Abstract
Given the limited number of new antibiotics in development and the decreasing effectiveness of those currently available, the miraculous impact of antibiotics in modern medicine appears to be nearing its end. Medicinal plants offer a promising alternative source for discovering new antimicrobial agents, given their vast diversity of biologically active constituents and the knowledge accumulated through centuries of use in traditional medicine.
In this review, we present a state-of-the-art overview of the antibacterial properties of five medicinal plants used to treat infections in ancient and medieval medicine and that continue to play a significant role in traditional therapeutic practices for addressing various human infections. The selected plants are Acorus calamus, Myrtus communis, and species of Boswellia, Urtica, and Plantago. The author conducted a comprehensive systematic search across PubMed, Scopus, and Google Scholar. The focus was on bioactive constituents, antibacterial susceptibility and spectrum, mechanisms of action, and suggested clinical applications in modern medicine for treating bacterial infections. This review synthesizes current knowledge, highlights the scarcity of pharmacological studies identifying medicinal compounds with specific antibacterial effects, and concludes that the development of new phytoantibacterial agents will depend on accelerating clinical research, particularly randomized controlled trials, to expedite their approval as new antibacterials.
Introduction
In less than a century since the onset of the antibiotic era, the discovery of new, potent antibiotics has declined, and the effectiveness of existing broad-spectrum antibiotics has diminished. On the other hand, emerging antimicrobial resistance is becoming a major global healthcare concern, with estimates indicating that more than 10 million deaths annually in 2050 will be attributable to or associated with antimicrobial resistance. 1 To overcome such an imminent threat, finding alternative therapy options along with other protective interventions has become more important than ever.
Returning to the roots, the plant kingdom is rich in bioactive components and secondary metabolites that have historically been used to treat various human illnesses, including infections. 2 Some medicinal plants featured in Greek and medieval medicine, as presented in “De Materia Medica” by Dioscorides and later in “The Canon of Medicine,” Avicenna’s medical encyclopedia, hold significant historical relevance for addressing diverse human infections, such as wound infections, skin and soft tissue infections, chest infections, and urinary tract infections (UTIs).
In fact, these ancient manuscripts continue to guide traditional medical practices in Mediterranean and European countries. 3 However, the use of medicinal plant compounds as antimicrobial agents in modern medicine is quite limited, despite the well-documented antimicrobial properties of certain medicinal plants, which may represent an appealing target for new antimicrobial discoveries.
The author selected five medicinal plants for this review that were historically used to treat human infections: plants are Acorus calamus, Myrtus communis, and species of Urtica, Boswellia, and Plantago:
A. calamus is a perennial subaquatic herb, originally found in South and Central Asia, and has spread to temperate and subtropical regions worldwide.
4
It has aromatic, creeping rhizomes that can reach over one meter in length.
5
This plant has long been used in traditional Chinese, Indian, and medieval medicine for memory issues and learning enhancement. Its aromatic rhizomes have also served as anti- inflammatory, antimicrobial, anthelmintic, and antidiarrheal agents in various traditional remedies.
6
M. communis, commonly known as myrtle, is an aromatic plant native to the Mediterranean region. The myrtle shrub can reach up to three meters tall, with dense branches covered with evergreen leaves that range from 2 to 5 cm. It has white or pinkish star‐shaped flowers and small fruits.
7
Myrtle remains a significant component of traditional medicine. It has been used to treat multiple medical conditions, such as epistaxis, hemorrhoids, skin diseases, and excessive sweating. In addition, due to its anti-inflammatory, antiseptic, and disinfectant properties, it has been used to treat conjunctivitis, wounds, pulmonary diseases, urethritis, vaginal discharge, urinary tract disorders, and diarrhea.7,8 Urtica species are flowering plants in the Urticaceae family, with Urtica dioica as the main medicinal representative. It is distributed in temperate areas of the Northern Hemisphere. The Urtica species leaves are covered with stiff stinging hairs, causing a hot, stinging sensation on contact and dermatitis. In traditional medicine, U. dioica leaves and stems were used to relieve joint pain and to treat wounds, cuts, urinary tract disorders, and upper respiratory tract problems.
9
Boswellia species belong to the Burseraceae family and are distributed widely in Asia, Africa, and the Middle East. The resinous extract, frankincense or olibanum, produced by a few species (Boswellia serrata, Boswellia carterii, Boswellia sacra, and Boswellia frereana) was applied in Chinese, Indian, and Mediterranean traditional medicines for improving blood circulation and addressing inflammation, boils, skin sores, wounds, eye ulcers, fever, and urinary tract issues. In addition, olibanum was used to manage cancer patients and patients with leprosy or gonorrhea. Furthermore, olibanum was used in mummification processes and in temples for religious activities and air purification.10,11 The Plantago genus belongs to the Plantaginaceae family. It includes approximately 275 annual and perennial species found across temperate and tropical regions worldwide.
