Plant Antimicrobial Compounds and Their Mechanisms of Action on Spoilage and Pathogenic Bacteria: A Bibliometric Study and Literature Review

Abstract

This research explored the potential of plant antimicrobial compounds as natural alternatives to synthetic antimicrobials in the food and pharmaceutical industries, emphasizing the urgent need to combat antimicrobial resistance. It detailed various mechanisms by which these plant-derived compounds inhibit microbial growth, including disrupting cell membrane integrity, impeding cell wall and protein synthesis, and preventing biofilm formation, ultimately leading to bacterial cell death. This study highlighted the specific effects of plant antimicrobials on bacterial cells, such as inhibiting biofilm formation, cellular respiration, and cell motility, while also modulating oxygen consumption and reactive oxygen species generation, which are vital in addressing biofilm-mediated infections. Additionally, these compounds can regulate the expression of virulence factors and efflux pumps, enhancing antibiotic efficacy. A bibliometric analysis revealed a growing trend in research output and international collaboration, particularly from China and the United States, with key journals including “Frontiers in Microbiology” and “Antimicrobial Agents and Chemotherapy.” The analysis identified six clusters related to plant antimicrobial research, underscoring the need for further investigation into the mechanisms and applications of these bioactive compounds. In conclusion, understanding the action of plant antimicrobials is important for their effective application in combating antimicrobial resistance.

1. Introduction

The increasing occurrence of antimicrobial resistance (AMR) has ignited a fresh interest in investigating natural compounds as potential substitutes for synthetic antibiotics [1]. Various classes of plant-derived compounds have shown significant antimicrobial activity. For example, flavonoids demonstrate notable antibacterial properties against pathogens such as Staphylococcus aureus and Escherichia coli. Findings emphasize the capacity to disrupt bacterial cell membranes and inhibit biofilm formation, essential in bacterial virulence and persistence [2,3,4].

Alkaloids like berberine and chelerythrine have demonstrated efficacy against resistant strains, including Methicillin-resistant S. aureus (MRSA). These compounds exert antimicrobial effects by targeting nucleic acid synthesis and preserving cell wall integrity, thus compromising bacterial survival [5,6,7]. Terpenes, such as carvacrol and thymol, demonstrate significant antimicrobial properties, especially against foodborne pathogens, through disrupting cellular functions and enhancing membrane permeability [8,9,10]. Organosulfur compounds, including allicin from garlic, are recognized for inhibiting bacterial growth and biofilm formation, rendering them significant for therapeutic applications and food preservation. The influence of these anti-microbial compounds transcends clinical applications, as they also serve an essential role in maintaining food safety. Bacterial biofilms pose considerable challenges in food processing and preservation; however, these natural compounds can effectively address these issues [11,12,13]. Flavonoids and terpenes inhibit biofilm formation by disrupting bacterial signaling pathways, which reduces their capacity to adhere to surfaces and form protective layers [14,15]. This enhances food product safety and shelf-life while minimizing the risk of foodborne illnesses [16,17,18,19]. Antimicrobial resistance poses a significant challenge to public health, significantly impacting treatment results and resulting in serious economic and clinical consequences. This situation highlights the pressing necessity for practical solutions as bacterial infections rise [20,21]. The effectiveness of traditional antibiotics is diminishing in the face of an increasing number of resistant strains, highlighting the urgent need to investigate alternative therapeutic approaches. The various mechanisms of action displayed by plant-derived antimicrobial compounds—such as the disruption of biofilm formation and direct antibacterial effects—make them promising candidates in the battle against AMR [22]. Ongoing investigation into these natural compounds is relevant for creating effective treatments and safeguarding global health in the context of emerging microbial challenges.

Conducting a bibliometric review of research trends on antimicrobial extracts and compounds over the past 20 years is essential for understanding the field’s evolution. The popularity of bibliometric analysis has surged due to advancements in software like Gephi, Leximancer, and VOSviewer, as well as access to databases such as Scopus and Web of Science [23]. This methodology helps identify research patterns, focus areas, and influential contributions, revealing the global landscape of antimicrobial research. Additionally, it highlights knowledge gaps and emerging research areas, guiding future studies and fostering innovative strategies in antimicrobial compounds [24,25].

The present study has two main objectives: (1) to analyze research trends regarding the mechanisms of action of plant antimicrobial compounds over the past 20 years (2004–2024) using publications from the Web of Science (WoS), and (2) to conduct a literature review that provides specific examples of various compounds with differing mechanisms of action. This study aims to emphasize these compounds’ technological applications and potential in developing food systems and advancing research in this area.

2. Bibliometric Analysis

2.1. Bibliometric Mapping and Analysis

Data collection was based on scientific articles published and indexed in the WoS. A WoS search was conducted to obtain the bibliographic data inputs on 3 March 2025. The research in the central collection of WoS was carried out in the “advanced search” section, applying the following logical operation: TS = (‘antimicrobial’ AND ‘mechanism* action’ OR ‘mode action’ AND ‘plant*’ AND ‘active compound*’) NOT KP = (‘antimicrobial’ AND ‘mechanism* action’ OR ‘mode action’ AND ‘plant*’ AND ‘active compound*’). This means that the publications are selected based on the chosen words included in the title, the abstract, and the author’s keywords, and not on the keywords-plus of each document, thus avoiding mismatches related to the terms that only appeared in the references and did not correspond to the main study topic. Book Chapters, Proceeding Papers, Early Access Articles, and Retracted Publications were excluded from the search.

Publications between 2004 and 2024 were analyzed, providing results corresponding to all records available in WoS, resulting in 8812 documents. Data were exported as BibTeX (dataset_wos.bib) and Research Information Systems (dataset_wos.ris) files using the “Record Content: Full Record” option. The analysis was performed with the software VOSviewer v. 1.6.20 and with software R-package bibliometrix version 4.1.4 [26] for the scientific mapping analysis, using R version 4.1.2 as the programming language (2021-11-01) [27] and R-studio (version 2023.09.1) as the integrated development environment [28]. The analysis was carried out using the function biblioshiny().

Table 1. Main information about the data.

Description	Results
Timespan	2004–2024
Sources (Journals, Books, etc.)	1698
Documents	8812
Annual Growth Rate %	13.84
Document Average Age	7.01
Average citations per doc	32.03
DOCUMENT CONTENTS
Keywords Plus (ID)	15,722
Author’s Keywords (DE)	17,417
AUTHORS
Authors	42,819
Authors of single-authored docs	134
AUTHORS COLLABORATION
Single-authored docs	142
Co-Authors per doc	7.23
International co-authorships %	29.35
DOCUMENT TYPES
Article	8716

shows the primary information about the data on academic production from 2004 to 2024. Regarding document growth and distribution, the analysis revealed an impressive average annual growth rate of 13.84%, indicating a constant increase in document production over time. This growth may be due to factors such as increased interest in research, technological advances, or changes in academic policies that encourage publication. With 8812 documents analyzed, it can be inferred that there is considerable research activity within the area studied. The average age of the papers is 7.01 years, suggesting that most of the research is focused on relatively recent topics.

