Effects of herbal medicines in combating antimicrobial resistance and its impacts on public health

Efeitos dos fitoterápicos no combate à resistência antimicrobiana e seus impactos na saúde pública

Abstract

The use of antibiotics in recent years in an accelerated and inappropriate manner has caused numerous problems for public health. Microorganisms have developed self-defense mechanisms capable of blocking the action of several antibiotics, in addition they are responsible for disseminating resistance genes in various environments. Phytotherapics present bioactive compounds with antimicrobial, anti-inflammatory and antioxidant effects already scientifically proven. This study aimed to identify the effects of herbal medicines in combating antimicrobial resistance and its impact on public health. The bibliographic research was carried out with the selection of articles in the following databases: ScienceDirect, Google Scholar, PubMed and Springer-Verlag. Based on the World Health Organization, health agencies have been looking for effective alternatives to combat bacterial resistance of pathogenic strains. Since these microorganisms are responsible for causing various diseases, among them pneumonia, endocarditis, skin and soft tissue infections, tuberculosis, blood infection or sepsis, gonorrhea and foodborne diseases. Research carried out with extracts and oils of medicinal plants show great antimicrobial potential capable of inhibiting and killing resistant bacterial strains. Combined with antibiotics, phytochemicals can modify and modulate bacterial resistance mechanisms. Solvent extracts from plants such as Curcuma longa, Zingiber officinale and Tinospora cordifolia showed bactericidal action against pathogenic strains. As well, hydromethanolic extracts of Berberis vulgaris, Cistus monspeliensis and Punica granatum demonstrated antimicrobial activity. Herbal medicines have been shown to be effective in the treatment of resistant pathogens. In addition to being a sustainable and natural source treatment option.

Keywords:
medicinal plants; bacterial resistance; health promotion

Resumo

O uso de antibióticos nos últimos anos de maneira acelerada e inadequada tem causado inúmeros problemas para saúde pública. Os microrganismos desenvolveram mecanismos de autodefesa capazes de bloquear a ação de diversos antibióticos, além disso são responsáveis por disseminar genes de resistência em vários ambientes. Os fitoterápicos apresentam compostos bioativos com efeitos antimicrobianas, anti-inflamatórias e antioxidantes já comprovados cientificamente. Este estudo teve como objetivo identificar os efeitos dos fitoterápicos no combate à resistência antimicrobiana e sua repercussão na saúde pública. A pesquisa bibliográfica foi realizada com a seleção de artigos nos seguintes bancos de dados: ScienceDirect, Google acadêmico, PubMed e Springer-Verlag. Com base na Organização Mundial da Saúde, os órgãos de saúde têm procurado alternativas eficazes para combater a resistência bacteriana de cepas patogênicas. Uma vez que esses microrganismos são responsáveis por causar várias doenças, entre elas pneumonia, endocardite, infecções de pele e tecidos moles, tuberculose, infecção no sangue ou sepsia, gonorreia e doenças transmitidas por alimentos. Pesquisas realizadas com extratos e óleos de plantas medicinais mostram grande potencial antimicrobiano capaz de inibir e matar cepas bacterianas resistentes. Combinados com antibióticos, os fitoquímicos podem modificar e modular mecanismos de resistência bacteriana. Extratos solventes de plantas como Curcuma longa, Zingiber officinale e Tinospora cordifolia apresentaram ação bactericida sobre cepas patogênicas. Como também, extratos hidrometanólicos de Berberis vulgaris, Cistus monspeliensis e Punica granatum demonstraram atividade antimicrobiana. Os fitoterápicos têm se mostrado eficazes no tratamento contra patógenos resistentes. Além de ser uma opção de tratamento sustentável e de fonte natural.

Palavras-chave:
plantas medicinais; resistência bacteriana; promoção da saúde

1. Introduction

Bacterial resistance is the condition in which microorganisms develop defense mechanisms against the action of some antibiotics used in human health, by the agricultural sector, food production, and others. In recent years, the indiscriminate use of antibiotics has generated numerous damages to public health, especially the increase in bacterial resistance (Buckner et al., 2018; Venter et al., 2017; Yu et al., 2020). It is estimated that the number of deaths caused by bacterial resistance by 2050 will reach 10 million lives per year (De Kraker et al., 2016). And due to the universal spread of these pathogens, this resistance is seen as one of the greatest threats to human health in the 21st century (Koulenti et al., 2020; Owen and Laird, 2018; Shriram et al., 2018).