12
Most species develop basal rosettes composed of leaves with distinct parallel venation, central stalks, and leafless flowering spikes.
13
Plantago species have been widely used in ancient and medieval medicine to treat various conditions, including constipation, infected burns and wounds, hemorrhoids, scrofula, pimples, malignant and chronic ulcers, deep wounds, erysipelas, elephantiasis, and tertian fever.14,15
The review aims to: (a) synthesize scientific evidence regarding the antibacterial properties of each plant and identify, based on published literature, its antibacterial compounds, proven antibacterial spectrum, potential mechanisms of action, and innovative techniques used to enhance their pharmacological properties; (b) discuss the recommended antibacterial applications in modern healthcare practice; (c) provide future insights focusing on opportunities to discover new antibacterials and on the obstacles that prevent the wider use of phytoantibacterials in modern clinical practice.
Materials and Methods
The Selection Rationale
Five medicinal plants were selected: A. calamus, M. communis, and species of Boswellia, Urtica, and Plantago (Figure 1). The selection rationale for these plants was based on:
Their historical use in ancient and medieval medicine to treat various human infections. A long-standing history of use in traditional Mediterranean medicine for treating infectious syndromes. Their richness in bioactive molecules that may act as antibacterials. Published studies have shown that plants’ crude extracts, essential oils, and specific bioactive compounds possess antibacterial activities, including anti-biofilm effects. The potential for antimicrobial synergy among plant components and observed synergistic effects between certain constituents and specific antimicrobial agents.

These reviewed plants were chosen as a small sample; other medicinal plants may also contain bioactive compounds that could act as antibacterial agents.
Inclusion and Exclusion Criteria
The author conducted a comprehensive systematic search across PubMed, Scopus, and Google Scholar databases from February 1 to August 15, 2025, to retrieve relevant articles. The following criteria were used to select screened articles for inclusion: (a) original clinical or preclinical peer-reviewed research articles or reviews of any type, (b) written in English, (c) published at any time, and (d) containing relevant data on the active antibacterial components of the selected plants, bacterial susceptibility, antimicrobial mechanisms of action, or proposed clinical applications for treating bacterial infections. Articles discussing other pharmacological properties of the selected plants, including antifungal, antiviral, or antiparasitic effects, were excluded. In addition, articles sourced from journals that are not indexed in reputable databases, and which exhibit ambiguous scope or lack transparency in their peer-review process, were excluded on the grounds of being potentially predatory or of low quality.
Search Strategy
The following combined title/abstract terms with medicinal plant names were used for the literature search: “antimicrobial,” “antibiotics,” “antibacterial,” and “infection.” To ensure a thorough narrative, Boolean operators [AND] and [OR] were used to combine or narrow search terms. After an initial screening of titles and abstracts, irrelevant or duplicate articles were excluded. Potentially relevant articles underwent full-text evaluation according to the predefined inclusion criteria. Additional relevant studies were identified through manual review of reference lists and citation tracking of selected articles. A qualitative narrative approach was applied to gather, organize, and interpret information on the active antibacterial components of the selected plants, bacterial susceptibility, antimicrobial mechanisms of action, synergistic effects with the available antibiotics, and proposed clinical applications for treating bacterial infections. Suitable critical appraisal tools were employed to evaluate the validity, bias, confounding, and applicability of the included studies, based on their respective designs.
The narrative review method was chosen due to the limited number of pharmacological and clinical studies investigating the antibacterial properties of these medicinal plants, as well as the heterogeneity of the related literature.
Results
The systematic search across PubMed, Scopus, and Google Scholar identified 688 articles on the antimicrobial properties of the selected medicinal plants. Through the screening process, 94 papers reporting antibacterial activities that met the inclusion criteria were included (Figure 2).
The Literature Search Flow Chart.
