Green Medicine: Advancing Antimicrobial Solutions with Diverse Terrestrial and Marine Plant-Derived Compounds

Abstract

Infectious diseases continue to cause global morbidity and mortality. The rise of drug-resistant pathogens is a major challenge to modern medicine. Plant-based antimicrobials may solve this issue; hence, this review discussed in detail plant-sourced antimicrobial drugs as an alternative toward bacterial, fungal, and viral pathogens. Plant-derived chemicals from various sources such as marine, medicinal, and non-medicinal sources have diverse antimicrobial properties. Complex chemical profiles from these sources allow these molecules to interact with several targets in the microbial pathogens. Due to their multi-component composition, these compounds are more effective and less likely to acquire resistance than single-target antibiotics. Medicinal herbs have long been used for their antimicrobial properties; however, non-medicinal plants have also been identified for their antimicrobial properties. Other interesting new pathways for the identification of antimicrobials include marine plants, which contain a wide variety of metabolites that are both distinct and varied. We have conducted a thorough literature search for the medicinal, non-medicinal, and marine plant-derived molecules with antimicrobial roles from databases which include Scopus, PubMed, Google Scholar, and Web of Science. The review also discussed the synergistic potential of combining these plant-derived compounds with traditional antimicrobial drugs to attenuate the microbial pathogenesis. Based on the existing research and advancements, the review article emphasizes the importance of continuing research into plant-based antimicrobials from these many sources and integrating them with existing therapies to combat the rising threat of drug-resistant infections.

1. Introduction

The infectious diseases that are caused by pathogenic microorganisms continue to be the largest cause of sickness and death throughout the globe, posing a continuing challenge to the health systems that are in place across the world [1]. Since the discovery of antibiotics, the treatment of bacterial infections has undergone a revolutionary change, which has resulted in a large reduction in the mortality and morbidity rates associated with these diseases [2]. On the other hand, the development and proliferation of multi-drug-resistant (MDR) infections have significantly reduced the effectiveness of standard antimicrobial treatments [3]. The presence of these resistant strains undermines the treatment procedures that are now in place, which results in longer illnesses, greater healthcare expenses, and increased fatality rates. The development of antibiotic resistance may be attributed to a number of different processes, one of which is variations in the permeability of the cell membrane. This can occur either by decreasing the drug’s capacity to penetrate the cell or by increasing the efflux pumps’ ability to eliminate the drug. Also, bacteria can deactivate antibiotics or change their targets, as well as other resistance mechanisms, as documented in the literature and shown in Figure 1 [4]. A similar pattern may be seen in fungal and viral infections, where the mechanisms of resistance provide an increasing challenge to the traditional treatments that are now available [5]. In fungi, resistance often develops due to the alteration of drug targets, the overexpression of efflux pumps, or the production of biofilm, all of which make it difficult for antifungal drugs to enter and work efficiently [6]. On the other hand, viruses can acquire resistance to antiviral treatments mostly due to genetic changes that modify the structure of viral proteins. This allows viruses to avoid the effects of antiviral drugs [7]. Because of this, one of the most important problems in modern medicine is the pressing need for novel antimicrobial treatments [8,9]. There is a renaissance in the exploration of alternate sources for new antimicrobial drugs [10], which is occurring in the context of the rising challenge of infection resistance. Compounds originating from plants, which include both terrestrial and marine flora, represent a potential new frontier among these possibilities. Traditional single-target antibiotics have a strategic disadvantage in comparison to these plant-based medicines because of their various chemical profiles, which offer a large reservoir of bioactive compounds and provide a strategic advantage [11,12]. Complex interactions with various microbial targets are made easier by the multidimensional character of plant-derived antimicrobials, which often include numerous active components. This complexity helps to circumvent or postpone the development of resistance, which is a key constraint associated with traditional drugs [13].

Over the course of many centuries, medicinal plants have been an essential component of traditional medical practices in various cultures. Their antimicrobial characteristics have been well researched and recorded, and a significant number of them have been exploited in the creation of therapeutic drugs that are now in practice [14]. It has been known for a long time that some plants, such as garlic (Allium sativum), neem (Azadirachta indica), and turmeric (Curcuma longa), have the capacity to suppress the growth of microorganisms via a variety of different methods [15,16,17]. Recent developments in phytochemistry and pharmacology have rekindled interest in these ancient treatments, with current research verifying and increasing their medicinal potential. In addition to well-known medicinal plants, non-medicinal plants—those not typically employed in medical contexts—are emerging as important sources of new antimicrobial agents [18]. These previously neglected plants have shown promising antimicrobial activity due to their distinct and frequently undiscovered chemical compositions [19]. Research into non-medicinal plants broadens the range of possible antimicrobial agents, perhaps leading to the identification of new compounds with novel modes of action. Marine plants, which include seaweeds and seagrasses, are another underexplored source of bioactive compounds [20]. The marine environment, with its extreme conditions and distinct biological niches, promotes the generation of varied and new metabolites with strong antimicrobial properties [21]. Marine plants such as red algae (e.g., Gracilaria and Gelidium species) and seagrasses have shown the potential to provide new classes of antimicrobial agents that may offer novel mechanisms of action against resistant pathogens [22,23,24]. The combination of plant-derived chemicals with conventional antibacterial medicines is a strategic approach to improving treatment results. Combining these chemicals has the potential to synergize with current therapies, increasing effectiveness while decreasing the chance of resistance development [25,26]. Furthermore, the use of plant-derived metabolites as scaffolds in the synthesis and semi-synthesis of new pharmaceuticals opens up a promising avenue for drug innovation, possibly leading to the creation of innovative therapeutic agents that address the limits of present therapies.

While commercially available plant-based antimicrobials such as tea tree oil (Melaleuca alternifolia), neem oil (A. indica), and cranberry extract (proanthocyanidins) are well known for their antimicrobial properties and are widely used in healthcare, agriculture, and cosmetics, the primary focus of this review is to investigate novel and less explored plant-derived compounds. These commercial drugs have been extensively researched and evaluated in the current literature, and they have well-established applications for treating infections and other health conditions [26,27]. However, many of these commercially accessible compounds have drawbacks such as chemical variability, a limited antimicrobial spectrum, and bioavailability difficulties [28]. While tea tree oil is often used for its antimicrobial properties, its efficiency varies depending on the source and technique of extraction, and some users report skin sensitivity in greater quantities [29]. These limitations underscore the need for more research into novel plant-based antimicrobials that may have greater therapeutic promise. This review provides a comprehensive overview of the potential of medicinal, non-medicinal, and marine plant-based antimicrobials in combating antimicrobial-resistant microbial pathogens. These well-studied and understudied plants have a wide reservoir of chemicals that may display broader antimicrobial action, increased effectiveness, and improved safety profiles, possibly presenting novel methods for combating multi-drug-resistant pathogens. By investigating compounds from these plants, the review emphasizes their varied antimicrobial capabilities and discusses their possible integration with traditional medicinal products. The review will support current research results, underlining the need to continue investigating these various sources and their relevance in establishing effective ways to fight resistant microbial pathogens.