Contamination of environments such as soil and water has facilitated and accelerated the process of propagation of resistance genes in the environment (Ben Said et al., 2016; Gothwal and Shashidhar, 2015). Much of this industrial, domestic, and hospital waste is improperly disposed of by pharmaceutical industries, hospitals, and livestock farmers. The transport of natural or synthetic substances to these environments drives the spread of bacterial resistance to various antimicrobials (Khare et al., 2021; Oyekale and Oyekale, 2017). For this reason, the World Health Organization (WHO) has focused on the production of new drugs capable of treating these infections, with the aim of ensuring adequate global treatment and reducing environmental impacts (The Lancet Infectious Diseases, 2017).

In recent years, the scientific community has been increasingly seeking effective, innovative, and natural methods with antimicrobial potential to combat resistant and multidrug-resistant pathogens (Yu et al., 2020). Secondary metabolites of medicinal plants, such as alkaloids, flavonoids, quinones, coumarins, and other phytochemicals, are an effective and sustainable alternative in combating bacterial infections (Anand et al., 2019, 2020; Mbaveng et al., 2015; Mohammed et al., 2021). Due to the relevance and need for updates on the subject, this work aims to identify the effect of phytotherapeutics in combating antimicrobial resistance and its impacts on public health.

2. Material and Methods

This is a narrative literature review, conducted through articles collected in English, Portuguese and Spanish from the ScienceDirect, Google Scholar, PubMed and Springer-Verlag databases. The following terms were used as Health Sciences Descriptors (DeCs): Medicinal plants, bacterial resistance and health promotion combined with the Boolean operators “AND” and “OR”. As an inclusion criterion, the articles should address subjects related to the descriptors already mentioned. Duplicate materials and those that did not answer the research question were excluded.

3. Results and Discussion

3.1. Antibiotic resistance mechanism

Since the discovery of penicillin in 1928 by the English physician Alexander Fleming, bacterial resistance to antibiotics has been increasing, causing most antibiotics to lose their effectiveness in treating infectious diseases. This problem has attracted the attention of international organizations, such as the WHO, which has already expressed concern about the shortage of new antibiotics, reporting that bacterial resistance is reaching a critical and alarming state. Unfortunately, this gradual increase has resulted in the emergence of infectious diseases without adequate treatment, which can be considered a major cause of mortality, becoming a major concern for global public health (Chinemerem Nwobodo et al., 2022; Ugwu et al., 2020; Zhu et al., 2022).

The WHO has released a list of major antibiotic-resistant pathogens, divided into three levels. Critical priority pathogens include “Acinetobacter baumannii, Pseudomonas aeruginosa, and members of the Enterobacteriaceae family (Klebsiella, Escherichia coli, Serratia, and Proteus).” High-priority pathogens include bacteria of the species “Enterococcus faecium, Staphylococcus aureus, Helicobacter pylori, Campylobacter spp., Salmonella sp., and Neisseria gonorrhoeae,” and medium-priority pathogens are strains of “Streptococcus pneumoniae, Haemophilus influenzae, and Shigella spp.” (Khare et al., 2021; WHO, 2017).

Infectious diseases such as pneumonia, endocarditis, complicated skin and soft tissue infections, tuberculosis, blood infection or sepsis, gonorrhea, and foodborne diseases are gaining momentum and establishing themselves as a challenge for the clinical community, since most of the antibiotics used in the treatment of these diseases are no longer effective (Chinemerem Nwobodo et al., 2022; Donkor et al., 2019; Hassoun et al., 2017; Kinney, 2010).

Bacteria are unicellular prokaryotic organisms that possess enzymes that act in protein synthesis, cell wall formation, RNA synthesis, DNA replication, and production of essential metabolites. In recent years, these enzymes and the pathways in which they act have been investigated as possible targets of antibiotics to kill (bactericidal) and inhibit the growth (bacteriostatic) of these microorganisms (Verma et al., 2022). However, bacteria use their own mechanisms to resist the action of some antibiotics. According to the European Centre for Disease Prevention and Control (ECDC) and the Centers for Disease Control and Prevention (CDC), these pathogens can be classified according to their resistance profile to certain antibiotics, as multidrug-resistant (MDR), extensively resistant (XDR), or pan-resistant (PDR) (Magiorakos et al., 2012).

Different self-defense mechanisms present in these microorganisms against antimicrobials, antibiotics, and pesticides have been identified over the years. This self-defense machinery is simultaneously stimulated in pathogens, especially in those that already have intrinsic antibiotic resistance in their genetic material, thus ensuring their survival against potent drugs. Studies have revealed that antibiotic-producing organisms also have self-defense mechanisms (Khare et al., 2021; Mak et al., 2014;). Once exposed to unfavorable environments, these microorganisms tend to adapt physiologically to ensure their survival and, when subjected to stress conditions, they are more permeable to foreign DNA or stimulate rapid mutations. Therefore, these pathogens are considered highly adaptable beings, which easily modify themselves in response to the place in which they are found (Khare et al., 2021).