Acorus calamus
A. calamus, commonly known as sweet flag, belongs to the Acoraceae family. It has been widely used in ancient Greek, Indian, and Chinese medicine, and it continues to serve as a key component of traditional medicine worldwide. A. calamus is utilized to address multiple health conditions, including fever, inflammation, cough, diarrhea, bronchitis, skin diseases, and digestive disorders. 16
Multiple constituents of A. calamus were identified, including alkaloids, anthraquinones, flavonoids, glycosides, phenols, resins, saponins, steroids, tannins, and terpenoids. 17 β-asarone, methyl isoeugenol, and cyclohexanone have been identified as the major constituents of the essential oil, leaves, and rhizomes.16,18 In addition, α-asarone, β-asarone, β-calacorene, and methyl isoeugenol have been identified as key bioactive constituents with notable antimicrobial properties (Figure 3). 19 Furthermore, β-cadinene, one of the main components, has been reported to exhibit antibacterial activities in silico. 20

The essential oils and various extracts (aqueous, methanol, ethanol, dimethyl sulfoxide, acetone, and hexane extracts) of A. calamus exhibit remarkable antibacterial activity against a range of Gram-positive bacteria, such as Staphylococcus aureus (including methicillin-resistant S. aureus [MRSA]), Streptococcus mutans, Bacillus cereus, Micrococcus luteus, Propionibacterium acnes, and Enterococcus faecalis, as well as Gram-negative bacteria, including Escherichia coli, Acinetobacter baumannii, Pseudomonas aeruginosa, Citrobacter freundii, Enterobacter aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus mirabilis, and Proteus vulgaris.17,18,21–23 Hexane extract and essential oil showed comparable antibacterial effects, with asarone as the main compound in both.18,21,24 In addition, the dimethyl sulfoxide leaf extract demonstrated significant bacterial inhibition, exceeding the efficacy of the standard tested antibiotic (amoxicillin) against S. mutans and P. aeruginosa. 22
Antimicrobial activities vary based on the constituents of A. calamus, the extraction methods, and the characteristics of the bacterial agents. 18 The antibacterial activities were evaluated in vitro against 11 bacterial agents known to cause UTIs. All agents were found to be susceptible to A. calamus extract, with the lowest minimum inhibitory concentrations (MICs) observed for S. aureus, E. aerogenes, and P. mirabilis. 17 In addition, the hexane extract of rhizomes has demonstrated effectiveness against multidrug-resistant pathogens, including P. aeruginosa, A. baumannii, and MRSA.21,25
The suggested antibacterial mechanisms in two previously published studies were the modulation of membrane fatty acids, which disrupt membrane integrity and enhance membrane permeability, leading to the release of cellular contents, including genetic material and proteins.19,25 The essential oil of A. calamus demonstrated bactericidal properties and a competitive effect with tetracycline and cefoperazone.19,24 In addition, synergistic interactions between asarone and ampicillin, as well as A. calamus extracts and specific antibiotics such as tetracycline, ciprofloxacin, cefuroxime, ceftazidime, and chloramphenicol, were observed against the tested bacteria.21,25,26
Notably, nanoparticle biosynthesis represents a novel and promising approach for creating potent antimicrobials with enhanced bacteriostatic and bactericidal properties. Green biosynthesized silver nanoparticles (AgNPs) using an aqueous extract of A. calamus rhizomes have shown significant antibacterial activity against S. aureus, E. coli, B. cereus, and Salmonella enterica, demonstrating dose-dependent inhibition of bacterial growth.25,27 Similarly, cerium oxide nanoparticles (CeO2-NPs) synthesized using aqueous extracts of A. calamus showed good activity against pathogenic bacteria. 28
Regarding the beneficial health applications (Table 3), A. calamus extracts are suggested as natural food preservatives. 23 Additionally, A. calamus fumigation has demonstrated antimicrobial activity against airborne pathogens, making it a promising air disinfectant. 29 Furthermore, specific constituents and green-synthesized CeO2- NPs using aqueous extracts have been proposed as antibiofilm agents.19,28 Moreover, A. calamus demonstrated potent activity against pathogens responsible for UTIs, suggesting further investigation for the development of alternative or complementary antibacterial agents to prevent or treat UTIs. 17 However, mutagenic effects and genotoxicity of α-asarone and β-asarone have been reported. 16
Myrtus communis
M. communis, commonly known as myrtle, is a member of the Myrtaceae family. It is an aromatic evergreen plant native to the Mediterranean region that has been highly valued in medieval and traditional medicine for its healing properties. According to Avicenna, myrtle was used in medieval medicine to treat various clinical conditions, including cough, skin ulcerations, gingivitis, burns, and hemorrhoids. 15 Additionally, myrtle remains a significant component of traditional medicine due to its antiseptic and disinfectant properties. 8