Regarding citations and academic relevance, the average of 32.03 citations per document indicates significant impact and recognition in the academic community. These data can be interpreted as an indication of the relevance and contribution of the papers to the scientific literature. However, it would be helpful to analyze the distribution of these citations better to understand the variability in the influence of individual documents.

Collaboration among authors plays a key role in international academic research. The fact that 29.35% of the documents involve international collaborations suggests a broad and diverse network of connections between researchers from different world regions. This international collaboration can enrich the quality of research by providing diverse perspectives and approaches.

Finally, regarding the keywords and research topics, 15,722 keywords were identified, suggesting a wide variety of issues within the study area. Analyzing these keywords can provide a detailed view of the dominant research trends and areas of interest throughout the analyzed period, as will be shown in a later section.

In a complementary way, Figure 1 provides a comprehensive view of the analysis. Concerning Figure 1a, the annual production of articles illustrates a consistent upward trend over the examined timespan (2004–2024), indicating a continual rise in scholarly output. Figure 1a displays the yearly distribution of articles, starting with 74 publications in 2004 and ending with the most outstanding production in 2024, with 988 articles published. Figure 1b presents the ten countries that most prominently contributed to this study area. China leads the list with 6095 items, closely followed by the United States with 5036. Brazil and India also play significant positions in production, contributing with 3426 and 2820 articles, respectively. These figures highlight the geographic diversity of research and suggest valuable opportunities for global collaboration, which may be essential to address microbiological challenges related to plant antimicrobial compounds’ mechanisms of action and promote collaborative scientific advances. Figure 1c shows that the publications are made in journals of different disciplines; “Frontiers in Microbiology” and “Antimicrobial Agents and Chemotherapy” stand out as the most relevant sources for published articles. Figure 1d illustrates the journals boasting the highest impact factors, employing the h-index as a metric for measurement, highlighting “Antimicrobial Agents and Chemotherapy” with an H-index of 58. The h-index at the author level assesses publications’ productivity and citation impact. The scrutiny of the h-index for the most influential sources implies a robust scientific foundation. It underscores the capacity of these journals to wield a substantial impact within the academic community [29].

Finally, this coincides with the results obtained about the interdisciplinarity of the area (Figure 1e). The classification of articles in specific disciplines shows a diversity of approaches in research in this area of knowledge. Disciplines such as Biochemistry and Molecular Biology, Microbiology and Pharmacology, and Pharmacy dominate the number of articles. This indicates a convergence of multiple disciplines towards studying the mechanisms of action of plant antimicrobial compounds, underlining their interdisciplinarity. The topics have been most studied from the perspective of Biochemistry Molecular Biology (1802 articles), Microbiology (1620), Pharmacology Pharmacy (1345), Chemistry Multidisciplinary (844), Chemistry Medicinal (741), Food Science Technology (638), Biotechnology Applied Microbiology (616), Biophysics (496), Infectious Diseases (496), and Multidisciplinary Sciences (487), Chemistry Physical (357), Plant Sciences (341), Materials Science Multidisciplinary (336), Immunology (330), and Nanoscience Nanotechnology (244), among others. In contrast, the areas of Chemistry Applied (207), Integrative Complementary Medicine (206), Materials Science Bio-materials (191), Chemistry Organic (178), Polymer Science (176), Medicine Research Experimental (169), Veterinary Sciences (166), Cell Biology (157), Environmental Sciences (119), and Physics Applied (128) presented a lower number of reported articles. This suggests that there is limited information, so it is necessary to focus efforts on carrying out scientific research.

2.2. Authors’ Keywords Analysis

The results of the authors’ keywords analysis are shown in Figure 2. In the 8812 analyzed publications, 42,819 authors’ keywords were found. The word cloud in Figure 2a highlights the most frequently occurring terms in the analyzed literature on plant antimicrobial compounds and their mechanisms of action. In this representation, the size of the letters corresponds to the frequency of each keyword, offering a graphical insight into the prevalence of specific terms. The most prominent words, such as “mechanism” (124 occurrences), “resistance” (98), “antimicrobial” (91), “Escherichia coli” (87), and “activity” (83), suggest that a significant portion of research focuses on understanding the specific ways in which antimicrobial compounds interact with spoilage and pathogenic bacteria. The frequent mention of “in vitro” (76) indicates that many studies rely on controlled experimental settings to evaluate antimicrobial efficacy. Additionally, terms like “antibacterial” (73), “peptides” (68), “antibiotics” (65), and “Staphylococcus aureus” (61) underscore the relevance of antimicrobial peptides and antibiotic resistance as key research themes. The presence of words such as “oxidative stress” (58), “membrane” (55), “binding” (52), and “gene expression” (49) suggests that mechanistic studies often explore molecular interactions and cellular targets. Thus, this word cloud provides a clear snapshot of research priorities over the past two decades, emphasizing both fundamental mechanisms and applied aspects of plant-derived antimicrobials.

Figure 2b–d show the scientometric mapping, carried out with the software VOSviewer v. 1.6.20 as follows:

• The option “Create map based on bibliographic data” was selected to extract keyword co-occurrence relationships from the dataset;
• In the “Choose data source” section, the option “Read data from reference manager files” was selected;
• A RIS file (Research Information Systems file) containing the bibliometric dataset was uploaded in the “Select files” step;
• In the “Choose type of analysis and counting method” section, “Co-occurrence” was selected as the type of analysis, “Keywords” as the unit of analysis, and “Full counting” as the counting method. At this stage, a thesaurus file (CSV format) was included to standardize terms by grouping similar expressions. Specifically, the terms “mechanism”, “mechanisms”, “mechanism of action”, “mechanisms of action”, “molecular-mechanisms”, and “molecular-mechanism” were replaced with “mechanisms”. Similarly, “system” and “systems” were unified under “systems”, “enzyme” and “enzymes” were grouped as “enzymes”, and “gene” and “genes” were consolidated under “genes”;
• A threshold was applied by setting the “Minimum number of documents of an author” to five, filtering out less frequently occurring terms. Of the initial 29,361 keywords, 2794 met the threshold;
• To refine the visualization, the “Number of keywords to be selected” was set to 1000, focusing on the most relevant terms;
• The map was generated, and three visualizations—network, overlay, and density—were created to illustrate keyword relationships, temporal trends, and research intensity;
• Finally, the visualizations were exported as PNG images for further analysis and inclusion in the study [30,31,32].

