Search Results (329)

Quercetin is a plant-derived flavonol positioned at the interface of metabolic health and food preservation. This review integrates quercetin chemistry, plant biosynthesis and metabolism, production-relevant extraction and microbial synthesis, bioavailability, mechanisms of action, preclinical and clinical evidence in metabolic syndrome (MetS), and applications in clean-label food preservation. Experimental studies indicate that quercetin modulates obesity-associated inflammation, dyslipidemia, hepatic steatosis, insulin resistance, hypertension, endothelial dysfunction, and gut-barrier impairment through interconnected Nrf2/HO-1, NF-κB/NLRP3, AMPK/SIRT1, PI3K/Akt, eNOS/NO, lipid metabolism, and microbiota-related pathways. Human evidence is narrower and heterogeneous: modest reductions in systolic blood pressure constitute the most consistent signal, whereas effects on fasting glucose, lipids, inflammatory markers, endothelial function, liver fat, and body weight vary by population, formulation, dose, and duration. In food systems, quercetin has been investigated as an antioxidant, antimicrobial, antibiofilm agent, and photodynamic photosensitizer. It is incorporated into edible films, coatings, freshness indicators, and controlled-release packaging, although most evidence remains laboratory-scale. Key translational challenges include limited aqueous solubility, variable bioavailability, incomplete long-term safety evidence, matrix-dependent efficacy, sensory constraints, manufacturing scale-up, migration, and regulation. Overall, quercetin is promising, but clinical use and industrial deployment require formulation-specific, adequately powered human studies and validation in clinically relevant populations and under commercially realistic processing conditions. Full article

Streptococcus mutans is the primary etiological agent of dental caries due to its ability to form acidogenic biofilms on tooth surfaces. Natural monoterpenes have attracted considerable interest as potential antibiofilm agents for oral healthcare. The present study investigated the antibiofilm activity and possible mechanism of action of (+)-endo-borneol isolated from the essential oil of Achillea millefolium against S. mutans. The chemical composition of the essential oil was characterized by gas chromatography–mass spectrometry (GC–MS), and (+)-endo-borneol was isolated by chromatographic separation. Antibiofilm activity was evaluated using the crystal violet biofilm assay, while antimicrobial activity was determined by minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) assays. The influence of subinhibitory concentrations of (+)-endo-borneol on the expression of the biofilm-associated genes gtfB and yycF was assessed by quantitative real-time PCR. Molecular docking was performed to investigate ligand–protein interactions, using a ligand geometry pre-optimized by density functional theory (DFT, B3LYP/6-31G**). The essential oil inhibited S. mutans biofilm formation by up to 98%, whereas isolated (+)-endo-borneol reduced biofilm biomass by 97–98% at concentrations of 2–10 mg/mL. The MIC and MBC values of (+)-endo-borneol were 2.5 and 5.0 mg/mL, respectively. Gene expression analysis demonstrated that subinhibitory concentrations of (+)-endo-borneol modulated the transcription of gtfB and yycF, indicating activation of bacterial regulatory responses. Molecular docking revealed favorable binding of (+)-endo-borneol to biofilm-related protein targets. These findings demonstrate that (+)-endo-borneol is a promising natural antibiofilm compound with potential application in the development of novel preventive and therapeutic oral healthcare products targeting S. mutans biofilms. Full article

The escalating crisis of bacterial antimicrobial resistance necessitates the discovery of novel antibacterial agents with distinct mechanisms of action. Ursolic acid (UA), a naturally abundant pentacyclic triterpenoid, serves as a promising scaffold for structural modification. In this study, a series of 26 novel UA derivatives (A1–A7 and B1–B19) were designed and synthesized by introducing various substituents at the C-28 carboxyl group via a chloroacetyl chloride linker. Their antibacterial activities were evaluated against S. aureus, S. epidermidis, E. coli, and P. aeruginosa using the microbroth dilution method. Among them, compound B1 exhibited the most potent activity, with a minimum inhibitory concentration (MIC) of 37.5 μg/mL against S. aureus and 75 μg/mL against E. coli. Antibacterial kinetic and time-kill curve assays confirmed the sustained bactericidal effect of B1. Furthermore, B1 significantly inhibited biofilm formation in both S. aureus and E. coli in a time-dependent manner. Molecular docking studies revealed that B1 binds spontaneously to the S. aureus SarA protein through three hydrogen bonds and π-π stacking interactions, providing a structural basis for its antibacterial and anti-biofilm activities. This study demonstrates that piperazine-modified UA derivative B1 is a promising antibacterial candidate and offers a new strategy for the structural optimization of ursolic acid. Full article