Regarding the identification of M. communis constituents, most previous studies have focused on its essential oil compounds. A few studies also investigated the antibacterial properties of crude or methanol extracts without identifying specific antibacterial components. The identified essential oil compounds are categorized into three main groups: terpenes, terpenoids, and phenylpropanoids. 8 Some of these compounds have been proven to possess antimicrobial properties, including 1,8-cineole, α-Pinene, linalool, cymene, eugenol, myretenol, α-terpineol, γ- terpinene, p-limonene, 3-carene, and β-linalool.8,30,31 The main components of M. communis essential oil with proven antibacterial activity were 1,8-cineole, α- and β-pinene, and linalool.30–32 In addition, phloroglucinol antibiotics, myrtucommulone and semimyrtucommulone (Figure 4) have been isolated from the leaves of myrtle. 33 Moreover, four isolated bioactive alkylphloroglucinol glycosides, among them gallomyrtucommulones D and G, exhibited selective antibacterial activity against S. aureus. 34

Antibacterial activities of myrtle have been proven against a range of Gram-positive pathogens, such as S. aureus, S. epidermidis, M. luteus, S. pneumoniae, S. pyogenes, Bacillus subtilis, S. agalactiae, E. faecalis, and L. monocytogenes, in addition to various Gram-negative bacteria, such as E. coli (including O157:H7 strain), P. aeruginosa, and other Pseudomonas spp., S. typhi, Shigella flexneri, Enterobacter cloacae, K. aerogenes, P. vulgaris, P. mirabilis, and Campylobacter jejuni8,35–38 (Table 1). Furthermore, multiple oral pathogens were found to be sensitive to myrtle essential oils and extracts, including Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, S. mutans, S. sanguinis, S. salivarius, S. pyogenes, and Eikenella corrodens.39,40
The proposed antimicrobial mechanisms include dysregulation of cytoplasmic membranes, interaction with membrane proteins, inhibition of enzyme synthesis, dissolution of lipids in the outer membrane, and coagulation of cellular contents. 8 The synthesized myrtucommulone analogs are proposed as a promising new class of antibiotics, demonstrating significant inhibition of DNA gyrase and topoisomerase IV. 41 Moreover, they reported the synergistic effects of myrtucommulone analog 27 in combination with cefepime, ceftazidime, ofloxacin, and amikacin. Furthermore, the synergistic effect of essential oils has been reported when combined with polymyxin B or ciprofloxacin against A. baumannii, a “superbug” pathogen with limited therapeutic options. 42
To enhance antibacterial activity, a myrtle niosomal essential oil formulation demonstrated more potent antibacterial effects compared to traditional myrtle essential oil against S. aureus, S. epidermidis, S. marcescens, and B. subtilis. 38 Additionally, the antibacterial activity of the crude myrtle preparation increased 18-fold after autoclaving at 121°C for 15 minutes against a range of Gram-positive and Gram-negative bacteria. 35 On the other hand, the essential oil and its constituents display substantially greater inhibitory activity against Gram-positive bacteria than against Gram-negative bacteria. 43
M. communis essential oils have shown antibacterial effects against H. pylori, suggesting potential use in duodenal ulcer treatment. 44 Additionally, the methanolic extract ointment has been shown in vivo to be effective in treating MRSA-infected burn wounds, supporting its use for treating burn wound infections. 45 Also, the potent activity of myrtle extract and essential oils against oral pathogens supports the use of plant constituents to prevent or treat periodontal diseases and other oral infections.39,40 Myrtle essential oil is also recommended for dairy processing due to its high effectiveness against L. monocytogenes, without harming the growth of native microflora. 46 Other researchers support its use as a preservative to enhance the safety of stored meat and lactic butter.30,36 Furthermore, using essential oils was recommended as a non-chemical disinfectant for vegetables and other organic products. 47
Urtica Species
Urtica spp. are perennial herbs belonging to the Urticaceae family, known as nettles. They have piqued the interest of healers for centuries. Different parts of the plant have been used in ancient Greek and medieval medicine to treat various human illnesses, including skin ulcers, wounds, respiratory disorders, urinary tract diseases, and arthritis.15,48
Multiple biologically active components of Urtica extracts were identified, including polyphenols, sterols, linalool, quercetin, oleanolic acid, 4-thujanol, hydroxycinnamic acids (chlorogenic, caffeic, and rosmarinic acids), camphor, carvacrol, di(butyl) phthalate, and steryl glycosides. The aerial parts are rich in polyphenols, whereas the roots contain more oleanolic acid and steryl glycosides.49–51
Most prior studies have focused on the medicinal benefits of U. dioica among other Urtica species. Various Urtica extracts (Aqueous, ethanol, hexane, hydroalcoholic, or ethyl acetate extracts) without identifying hydroalcoholic extract antimicrobial compounds, have frequently demonstrated antibacterial potency against a long list of pathogenic bacteria, including Gram-positive bacteria such as S. aureus, S. epidermidis, S. pneumoniae, S. pyogenes, M. luteus, B. subtilis, B. cereus, L. monocytogenes, and E. faecalis, as well as Gram-negative bacteria like P. aeruginosa, E. coli, E. aerogenes, Citrobacter koseri, P. mirabilis, P. vulgaris, K. pneumoniae, S. marcescens, S. enteritidis, S. typhi, S. paratyphi B, S. typhimurium, Acinetobacter calcoaceticus, S. flexneri, Shigella dysenteriae, Aeromonas hydrophila, and Vibrio parahaemolyticus (Table 1).49,52–54
Antibacterial Susceptibility of Gram-positive and Gram-negative Bacteria to Tested Extracts, Essential Oils, or Specific Components of the Selected Medicinal Plants.