The closely related terms have been organized into 7 clusters, each indicated by a distinct RGB color. As illustrated in Figure 2b, the network visualization depicts 1000 items distributed across 7 clusters, interconnected by 77,386 links, resulting in a total link strength of 194,316. The size of both letters and circles is a visual indicator of the frequency of occurrences, highlighting their significance within the research field. The proximity of keywords in the visualization signifies the strength of their association in terms of occurrence links; keywords situated closer together exhibit a more immediate connection. Conversely, the distances between keywords can be interpreted as representing knowledge gaps. Addressing these gaps requires further scientific and technological research to diminish information disparities within the field [33].

The seven clusters identified in the network visualization (Figure 2a) reveal distinct thematic areas within the study of plant antimicrobial compounds and their mechanisms of action. Each cluster is characterized by its primary research focus, most frequently occurring terms, and temporal evolution.

The first cluster, “Molecular mechanisms of antimicrobial action” (Red; RGB: 220, 50, 50), represents the fundamental biochemical interactions underlying antimicrobial efficacy. The most frequent terms in this cluster were mechanisms (1732 occurrences), binding (1406), and protein (1204). The frequent occurrence of terms related to mechanisms and binding suggests that research is concentrated on how these compounds interact with microbial cells at a molecular level. The high weight links (34,479) and weight total link strength (88,377) indicate that this cluster is central to antimicrobial research, with strong interconnections to other thematic areas, highlighting the importance of a multidisciplinary approach in addressing the complex challenges posed by antimicrobial resistance. The presence of terms such as “pore formation”, “dynamics”, and “model” suggests that structural biology and computational methods are increasingly used to elucidate these mechanisms. With an average publication year of 2016.64, this research field has been well established, yet it continues to evolve with new molecular insights. For example, isothiocyanates derived from Brassicaceae plants disrupt bacterial cell membranes by forming pores, which leads to the leakage of intracellular substances. The antibacterial effectiveness of these compounds is highly dose-dependent and closely linked to their chemical structure. Variations in the structure of isothiocyanates significantly influence their antimicrobial activity, highlighting the importance of specific chemical features in determining their effectiveness against bacteria [34].

The “Molecular mechanisms of antimicrobial action” cluster highlights how plant-derived antimicrobial compounds interact with bacterial membranes, target key proteins, and present potential strategies to combat AMR. One of the primary mechanisms involves membrane disruption, where compounds such as chitosan derivatives and thymol destabilize lipid bilayers, leading to intracellular leakage and bacterial lysis [35,36]. The carpet mechanism observed in antimicrobial peptides (AMPs) further supports this mode of action, as these molecules integrate into bacterial membranes, causing structural collapse [37,38]. Molecular modeling has provided insights into how amphiphilic plant compounds, such as kaempferol derivatives, interact with membranes, making resistance development more challenging [39,40]. Additionally, these bioactive compounds target intracellular proteins, inhibiting metabolic pathways essential for bacterial survival, as observed with extracts from Moringa oleifera [41,42]. Given the rise of AMR, plant antimicrobials are increasingly studied for their synergistic effects with conventional antibiotics, enhancing their efficacy and reducing bacterial resistance [40,43]. Combining AMPs with traditional drugs has shown promising results against drug-resistant pathogens, emphasizing the potential of plant-based compounds in antimicrobial therapy [44].

The second cluster, “Antimicrobial activity and resistance” (Green; RGB: 50, 180, 50), focuses on evaluating the effectiveness of plant-derived antimicrobials and their relationship with bacterial resistance mechanisms. The most common words in this cluster are antimicrobial activity (1591 occurrences), biofilm formation (1213), and antimicrobial resistance (1032). This cluster has a weight links of 31,604 and a weight total link strength of 80,628, emphasizing its strong relevance in microbiology and food safety research. The frequent mention of pathogens such as Pseudomonas aeruginosa and Listeria monocytogenes suggests a growing focus on public health applications. With an average publication year of 2018.67, this field is rapidly expanding, likely influenced by global concerns regarding AMR. For instance, P. aeruginosa is a key pathogen in the study of antimicrobial activity and resistance, showcasing both intrinsic and acquired resistance mechanisms, particularly through biofilm formation, which is a common theme in this cluster. Furthermore, it highlights the urgent need for new therapeutic strategies to combat P. aeruginosa infections, reflecting the growing emphasis on public health applications related to antimicrobial resistance [45].

On the other hand, the interaction between plant-derived antimicrobial compounds and bacterial resistance mechanisms presents a promising avenue for combating multidrug-resistant (MDR) bacterial infections, particularly by targeting biofilm formation, efflux pumps, and bacterial membrane integrity. Biofilms, which contribute to chronic diseases and antibiotic resistance, are notably susceptible to disruption by certain natural polyphenols and tannic acid, which interfere with bacterial adhesion and biofilm maturation [46,47]. Additionally, incorporating plant-derived compounds into silver nanoparticle composites has demonstrated superior anti-biofilm activity, offering an enhanced strategy compared to conventional antibiotics alone [48].

Plant-derived antimicrobials also inhibit efflux pump activity, restoring antibiotic efficacy against MDR bacteria by preventing drug extrusion [49,50]. The synergistic effects between phytochemicals and conventional antibiotics amplify antimicrobial action while minimizing resistance development [40,51]. Another mechanism involves flavones disrupting bacterial membranes, targeting resistance-associated modifications that bacteria employ for survival [39,52].

Given their broad-spectrum activity, plant-derived antimicrobials are increasingly explored for food preservation and public health applications, offering a natural and effective alternative to synthetic preservatives [53,54]. Furthermore, combining these compounds with nanotechnology-based delivery systems enhances their stability and bioavailability, improving their efficacy against resistant pathogens [55]. Integrating plant-based antimicrobials with antibiotics and nanocarriers thus represents a multi-targeted strategy that could significantly mitigate antimicrobial resistance [56,57].

The third cluster, “Regulatory systems and gene expression” (Blue; RGB: 50, 100, 200), centers on bacterial adaptation mechanisms in response to antimicrobial compounds. The most frequently occurring terms are 2-component regulatory system (1311 occurrences), gene expression (1002), and virulence (891). This cluster has weight links of 34,479 and weight total link strength of 88,377, highlighting its importance in understanding bacterial resistance at a genetic level. The presence of terms such as “mutants”, “outer membrane”, and “purification” suggests an emphasis on molecular genetics and bacterial physiology. With an average publication year 2018.12, this area remains at the forefront of research, particularly in developing targeted antimicrobial strategies. Bacteria adapt to environmental changes through a mechanism called the two-component regulatory system (TCS), which consists of a sensor kinase that detects stimuli and a response regulator that modifies gene expression for survival. Initially identified in E. coli, TCS’s are present in all bacteria, including pathogens. Some TCS’s are vital for growth, while others contribute to virulence and antibiotic resistance. Targeting TCS’s is proposed as a potential antimicrobial strategy, as it may inhibit bacterial growth or reduce virulence without killing the cells. This approach could help develop therapies for infections caused by AMR [58].