One of the most widely used resistance mechanisms by bacterial strains is horizontal gene transfer, where those that have already undergone genetic mutation produce generations of mutant bacteria that spread drug-resistant genes, as well as mobile genetic elements to other non-resistant bacteria in the surrounding area (Khare et al., 2021). Horizontal gene transfer mechanisms involve genetic transformation, transduction, conjugation, and transposition (Claverys et al., 2009; Dubnau and Blokesch, 2019); which consequently allows the rapid acquisition of new metabolic abilities and microbial phenotypes, allowing rapid adaptation (Hall et al., 2017; Saak et al., 2020; Wiedenbeck and Cohan, 2011).

Genes that act in the production of new virulence assets or new metabolic pathways to promote these adaptations are commonly found in mobile genetic elements. Depending on their mode of mobilization and structure, these elements can be called plasmids, phages and transposable elements, which move from one cell to another, exchanging DNA information in their genome or even within the host genome (Saak et al., 2020).

Bacteria also use another method to block the action of antibiotics, producing enzymes capable of modifying the active portions of the antibiotics or acting to destroy them (Fischbach and Walsh, 2009). Many of the enzymes involved in these processes, in both Gram-negative and Gram-positive pathogens, are already known (Wilson, 2014). Phosphorylation, adenylation and acetylation are the most frequently observed chemical modifications in antibiotics, in addition to the enzymes that are usually found in mobile genetic elements, better known as Aminoglycoside Modifying Enzymes (AMEs) and Chloramphenicol Acetyltransferase (CAT). These changes reduce treatment options and, in many cases, lead to an increase in the Minimum Inhibitory Concentration (MIC), which can be harmful to patients (Munita and Arias, 2016; Khare et al., 2021). Furthermore, enzymes belonging to the β-lactamase class have considerable potential to destroy the tested antibiotics, as they act by destroying the amide bond of the β-lactam ring, preventing their effectiveness (Tooke et al., 2019).

Furthermore, pathogenic bacteria have developed mechanisms that prevent antibiotics from entering the cell; a clear example of this is the reduced or differentially regulated expression of porins (Pagès et al., 2008). Resistant bacterial strains have efflux pumps that function by transporting antibiotic molecules out of the cell, minimizing the concentration inside it (Shriram et al., 2018). Modifying the target sites of antibiotics was another way that bacteria found to circumvent the activity of antimicrobials. Target modifications can include: 1) enzymatic modification of the binding sites on the targets; 2) replacement of the original targets; and 3) mutation in the target-coding genes (Munita and Arias, 2016).

3.2. Overview of plant-derived bioactive compounds

Since ancient times, medicinal plants have been used as part of traditional medicine for therapeutic purposes by people all over the world. Individuals responsible for handling herbal medicines were seen as front-line health care providers (Malami et al., 2020). Over the years, numerous plant species have been applied in traditional folk medicine for the treatment of infections of bacterial origin. The WHO has already registered more than 20,000 species of medicinal plants, highlighting them as potential sources of new medicines (Srinivasan et al., 2001; Yadav and Agarwala, 2011).

Phytotherapeutics have been standing out not only for their therapeutic action, but also for presenting biological activities such as antimicrobial, anti-inflammatory and antioxidant activities (Mehta et al., 2001). Since they have antimicrobial properties capable of inhibiting the growth of bacteria, fungi, viruses and protozoa, some compounds, when active, are capable of acting on intrinsic bacterial resistance (Shankar et al., 2010); although some are ineffective as antibiotics by themselves, they can interact with other antibiotics providing a synergistic effect, helping to combat these resistant microorganisms (Lewis and Ausubel, 2006; Ody, 2017; Ruddaraju et al., 2020).

These bioactive compounds are derived from the plant's secondary metabolism (Stefanović and Comic, 2012), and their composition and concentration in plants depend on biotic and abiotic factors conditioned by them, such as variations in light, temperature, soil composition and humidity of the country of origin (Arima et al., 2002; Assob et al., 2011; Merkl et al., 2010); in turn, these factors will also influence the antimicrobial activity of the compounds.

Secondary metabolites have great chemical diversity, with different structures, number and position of substituent groups, presence of glycosidic bonds and alkylation of OH groups (Arima et al., 2002). Approximately 30,000 antimicrobial compounds have been isolated from plants, and more than 1,340 plant species have been scientifically proven to have antimicrobial activity (Tajkarimi et al., 2010; Vaou et al., 2021). Several studies with satisfactory results have been carried out using these compounds, with the aim of investigating their action on pathogens and parasites (Archana and Geetha Bose, 2022; Kiselova et al., 2006).