Water and ethanol extracts from Urtica roots showed stronger antibacterial activity than those from stems or leaves. 55 Urtica’s antibacterial properties have been linked to specific components, such as terpenes and flavonoids. 52 The antibacterial activities are partly attributed to the affinity of Urtica agglutinins, which influence bacterial cell wall synthesis by targeting chitosan-containing glycans. 55 Furthermore, Cliotide U1, a purified 35-amino-acid peptide derived from U. dioica, has shown significant antimicrobial activity. 56 It was suggested as a potential novel antibacterial agent, demonstrating proven activity against S. aureus, E. coli, A. baumannii, and P. aeruginosa.
Green-synthesized AgNPs using U. dioica extracts in ethyl acetate demonstrated broad-spectrum effects, with a larger inhibition zone against P. aeruginosa than ciprofloxacin, the control antibiotic. 57 Additionally, the synthesized AgNPs demonstrated synergistic effects when combined with various antibiotics. The maximum synergistic effect was observed with amoxicillin against S. marcescens, which showed a 17.8-fold increase in the inhibition zone. 58 Furthermore, synthesized zinc oxide nanoparticles (ZnONPs) using U. dioica extracts demonstrated excellent antistaphylococcal activity against S. aureus with a 90% decrease in the expression of S. aureus virulence genes (lukED and RNAIII genes). 50 Moreover, synthesized selenium nanoparticles using U. dioica leaf extract demonstrated significant antibacterial activity against E. coli, P. aeruginosa, B. subtilis, and S. aureus. 59
Promising medical applications of Urtica species have been suggested. Some researchers have demonstrated antibiofilm properties against S. mutans, supporting their use as a mouthwash. 60 Others have reported the potent antibacterial activity of U. dioica-ZnONPs and suggested this preparation as a reliable antibacterial agent for treating diabetic foot infections (Table 3). 50
Boswellia Species
Boswellia species belong to the Burseraceae family. Their essential oils and resins, commonly known as frankincense, have a rich history in ancient medicine, dating back to around 3000
The identified bioactive constituents of Boswellia include thujene, α-pinene, β-thujone, limonene, trans- verbenol, oleic acid, n-hexadecanoic acid, squalene, p-cymene, m-cymene, and sabinene.61–64 Dandashire et al. identified three main compounds of crude aqueous extract of B. dalzielii stembark (oleic acid, squalene, and n-hexadecanoic acid) that showed antibacterial activity. 62
Boswellia essential oils, resins, and extracts (mainly aqueous or hydro-alcoholic extract) have been proven effective against Gram-positive bacteria, such as Staphylococcus hominis, S. aureus, S. epidermidis, S. mutans, S. pyogenes, B. cereus, B. subtilis, E. faecalis, P. acnes, L. monocytogenes, and Clostridium perfringens, as well as against Gram-negative bacteria, including E. coli, P. aeruginosa, K. pneumoniae, S. typhi, S. Typhimurium, P. mirabilis, S. flexneri, Haemophilus influenzae, and Pasteurella multocida (Table 1).61,62,64–66 Boswellic acids, especially acetyl-11-keto-β-boswellic acid (AKBA) (Figure 5), have demonstrated excellent antibacterial activity against Gram-positive bacteria, including multidrug-resistant pathogens like MRSA and vancomycin-resistant Enterococci.67,68 Furthermore, certain oral microbiota, such as S. mutans, P. gingivalis, and A. actinomycetemcomitans, have been found to be susceptible to Boswellia constituents.69–71

Disrupting the structure of bacterial membranes may serve as a potential antibacterial mechanism for AKBA. 67 Boswellia constituents were less effective against Gram-negative bacteria than against Gram-positive ones. The diminished antibacterial activity against Gram-negative bacteria may be linked to the outer membrane structure, which mainly consists of lipopolysaccharides that serve as a hydrophilic permeability barrier.64,67
Synergistic antibacterial effects of B. carterii alcoholic extract were observed when combined with penicillin and streptomycin. 63 Additionally, encapsulating B. sacra essential oils into β-cyclodextrin nanoparticles showed a four- and eight-fold increase in effectiveness against Gram-positive bacteria (S. aureus and B. subtilis) and Gram-negative bacteria (E. coli and Pseudomonas putida), respectively. 72 Furthermore, green-synthesized AgNPs using B. sacra extract have proven to be safe and effective antibacterial agents, demonstrating synergistic effects between AgNPs and Boswellia extract.73,74 Moreover, boswellic acid extract had an additive inhibitory effect on bacterial growth when combined with erythromycin or polymyxin B. 68
Regarding the antibacterial applications of Boswellia constituents in healthcare, Boswellia oils and smoke have shown antimicrobial activity against airborne pathogens, supporting the use of Boswellia liquids and vapors to clean contaminated air. 10 Additionally, AKBA, encapsulated in β-cyclodextrin nanoparticles, and Boswellia extracts have antibiofilm properties with promising applications in infection control and periodontal disease management.67,69,72,75 Moreover, the lecithin-based delivery form of Boswellia has been proven effective and safe in treating acute diarrhea, reducing stool frequency, abdominal pain, and nausea, and shortening the duration of the illness compared to a placebo. 76 Finally, B. carterii alcoholic extract demonstrated an excellent wound-healing effect in vivo at a concentration of 5%. 63