TCS’s are required for modulating antimicrobial resistance, virulence, and gene expression, allowing bacteria to adapt to environmental stressors. Systems such as PhoPQ, VraSR, and CpxAR regulate resistance mechanisms, including membrane permeability modifications and efflux pump activation [59,60]. PhoPQ contributes to antibiotic resistance in Salmonella and E. coli by modulating outer membrane integrity, while VraSR enhances S. aureus resistance to cell wall-targeting antibiotics by altering cell membrane composition and activating efflux systems [59,60]. Similarly, CpxAR regulates envelope stress responses, playing a crucial role in bacterial adaptation to antibiotic exposure [61].

Targeting TCS as an antimicrobial strategy offers potential for weakening resistance pathways without directly killing bacteria, thereby reducing selective pressure for resistance development. Studies show that inhibiting VraSR and CpxAR reduces resistance levels in S. aureus, making pathogens more susceptible to conventional antibiotics [60]. Natural and synthetic TCS inhibitors, including antimicrobial peptides, have shown promise in altering resistance gene expression and restoring antibiotic efficacy. These approaches could also support biotechnological advancements, such as rapid diagnostic tools to detect TCS-dependent resistance mechanisms [62].

Despite these advancements, TCS-targeting strategies face challenges. Variability in TCS expression among bacterial strains and the potential for compensatory resistance mechanisms complicate universal therapeutic applications [63]. Additionally, concerns about resistance to TCS inhibitors highlight the need for further research on their long-term effectiveness [64]. A deeper understanding of TCS interactions with other resistance pathways and interdisciplinary approaches integrating diagnostics and therapeutics will be critical to addressing antimicrobial resistance effectively [65,66].

The fourth cluster, “Phytochemicals and antioxidant properties” (Purple; RGB: 150, 50, 150), focuses on plant-derived antimicrobial compounds and their potential functional benefits. The most commonly occurring words in this cluster are essential oils (1403 occurrences), alkaloids (1117), and antioxidant (999). With a weight links of 23,880 and a weight total link strength of 48,047, this cluster highlights the strong interconnection between natural product chemistry and antimicrobial research. The inclusion of terms such as “growth”, “toxicity”, and “extraction” suggests a dual focus on antimicrobial efficacy and safety. The average publication year 2017.45 indicates ongoing interest in phytochemicals for functional food applications and alternative medicine. The significance of plant-derived antimicrobial compounds lies in their multifaceted functional benefits, which include not only antimicrobial properties but also antioxidant effects that contribute to overall health. Gallic acid (GA) is a phenolic compound found in various fruits and vegetables, known for its extensive health benefits. It has antimicrobial, antioxidant, anticancer, anti-inflammatory, and antiviral properties. GA’s strong antioxidant ability helps neutralize free radicals, reduce oxidative stress, and protect cellular integrity. Additionally, it inhibits inflammatory cytokines and enzymes, positioning it as a potential treatment for inflammatory conditions. GA also shows promise in cancer therapy by hindering tumor growth and inducing apoptosis. Furthermore, it offers cardiovascular advantages, including lowering blood pressure and cholesterol levels, and enhancing endothelial function, which may aid in preventing and managing cardiovascular diseases [67].

Beyond antimicrobial effects, phytochemicals possess strong antioxidant capacity, which enhances stability and bioactivity but may degrade over time due to environmental factors [68]. To address this, nanotechnology-based approaches, such as encapsulation in lipid-based carriers or metal nanoparticles, have significantly improved bioavailability and prolonged stability [69,70]. However, concerns regarding toxicity and safe dosage persist, necessitating controlled formulations and synergistic combinations with pharmaceuticals to mitigate adverse effects [71,72]. Integrating phytochemicals into functional foods and biomedical formulations offers novel therapeutic potential, especially when combined with chemotherapeutic agents to enhance drug efficacy and reduce resistance [73,74]. Despite their promise, challenges remain in standardization, chemical consistency, and large-scale production, requiring advances in engineered biosynthesis and phytonanotechnology to optimize industrial applications and ensure reproducibility [75,76]. Developing eco-friendly, nanoparticle-based delivery systems using plant extracts further highlights the potential for safer, more effective phytochemical applications in medicine and food preservation [69,77].

The fifth cluster, “Nanotechnology and delivery systems” (Yellow; RGB: 230, 210, 50), explores the application of nanostructured antimicrobial agents, particularly in enhancing the stability and efficacy of plant-derived compounds. The most common words in this cluster are silver nanoparticles (1278 occurrences), adsorption (987), and green synthesis (876). This cluster has a weight links of 22,049 and a weight total link strength of 56,819, reflecting a growing research trend in advanced antimicrobial delivery systems. The presence of terms such as “biological evaluation” and “cytotoxicity” suggests increasing attention to nanoparticle biocompatibility. With an average publication year of 2018.93, this is one of the most recent and rapidly expanding fields, driven by the potential applications of nanotechnology in antimicrobial formulations. Phytocomponent-conjugated silver nanoparticles (AgNPs) are extensively researched for their therapeutic benefits, including antimicrobial, antioxidant, anticancer, anti-inflammatory, antidiabetic, and anticoagulant effects. Bio-conjugation with plant extracts reduces AgNP toxicity and enhances their efficacy. The diverse phytochemicals from these extracts, along with the small size and large surface area of AgNPs, improve the adsorption of these agents, boosting their therapeutic potential [78].

AgNPs represent a promising advancement in antimicrobial strategies, particularly when conjugated with plant-derived compounds. Biosynthesized AgNPs offer superior efficacy and biocompatibility compared to chemically synthesized counterparts, as phytochemicals facilitate silver ion reduction while enhancing antimicrobial activity through cell wall disruption and reactive oxygen species (ROS) generation [79,80,81]. The primary mechanism behind AgNP antimicrobial action involves binding to sulfur and phosphorus in bacterial membranes, impairing respiration and cell division, leading to cell death [82]. Moreover, functionalization with plant extracts improves nanoparticle uptake, increasing their effectiveness against bacterial pathogens [83,84]. Despite their potential, cytotoxicity and biocompatibility remain critical concerns, particularly for clinical and food applications. Studies indicate that low-concentration AgNP formulations using plant extracts, such as Calotropis gigantea, can balance antimicrobial efficacy while minimizing cytotoxic effects [85]. Alternative nanomaterials like zinc oxide (ZnO) and titanium dioxide (TiO₂) provide additional antimicrobial benefits, mainly through photodynamic activity and ROS production, which may enhance antibacterial action under specific conditions [80,86]. Encapsulation in polymer matrices or conjugation with other nanoparticles has been explored to improve stability and controlled release, extending shelf-life and reducing toxicity risks [86]. However, toxicity, biodegradability, and regulatory challenges persist, with ecotoxicological concerns surrounding AgNP environmental accumulation and potential harm to non-target organisms [87]. Regulatory approval demands extensive safety assessments, emphasizing the need for standardized protocols and long-term impact studies to facilitate clinical and commercial applications [85].