Elizabethkingia species have emerged as important nosocomial pathogens associated with multidrug resistance and persistent infections. This study aimed to characterize clinical Elizabethkingia isolates from Northern Thailand regarding antimicrobial susceptibility, virulence-associated phenotypes, and biofilm formation, and to evaluate the antimicrobial and anti-biofilm activity of dialdehyde cellulose (DAC) film. A total of 49 clinical isolates were identified by MALDI-TOF mass spectrometry, with species identification confirmed by 16S rRNA gene sequencing. Antimicrobial susceptibility was determined against 12 agents. Virulence traits (protease, lipase, lecithinase, and hemolysin production) and biofilm formation were assessed using standard phenotypic assays. DAC films were evaluated against selected resistant isolates. Elizabethkingia anophelis predominated, and most isolates exhibited multidrug or extensive drug resistance, with high resistance to carbapenems and cephalosporins. Piperacillin–tazobactam, levofloxacin, and trimethoprim–sulfamethoxazole showed the greatest activity. All isolates demonstrated protease production and time-dependent hemolysis, while lipase and lecithinase activities were absent. Biofilm formation varied among isolates, while DAC films inhibited bacterial growth and prevented detectable biofilm formation in the tested isolates. No significant difference was observed between DAC and DAC supplemented with meropenem in inhibition zone diameters (p = 0.555). Clinical Elizabethkingia isolates demonstrated extensive antimicrobial resistance with conserved virulence traits and heterogeneous biofilm formation. DAC films demonstrated antimicrobial activity and prevented detectable biofilm formation under the experimental conditions. Further studies are warranted to evaluate their mechanism of action and potential applications. Full article

Candida spp. can cause systemic infections with high mortality in immunocompromised patients. Phytotherapy may be an alternative for adjunctive treatment of fungal infections. This study evaluated the phytochemical profile, cytotoxicity, genotoxicity, and antibiofilm activity of the hydroalcoholic extract of Origanum vulgare L. against Candida albicans, Candida tropicalis, and Candida dubliniensis. The extraction and quantification (flavonoids and phenols) were performed, and its antioxidant activity (DPPH) and the presence of bio-active compounds were investigated using high-performance liquid chromatography with Diode Array Detection (HPLC-DAD). Cytotoxicity and genotoxicity tests were conducted using HaCat cell lines. Antifungal activity on planktonic cultures was evaluated using the standard (CLSI M27-S4). The analysis of the extract on biofilms was verified with different exposure times. The extract demonstrated the presence of bioactive molecules, and antioxidant activity. The cytotoxicity test showed viability >70%. Genotoxicity revealed the presence of a few micronuclei in some dilutions. The Minimum Fungicidal Concentration was obtained for C. albicans and C. tropicalis. In the biofilm analysis, there was a reduction of more than 60% in all Candida spp. species at the 24 h exposure time. The findings suggest that the O. vulgare extract exhibits activity against Candida spp. and shows biocompatibility in human keratinocytes. Full article

One of the most pressing challenges facing healthcare today is the rise of biofilm infections and antibiotic-resistant bacteria, which demand entirely new therapeutic strategies beyond conventional antibiotic reliance. A biofilm is a structured community of microorganisms encased in a self-produced extracellular polymeric substance (EPS) matrix, which confers resistance to host immune defenses and antimicrobial agents. Accumulating evidence demonstrates that plant-derived secondary metabolites—including flavonoids, phenolic acids, tannins, terpenoids, and alkaloids—exert potent antibacterial and antibiofilm activities through diverse mechanisms of action. These natural compounds inhibit biofilm formation by disrupting bacterial adhesion, suppressing quorum sensing, degrading the EPS matrix, and impairing bacterial motility. Beyond independent bioactivity, phytochemicals demonstrate significant synergistic potential when combined with conventional antibiotics, revitalizing antimicrobial efficacy against drug-resistant pathogens. Nanoformulation and biogenic carrier technologies further enhance the bioavailability and therapeutic potency of these compounds. Despite these advances, critical challenges persist, including poor bioavailability, physicochemical instability, dose-dependent toxicity, and the risk of resistance development. This review presents a critical and integrative analysis of the pharmacological mechanisms of plant secondary metabolites, with particular emphasis on their role in combating biofilm-associated infections and antibiotic resistance, and discusses translational opportunities including structure–activity relationship (SAR)-guided optimization, high-throughput screening platforms, and advanced drug delivery systems. Collectively, plant secondary metabolites represent a scientifically compelling and clinically relevant pipeline for the development of next-generation antimicrobial and antibiofilm therapeutics. Full article