Plantago Species
The Plantago genus belongs to the Plantaginaceae family. It includes approximately 275 annual and perennial species that are distributed worldwide. 12 However, the antibacterial properties of constituents from Plantago have been studied for only a few species, specifically P. major, P. lanceolata, P. ovata, Plantago asiatica, P. lagopus, and P. boissieri. Plantago species have been widely utilized in ancient and medieval medicine to address various infectious conditions such as scrofula, infected burns, pimples, malignant and chronic ulcers, deep wounds, erysipelas, elephantiasis, and tertian fever. 15
The non-volatile constituents of Plantago include plantamajoside, flavonoids, phenols, phenylpropanoid glycosides, coumarins, tannins, acteoside, cinnamic acids, and lignans. The primary volatile constituents are α-caryophyllene, β-caryophyllene, and D-limonene.77–79
A significant number of previously conducted studies revealed the antibacterial activity of Plantago extracts (hexane, methanol, ethanol, or aqueous extracts) without identification for specific compounds against Gram-positive pathogens, such as S. aureus, L. monocytogenes, B. cereus, Enterococcus species, Streptococcus species, and Lactobacillus species,77,79 as well as Gram-negative pathogens, including E. coli, P. aeruginosa, Proteus species, K. pneumoniae, S. paratyphi, S. typhimurium, and Borrelia burgdorferi (Table 1).78,79,80,81 Additionally, significant antimicrobial activity was noted against oral pathogens, including A. actinomycetemcomitans, Actinomyces viscosus, P. gingivalis, S. mutans, Lactobacillus acidophilus, Prevotella melaninogenica, Prevotella intermedia, and Fusobacterium nucleatum.79,82
The proposed antibacterial mechanisms of Plantago depend on three active constituents: polyphenols, tannins, and terpenoids that work together; flavonoids inhibit the synthesis of bacterial DNA and RNA and block energy production, disrupting the regulation of cytoplasmic membranes and decreasing the fluidity of bacterial cell walls. Conversely, phenols show bacterial toxicity through their hydroxyl groups, interacting non-specifically with bacterial proteins, while tannins deactivate bacterial adhesins, protein transport, and enzymes. 79 Additionally, a reduction in the Tox-A gene expression, which encodes exotoxin A of P. aeruginosa, has been reported. 83 Furthermore, aucubin and its more stable derivative aucubigenin (Figure 6), found in Plantago species, act as bactericidal agents by denaturing bacterial proteins. 84 Moreover, plantamajoside hinders S. aureus from adhering to fibrinogen and prevents the anchoring of staphylococcal protein A to the cell wall by inhibiting sortase A in S. aureus. 85

The green synthesis of AgNPs using Plantago extracts has demonstrated promising results in enhancing the antibacterial activity. Previously conducted studies reported strong antimicrobial effects against M. luteus, S. aureus, E. coli, and P. aeruginosa.86,87 Additionally, the synergistic effect of Plantago extracts when combined with amoxicillin/clavulanic acid or ceftriaxone has been noted. 79
Several health benefits of Plantago constituents and extracts have been proposed; some researchers have suggested using them as natural antibacterial agents or in combination with antibiotics.88,89 The remarkable anti-inflammatory and antibacterial properties of Plantago compounds against periodontal pathogens and cariogenic flora support their use in treating periodontal disease and other oral hygiene applications. 77 The wound-healing properties demonstrated in an in vivo study support utilizing Plantago extracts for wound care. 90 Furthermore, P. major pectin-like polysaccharide demonstrated a protective effect against systemic S. pneumoniae infection. 91 Moreover, green-synthesized AgNPs from Plantago seeds appear promising for various healthcare applications, including the production of personal protective equipment such as surgical gowns and face masks. 87
Table 1 demonstrates the susceptibility of Gram-positive and Gram-negative bacteria to tested extracts, essential oils, or specific components of the selected medicinal plants; Table 2 presents the identified antibacterial compounds from the selected medicinal plants, and their proposed antibacterial mechanisms; and Table 3 presents the proposed antibacterial applications in modern medicine.
Identified Antibacterial Compounds from the Selected Medicinal Plants and Their Proposed Antibacterial Mechanism.
Discussion
The anticipated rise in morbidity and mortality worldwide due to severe, life-threatening infections caused by multidrug-resistant pathogens in the impending post- antibiotic era necessitates the pursuit of proactive solutions. This narrative review highlights promising avenues for developing effective phytoantibacterials and sheds light on the obstacles hindering their rapid development.