The sixth cluster, “Antifungal activity” (Cyan; RGB: 50, 200, 200), focuses on the potential of plant-based compounds to combat fungal pathogens. The most frequent words in this cluster are antifungal activity (368 occurrences), Candida albicans (305), and candidiasis (178). The repeated presence of Candida and related terms suggests a strong focus on this fungal pathogen responsible for significant opportunistic infections. The cluster highlights research on traditional antifungal agents such as Amphotericin B and novel plant-derived compounds. The average publication year of 2017.89 suggests that while this research field is well established, it continues to evolve with emerging therapeutic strategies. For instance, Hinokitiol exhibited antifungal activity against fluconazole- and caspofungin-resistant C. albicans strains, with a minimum inhibitory concentration (MIC) of 8.21 μg/mL [88].

Plant-derived antifungal compounds exhibit potent activity against C. albicans and other fungal pathogens, primarily by disrupting cell membrane integrity, interfering with ergosterol biosynthesis, and modulating metabolic pathways [89,90,91]. Additionally, phytochemicals enhance ergosterol disruption, reinforcing their antifungal action [90,91].

While plant-based antifungals often exhibit lower potency than fluconazole or amphotericin B, they have demonstrated synergistic effects when combined with conventional drugs, improving their efficacy by inhibiting drug efflux and increasing membrane damage [92]. This synergy suggests that integrating natural compounds into antifungal regimens may enhance therapeutic outcomes while reducing synthetic drug doses, potentially mitigating resistance development [93]. Furthermore, plant-derived antifungal proteins offer alternative mechanisms that interfere with fungal resistance pathways, highlighting new strategies for circumventing traditional antifungal resistance [94,95]. Beyond clinical applications, plant-derived antifungals are increasingly used in food preservation, where essential oils and phytochemicals inhibit fungal contamination, extending shelf-life [74,96]. Compounds such as eugenol, which is classified as GRAS (Generally Recognized as Safe), demonstrate dual functionality in food safety and health applications [96]. Additionally, these compounds are being explored for biomedical coatings and medical devices, as they offer broad-spectrum antifungal activity with lower toxicity than synthetic antifungals [97,98].

However, challenges remain in the stability and bioavailability of plant-based antifungals, as many compounds are prone to degradation under environmental conditions [93]. Nanotechnology-based delivery systems are being investigated to enhance stability, targeted delivery, and sustained release, ensuring consistent antifungal activity [98]. Additionally, metabolic engineering approaches are being explored to optimize large-scale production, making these compounds more viable for pharmaceutical and industrial applications [99]. These advancements highlight the growing potential of phytochemicals in antifungal therapy, both in medicine and food safety, while addressing limitations in formulation and scalability.

The seventh cluster, “Immunomodulation and host-microbe interactions” (Light green; RGB: 130, 200, 130), is related to the effects of antimicrobial compounds on the immune system and host–pathogen interactions. The most common words in this cluster are activation (284 occurrences), cell line (276), mouse (274), and apoptosis (239). This cluster highlights the role of plant-based antimicrobials in modulating inflammatory responses and immune defense mechanisms. The weight links of 24,009 and weight total link strength of 50,112 suggest that this field is well connected to both molecular biology and clinical applications. The average publication year of 2017.34 indicates ongoing interest in the potential therapeutic applications of immunomodulatory antimicrobial agents. Understanding how antimicrobial chemicals impact the immune system and the dynamics between hosts and pathogens requires an understanding of immunomodulation and host–microbe interactions. Instead of depending just on conventional antibiotics, new treatment approaches that target the host–pathogen interface are being investigated in an effort to boost immune responses. Increasing the inherent antibacterial activity of immune cells such as neutrophils and macrophages is one of these strategies, which can enhance the removal of MDR infections while maintaining the health of the microbiome [100].

Plant-derived antimicrobial compounds are required to modulate immune responses and enhance host defense mechanisms against MDR infections. Rather than directly targeting pathogens, these compounds regulate cytokine production, induce apoptosis, and activate immune cells, such as macrophages and neutrophils, to strengthen the body’s natural defenses [101]. Sennosides and emodin from Senna spp., for example, have been shown to stimulate interleukin-1β and interleukin-18, key cytokines involved in macrophage activation and pathogen clearance [102]. Additionally, the induction of apoptosis in infected cells provides a dual mechanism of pathogen elimination and immune homeostasis, reducing chronic inflammation associated with persistent infections [101].

The interplay between plant-derived antimicrobials and the microbiome is another crucial factor influencing immune modulation. These compounds can selectively suppress pathogenic bacteria while preserving beneficial microbial populations, maintaining microbiome diversity and immune function [103]. Studies suggest that plant-associated microbial metabolites further enhance host–microbe interactions, improving immunity and reducing pathogenicity [104].

These immunomodulatory compounds have potential applications beyond infectious diseases. They can also treat chronic infections and inflammatory disorders, including drug-resistant Salmonella and E. coli infections. Enhancing macrophage function and cytokine responses provides an alternative strategy to combat pathogens without promoting resistance [105,106].

Despite their promise, challenges in clinical translation remain, particularly regarding bioavailability, stability, and effective delivery. Nanotechnology-based formulations offer a viable solution by improving solubility, targeted delivery, and sustained release of these compounds. Nanoparticles facilitate higher antimicrobial concentrations at infection sites, maximizing efficacy while minimizing adverse effects [107]. Furthermore, combining natural antimicrobials with nanotechnology may yield synergistic effects against MDR pathogens, paving the way for novel immunomodulatory therapies [108].

The overlay visualization generated using VOSviewer v. 1.6.20 (Figure 2c) provides a temporal perspective on the evolution of research themes in antimicrobial compounds and their mechanisms of action. The color scale at the bottom right corner, ranging from purple (older publications, around 2015) to yellow (more recent publications, around 2020), indicates the average publication year for each term.

In the network, central and highly connected terms such as “mechanisms”, “antimicrobial activity”, and “resistance” appear predominantly in green tones, suggesting that these core topics have been consistently studied over time. However, peripheral terms display a more varied color distribution, indicating emerging or declining research interests. For instance, “silver nanoparticles”, “green synthesis”, and “antioxidant” appear in yellowish green, implying increased attention in recent years. This aligns with the growing interest in alternative antimicrobial strategies based on nanotechnology and natural extracts.

On the other hand, terms such as “antibacterial peptides”, “lipid bilayers”, and “pore formation” are primarily in purple or blue tones, suggesting that their research peak occurred earlier, around 2015–2017. This might reflect an initial surge in investigations on peptide-based antimicrobials and their interaction with bacterial membranes, followed by a shift towards newer approaches or refinements of existing knowledge. The presence of recent terms like “melittin”, “cationic antimicrobial peptides”, and “binding” in green or yellow shades indicates that there is still ongoing research into peptide-based antimicrobial strategies, with refinements in their molecular mechanisms and design strategies.