2. Plant-Based Antimicrobials

Plant-based antimicrobials represent a diverse and potent group of compounds derived from medicinal, non-medicinal, and marine plants, offering novel solutions to combat microbial infections [30]. These compounds, developed as part of plants’ natural defense mechanisms, exhibit various activities against bacteria, fungi, and viruses [31]. As illustrated in Figure 2, examples of these bioactive compounds include rhein and luteolin from medicinal plants, berberine and abietic acid from non-medicinal plants, and fucoxanthin and pheophytin from marine plants. These compounds showcase the diversity of plant-derived antimicrobials and their varying structures across different plant sources. With the increasing threat of antimicrobial resistance, exploring plant-derived bioactive substances has gained momentum, providing alternative and complementary strategies to conventional antibiotics. Plant-based antimicrobials hold immense potential for advancing infection management in healthcare and agricultural settings by targeting multiple microbial pathways and showing synergistic effects with existing drugs [32,33].

2.1. Medicinal Plants

Medicinal plants have been a cornerstone of traditional remedies across cultures and civilizations for centuries. The antimicrobial properties of plants were harnessed to treat infections long before modern antibiotics were discovered [34]. Some of the earliest records of plant use come from ancient civilizations like the Egyptians, Greeks, and Chinese, who used herbs like Echinacea purpurea (coneflower) and Curcuma longa (turmeric) to treat wounds and infections [35]. These plants, often referred to as “green medicine”, were passed down through generations, each culture contributing to the vast repository of knowledge on natural therapies [36]. Today, many of these medicinal plants have become the subject of rigorous scientific research, confirming their efficacy and uncovering the mechanisms by which they exert antimicrobial activity (Table 1). Lantana camara, a plant widely recognized for its medicinal value in tropical regions, is a source of lectins, a class of proteins with carbohydrate-binding abilities [37]. Lectins have been found to disrupt bacterial cell membranes, preventing the growth of microbial pathogens. Studies have demonstrated that lectins from L. camara are effective at a concentration of 10 µg/disk against a spectrum of bacterial strains, including Klebsiella pneumoniae, Pseudomonas aeruginosa, and Escherichia coli. These pathogens are often associated with serious infections, particularly in healthcare settings, where antibiotic resistance is rampant. In addition to its antimicrobial properties, the lectin from L. camara has shown the ability to inhibit the proliferation of cancer cells, such as HT29 colon cancer cells. This dual activity—both antimicrobial and anticancer—suggests that lectins from this plant could have broad therapeutic applications, particularly in addressing multi-drug resistant (MDR) infections and potentially cancer.

Figure 2. The substances of plant-based antimicrobials.

Figure 2. The substances of plant-based antimicrobials.

Also, Desmodium styracifolium, a plant used in traditional Chinese medicine, is a rich source of flavonoids, including 5,7-dihydroxy-2′,3′,4′-trimethoxyflavone [38]. This compound has been shown to inhibit the growth of Acidovorax avenae subsp. cattleyae, a bacterial pathogen that affects crops. At a concentration of 125 µg/mL, this flavonoid effectively suppressed bacterial growth, making it a promising bioactive agent for plant disease control. Moreover, its ability to inhibit Magnaporthe oryzae, a fungal pathogen responsible for rice blast, in both in vitro and in vivo studies further underscores its versatility. The dual antimicrobial activity of this compound against both bacterial and fungal pathogens presents exciting possibilities for its use in integrated pest management and medical antimicrobial strategies. Resveratrol, a well-known polyphenolic molecule, has been shown in many studies to have strong antibacterial and antifungal action. For example, in in vivo experiments, resveratrol was tested against Staphylococcus aureus, P. aeruginosa, and Candida albicans, and it was discovered to reduce an acute antigen-dependent reaction by regulating the immune response, favoring the Th2 response over the Th1-type response [39]. A similar pattern has been seen with Zataria multiflora, which has shown significant antibacterial activity, notably against Acinetobacter baumannii. Treatment with Z. multiflora extract resulted in no identifiable colonies in lung tissue cultures of pneumonic mice that were infected with clinical isolates of A. baumannii [40]. This demonstrates the potential of Z. multiflora as a natural antibacterial agent. Research conducted in clinical settings has shown that the bioactive molecule known as rhodmyrtone has antibacterial properties. Because it has been shown to be both effective and safe in treating inflammatory acne lesions, rhodomyrtone has emerged as a potentially useful natural alternative to synthetic antibiotics, especially in dermatological applications [41].

Research has shown that medicinal plant bioactive compounds, such as flavonoids, terpenoids, alkaloids, and polyphenols, can interfere with microbial processes in multiple ways [42]. They can inhibit bacterial cell wall synthesis, disrupt membrane integrity, interfere with DNA replication, and prevent biofilm formation—one of the key challenges in combating antibiotic resistance [43]. In addition, these compounds often have multiple targets within the microbial cell, making it more difficult for resistance to develop [44]. Medicinal plants offer not only an alternative but also an adjunct to conventional antibiotics [45]. Studies have demonstrated the synergistic effects of plant compounds when used in combination with standard antibiotics, enhancing their effectiveness and reducing the required dosage [46,47]. This holds significant potential in treating infections caused by multi-drug-resistant pathogens [48]. Also, the evidence supporting their effectiveness in both in vitro and in vivo studies, as well as in clinical trials, underscores the importance of further research and the development of these plant-based compounds.

Table 1. Active compounds derived from medicinal, non-medicinal, and seaweeds with antimicrobial roles toward diverse microbial pathogens.