The medicinal values ​​of these plants are highlighted by phytochemical groups such as flavonoids, alkaloids, terpenoids, tannins, phenolic compounds, steroids, resins and other metabolites. Natural flavonoids have antibacterial, anticancer, anti-inflammatory and antioxidant properties, in addition to having low toxicity (Serafini et al., 2010; Gutiérrez-Grijalva et al., 2017). Alkaloids are frequently used as medicines, have a wide range of compounds, and have only one basic nitrogen atom in common (Ziegler and Facchini, 2008).

Terpenes or isoprenoids are considered the most heterogeneous group of phytochemicals, responsible for participating in the primary structure of cells and assisting in the cellular functions of plants (Oldfield et al., 2012; Paduch et al., 2007). Phenolic compounds have varied mechanisms of action against different microbial strains; however, with regard to pathogenic bacteria, the literature reveals that their activity is generally weak and often nonspecific (Srivastava et al., 2014; Vaou et al., 2021). In addition to presenting antimicrobial activity, coumarins also have the ability to inhibit biofilm formation and the production of virulence factors in pathogenic microorganisms (Freitas Araújo et al., 2011; Reen et al., 2018; Smyth et al., 2009; Zhang et al., 2018).

Plant compounds have attracted considerable interest in the pharmaceutical production market, resulting in the production of almost a quarter of the drugs. Hence, the importance of research into the therapeutic use of these bioactive molecules against microorganisms, cancer, wounds, and numerous diseases (Guadie et al., 2020). Depending on the region, the concentration and composition of bioactive compounds in plants may vary. Cameroonian plants contain phytochemicals such as phenolics, alkaloids, flavonoids, triterpenes, and steroids with relevant antimicrobial activity (Dzotam and Kuete, 2017; Kuete, 2010).

3.3. Antimicrobial potential of herbal medicines

The practice of herbal medicine is quite common in traditional communities, where ancient civilizations in China, India, and Egypt reported the effects of medicinal plants involved in cults and religions. To this day, some cultures still maintain a strong tradition of using herbal medicines, such as the Khyang tribe in Bangladesh, which has used Vetiveria zizanioides and Curcuma longa to treat skin infections for 2,000 years (Hossan et al., 2018). Hydrastis canadensis and Scutellaria baicalensis Georgi are still widely used in the treatment of bacterial infections (Cech et al., 2012), and Garcinia mangostana may be indicated for the treatment of diarrhea, sprains, typhoid fever, ulcers, and skin infections (Wang et al., 2017).

Several studies have addressed the antimicrobial activity of plant extracts, essential oils and their isolated compounds, including with the aim of promoting improvements in the treatment of patients who are often terminally ill (Table 1). Different types of plant extracts can be used to combat bacteria commonly known for their high rates of resistance to usual antimicrobials. Extracts of C. longa, Zingiber officinale and Tinospora cordifolia showed bactericidal action against S. aureus, P. aeruginosa, K. pneumoniae, E. coli, Bacillus subtilis and Proteus mirabilis (Chakraborty et al., 2014).

Table 1
Antimicrobial effect of medicinal plants against certain microorganisms.

Medicinal plant	Antimicrobial action	Reference
C. longa, Zingiber officinale, Tinospora cordifolia	S. aureus, P. aeruginosa, K. pneumoniae, E. coli, B. subtilis, P. mirabilis	Chakraborty et al. (2014)
Oxalis corniculata, Artemisia vulgaris, Cinnamomum tamala, Ageratina adenofora	E. coli, Salmonella Typhi, K. pneumoniae, S. aureus, Citrobacter koseri	Manandhar et al. (2019)
Berberis vulgaris, Cistus monspeliensis, Punica granatum	S. aureus, Enterococcus faecalis, Enterobacter cloacae	Bereksi et al. (2018)
Myrtus communis, Verbena officinalis	S. aureus, S. Typhi, P. aeruginosa	Wangchuk et al. (2011)
Origanum minutiflorum	Campylobacter jejuni	Aslim and Yucel (2008), Sudjana et al. (2009)
Salvia reuterana, Rosmarinus officinalis	E. coli	Esmaeili et al. (2008), Gachkar et al. (2007), Tajkarimi et al. (2010)
R. officinalis	Listeria monocytogenes	Gachkar et al. (2007)
Daucus carota, Melaleuca alternifolia	H. pylori, Mycoplasma pneumoniae	Wangchuk et al. (2011)
Aminotiazol, berberina	A. baumannii	Gao et al. (2018).
Cornus mas	Pseudomonas luteola	Aurori et al. (2024)
Sorbus aucuparia	E. faecalis	Aurori et al. (2024)
Larrea tridentata, Origanum vulgare	S. aureus	Montemayor et al. (2023)
Biancaea sappan (L.), Bauhinia malabarica Roxb	S. aureus, Staphylococcus epidermidis	(Karuncharoenpanich et al., 2025)