Thus, the overlay visualization effectively highlights the temporal evolution of antimicrobial research, showing how some topics remain central while others emerge or decline. The increasing focus on green synthesis, silver nanoparticles, and antioxidant-based approaches suggests a shift towards more sustainable and multifunctional antimicrobial strategies. At the same time, the continued interest in resistance mechanisms and biofilm formation underscores the persistent challenges in combating bacterial infections.

VOSviewer v. 1.6.20 applied colors to keywords based on the year they appeared in the literature. Keywords in blue appeared early, followed by green and yellow colors, while keywords in red appeared later (Figure 2c).

Finally, the density map shows the citation concentration areas for keywords (Figure 2d) [109]. Density visualization in VOSviewer v. 1.6.20 represents the concentration of items within a network. This visualization method is particularly useful in bibliometric analyses, as it identifies areas of high density, which may indicate significant research themes or areas of intense collaboration [110].

The word cloud analysis (Figure 2a) aligns closely with the thematic clusters in the network visualization (Figure 2b), reinforcing research priorities in plant antimicrobial compounds. The prominence of terms such as “mechanisms”, “antimicrobial”, and “resistance” reflects their strong association with Cluster I (Molecular mechanisms of antimicrobial action) and Cluster II (Antimicrobial activity and resistance). These findings show that a substantial portion of the literature is dedicated to understanding antimicrobial efficacy’s biochemical and genetic foundations. Similarly, the frequent appearance of “oxidative stress”, “gene expression”, and “membrane” highlights their connection to Cluster III (Regulatory systems and gene expression), emphasizing the growing focus on bacterial adaptation and response mechanisms. The presence of “essential oils”, “alkaloids”, and “antioxidant” in the word cloud mirrors Cluster IV (Phytochemicals and antioxidant properties), indicating the persistent interest in exploring plant-derived bioactive compounds for both antimicrobial and functional applications. The increasing relevance of nanotechnology is evident in the recurrence of terms such as “silver nanoparticles” and “green synthesis”, which are central to Cluster V (Nanotechnology and delivery systems), suggesting that research is shifting toward the development of novel delivery strategies to enhance the stability and efficacy of plant antimicrobials. While well-established topics such as “biofilm formation” and “Staphylococcus aureus” remain dominant, emerging terms related to immunomodulation and host–pathogen interactions in Cluster VII indicate a potential avenue for expanding research beyond direct antimicrobial effects. These associations demonstrate how the Scientometric mapping of Authors’ keywords analysis confirms current research foci and reveals gaps that can inform future studies, particularly optimizing antimicrobial compound applications in clinical and food safety contexts.

3. Mechanisms of Action of Antimicrobial Compounds

The mechanisms by which plant extracts and compounds exert their effects on microbes are varied and complex. These substances can target one or multiple sites, with their effects potentially being additive, synergistic, or antagonistic, thereby influencing bacterial cells through various pathways (Figure 3) [43,111].

I. Alteration in membrane permeability: The plasma membrane is an essential component of bacterial cells, playing a vital role in maintaining cellular integrity, homeostasis, and overall survival. This selectively permeable barrier is primarily composed of a phospholipid bilayer interspersed with proteins that regulate the transport of nutrients, ions, and waste products. Beyond serving as a physical barrier, the membrane houses enzymes essential for energy production, such as those involved in ATP (Adenosine triphosphate) synthesis via the electron transport chain, and facilitates signal transduction and cellular communication. The disruption of the plasma membrane can compromise these essential functions, leading to leakage of intracellular components and ultimately resulting in cell death [113,114].

Given its important function, the bacterial plasma membrane is a primary target for antimicrobial agents, including those derived from plants. Plant-based antimicrobials, often referred to as phytochemicals, have been utilized for centuries in traditional medicine and have recently gained attention as potential alternatives or supplements to conventional antibiotics. Many of these natural compound’s function by altering the permeability of the bacterial membrane, disrupting cellular function, and inducing bacterial cell death [115].

Phenolic compounds, a class of secondary metabolites found in plants, have been shown to damage membrane integrity in a nonspecific manner and inhibit certain electron transport enzymes, thereby exhibiting antimicrobial activity [116]. AMPs represents another promising alternative to traditional antibiotics due to their unique physicochemical properties, effectiveness against a broad spectrum of bacterial species, and distinct mechanisms of action. Typically, AMPs eliminate bacteria by either compromising membrane integrity or penetrating bacterial cells to interact with internal components [117].

For instance, thymol has been shown to affect the permeability of the Enterobacter sakazakii membrane by causing extensive membrane damage, leading to cell death. Thymol treatment results in membrane depolarization, decreased intracellular ATP levels, and alterations in membrane integrity, indicating that it disrupts the membrane’s ability to maintain its internal environment [118]. Similarly, eugenol disrupts the cytoplasmic membrane of E. coli, increasing membrane permeability and causing leakage of intracellular contents. This disruption is evidenced by morphological changes observed through scanning electron microscopy (SEM) and transmission electron microscopy (TEM), which reveal damage to the outer membrane and irregular cell shapes. Treatment with eugenol leads to the drainage of cytoplasmic content and a significant release of intracellular ATP, indicating membrane permeabilization. Furthermore, eugenol causes the depolarization of the cytoplasmic membrane, which is crucial for the active uptake of metabolites, ultimately resulting in cell death [119]. Naringenin alters the membrane fluidity and fatty acid profiles of bacterial cells, compromising their structural integrity and function in both Gram-positive and Gram-negative bacteria. In addition to its effects on membrane fatty acids and proteins, this bioflavonoid has also been shown to bind to the DNA of S. aureus [120]. Other specific examples are shown in

Table 2. Mechanism of action of some important compounds extracted from plants.

