkar Huerta-Castellanos, Guillermo Tellez-Isaias and Efigenia Montalvo-González

Submitted: 29 January 2024 Reviewed: 06 May 2024 Published: 03 June 2024

© 2024 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution 3.0 License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.