For some methanolic extracts of Oxalis corniculata, Artemisia vulgaris, Cinnamomum tamala and Ageratina adenofora, antimicrobial properties were observed against important pathogens such as E. coli, S. Typhi, K. pneumoniae, S. aureus and Citrobacter koseri (Manandhar et al., 2019). Positive antibacterial effects were also observed with the use of hydromethanolic extracts of Berberis vulgaris, Cistus monspeliensis and Punica granatum to combat S. aureus, E. faecalis and E. cloacae (Bereksi et al., 2018).

Natural compounds can present a broad spectrum of action, specific mechanisms of action and selective toxicity (Figure 1). This can be exemplified with the bacterium E. coli, by the wide variety of antimicrobial effects observed using guarana extracts (Majhenič et al., 2007), chloroform extract of the plant Abrus precatorious (Zore et al., 2007) and sorghum extracts and their fractions (Kil et al., 2009). In addition to E. coli, other important pathogens, such as S. aureus, S. Typhi and P. aeruginosa, showed sensitivity to the presence of extracts of Myrtus communis and Verbena officinalis leaves, proving their antibacterial activities (Wangchuk et al., 2011).

Figure 1
Antibacterial and antifungal mechanisms of action of plant compounds. Source: Fik-Jaskółka et al. (2024).

Advances in this research have yielded promising findings, such as the case of C. jejuni, which was shown to be more sensitive to natural antimicrobials, such as the essential oil of Origanum minutiflorum (Aslim and Yucel, 2008; Sudjana et al., 2009). Other essential oils, such as those extracted from the leaves, stems and flowers of Salvia reuterana (Esmaeili et al., 2008) and Rosmarinus officinalis (Gachkar et al., 2007), have demonstrated a variety of antimicrobial effects against E. coli (Tajkarimi et al., 2010). R. officinalis oil has also demonstrated antibacterial effects against L. monocytogenes (Gachkar et al., 2007). Respectively, Daucus carota seed oil and Melaleuca alternifolia oil express antimicrobial activity against H. pylori and Mycoplasma pneumoniae (Wangchuk et al., 2011).

Some isolated natural compounds also demonstrate antibacterial potential, such as aminothiazole and berberine derivatives, to which the bacterium A. baumannii, commonly involved in hospital outbreaks and difficult to treat, has already shown itself to be sensitive (Gao et al., 2018). In studies carried out with Capparis spinosa, it was possible to observe that compounds such as spermidine, rutin, quercetin, tocopherol and carotenoids presented antimicrobial, antioxidant, anti-inflammatory and antiviral activities (Tlili et al., 2011).

Furthermore, studies have been carried out to investigate the synergistic effect between plants and antibiotics. This combination, in addition to causing an increase in antimicrobial activity, can modify and modulate bacterial resistance mechanisms. Studies show that the combination of Salvia spp. and Martiaria recutita with oxacillin significantly increases their efficacy (Chovanová et al., 2013; Vaou et al., 2021). Bioactive compounds isolated from mangosteen fruit, such as α-mangostin, when combined with β-lactams, have the potential to increase the efficacy of therapy against β-lactam-resistant bacteria (Phitaktim et al., 2016).

4. Final Considerations

In short, the spread of antibiotic-resistant pathogens in hospital settings, aquatic environments, and others has been a concern for researchers and health organizations worldwide. These resistant microorganisms cause several diseases and are responsible for high rates of mortality and morbidity worldwide. In addition, pathogenic microbes have developed survival mechanisms that reduce the effectiveness of antibiotics, thus reducing treatment options. The pharmaceutical industry has been searching for new, effective, sustainable, and natural treatment options for the manufacture of antimicrobials. Plant diversity allows the use of natural and phytotherapeutic resources that meet the expected requirements, as they present a wide variety of bioactive substances capable of eliminating and circumventing resistance mechanisms of pathogenic strains.

Data Availability Statement

Not applicable.

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Edited by

• Editor:
  Marcelo A.M. Esquisatto

Publication Dates

• Publication in this collection
  17 Nov 2025
• Date of issue
  2025

History

• Received
  04 Nov 2024
• Accepted
  22 May 2025