Name of Compounds	Name of Plant	Structure	Active Concentration	Microbial Pathogens	Biological Role	References
Medicinal plant
Lectin	Lantana camara	-	10 μg/disk	Klebsiella pnuemoniae, Pseudomonas aeruginosa, Escherichia coli	- Growth inhibitory effects on HT29 cells - Antibacterial and antifungal activity	[37]
Lantic acid			7.81 mg/mL 0.97 mg/mL	E. coli, Staphylococcus aureus	- Antibacterial activity	[49]
Rhein	Cassia alata L.		IC50 of 2.5 μg/mL	Acidovorax avenae subsp. cattlvae	- Effectively controlled rice blast, tomato late blight, wheat leaf rot, and red pepper anthracnose in vivo - Antibacterial effect	[50]
Emodin			32 μg/mL 64 μg/mL	Candida albicans, C. parapsilosis	- Antifungal activity - Quorum sensing inhibitory acitivty - Significant inhibitory effect on violacin production - Biofilm inhibition and eradication activities	[51]
Kaempferol			13.0 μg/mL	Methicillin-resistant Staphylococcus aureus (MRSA)	- Antibacterial activity	[52]
Waltherione G	Waltheria indica (Malvaceae)		100 μg/mL	Staphylococcus epidermidis	- Antibacterial activity	[53]
Dalpanitin	Derris scandens		23 μg/mL 94 μg/mL 94 μg/mL	S. aureus, E. coli, P. aeruginosa	- Antibacterial activity	[54]
5,7-dihydroxy-2′,3′,4′-trimethoxyisoflavanone	Desmodium styracifolium		125 μg/mL	Acidovorax avenae subsp.cattleyae.	- Antibacterial activity	[38]
Luteolin	Euphorbia humifusa		32 μg/mL	S. aureus	- Inhibition of biofilm formation - Synergy with quercetin	[55]
3-[3-(3-pyridinyl)-1,2,4- oxadiazol-5-yl] benzonitrile	Tropaeolum tuberosum		100 μg/mL 100 μg/mL 150 μg/mL	Bacillus cereus, S. aureus, P. aeruginosa	- Antibacterial activity	[56]
Hyperin	Canarium patentinervium		50 μg/mL	S. aureus	- Antibacterial activity	[57]
3-phenylpropionic acid	Zygophyllum mandavillei		15.62 μg/mL 7.81 μg/mL 7.81 μg/mL 3.90 μg./mL	Xanthomonas oryzae, Pseudomonas syringae, Aspergillus flavus, Fusarium solani	- Antibacterial and antifungal activity	[58]
3,3′-di-O-methyl ellagic acid	Afzelia africana		2.5 μg/mL 2.5 μg/mL 1.25 μg/mL	Streptococcus mutans, S. aureus, Bacillus subtilis	- Antimicrobial and antioxidant activities	[59]
Galangin 3-methyl ether	Lychnophora markgravii		>0.5 μg/mL 0.05 μg/mL 0.5 μg/mL 0.055 μg/mL	Kocuria rhizophila, S. aureus, S. epidermidis, S. mutans	- Antibacterial and antifungal activity	[60]
Allicin	Allium sativum		128 μg/mL 64 μg/mL 64 μg/mL	K. penumonia, P. aeruginosa, S. agalactiae	- Antibacterial activity	[61]
Resveratrol	Picea abies		-	S. aureus, P. aeruginosa, C. albicans	- Antibacterial activity - Antifungal activity - Suppressing acute antigen-dependent Th1 reaction for Th2 response	[39]
Extract	Zataria multiflora Boiss	-	-	Acinetobacter baumannii	- Antibacterial activity - No colony was found in pneumonic mice infected with standard or clinical isolate lung tissue culture	[40]
Extract	Casearia sylvestris	-	-	Helicobacter pylori	- Antibacterial activity - Antibiofilm activity - Decreased ulcerative lesion size (in vivo)	[62]
Rhodomyrtone	Rhodomyrtus tomentosa		-	Propionibacterium acnes	- Effective and safe in treating inflammatory acne lesions	[41]
Extract	Nigella sativa	-	-	P. acnes	- Significant reductions in number of comedones, papules, and pustules (clinical trial)	[63]
Rhodomyrtosone B	Rhodomyrtus tomentosa		1.25 µg/mL 0.62 µg/mL 0.62 µg/mL	S. aureus, MRSA, B. cereus	- Antibacterial activity - Single injection of 40 µg RDSB per animal significantly reduced production of skin ulcers in murine model of MRSA infection	[64]
Extract	Daphne genkwa	-	35,000 mg/mL	MRSA	- Antibacterial activity - PBP2a and PBP4 inhibition	[65]
Thymohydroquinone dimethyl ether	Ayapana triplinervis		IC50 45 µg/mL	Zika Virus	- Antiviral activity - Inhibit ZIKV infection in human cells	[66]
Methyl gallate	Polygonum chinense Linn		-	Influenza virus	- Antiviral activity	[67]
Non-medicinal
Lectin	Portulaca elatior	-	0.185 μg/mL 1.48 μg/mL 1.48 μg/mL 1.48 μg/mL	Pectobacterium sp., C. albicans, Candida tropicalis, Candida krusei	- Antibacterial activity	[68]
			8.1 μg/mL 32.5 μg/mL 4.06 μg/mL 16 μg/mL	E. faeclis, P. aeruginosa, S. aureus, C. albcans	- Antibacterial activity - Antifungal activity	[69]
Asiatic acid	Punica granatum L.		64 μg/mL 16 μg/mL	Mycobacterium smegmatis, S. aureus	- Antibacterial activity	[70]
Punicalagin			1.2 μg/mL 0.6 μg/mL 0.6 μg/mL	C. albicans, P. aeruginosa, S. epidermidis	- Antifungal activity - Antibacterial activity	[71]
Ellagic acid			31.62 μg/mL	MRSA	- Antibacterial activity	[72]
1,4-naphthalenedione-5-hydroxy-2-methyl	Diospyros maritima		5 μg/mL 0.625 μg/mL	Aeromonas hydrophila, S. aureus	- Antibacterial activity	[73]
1,2,4,6-tetra-O-galloyl-β-glucose	Sedum takesimense		32 μg/mL 128 μg/mL 128 μg/mL 32 μg/mL 128 μg/mL 16 μg/mL	E. coli, P. aeruginosa, Salmonella tyrphimurium, B. cereus, Listeria monocytogenes, S. aureus	- Antibacterial activity and synergy effect with conventional antibiotics	[74]
3″,4′,4′″,5,5″,7,7″-heptahydoxy-3-8″-biflavone	Garcinia kola		64 μg/mL 64 μg/mL 64 μg/mL	S. mutans, Streptococcus mitis, Streptococcus downei	- Antibacterial activity - Inhibited water-insoluble glucan synthesis by glucosyltransferases	[75]
(8E)-4- geranyl-3,5-dihydroxybenzophenone			162.5 μg/mL 15.6 μg/mL	Prophyromonas gingivalis, Streptococcus sobrinus	- Antimicrobial activity	[76]
(E)-3-(1-oxobut-2-en-2-yl)glutaric acid	Olea europaea		18 mg/mL	P. syringae	- Cytoprotective and antimicrobial properties	[77]
Oleuropein			625 μg/mL 625 μg/mL 625 μg/mL	S. mutans, P. gingivalism, Fusobacterium nucleatum	- Antibacterial activity	[78]
Berberine	Berberis hispanica		5 μg/mL	S. aureus	- Antibacterial activity	[79]
2-hydroxy-1,4-naphthoquinone	Plumbago zeylanica		100 μg/mL	E. coli	- Synergy effect with kanamycin - Not toxic to mammalian cells - Curing of plasmid	[80]
Heneicosane			10 μg/mL	S. pneumoniae, A. fumigatus	- Antibacterial activity - Antifungal activity	[81]
Abietic acid	Pinus merkusii		9.36 μg/mL	S. mutans	- Antibacterial activity	[82]
3-(2′,4′,6′,6′-tetramethylcyclohexa-1′,4′-dienyl)acrylic acid	Viola odorata		64 μg/mL 128 μg/mL 32 μg/mL	S. aureus, P. aeruginosa, S. pyogenes	- Antibacterial activity	[83]
Aromadendrin-4′-methyl ether	Ventilago madraspatana		78 μg/mL 312 μg/mL	S. aureus, C. albicans	- Antimicrobial and antioxidant activity	[84]
Mangiferin	Mangifera indica		7.81 μg/mL 1.95 μg/mL 1.95 μg/mL	E.coli, S.aureus, C. albicans	- Antioxidant efficacy - Antibacterial action and anticandidal action - Negligible cytotoxicity against normal cells	[85]
Myricetin-3- O-rhamnoside	Prosopis africana		8 μg/mL 8 μg/mL 16 μg/mL 16 μg/mL 32 μg/mL	S. aureus, Enterococcus faeclais, P. aeruginosa, E. coli, K. pneumoniae	- Antibacterial and antioxidant activity	[86]
Extract	Arachis hypogaea L.	NA	IC50 1.3 μg/mL	Human influenza viruses	- Inhibited replication of influenza virus A/WSN/33	[87]
Extract	Prunus dulcis	NA	0.2 mg/mL	Herpes simplex virus 1	- Antiviral activity - No cytotoxicity	[88]
Seaweeds
Digalactosyldiacylglycerol	Fucus vesiculosus		IC50 87 μg/mL	S. aureus	- Antibacterial activity	[89]
Fucoidan		-	3.13 mg/mL 0.2 mg/mL	E. coli, S. typhimurium	- Antibacterial activity - Antirotaviral activity	[90]
Hydroxyphenophytin B	Chlorella vulgaris		0.3 mg/mL 1.2 mg/mL	A. ochraceus, A. carbonarus	- Antifungal activity	[91]
Fucofuroeckol-A	Eisenia bicyclis		16~32 μg/mL	L. monocytogenes	- Antibacterial activity - Synergy effect with streptomycin	[92]
Pheophytin a	Syringodium isoetifolium		6.2 μg/mL 12.5 μg/mL 12.5 μg/mL	Salmonella typhi, E. coli, P. aeruginosa	- Antibacterial activity	[93]
β-carotene	Halopteris scoparia		0.225 μg/mL 0.1125 μg/mL 0.225 μg/mL	L. monocytogenes, S. aureus, S. enterica	- Inhibition of α-amylase and trypsin - Antibacterial activity	[94]
Fucoxanthin	Himanthalia elongata		6.2 μg/mL 12.5 μg/mL	Salmonella typhi, E. coli, P. aeruginosa	- Antibacterial activity	[95]
Ascophyllan HS	Ascophyllum nodosum	-	167 mg/10 mL/kg	S. penumoniae	- Therapeutic impact on S. pneumoniae infection by stimulating host’s defensive mechanisms - Bacterial burdens in lungs were significantly reduced	[96]
Fucoidan	Undaria pinnatifida	-	3.52 mg/day	Influenza A (H1N1, PR8)	- Gross lung pathology (consolidation) was significantly reduced	[97]
Fucoidan	Sargassum swartzii	-	1.56 μg/mL	HIV-1 p24	- Antiviral activity - No cytotoxic effect	[98]