This review examines the bioactive compounds of ginger (Zingiber officinale Roscoe), with a particular focus on metabolites and antimicrobial peptides exhibiting antimicrobial activity. The chemical composition, biological properties, and mechanisms of action of the major ginger-derived compounds are discussed, with emphasis on their antibacterial, antifungal, anti-inflammatory, and antibiofilm potential. Particular attention is given to their antimicrobial spectrum and to potential synergistic interactions with other natural bioactive compounds that may enhance their efficacy against pathogenic microorganisms. Despite their promising therapeutic properties, the application of ginger-derived molecules against skin-associated pathogens remains challenging due to their limited stability, poor bioavailability, and the protective effects of microbial biofilms, which reduce treatment effectiveness and contribute to persistent infections. Current strategies designed to overcome these limitations, including chemical modification, liposomes, nanoemulsions, and hydrogel-based delivery systems, are reviewed. In addition, this review highlights the potential of microalgae-based encapsulation systems as innovative and sustainable platforms for the delivery of ginger bioactives. Owing to their diverse biochemical composition and structural characteristics, microalgae represent a promising source of natural biomaterials for the development of diverse encapsulation strategies. These emerging systems may potentially improve the stability, controlled release, bioavailability, and antibiofilm efficacy of ginger-derived compounds, supporting the development of novel formulations for the management of biofilm-associated skin infections. Full article

Biofilms are structured communities of microorganisms embedded in a self-produced extracellular polymeric substance (EPS) matrix, whose development significantly enhances microbial resistance to antibiotics, disinfectants, and host immune defenses, posing major challenges in clinical, industrial, and environmental settings. Compared with planktonic cells, biofilm-associated microorganisms can exhibit up to 10- to 1000-fold increased tolerance to antimicrobial agents, contributing to the persistence of biofilm-associated infections (BAIs). These infections remain difficult to eradicate due to reduced penetration, altered metabolic states, and the presence of dormant or persister cells. Anti-biofilm strategies can be broadly classified into physical approaches (e.g., ultrasound, mechanical stress, and light-based approaches) that target biofilm structure; chemical and enzymatic methods (e.g., EPS-degrading enzymes) that destabilize the matrix; and biological and molecular strategies (e.g., quorum-sensing (QS) inhibitors, anti-virulence agents, bacteriophages, phage-derived antimicrobial molecules, antimicrobial peptides, and natural bioactive compounds) that modulate biofilm development and integrity by targeting regulatory pathways and matrix stability through distinct mechanisms of action. Natural compounds, including lactoferrin, lactoferrin-derived peptides, and probiotic and postbiotic fractions of lactic acid bacteria (LAB), as well as plant-derived metabolites, have shown promising anti-biofilm effects, with efficacy often enhanced through complementary or potentially synergistic interactions. However, despite these advancements, clinical translation remains limited. For example, BAIs account for approximately 80% of chronic infections, with high recurrence rates and therapeutic failure reported in device-associated infections and chronic wounds. These limitations highlight the need for clinically translatable, multimodal approaches that integrate structural biofilm disruption, antimicrobial targeting, and host response modulation to design more effective and sustainable anti-biofilm strategies. Full article

Bacterial biofilms pose a major public health challenge by increasing the antimicrobial tolerance in pathogenic bacteria, thereby limiting the effect of medication-based treatment and promoting the development of antimicrobial resistance. Hence, there is a need to discover new molecules with the ability to prevent biofilm formation. We screened seven synthetic analogues of the breitfussin family of natural products for antimicrobial and antibiofilm activity using a broth microdilution and crystal violet method, respectively. Two compounds inhibited the growth of Gram-positive bacteria in their planktonic state at concentrations of 50 µM, of which one compound (2) demonstrated the ability to inhibit the biofilm formation of Staphylococcus epidermidis at sub-growth-inhibitory, low micromolar concentrations. Compound 2 did not inhibit biofilm growth in Staphylococcus aureus or Listeria monocytogenes, or the ability to eradicate pre-established biofilms. Initial Mode of Action (MoA) studies with compound 2 against S. epidermidis showed a modest impact on the cell surface hydrophobicity and early-stage adhesion to polystyrene. These findings highlight the breitfussin framework as a promising scaffold for the development of new antimicrobial and antibiofilm agents. Full article