Plant Source	Compound	Mechanism of Action	Susceptible Microorganism	Concentration (µg/mL)	Reference
Antimicrobial peptides
Nigella sativa	Thionins NsW1 and NsW2	Disruption of cell membrane integrity	Bacillus subtilis and Staphylococcus aureus	3.25 6.25	[3]
Medicago truncatula	Defensin MtDef5	Disruption of cell membrane integrity/Inhibition of protein biosynthesis/Interfering with nucleic acid synthesis or expression	Xanthomonas campestris	12	[121]
Phenolic compounds
Camellia sinensis	Epigallocatechin-3-gallate-stearate (EGCG-S)	Inhibition of bacterial biofilm formation	Escherichia coli	100	[122]
Agrimonia pilosa Ledeb.	Wogonin	Inhibition of bacterial biofilm formation	Pseudomonas aeruginosa	30	[2]
Saccharum officinarum	Mixture of gallic acid coumaric acid, and chlorogenic acid	Disruption of cell membrane integrity	S. aureus	0.625	[4]
Vaccinium myrtillus, V. vitis-idaea, V. oxycoccos, Rubus idaeus var. Ottawa, and others	Ellagic acid	Disruption of cell membrane integrity	Salmonella enterica serovar Typhimurium	40	[123]
Vaccinium myrtillus, V. vitis-idaea, V. oxycoccos, Rubus idaeus var. Ottawa, and others	Gallic acid	Disruption of cell membrane integrity	S. Typhimurium	600	[123]
Punica granatum	Punicalagin	Disruption of cell membrane integrity /Inhibition against quorum sensing	S. aureus S. Typhimurium SL1344	250 500	[124] [125]
Bambusa vulgaris, Oryza sativa, and others	Ferulic acid	Disruption of cell membrane integrity	E. coli and P. aeruginosa S. aureus Listeria monocytogenes	100 1100 1250	[126]
Coffea arabica, Olea europaea, and others	Caffeic acid	Inhibition of energy metabolism/Disruption of cell membrane integrity	S. aureus ATCC 25923	62.5	[127]
Ampelopsis grossedentata	Dihydromyricetin	Inhibition of energy metabolism/Disruption of cell membrane integrity/Inhibition of cell wall biosynthesis	S. aureus E. coli	625 312.5	[128] [128]
Sonchus grandifolius, Aesculus turbinata, and others	Esculetin	Inhibition against quorum sensing	Burkholderia cepacia	500	[129]
Cinnamomum cassia	Coumarin	Inhibition against quorum sensing	E. coli O157:H7	50	[130]
Hibiscus sabdariffa	Hibiscus acid	Disruption of cell membrane integrity	S. Typhimurium Enterohemorrhagic E. coli	7000 7000	[131]
Alkaloids
Toddalia asiatica (Linn) Lam	Chelerythrine	Disruption of cell membrane integrity/Inhibition of protein biosynthesis	S. aureus Methicillin-resistant S. aureus	156 156	[5]
Macleaya cordata	Sanguinarine	Disruption of cell membrane integrity	S. aureus	128	[132]
Rhizoma coptidis and, Cortex phellodendri	Berberine	Inhibition against quorum sensing Inhibition of energy metabolism/ Inhibition of protein biosynthesis/ Interfering with nucleic acid synthesis or expression	E. coli Streptococcus pyogenes	2560 80	[6] [133]
Sophora flavescens	Matrine	Inhibition of protein biosynthesis Inhibition against quorum sensing	E. coli S. aureus E. coli	2500 10000 5120	[7] [6]
Organosulfur compound
Allium sativum	Allicin	Interfering with nucleic acid synthesis or expression	E. coli	130	[11]
Allium sativum	Diallyl trisulfide	Disruption of cell membrane integrity	Campylobacter jejuni	32	[12]
Allium sativum	Ajoene	Inhibition against quorum sensing	S. aureus	20	[13]
Terpenes
Andrographis paniculata	Andrographolide	Interfering with nucleic acid synthesis or expression/ Inhibition of cell wall biosynthesis	S. aureus MTCC 96	100	[9]
Cinnamomum camphora L.	Terpinen-4-ol	Interfering with nucleic acid synthesis or expression/inhibition of protein biosynthesis/Disruption of cell membrane integrity	Streptococcus agalactiae	98	[8]
Origanum majorana, Agastache mexicana, Lavandula angustifolia, and Thymus vulgaris L.	Linalyl anthranilate	Disruption of cell membrane integrity	Klebsiella pneumoniae	2.5	[134]

.

II. Inhibition of bacterial biofilm formation: A biofilm is a structured community of bacteria that encases itself in a self-produced matrix made up of extracellular DNA, polysaccharides, and proteins. This matrix not only supports bacterial growth but also provides protection against external threats [135]. Recent studies have highlighted the anti-biofilm and anti-adhesion properties of various plant-based extracts and phytochemicals. These natural agents can effectively inhibit bacterial adhesion, prevent biofilm maturation, disrupt the extracellular matrix, and eliminate bacteria within established biofilms. The formation and regulation of biofilms are largely controlled by a bacterial communication system known as “quorum sensing” [136].

For instance, wogonin, a plant-derived compound, has been shown to suppress the expression of quorum sensing-related genes and reduce the production of virulence factors, such as elastase, pyocyanin, and proteolytic enzymes. Additionally, wogonin decreases the synthesis of extracellular polysaccharides and inhibits bacterial motility, including twitching, swimming, and swarming, ultimately preventing biofilm formation [2]. Similarly, carvacrol and 2-aminobenzimidazole (2-ABI) have demonstrated significant antibiofilm activity against Salmonella serovars. Notably, 2-ABI effectively inhibited biofilm formation at a concentration of 1.5 mM, making it a promising new option for combating Salmonella biofilms, particularly in poultry-related infections. These findings suggest that both compounds could serve as supportive or alternative treatments for biofilm-associated infections [137].

Another example is limonene, which has been shown to inhibit the growth of both planktonic and mono/polymicrobial biofilms formed by P. aeruginosa and S. aureus [138].

Similarly, the phenolic compounds extracted from pomegranate peel (PPE) exhibited notable antibiofilm activity against a range of microorganisms, including S. aureus, L. monocytogenes, Salmonella bongori, E. coli, Lacticaseibacillus casei, and Limosilactobacillus reuteri. The primary compounds identified in these extracts are punicalagin, ellagic acid, gallic acid, and chlorogenic acid [139].

Other study focused on the antimicrobial effects of sulfur derivatives of camphor, specifically rac-thiocamphor (1a) and (S, S)-(+)-thiocamphor (2a), against various bacterial strains, including both Gram-positive and Gram-negative bacteria. Both compounds were evaluated for their ability to eradicate biofilms formed by bacterial strains. Compound 2a showed superior efficacy compared to compound 1a, particularly against Staphylococcus epidermidis, achieving up to 94% biofilm reduction at 4 × MIC. The authors suggest that these compounds could be useful in the treatment and prevention of skin infections, highlighting the need for further research to explore their use in antiseptics and disinfectants, especially in the context of increasing antibiotic resistance [140].

III. Inhibition of cell wall synthesis: The bacterial cell wall is a fundamental structure that plays an essential function in maintaining cell shape, integrity, and protection, ensuring the survival of bacteria under various environmental conditions [141]. Composed primarily of peptidoglycan (PG), a cross-linked polymer, the cell wall forms a rigid layer that surrounds the cytoplasmic membrane, shielding it from osmotic stress and mechanical damage. This unique structure not only defines the bacterial shape but also provides the strength needed to withstand the high intracellular osmotic pressure, preventing cell lysis. Because the cell wall is exclusive to bacteria and absent in human cells, it has become a prime target for antibiotics and antimicrobial agents [142].