Table 1. Active compounds derived from medicinal, non-medicinal, and seaweeds with antimicrobial roles toward diverse microbial pathogens.

Name of Compounds	Name of Plant	Structure	Active Concentration	Microbial Pathogens	Biological Role	References
Medicinal plant
Lectin	Lantana camara	-	10 μg/disk	Klebsiella pnuemoniae, Pseudomonas aeruginosa, Escherichia coli	- Growth inhibitory effects on HT29 cells - Antibacterial and antifungal activity	[37]
Lantic acid			7.81 mg/mL 0.97 mg/mL	E. coli, Staphylococcus aureus	- Antibacterial activity	[49]
Rhein	Cassia alata L.		IC50 of 2.5 μg/mL	Acidovorax avenae subsp. cattlvae	- Effectively controlled rice blast, tomato late blight, wheat leaf rot, and red pepper anthracnose in vivo - Antibacterial effect	[50]
Emodin			32 μg/mL 64 μg/mL	Candida albicans, C. parapsilosis	- Antifungal activity - Quorum sensing inhibitory acitivty - Significant inhibitory effect on violacin production - Biofilm inhibition and eradication activities	[51]
Kaempferol			13.0 μg/mL	Methicillin-resistant Staphylococcus aureus (MRSA)	- Antibacterial activity	[52]
Waltherione G	Waltheria indica (Malvaceae)		100 μg/mL	Staphylococcus epidermidis	- Antibacterial activity	[53]
Dalpanitin	Derris scandens		23 μg/mL 94 μg/mL 94 μg/mL	S. aureus, E. coli, P. aeruginosa	- Antibacterial activity	[54]
5,7-dihydroxy-2′,3′,4′-trimethoxyisoflavanone	Desmodium styracifolium		125 μg/mL	Acidovorax avenae subsp.cattleyae.	- Antibacterial activity	[38]
Luteolin	Euphorbia humifusa		32 μg/mL	S. aureus	- Inhibition of biofilm formation - Synergy with quercetin	[55]
3-[3-(3-pyridinyl)-1,2,4- oxadiazol-5-yl] benzonitrile	Tropaeolum tuberosum		100 μg/mL 100 μg/mL 150 μg/mL	Bacillus cereus, S. aureus, P. aeruginosa	- Antibacterial activity	[56]
Hyperin	Canarium patentinervium		50 μg/mL	S. aureus	- Antibacterial activity	[57]
3-phenylpropionic acid	Zygophyllum mandavillei		15.62 μg/mL 7.81 μg/mL 7.81 μg/mL 3.90 μg./mL	Xanthomonas oryzae, Pseudomonas syringae, Aspergillus flavus, Fusarium solani	- Antibacterial and antifungal activity	[58]
3,3′-di-O-methyl ellagic acid	Afzelia africana		2.5 μg/mL 2.5 μg/mL 1.25 μg/mL	Streptococcus mutans, S. aureus, Bacillus subtilis	- Antimicrobial and antioxidant activities	[59]
Galangin 3-methyl ether	Lychnophora markgravii		>0.5 μg/mL 0.05 μg/mL 0.5 μg/mL 0.055 μg/mL	Kocuria rhizophila, S. aureus, S. epidermidis, S. mutans	- Antibacterial and antifungal activity	[60]
Allicin	Allium sativum		128 μg/mL 64 μg/mL 64 μg/mL	K. penumonia, P. aeruginosa, S. agalactiae	- Antibacterial activity	[61]
Resveratrol	Picea abies		-	S. aureus, P. aeruginosa, C. albicans	- Antibacterial activity - Antifungal activity - Suppressing acute antigen-dependent Th1 reaction for Th2 response	[39]
Extract	Zataria multiflora Boiss	-	-	Acinetobacter baumannii	- Antibacterial activity - No colony was found in pneumonic mice infected with standard or clinical isolate lung tissue culture	[40]
Extract	Casearia sylvestris	-	-	Helicobacter pylori	- Antibacterial activity - Antibiofilm activity - Decreased ulcerative lesion size (in vivo)	[62]
Rhodomyrtone	Rhodomyrtus tomentosa		-	Propionibacterium acnes	- Effective and safe in treating inflammatory acne lesions	[41]
Extract	Nigella sativa	-	-	P. acnes	- Significant reductions in number of comedones, papules, and pustules (clinical trial)	[63]
Rhodomyrtosone B	Rhodomyrtus tomentosa		1.25 µg/mL 0.62 µg/mL 0.62 µg/mL	S. aureus, MRSA, B. cereus	- Antibacterial activity - Single injection of 40 µg RDSB per animal significantly reduced production of skin ulcers in murine model of MRSA infection	[64]
Extract	Daphne genkwa	-	35,000 mg/mL	MRSA	- Antibacterial activity - PBP2a and PBP4 inhibition	[65]
Thymohydroquinone dimethyl ether	Ayapana triplinervis		IC50 45 µg/mL	Zika Virus	- Antiviral activity - Inhibit ZIKV infection in human cells	[66]
Methyl gallate	Polygonum chinense Linn		-	Influenza virus	- Antiviral activity	[67]
Non-medicinal
Lectin	Portulaca elatior	-	0.185 μg/mL 1.48 μg/mL 1.48 μg/mL 1.48 μg/mL	Pectobacterium sp., C. albicans, Candida tropicalis, Candida krusei	- Antibacterial activity	[68]
			8.1 μg/mL 32.5 μg/mL 4.06 μg/mL 16 μg/mL	E. faeclis, P. aeruginosa, S. aureus, C. albcans	- Antibacterial activity - Antifungal activity	[69]
Asiatic acid	Punica granatum L.		64 μg/mL 16 μg/mL	Mycobacterium smegmatis, S. aureus	- Antibacterial activity	[70]
Punicalagin			1.2 μg/mL 0.6 μg/mL 0.6 μg/mL	C. albicans, P. aeruginosa, S. epidermidis	- Antifungal activity - Antibacterial activity	[71]
Ellagic acid			31.62 μg/mL	MRSA	- Antibacterial activity	[72]
1,4-naphthalenedione-5-hydroxy-2-methyl	Diospyros maritima		5 μg/mL 0.625 μg/mL	Aeromonas hydrophila, S. aureus	- Antibacterial activity	[73]