Biofilm formation constitutes a major factor in antibiotic treatment failure, shielding bacteria from drugs and promoting persistence. This study demonstrates that the anti-biofilm action of clove oil enhances the efficacy of fosfomycin against Escherichia coli O157:H7 (E. coli O157). Using a luxS-eGFP reporter system, it was found that clove oil inhibited E. coli O157 biofilm formation by up to 80% via suppression of the LuxS/AI-2 quorum sensing (QS) system and bacterial motility. Crucially, this disruption was shown to correlate with a strong synergistic effect when combined with fosfomycin in vitro. In a murine peritoneal infection model, the combination therapy demonstrated superior efficacy compared to monotherapy. Specifically, bacterial loads in the liver, spleen, and small intestine were significantly reduced, and histopathological damage was alleviated. Mechanistically, these effects were linked to the downregulation of the QS. These findings indicate that clove oil acts as a potent adjuvant to fosfomycin by disrupting biofilms, offering a promising strategy against systemic infections caused by E. coli O157. Full article

Baicalin, a natural plant-derived compound, holds promise in addressing clinical bacterial resistance when combined with antibiotics. This study evaluated the antibacterial activity of the combination of baicalin and cefotaxime and explored its mechanism of action on the cell wall and biofilm of multidrug-resistant Pseudomonas aeruginosa (MRPA). The results showed that the combination of baicalin and cefotaxime exerted a synergistic inhibitory effect on the growth of MRPA, with a fractional inhibitory concentration index (FICI) of 0.28. Mechanistically, compared with cefotaxime alone, the combination of baicalin and cefotaxime enhanced the permeability of the cell membrane and cell wall of MRPA, thereby increasing cell damage. It also exhibited stronger antibiofilm activity by inhibiting numerous virulence factors (pyocyanin, elastase, lectin), reducing cellular metabolic activity, and downregulating the expression of biofilm genes (pslA, pelA, algD) and quorum-sensing genes (lasl, lasR, rhll, rhlR, pqsA, pqsR). The molecular docking results revealed that baicalin could stably bind to wbpE, LasR, and RhlR. Therefore, this interaction may indirectly influence the processes related to antibiotic resistance and biofilm formation in bacterial cells. Metabolomic analysis revealed that the combination of baicalin and cefotaxime upregulated 863 metabolites and downregulated 587 metabolites. These metabolites mainly included amino acids, lipids, nucleotides, carbohydrates, and secondary metabolites. The combination primarily enriched key pathways such as amino acid metabolism, lipid metabolism (sphingolipid metabolism) and secondary metabolite biosynthesis. Through these pathways, it triggers significant metabolic reprogramming, thereby interfering with the supply of cell wall synthesis precursors, membrane structural stability, and the generation of biomembrane matrix. Ultimately, it synergistically enhances the effects of cell wall damage and biomembrane inhibition. In conclusion, this study confirms that the combination of baicalin and cefotaxime exerts significant synergistic antibacterial activity against MRPA. It also reveals the mechanism of action of the combination on the cell wall and biofilm of MRPA at the metabolic level, providing theoretical support for the development of novel strategies to combat MRPA. Full article

Oral biofilms are complex polymicrobial communities involved in the development of dental caries and periodontal diseases. Chemical antiseptics are commonly used as adjuncts to mechanical plaque control; however, their antimicrobial efficacy varies depending on composition and mechanism of action. The aim of this study was to comparatively evaluate the antimicrobial and antibiofilm activities of four commercially available dental products (Corsodyl, Ozosan, HybenX, and Elugel) against a broad spectrum of oral microorganisms. This in vitro study included Gram-positive and Gram-negative bacterial strains, comprising both reference strains and clinical isolates, as well as Candida albicans. Antimicrobial activity was assessed using the disc diffusion assay, while antibiofilm activity was evaluated using a crystal violet microplate assay. All experiments were performed in triplicate. Statistical analysis was conducted using two-way ANOVA followed by Tukey’s post hoc test (p < 0.05). All tested products exhibited antimicrobial activity. Inhibition zones ranged from 9 to 56 mm for Gram-positive bacteria, 12 to 38 mm for Gram-negative bacteria, and 13 to 43 mm for Candida albicans. Two-way ANOVA revealed a significant effect of the dental product (p < 0.001), while incubation time was not significant (p > 0.05). HybenX showed the highest antimicrobial efficacy, while chlorhexidine-based products demonstrated consistent activity. Antibiofilm inhibition exceeded 80% for several strains. Dental antiseptics exhibit significantly different antimicrobial and antibiofilm profiles, highlighting the importance of appropriate product selection in oral biofilm control. Full article