Beyond its architectural function, the cell wall acts as the primary interface between the bacterium and its external environment, regulating interactions with surrounding substances and protecting internal cellular components. Plant-derived compounds have emerged as valuable tools in targeting the bacterial cell wall, offering innovative therapeutic strategies to inhibit its synthesis and disrupt its integrity [143]. For instance, compounds like dihydromyricetin have been shown to compromise the cell wall and membrane, leading to the leakage of intracellular components, such as alkaline phosphatase (AKP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT). This loss of structural integrity ultimately results in bacterial cell death. By targeting the cell wall, these plant-based compounds provide a promising approach to combating bacterial infections while minimizing harm to host cells [128].

For instance, diterpenes extracted from Lepechinia meyenii, including carnosol, along with its derivatives 20-methyl carnosate and carnosic acid-γ-lactone, disrupt the activity of the enzymes MurA and MurF. These enzymes participate in the cell wall synthesis of bacteria such as S. aureus and E. coli [144].

IV. Inhibition of protein biosynthesis: Bacterial protein synthesis is a primary target for many natural and synthetic antibacterial agents [145]. Plant compounds inhibit protein synthesis by interfering with various stages of the process, including activation, initiation, disruption of peptide chain elongation, blockage of the ribosome’s A site, misreading of the genetic code, and prevention of the binding of oligosaccharide side chains to glycoproteins [146]. Terpinen-4-ol may interfere with protein synthesis by inhibiting the synthesis of DNA [8]. Plant compounds such as berberine, matrine, and sanguinarine interfere with various stages of this process, including ribosomal function, tRNA binding, and the activity of aminoacyl-tRNA synthetases [6,132]. For example, berberine binds to the 50S ribosomal subunit, preventing peptide bond formation, while matrine disrupts ribosomal activity, halting protein synthesis in bacteria like E. coli and S. aureus as shown in Table 2. By targeting these critical steps, plant-derived compounds effectively halt bacterial protein production, leading to growth arrest and cell death.

V. Interfering with nucleic acid synthesis or expression: Plant compounds disrupt nucleic acid synthesis by targeting various stages of RNA and DNA production through multiple mechanisms. They can inhibit essential enzymes involved in replication and transcription [112]. Nucleic acids, including DNA and RNA, are essential for bacterial replication, transcription, and translation, making them key targets for antimicrobial action. As seen in Table 2, plant compounds such as berberine, andrographolide, and terpinene-4-ol disrupt these processes by inhibiting enzymes involved in DNA replication, RNA synthesis, or nucleic acid metabolism [6,8,9]. For instance, berberine interferes with DNA gyrase and topoisomerase IV, enzymes crucial for DNA replication and repair, while andrographolide inhibits RNA polymerase, halting transcription. Allicin inhibits DNA gyrase by preventing the formation of RNA and partially inhibiting the synthesis of DNA and proteins. This suggests that RNA is the primary target of allicin, which ultimately disrupts the processes necessary for bacterial growth and replication [11]. By targeting nucleic acid synthesis or expression, these plant-derived compounds effectively halt bacterial growth and reproduction, ultimately causing cell death.

On the other hand, Table 2 provides information on the plant source, antimicrobial compounds, class, mechanism of action, concentration (µg/mL), the pathogens against which they exhibit antimicrobial activity, and reference. This table shows information on different natural compounds obtained from plants that can be used against pathogenic bacteria. These compounds belong to several classes such as phenolics, terpenes, alkaloids, and organosulfur compounds. They show various mechanisms of action against microorganisms, suggesting that they can affect different stages of the bacterial life cycle, such as cell membrane integrity, nucleic acid synthesis, and protein biosynthesis. For instance, Chelerythrine, an alkaloid found in Toddalia asiatica, disrupts the cell membrane integrity and inhibits protein biosynthesis, thereby showing activity against Staphylococcus aureus and Methicillin-resistant S. aureus. On the other hand, organosulfur compounds such as Allicin and Diallyl trisulfide from Allium sativum interfere with nucleic acid synthesis and affect cell membrane integrity, respectively. Phenols, by contrast, mainly affect cell membrane integrity and, in some cases, inhibit quorum sensing. Ellagic acid, Gallic acid, and Punicalagin are some of the phenolic compounds that show antimicrobial properties, specifically against microorganisms such as Salmonella Typhimurium and S. aureus. Additionally, some terpenes, such as Terpinen-4-ol from Cinnamomum camphora L. and Andrographolide from Andrographis paniculata, also exhibit antimicrobial activities by affecting nucleic acid synthesis, cell wall biosynthesis, and cell membrane integrity. Although the effective concentration varies between compounds and microorganisms, the data presented in Table 2 suggest that these natural compounds have the potential to be developed as antimicrobial agents. However, it is important to consider that these studies are based on in vitro testing, and further investigation is required to determine their efficacy and safety in complex settings. Furthermore, bioavailability and toxicity should also be addressed in future studies to fully evaluate the therapeutic potential of these antimicrobial compounds obtained from plant sources.

4. Concluding Remarks and Perspectives

This article underscores the urgent necessity of comprehending the mechanisms of action of plant antimicrobials to combat antimicrobial resistance effectively. It highlights the potential of plant-derived compounds as viable natural alternatives to synthetic antimicrobials, which can significantly mitigate pathogenic threats and enhance food safety. This study also notes a burgeoning trend in international collaboration, particularly between researchers in China and the United States, which enriches the quality of research by integrating diverse perspectives and methodologies.

Plant antimicrobial compounds present promising solutions to the pressing challenge of antimicrobial resistance. Their mechanisms of action include disrupting cell membranes and inhibiting biofilm formation, both of which are critical in preventing bacterial survival and proliferation. A bibliometric analysis indicates a notable surge in research interest, especially in prestigious journals such as “Frontiers in Microbiology” and “Antimicrobial Agents and Chemotherapy”, reflecting the growing recognition of the importance of these compounds in the scientific community.

Scientometric mapping identified seven research clusters, covering molecular mechanisms of action, antimicrobial resistance, gene regulation, phytochemical properties, nanotechnology applications, antifungal activity, and immunomodulation. The literature review detailed how plant antimicrobials disrupt bacterial membranes, inhibit biofilm formation, suppress efflux pumps, and interfere with virulence factors. Synergistic interactions with conventional antibiotics were also noted, reinforcing their potential in improving treatment efficacy against resistant pathogens. Advances in nanotechnology have further expanded their applications by improving stability, bioavailability, and controlled release.

Moving forward, research should focus on refining the technological applications of these bioactive compounds, optimizing large-scale production while addressing challenges related to standardization, bioavailability, and toxicity. Strategies such as metabolic engineering and nanocarrier-based delivery systems could enhance their therapeutic and industrial potential. A deeper understanding of their molecular interactions with bacterial targets will contribute to developing targeted antimicrobial agents that mitigate resistance. Additionally, fostering collaboration between researchers and industry stakeholders, establishing standardized extraction and testing protocols, and integrating these findings into clinical and food safety frameworks will translate scientific advancements into practical solutions. Expanding interdisciplinary approaches through genomics, bioinformatics, and biotechnology will strengthen efforts to harness plant-derived antimicrobials for global health and food preservation.