1,2,4,6-tetra-O-galloyl-β-glucose	Sedum takesimense		32 μg/mL 128 μg/mL 128 μg/mL 32 μg/mL 128 μg/mL 16 μg/mL	E. coli, P. aeruginosa, Salmonella tyrphimurium, B. cereus, Listeria monocytogenes, S. aureus	- Antibacterial activity and synergy effect with conventional antibiotics	[74]
3″,4′,4′″,5,5″,7,7″-heptahydoxy-3-8″-biflavone	Garcinia kola		64 μg/mL 64 μg/mL 64 μg/mL	S. mutans, Streptococcus mitis, Streptococcus downei	- Antibacterial activity - Inhibited water-insoluble glucan synthesis by glucosyltransferases	[75]
(8E)-4- geranyl-3,5-dihydroxybenzophenone			162.5 μg/mL 15.6 μg/mL	Prophyromonas gingivalis, Streptococcus sobrinus	- Antimicrobial activity	[76]
(E)-3-(1-oxobut-2-en-2-yl)glutaric acid	Olea europaea		18 mg/mL	P. syringae	- Cytoprotective and antimicrobial properties	[77]
Oleuropein			625 μg/mL 625 μg/mL 625 μg/mL	S. mutans, P. gingivalism, Fusobacterium nucleatum	- Antibacterial activity	[78]
Berberine	Berberis hispanica		5 μg/mL	S. aureus	- Antibacterial activity	[79]
2-hydroxy-1,4-naphthoquinone	Plumbago zeylanica		100 μg/mL	E. coli	- Synergy effect with kanamycin - Not toxic to mammalian cells - Curing of plasmid	[80]
Heneicosane			10 μg/mL	S. pneumoniae, A. fumigatus	- Antibacterial activity - Antifungal activity	[81]
Abietic acid	Pinus merkusii		9.36 μg/mL	S. mutans	- Antibacterial activity	[82]
3-(2′,4′,6′,6′-tetramethylcyclohexa-1′,4′-dienyl)acrylic acid	Viola odorata		64 μg/mL 128 μg/mL 32 μg/mL	S. aureus, P. aeruginosa, S. pyogenes	- Antibacterial activity	[83]
Aromadendrin-4′-methyl ether	Ventilago madraspatana		78 μg/mL 312 μg/mL	S. aureus, C. albicans	- Antimicrobial and antioxidant activity	[84]
Mangiferin	Mangifera indica		7.81 μg/mL 1.95 μg/mL 1.95 μg/mL	E.coli, S.aureus, C. albicans	- Antioxidant efficacy - Antibacterial action and anticandidal action - Negligible cytotoxicity against normal cells	[85]
Myricetin-3- O-rhamnoside	Prosopis africana		8 μg/mL 8 μg/mL 16 μg/mL 16 μg/mL 32 μg/mL	S. aureus, Enterococcus faeclais, P. aeruginosa, E. coli, K. pneumoniae	- Antibacterial and antioxidant activity	[86]
Extract	Arachis hypogaea L.	NA	IC50 1.3 μg/mL	Human influenza viruses	- Inhibited replication of influenza virus A/WSN/33	[87]
Extract	Prunus dulcis	NA	0.2 mg/mL	Herpes simplex virus 1	- Antiviral activity - No cytotoxicity	[88]
Seaweeds
Digalactosyldiacylglycerol	Fucus vesiculosus		IC50 87 μg/mL	S. aureus	- Antibacterial activity	[89]
Fucoidan		-	3.13 mg/mL 0.2 mg/mL	E. coli, S. typhimurium	- Antibacterial activity - Antirotaviral activity	[90]
Hydroxyphenophytin B	Chlorella vulgaris		0.3 mg/mL 1.2 mg/mL	A. ochraceus, A. carbonarus	- Antifungal activity	[91]
Fucofuroeckol-A	Eisenia bicyclis		16~32 μg/mL	L. monocytogenes	- Antibacterial activity - Synergy effect with streptomycin	[92]
Pheophytin a	Syringodium isoetifolium		6.2 μg/mL 12.5 μg/mL 12.5 μg/mL	Salmonella typhi, E. coli, P. aeruginosa	- Antibacterial activity	[93]
β-carotene	Halopteris scoparia		0.225 μg/mL 0.1125 μg/mL 0.225 μg/mL	L. monocytogenes, S. aureus, S. enterica	- Inhibition of α-amylase and trypsin - Antibacterial activity	[94]
Fucoxanthin	Himanthalia elongata		6.2 μg/mL 12.5 μg/mL	Salmonella typhi, E. coli, P. aeruginosa	- Antibacterial activity	[95]
Ascophyllan HS	Ascophyllum nodosum	-	167 mg/10 mL/kg	S. penumoniae	- Therapeutic impact on S. pneumoniae infection by stimulating host’s defensive mechanisms - Bacterial burdens in lungs were significantly reduced	[96]
Fucoidan	Undaria pinnatifida	-	3.52 mg/day	Influenza A (H1N1, PR8)	- Gross lung pathology (consolidation) was significantly reduced	[97]
Fucoidan	Sargassum swartzii	-	1.56 μg/mL	HIV-1 p24	- Antiviral activity - No cytotoxic effect	[98]

2.2. Non-Medicinal Plants

The term “non-medicinal plants” refers to plants that have not been historically used in medicinal practices in contrast to the medicinal plants, which have been employed for therapeutic reasons over the course of history. The potential health advantages of these plants have been overlooked throughout history since they are often grown for decorative, agricultural, or industrial uses. When referring to plants that were not first recognized for their therapeutic characteristics in traditional or contemporary medicine, the word “non-medicinal” is used to characterize them [99]. On the other hand, recent research has shown that these plants have hidden potential, since they contain many bioactive chemicals with strong antibacterial characteristics (Table 1).

For example, evidence suggests that the plant Portulaca elatior, more generally referred to as purslane, which has historically been grown for its decorative and culinary qualities, has strong antimicrobial properties [68]. In a similar vein, the Punica granatum (pomegranate), which is largely cultivated for its fruit in agricultural settings, has been shown to have considerable antimicrobial components such as asiatic acid, which are effective against bacterial infections, notably against S. aureus [70].