Background/Objectives: Oral diseases remain among the most prevalent noncommunicable conditions worldwide, with biofilm-driven dysbiosis playing a central role in dental caries, gingivitis, periodontitis, and oral candidiasis. Curcumin has attracted considerable interest because of its anti-inflammatory, antioxidant, antimicrobial, and regenerative properties. However, its clinical use remains limited by poor water solubility, chemical instability, rapid metabolism, and low bioavailability. This review aimed to provide a comprehensive analysis of curcumin-based nanoformulations for oral health applications, with emphasis on their mechanistic actions, antibiofilm activity, and translational relevance. Methods: This review examined representative nanocarrier systems developed for curcumin delivery in oral health. These included polymeric nanoparticles, nanomicelles and nanoemulsions, solid lipid nanoparticles and nanostructured lipid carriers, nanogels, hydrogels, mucoadhesive films, and metallic or hybrid nanosystems. The analysis focused on molecular mechanisms of action, antimicrobial and antibiofilm effects against major oral pathogens, and key translational challenges. Results/Findings: Across the reviewed studies, nanoformulations consistently improved curcumin solubility, stability, tissue penetration, mucosal retention, and controlled release. Mechanistically, they enhanced anti-inflammatory activity through inhibition of nuclear factor kappa B (NF-κB), strengthened antioxidant defenses via the nuclear factor erythroid 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) axis, supported tissue repair and osteogenic responses, disrupted oral biofilms, and modulated local immune responses. Antimicrobial activity was reported against Streptococcus mutans, Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, and Candida albicans, with reduced exopolysaccharide production, impaired adhesion, and improved biofilm penetration. Conclusions: Curcumin-based nanoformulations represent promising adjunctive platforms for oral healthcare. However, their clinical translation still requires improved stability in the oral-environment standardized manufacturing and characterization, rigorous safety evaluation, and well-designed controlled clinical studies. Full article

Biofilm formation is a complex phenomenon employed by microbes to counteract antimicrobials. Biofilm-associated infections are a challenging threat to modern medicine. Antimicrobial peptides (AMPs) are recognized as some of the most promising therapeutics to tackle biofilm-producing and multidrug-resistant (MDR) pathogens. However, stability, toxicity, and potency are key issues in the case of naturally occurring AMPs. Next-generation antibiofilm tools, such as synthetic or engineered AMPs, have emerged as a potent therapeutic choice. Synthetic peptides offer structural simplicity, versatility for chemical modification, and increased stability, which makes them capable of effectively disrupting both the biofilm matrix and the bacterial membrane. For engineered peptides, rational sequence modification, hybridization, and computational design are used to overcome limitations related to selectivity, biofilm-specific targeting and regulatory pathway modulation. This review provides a critical evaluation of synthetic and engineered AMPs from various perspectives, such as design strategies, antibiofilm action mechanisms, therapeutic performance, and translational potential. This study sheds light on current advances and emerging technologies, including AI-guided peptide optimization and multifunctional peptide platforms, and thereby sets the stage for the rational development of peptide-based therapeutics aimed at overcoming biofilm-mediated antimicrobial resistance (AMR). Full article

Background: The escalating spread of drug-resistant bacteria is intensifying the antibiotic resistance crisis, necessitating the urgent development of novel antimicrobial agents to address the resulting high global mortality rates and significant socioeconomic burden. Objectives: This study aimed to aminate the C-6 position of β-carboline and investigate the antibacterial activity and mechanism of action of the derivatives. Results: For the first time, 16 derivatives with various nitrogen-containing moieties, including aliphatic- and phenyl-amino, imidazolium, pyridinium, and quinolinium, were synthesized via amination at the C-6 position of β-carboline. These compounds exhibited moderate to good activity against Gram-positive methicillin-resistant Staphylococcus aureus (MRSA) and Bacillus subtilis, with minimum inhibitory concentration (MIC) values ranging from 1.56 to 100 μg/mL. The study reveals that elongating an alkyl chain, incorporating a cationic scaffold, and expanding a π-delocalized system can enhance antibacterial activity. The most potent derivative from each series was selected for further mechanistic investigation against MRSA. All studied compounds demonstrated low hemolytic activity and low cytotoxicity. Studies on the antibacterial mechanism indicated that the compounds exert their antibacterial effects by disrupting bacterial cell walls and membranes. Additionally, two of the compounds were found to potentially disrupt the secondary structure of DNA. All tested compounds exhibited antibiofilm activity. Conclusions: Our findings demonstrate that amination modification at the C-6 position of β-carboline can enhance antibacterial activity by disrupting the cell wall membranes and interacting with bacterial DNA. These results provide a basis for further optimization of antibacterial agents based on β-carboline. Full article