Previous biochemical studies identified several bioactive compounds in each selected medicinal plant; however, only limited research has focused on identifying compounds with antibacterial activities. In contrast, the antimicrobial activities of plant extracts or essential oils were frequently tested.19,92 Of the reviewed bioactive compounds from the selected plants, 12 exhibit promising antibacterial properties, namely asarone, β-cadinene and methyl isoeugenol from A. calamus, 19 Myrtucommulone analogs, Semimyrtucommulone, and gallomyrtucommulone, isolated from M. communis,33,34 agglutinins and cliotide U1 peptide from U. dioica,55,56 AKBA from Boswellia species, 67 as well as plantamajoside, aucubin, and aucubigenin from Plantago species.84,85
In terms of the antibacterial spectrum, the studied constituents from all five plants exhibited broad in vitro activity (Table 1). However, most documented antibacterial properties have not been proven in vivo. Furthermore, microbiological studies often reported the extent of inhibition zones or the MICs of plant extracts or essential oils as a whole, rather than focusing on those parameters for individual antibacterial compounds.
Regarding the antimicrobial mechanisms of phytocomponents, most published studies describe altering bacterial cell walls, disrupting microbial membranes, or interfering with cell contents as their mode of action.8,19,21,67 However, the exact mechanism of interaction and modulation of the microbial membrane by phytocomponents was not clearly explained. Nevertheless, some researchers move another step forward to identify the antimicrobial mode of action of selected phytocomponents. Yang et al. found that phytoantibacterial myrtucommulone analogs are inhibitors of DNA gyrase and topoisomerase IV. 41 Both enzymes are inhibited by fluoroquinolones, which exhibit potent antibacterial activity against a wide spectrum of pathogens, including Gram-negative and multiple Gram-positive agents, as well as atypical pathogens. 93 However, the increasingly emerging fluoroquinolone resistance indicates the need for alternative agents. Some myrtucommulone analogs could be promising candidates for developing a new class of DNA gyrase/topoisomerase IV inhibitors. Conversely, the shared antibacterial mechanism of fluoroquinolones and myrtucommulone analogs under development raises concerns regarding potential cross-resistance. It is also essential to investigate the contribution of phytocomponents, such as DNA gyrase inhibitors, in promoting antibacterial resistance.
Other researchers found U. dioica agglutinins target chitosan-containing glycans on bacterial cell walls, 55 α-pinene and limonene derived from Boswellia species, interact with tyrosyl-tRNA synthetase, DNA gyrase, and peptide deformylase, through hydrogen bonding. 64 Furthermore, plantamajoside from P. asiatica inhibits S. aureus sortase A, 85 which is a key virulence factor located on the S. aureus cell surface. Its inhibition can significantly decrease S. aureus virulence without affecting bacterial growth or promoting drug resistance. 94 This key finding enables the use of phytocomponents like plantamajoside as anti-virulence agents to help combat infections caused by pathogens that rely on sortase A as a virulence factor.
The synergistic effects with various antibiotics observed in some constituents of all five reviewed medicinal plants were another important property reported. For instance, synergistic interactions were reported for asarone with ampicillin, 21 A. calamus extracts with tetracycline, ciprofloxacin, cefuroxime, ceftazidime, and chloramphenicol,21,25,26 myrtucommulone analog 27 in combination with cefepime, ceftazidime, ofloxacin, and amikacin, 41 M. communis essential oils in combination with polymyxin B or ciprofloxacin. 42 In addition, synthesized AgNPs using U. dioica extracts with amoxicillin, 58 B. carterii alcoholic extract with penicillin and streptomycin, 63 and Plantago extracts with amoxicillin/clavulanic acid or ceftriaxone also demonstrate significant synergistic effects. 79 These antibacterial synergies of such combinations open the door for establishing further clinical applications as complementary agents.
Green synthesis of specific metals using plant components demonstrates new potential for improving antimicrobial effects of phytoantimicrobials, including Green-synthesized AgNPs or ZnONPs using U. dioica extracts, AgNPs or CeO2-NPs using an aqueous extract of A. calamus, or AgNPs using Plantago extracts.27,28,50,57,87 This promising approach improves the antibacterial activity of the tested phytocompounds. Green-synthesized antimicrobials could be novel options for the topical treatment of wounds or oral infections.