A lesser known compound, (E)-3-(1-oxobut-2-en-2-yl), has been identified in olives and is shown to have important antimicrobial and cytoprotective properties [77]. With an active concentration of 18 mg/mL, this compound inhibited the growth of Pseudomonas syringae, a bacterium that causes diseases in a variety of plants. In addition to its antimicrobial activity, this compound also exhibits significant cytoprotective effects, which may be useful in developing treatments that combine antimicrobial and protective effects on human cells. Its dual action makes it a potential candidate for use in both agricultural and medical applications. In addition, aromadendrin-4′-methyl is a flavonoid found in Ventilago madraspatana that has demonstrated strong antimicrobial and antioxidant activities [84]. It effectively inhibits the growth of both S. aureus and C. albicans at concentrations of 78 µg/mL and 312 µg/mL, respectively. This compound was also found to be highly active in antioxidant efficacy. The compound’s dual action properties further enhance its therapeutic potential, as it could help reduce oxidative stress in infected tissues while simultaneously eliminating pathogens.

These findings highlight the potential of non-medicinal plants as a source of novel antimicrobial agents. The discovery of antimicrobial compounds in non-medicinal plants also has opportunities for their application in industries beyond healthcare. The food industry could benefit from natural plant-based preservatives that inhibit the growth of food pathogens, reducing the need for synthetic additives. Similarly, eco-friendly plant-based disinfectants could offer a sustainable alternative to chemical agents, minimizing the environmental impact. However, despite the fact that non-medicinal plants have the potential to be a source of antimicrobial agents, there is a significant lack of studies addressing the bioactive chemicals that they contain, especially in the context of in vivo and clinical trials. Although in vitro studies have shown that various plant-derived chemicals effectively reduce the development of microorganisms, our knowledge of their genuine therapeutic potential and safety in practical applications is limited due to the absence of substantial in vivo and clinical tests. To fully exploit the antimicrobial capabilities of plants not used for therapeutic purposes, it is necessary to carry out thorough in vivo studies that investigate the efficiency of these plants inside biological systems. Researchers have the ability to unleash the full potential of these bioactive chemicals and establish non-medicinal plants as viable sources of natural antimicrobial drugs if they extend their investigations into the in vivo and clinical domains.

2.3. Marine Plants

While terrestrial plants have been the focus of much of the research on plant-based antimicrobials, marine plants offer an equally rich and largely unexplored source of bioactive compounds. Marine ecosystems, particularly those in extreme environments, have evolved unique secondary metabolites that exhibit potent antimicrobial activity. Seaweeds, algae, and other marine plants have adapted to survive in conditions of high salinity, temperature variation, and microbial competition, producing diverse chemicals with powerful defensive properties (Table 1) [100,101].

For instance, carotenoids are well known for their antioxidant properties, but β-carotene, isolated from the brown alga Halopteris scoparia, has also shown antimicrobial potential [94]. At concentrations as low as 0.225 µg/mL, β-carotene effectively inhibited the growth of Listeria monocytogenes, S. aureus, and Salmonella enterica. Fucoxanthin, another carotenoid derived from the brown seaweed Halomonas elongata, has exhibited both antimicrobial and antioxidant properties [95]. Fucoxanthin was particularly effective against L. monocytogenes, showing a zone of inhibition of 10.72 mm at a concentration of 25 µg per disk. This compound’s ability to inhibit the growth of a major foodborne pathogen, combined with its antioxidant activity, underscores its potential for use in both pharmaceutical and food industries. Its dual action as an antimicrobial and antioxidant makes fucoxanthin an attractive candidate for developing natural preservatives and health supplements aimed at preventing bacterial infections while promoting overall health. In addition to these compounds, ascophyllan HS, a bioactive polysaccharide derived from the brown seaweed Ascophyllum nodosum, has shown therapeutic effects against Streptococcus pneumoniae infection. At a dosage of 167 mg/10 mL/kg, ascophyllan HS significantly reduced bacterial burdens in the lungs of infected subjects by activating host defense systems [96]. Also, one of the most exciting discoveries in marine plant research is the antimicrobial activity of fucoidans, sulfated polysaccharides found in brown algae [102]. Fucoidans have demonstrated strong antiviral properties, particularly against viruses like influenza and herpes simplex [103]. Additionally, they have shown potential in combating biofilm-associated infections, which are notoriously difficult to treat with conventional antibiotics [104]. The chemical diversity of marine plants offers a unique advantage in the search for new antimicrobials. This chemical novelty is particularly valuable in the control against antibiotic-resistant pathogens, as it opens up new avenues for drug development [105].

3. Mechanisms of Action

The antimicrobial activity of plant-derived compounds is underpinned by complex mechanisms of action that often differentiate them from conventional antibiotics [106]. Unlike many synthetic drugs, which target a single bacterial process, plant-based compounds frequently exhibit multi-target interactions and synergistic effects. These characteristics enhance their antimicrobial efficacy and offer solutions to the growing issue of antibiotic resistance [13,107]. In this section, we delve into the primary mechanisms of action of plant-derived antimicrobials, emphasizing their ability to interact with multiple biological targets and to synergize with conventional antibiotics.

3.1. Multi-Target Interactions

A significant advantage of plant-based antimicrobial compounds is their ability to simultaneously affect multiple microbial pathways. Traditional antibiotics often focus on a specific bacterial function, such as cell wall synthesis, protein production, or DNA replication [108]. While these drugs can be highly effective, their singular mode of action increases the likelihood that bacteria will evolve resistance through mutations or the acquisition of resistance genes [109]. In contrast, many plant-derived compounds exert their antimicrobial effects by interacting with several targets within the microbial cell, making it more difficult for pathogens to develop resistance [110,111].

Plant secondary metabolites, including flavonoids, alkaloids, terpenoids, and phenolic compounds, often demonstrate this multi-target behavior. These compounds exert their antibacterial activities using a variety of mechanisms (Figure 3) [112]. For example, flavonoids, a diverse class of plant compounds, are known to interfere with microbial processes in several ways [113]. They can disrupt bacterial cell membranes, inhibit key enzymes involved in energy production, and interfere with the synthesis of nucleic acids. Similarly, alkaloids and terpenoids can cause membrane damage, increase permeability, and ultimately lead to cell death by affecting cellular respiration and ATP synthesis. This multi-pronged attack ensures the rapid eradication of pathogens and reduces the probability that any one mutation will confer resistance. A well-known flavonoid, quercetin, found in various fruits and vegetables, has been shown to interfere with bacterial cell membrane integrity and inhibit nucleic acid synthesis [114]. Similarly, another flavonoid, catechin, can block essential microbial enzymes and reduce oxidative stress, further contributing to its antimicrobial properties [115]. Alkaloids also demonstrate this multi-target interaction. One such compound, berberine, derived from Berberis species, exhibits broad-spectrum antimicrobial activity by inhibiting DNA replication and damaging bacterial cell membranes [116]. Morphine, although primarily known for its analgesic properties, has shown antimicrobial effects by disrupting cellular respiration in some pathogens, highlighting the versatility of alkaloids [117]. Terpenoids, another class of plant secondary metabolites, offer potent antimicrobial actions. Thymol, extracted from thyme, effectively disrupts bacterial cell membranes and inhibits the activity of key enzymes necessary for microbial survival [118]. Lastly, phenolic compounds such as gallic acid, commonly found in various fruits, inhibit microbial growth by disrupting essential microbial enzymes and interfering with nucleic acid processes [119]. Ellagic acid, another phenolic compound, has shown significant antimicrobial effects, particularly against Gram-positive bacteria, by inhibiting enzymes critical for microbial metabolism [120].

An example of this multi-target behavior is seen with diallylthiosulfinate (allicin), a compound extracted from garlic (A. sativum), which has demonstrated antibacterial activity against K. pneumoniae, P. aeruginosa, and Streptococcus agalactiae (Table 1) [61]. Allicin exerts its antimicrobial effects by inhibiting both protein and DNA synthesis, contributing to its broad-spectrum antibacterial activity. Additionally, tomatidin, a compound derived from Berberis vulgaris, has been shown to inhibit ATP synthase, leading to antibacterial activity against Listeria, Bacillus, and Staphylococcus species through this mechanism [121]. These examples underscore the potential of plant-based compounds to disrupt multiple microbial processes, enhancing their efficacy and reducing the likelihood of resistance development.

3.2. Synergistic Interactions

Another notable aspect of plant-based antimicrobial compounds is their synergistic ability with conventional antibiotics. Synergistic interactions occur when two or more agents are combined to produce an effect greater than the sum of their individual effects. In the context of antimicrobial therapy, plant extracts can enhance the efficacy of synthetic antibiotics, often allowing for reduced dosages and minimizing potential side effects [122,123]. This combination of treatments can be precious in addressing infections caused by antibiotic-resistant bacteria [124].

However, despite the fact that non-medicinal plants have the potential to be a source of antimicrobial agents, there is a significant lack of studies addressing the bioactive chemicals that they contain, especially in the context of in vivo and clinical trials. Although in vitro studies have shown that a variety of plant-derived chemicals are effective in reducing the development of microorganisms, our knowledge of their genuine therapeutic potential and safety in practical applications is limited due to the absence of substantial in vivo and clinical tests. For the purpose of fully exploiting the antibacterial capabilities of plants that are not used for therapeutic purposes, it is necessary to carry out thorough in vivo studies that investigate the efficiency of these plants inside biological systems. Researchers have the ability to unleash the full potential of these bioactive chemicals and establish non-medicinal plants as viable sources of natural antimicrobial drugs if they extend their investigations into the in vivo and clinical domains (Figure 4) [125].

Building on this idea, specific examples illustrate the significant potential of plant-derived compounds to act synergistically with conventional antibiotics (

Table 2. Synergistic interactions between plant-derived compounds and conventional antibiotics/antifungals against resistant pathogens.

Compound	Plant	Activity	Bacteria	Synergistic Effects	Reference
Extract	Daphne genkwa	35,000 mg/mL	Methicillin-resistant Staphylococcus aureus (MRSA)	- Synergistic effect with oxacillin	[65]
Ellagic acid	-	31.62 μg/mL	MRSA	- Synergistic effect with moxifloxacin	[72]
1,2,4,6-tetra-O-galloyl-β-glucose	Sedum takesimense	32 μg/mL 128 μg/mL 128 μg/mL 32 μg/mL 128 μg/mL 16 μg/mL	Escherichia coli Pseudomonas aeruginosa Salmonella tyrphimurium Bacillus cereus Listeria monocytogenes Staphylococcus aureus	- Synergistic effect with conventional antibiotics	[74]
2-hydroxy-1,4-naphthoquinone	Plumbago zeylanica	100 μg/mL	E. coli	- Synergistic effect with kanamycin	[80]
Fucofuroeckol-A	Eisenia bicyclis	16–32 μg/mL	L. monocytogenes	- Synergistic effect with streptomycin	[92]
		512 μg/mL	Fluconazole-resistant Candida albicans	- Synergistic effect with fluconazole	[126]
Extract	Commiphora molmol	3.12 mg/mL	C. albicans	- Synergistic effect with fluconazole (FICI = 0.45)	[127]
8,8-bis(dihydroconiferyl) diferulate	Hypericum roeperianum	4 μg/mL 128 μg/mL 32 μg/mL	E. coli Enterobacter aerogenes Klebsiella pneumoniae	- Synergistic activity of cloxacillin, doxycycline, and tetracycline	[128]
Extract-	Laurus nobilis L.	0.25 μg/mL 0.25 μg/mL 0.25 μg/mL	C. albicans C. glabrata C. krusei	- Synergistic activity with fluconazole	[129]
Chrysoeriol	Artemisiarupestris	32 μg/mL	MRSA	- Synergistic activity with ciprofloxacin	[130]
Phlorofucofuroeckol-A	Eisenia bicyclis	32 μg/mL	MRSA	- Synergistic effect with ampicillin, penicillin, and oxacillin	[131]
		32 μg/mL	Propionibacterium acnes	- Synergistic effect with erythromycin and lincomycin	[132]

). For instance, fucofuroeckol-A, a phlorotannin isolated from the brown seaweed Eisenia bicyclis, has demonstrated potent antibacterial activity, particularly against L. monocytogenes at concentrations of 16–32 µg/mL [92]. More importantly, when combined with streptomycin, fucofuroeckol-A exhibited significant synergistic effects, enhancing the antibiotic’s ability to combat bacterial infections. Another powerful example is 1,2,4,6-tetra-O- galloyl-β-D-glucose, derived from Sedum takesimense [74]. This compound has shown antibacterial activity against a broad spectrum of pathogens, including E. coli, P. aeruginosa, S. typhimurium, B. cereus, L. monocytogenes, and S. aureus. Additionally, 2-hydroxy-1,4-naphthoquinone, a compound isolated from Plumbago zeylanica, has been found to enhance the activity of kanamycin against E. coli at a concentration of 100 µg/mL [80]. This compound demonstrated a notable synergy with kanamycin. Moreover, this compound has the potential to assist in the curing of plasmids, further weakening bacterial resistance mechanisms and ensuring the effectiveness of the antibiotic treatment.

Other examples include ellagic acid, which exhibits synergy with moxifloxacin against methicillin-resistant Staphylococcus aureus (MRSA) [72], and chrysoeriol, derived from Artemisia rupestris, which has shown synergistic effects with ciprofloxacin against MRSA [130]. Phlorofucofuroeckol-A, another compound from E. bicyclis, has demonstrated synergistic activity with erythromycin and lincomycin against Propionibacterium acnes, making it a promising compound for dermatological applications [132]. These studies show the potential of plant-based compounds to enhance the efficacy of conventional antimicrobial therapies. By leveraging the natural bioactivity of these compounds in synergy with antibiotics, we can develop more effective treatment strategies for managing antibiotic-resistant infections.

4. Development and Applications

The utilization of plant metabolites in drug development has become a focal point in the search for novel antimicrobial agents [133]. Plant metabolites, the secondary compounds produced by plants as part of their defense mechanisms, offer a rich source of chemical diversity. These compounds have long served as the foundation for the development of various therapeutic agents, particularly in antimicrobial therapies [134]. Recent advancements in biotechnology and chemical synthesis have further enhanced the potential of plant metabolites to serve as scaffolds for new drug design [135]. This section explores how plant-derived compounds are being used in drug development and highlights innovations in the synthesis and semi-synthesis of new antimicrobial agents.