Biofilm formation is a key pathogenic mechanism contributing to infection chronicity and the rise in antibacterial resistance. Antibiofilm activities of the reviewed medicinal plants were reported for CeO2-NPs using aqueous extracts of A. calamus, U. dioica extracts, AKBA encapsulated in β-cyclodextrin nanoparticles, and Boswellia extracts.19,60,67,69,72,75
In terms of gaps and obstacles to the rapid development of phytoantibacterials, we found that variations in plant constituent concentrations, including antimicrobial ones, could hinder the generalization of microbiological findings. In fact, the medicinal plant’s antimicrobial properties are influenced by the concentration of biologically active compounds, which often vary among different specimens of the same species and can fluctuate within the same plant based on factors like location, farming conditions, season, the plant’s life cycle, and the specific plant parts analyzed. 49 Additionally, climate change and increasing pollution may change bioactive plant compounds or contaminate plant extracts.
The research methods in phytomedicine show remarkable heterogeneity; some researchers investigate the potential medical applications of whole plant extracts or essential oils as were used in traditional medicine, seeking scientific evidence of clinical benefits, while others focus on the medical properties of single biochemical compounds derived from certain medicinal plants. A promising new approach, harnessing the power of artificial intelligence and in silico methods while exploring the genomic, proteomic, and metabolomic properties of medicinal plants, could be the proper key to developing phytoantibacterials.
Another notable gap is the limited research on the pharmacological aspects, including pharmacokinetics, pharmacodynamics, and toxicity of the proposed phytoantibacterials, which have been rarely studied. Addressing this gap will be essential for developing and implementing phytoantibacterial agents on a large scale.
Contemporary research often generalizes the medicinal benefits of plants, frequently suggesting their effectiveness in treating various diseases. This approach typically fails to clearly distinguish between using plants as medical foods, herbal supplements, or treatments for specific ailments. In addition, the antibacterial applications of the tested extracts, essential oils, and other specific phytocompounds have not been widely investigated.
The use of phytoantibacterials derived from Urtica and Boswellia species, as well as A. calamus, has been suggested for antibiofilm applications.19,28,72,95 Also, the use of components from A. calamus, M. communis, and Plantago species as natural food preservatives has been suggested.17,36,96 However, the suggested clinical applications remain limited to topical use, mainly for wound care, oral hygiene, or treatment of periodontal diseases (Table 3). Systemic applications were rarely suggested, such as the use of lecithin-based delivery forms of B. serrata for treating acute diarrhea, M. communis essential oils for duodenal ulcers, and A. calamus extracts to treat or prevent UTIs.17,44,76
Proposed Antibacterial Applications of the Selected Medicinal Plants in Modern Medicine.
Despite the aforementioned applications and newly suggested phytoantibacterial constituents, most current research on the antimicrobial properties of medicinal plants remains in its early stages, primarily focusing on chemical and microbiological studies. The main challenge lies in the scarcity of relevant data on the safety and toxicity of the suggested phytoantibacterials. Only limited data derived from preclinical studies were available regarding asarones, indicating that asarone isomers exhibit hepatotoxicity, cardiotoxicity, reproductive hazards, and mutagenic effects. 97 The genotoxicity of α- and β-asarones has been reported in vitro, and this effect is mainly influenced by the status of cellular enzymes and their genotoxic metabolites. 98 In addition, the development of small intestinal leiomyosarcoma and hepatic neoplasm in vivo has been reported in rats after feeding or intraperitoneal injections of α- and β-asarones. 99 However, less supporting toxicity data are available regarding α- and γ-asarones. Hence, the American regulatory agency bans β-asarone in food and herbal products, whereas the European Medicines Agency has imposed strict exposure limits.97,99
Approving traditional antimicrobial applications and accelerating plant-based antimicrobial discoveries, as well as enhancing their medical applications, requires accurately identifying suitable plant species, geographic locations, agricultural conditions, and plant parts, as well as determining the optimal timing for extracting plant compounds with antimicrobial properties. Refining the extraction methodology is essential, along with standardizing analytical procedures and investigative methods to ensure the accurate identification of suitable plant constituents.
Conclusions
Our literature review on the antibacterial properties of the selected medicinal plants shows promising activity from various phytoconstituents. However, there is a shortage of pharmacological studies that pinpoint medicinal compounds with specific antimicrobial effects. Priority should be given to identifying the mechanisms of action of plant-derived antibacterials, their pharmacokinetic and pharmacodynamic properties, their synergistic effects with other commonly used antimicrobials, and any side effects, safety, toxicity, and interactions with other substances and medications. Additionally, a significant gap exists in clinical research, particularly a paucity of randomized controlled trials that assess the antibacterial effectiveness of medicinal constituents. The development of new plant-derived antibacterial agents will rely on accelerating clinical research, particularly randomized controlled trials, for compounds that show initial benefits to expedite approval as new antimicrobials.
Footnotes
Author’s Contribution
The author made substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; took part in drafting the article or revising it critically for important intellectual content; agreed to submit to the current journal; gave final approval of the version to be published; and agreed to be accountable for all aspects of the work. The author is eligible to be author as per the International Committee of Medical Journal Editors (ICMJE) requirements/guidelines.
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Data Availability Statement
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