Drug Development from Plant Metabolites

Plant metabolites, such as alkaloids, flavonoids, terpenoids, and phenolics, possess complex and unique chemical structures that can serve as ideal scaffolds for drug development [136]. These compounds have evolved over millions of years to protect plants from microbial infections, pests, and environmental stressors, making them well suited to being starting points for designing antimicrobial drugs. One of the key advantages of using plant metabolites as scaffolds is their structural complexity, which often includes multiple functional groups that can interact with different biological targets. These metabolites are not only biologically active but also provide the chemical backbone needed for the development of synthetic derivatives [137,138]. By modifying the core structure of these metabolites, researchers can enhance their pharmacological properties, such as improving solubility, increasing potency, or reducing toxicity [139,140]. The process for this is shown in Figure 5 [141].

In addition to their potential for therapeutic applications, it is crucial to determine the toxicity and appropriate dosage of plant-derived compounds through rigorous in vitro and in vivo assays before they can be developed into safe and effective drugs [142]. Assays to determine toxicity and dosage play a key role in evaluating the safety profile of these compounds, as some plant metabolites can exhibit cytotoxic effects at certain concentrations. Understanding their toxicity and therapeutic windows is critical for their application in clinical settings [30]. Without these assessments, even promising compounds may pose risks or fail to achieve the desired therapeutic outcomes.

For instance, the alkaloid quinine, originally derived from the bark of the Cinchona tree, has been used as the scaffold for developing antimalarial drugs [143]. Similarly, artemisinin, a compound isolated from Artemisia annua, is the foundation for semi-synthetic derivatives used in modern malaria treatments [144]. These examples demonstrate how plant metabolites can be chemically modified to create more effective and targeted therapies. Furthermore, semi-synthetic flavonoids, such as diosmin, a derivative of hesperidin, have been used for the treatment of venous diseases, while hydroxyethylrutosides (HRs), derived from rutin, are employed for treating capillary fragility and venous insufficiency [145]. These modifications enhance the natural activity of flavonoids, making them more effective in clinical settings [146]. Another semi-synthetic flavonoid, 7-O-galloyl quercetin, is an example of how modifications to the core structure of natural flavonoids can result in enhanced antimicrobial activity [147]. On the other hand, the development of synthetic flavonoid derivatives like flavopiridol highlights the potential of completely synthesized compounds [148].

While natural plant metabolites are valuable in their own right, innovations in chemical synthesis and semi-synthesis have allowed scientists to expand their potential by creating novel derivatives that may not exist in nature. Semi-synthesis involves the chemical modification of a natural product to create a new compound with improved pharmacokinetics, enhanced antimicrobial activity, or reduced side effects [149].

One area of innovation lies in the semi-synthesis of plant-derived compounds, where the core structure of a plant metabolite is retained but functional groups are modified to optimize drug properties. In the context of antimicrobial drug development, similar approaches have been applied [150,151]. For example, flavonoids such as quercetin and catechin have been chemically modified to create derivatives with enhanced antibacterial properties [152,153]. These semi-synthetic flavonoids show improved activity against resistant bacterial strains, making them promising candidates for future drug development [154].

Moreover, advancements in synthetic biology have enabled the full chemical synthesis of complex plant metabolites, further expanding the possibilities for drug discovery. By synthesizing plant-derived compounds in the laboratory, researchers can improve production yields and introduce modifications that may improve the compound’s stability, efficacy, and delivery in the human body. These innovations in synthetic chemistry are paving the way for a new generation of antimicrobial agents that combine the best attributes of natural products with the precision of modern drug design [155,156,157].

5. Data Collection

Utilizing several databases, including Scopus, PubMed, Google Scholar, and Web of Science, we searched for the literature that was related to the proposed objective of the review paper. A number of different keywords were used in the search, some of which were as follows: “antimicrobial from medicinal plants”, antifungal from medicinal plants, antivirals from medicinal plants, “antibacterial agents from plants”, antifungals from marine seaweeds, “antimicrobial from plant-derived compounds”, “medicinal compounds”, “antimicrobial compounds from seaweeds”, “antimicrobial from non-medicinal plants”, and synergistic effects of plant-derived compounds.

6. Conclusions and Future Perspectives

A wide variety of compounds with significant therapeutic potential have been discovered via the investigation of plant-based antimicrobials. These antimicrobials include those that are produced from medicinal, non-medicinal, and marine plants. There is a solid basis for current antimicrobial research that is provided by traditional medicinal plants, notably in the fight against infections that are resistant to several treatments. Furthermore, new discoveries on non-medicinal and marine plants have brought to light their unrealized potential, particularly in creating natural preservatives and antimicrobial substances that are benign to the environment. The capacity of plant-derived antimicrobials to target numerous microbial activities and to synergize with conventional antibiotics/antifungals is a defining characteristic of their modes of action. The use of this multi-target method not only improves their efficiency but also offers significant solutions for the fight against antibiotic resistance. The use of plant metabolites as scaffolds for the creation of novel antimicrobial drugs is becoming more possible as a result of developments in drug research. Through advancements in chemical synthesis and semi-synthesis, it is now possible to produce unique derivatives that have qualities that have been improved. The complexity and variety of plant metabolites are being used by researchers in order to produce medicines that are more successful and are more specifically targeted. However, despite the fact that they hold a great deal of potential, plant-based antimicrobials have some drawbacks. Inconsistent effectiveness may be caused by variations in chemical composition, which can be influenced by variables such as the origin of the plant and the extraction procedures used. This presents difficulties for the process of standardization pertaining to therapeutic use. The limited bioavailability of plant-derived chemicals is another cause for concern. This is because many of these compounds have low solubility, which reduces their usefulness in treating systemic diseases. In addition, some substances, when present in larger quantities, have the potential to produce toxicity and adverse consequences. For instance, tea tree oil and neem oil are known to cause irritation to the skin. If these substances are used in an incorrect manner or for an extended length of time, there is still a possibility that resistance may develop. Finally, the wide-scale manufacturing of plant-based antimicrobials may give rise to issues about the environment and sustainability. Furthermore, the overharvesting of these plants may pose a danger to the world’s biodiversity.

To broaden our knowledge of the mechanisms and therapeutic potential of plant-derived products in the fight against microbial infections, the following research should be carried out in the future:

• Continuous research and innovation are very necessary in order to address newly developing health risks and to enhance the efficacy of therapies that are already available. This involves broadening the scope of investigations to include a greater variety of plant species, especially those not used for medical purposes and marine plants, to discover new chemicals that possess distinctive characteristics.
• A dynamic approach to the development of antimicrobial solutions that are both sustainable and effective is presented by the integration of traditional knowledge with new scientific breakthroughs.
• In order to tackle antibiotic resistance, it will be helpful to conduct in-depth research on the multi-target mechanisms of plant-derived antimicrobials and the synergistic effects that these antimicrobials have with conventional antibiotics.
• The enhancement of the pharmacological characteristics of plant metabolites should be the primary focus of developments in semi-synthesis and chemical modification. This will allow for the development of medicines that are more effective and more precisely targeted.
• The development of natural alternatives to synthetic chemicals requires more investigation into plant-based antimicrobials for applications in agriculture, food preservation, and environmental management. This is crucial for the development of natural alternatives.
• In order to advance the study and translate laboratory discoveries into practical applications that can be used in the real world, it will be essential to collaborate across several disciplines, including medicine, chemistry, pharmacology, and botany.