Search Results (93)

Antimicrobial resistance is a critical global health challenge, driven by the rapid emergence of multidrug-resistant bacterial pathogens and exacerbated by extensive antibiotic use, which imposes intense selective pressure and disrupts host-associated microbial communities. In this context, quorum sensing (QS), a conserved molecular communication system that coordinates population-level gene regulation, virulence expression, and biofilm development, has emerged as an attractive target for anti-virulence intervention. A growing body of evidence indicates that phytochemicals, such as curcumin, carvacrol, carnosol, eugenol, and chlorogenic acid, can modulate key QS pathways, including acyl-homoserine lactone-, autoinducing peptide-, and LuxS/AI-2-mediated signaling, thereby attenuating pathogenic behaviors at sub-inhibitory concentrations that do not directly impair bacterial viability. Despite this promise, the translational development of phytochemical-based QS inhibitors remains limited. Because QS also regulates cooperative and homeostatic functions in beneficial bacteria, QS-targeted interventions raise concerns about microbiome disruption and ecological imbalance. Furthermore, the literature is marked by substantial methodological heterogeneity, reliance on indirect phenotypic endpoints, limited molecular target validation, and insufficient assessment of toxicity, bioavailability, and pharmacokinetics. The predominance of simplified in vitro models further constrains extrapolation to complex host-associated and polymicrobial environments. This review critically examines the molecular mechanisms underlying phytochemical modulation of bacterial QS, synthesizes pathogen-focused experimental evidence, and evaluates key translational challenges arising from QS conservation, microbiome considerations, and methodological limitations. Addressing these barriers through mechanism-resolved experimentation, standardized evaluation frameworks, and microbiome-aware testing strategies will be essential for advancing phytochemical QS inhibitors toward clinically and industrially relevant anti-virulence applications. Full article

Due to the content of carnosic acid (CA), carnosol (C), and rosmarinic acid (RA), sage (Salvia officinalis L.) has antioxidant, anti-inflammatory, anticancer, antidiabetic, neuroprotective, antiaging, antimicrobial, and antiviral properties. However, current standardization and quality assessment procedures do not specify the content of these key substances in dried sage. The aim of this study was to analyze polyphenolic components, including CA, C, and RA, as well as basic nutrients, such as protein, fat, carbohydrates, and ash content in dried Salvia officinalis. Thirteen products available for sale in Poland were analyzed. HPLC studies have shown a very large variation in terms of CA, C, and RA (CA: 1.25–32.42 mg/g, C: 0–9.06 mg/g, and RA: 3.2–20.6 mg/g). Similarly, significant differences between samples were observed for the proximate composition. An appropriate system of standardization of herbs and spices could ensure the repeatability of the concentration of key, non-volatile active substances, which in adequate doses may have a beneficial effect on certain body functions, as well as on the shelf life and sensory characteristics of food. Full article

The aim of this study was to compare the effectiveness of edible oil (as an extractant) for the extraction of CA (carnosic acid), C (carnosol), and RA (rosmarinic acid) from sage with popular solvents (methanol, ethanol, 70% methanol, 70% ethanol, and water), as well as to assess the stability and fit the kinetic reaction model to the course of CA and RA degradation in oil macerate and various extracts. The degradation rate constant and half-life of CA and RA were also estimated and compared. CA was most efficiently extracted from sage using ethanol and methanol (9.3–10.1 mg/g of sage), followed by oil (7.10 mg/g). For C and RA, the most suitable solvents were 70% ethanol and 70% methanol (C: 3.08–4.01 mg/g; RA: 19.16–20.24 mg/g). CA was most stable in oil, followed by ethanol > methanol > 70% ethanol > 70% methanol. CA degradation followed a first-order kinetic model. RA was very stable in all extracts, except water, where the kinetics of RA degradation most closely followed a second-order model. Although oil extracts smaller amounts of phytochemicals from sage than solvents, CA in oil was the most stable, and the maceration of sage in oil is safe and consistent with the concept of sustainable development. Full article

Cancer remains a major global health challenge, emphasizing the need for new and effective therapies. This study investigates the anticancer potential of bioactive compounds from rosemary (Rosmarinus officinalis) using an integrative network pharmacology and computational approach. Twelve phytochemicals with favorable pharmacological profiles, optimal pharmacokinetics, and acceptable toxicological properties were evaluated, revealing 178 putative cancer-related targets. Protein–protein interaction (PPI) analysis highlighted ten key genes—EGFR, ESR1, HIF1A, HSP90AA1, MAPK1, BCL2, STAT3, TP53, CASP3, and SRC—implicated in the progression of various cancers, including breast, colorectal, liver, and lung tumors. Functional enrichment analysis demonstrated their involvement in multiple cancer-associated pathways. Among these, HSP90AA1 emerged as a critical target. Molecular docking revealed Rosmanol, Chlorogenic acid, and Carnosol as the most promising HSP90AA1 binders with strong predicted affinities. ADMET profiling confirmed their excellent drug-likeness and safety profiles, while molecular dynamics simulations validated the stability of the compound–protein complexes, further supporting their potential as HSP90 inhibitors. These findings suggest that rosemary-derived compounds may represent valuable candidates for anticancer drug development, though experimental validation is required to confirm their therapeutic efficacy. Full article

Perovskia atriplicifolia Benth., a perennial aromatic plant widespread in Iran’s Sistan and Baluchestan region, is known for its essential oil composition, rich in aromatic and non-aromatic sesquiterpenes. To the best of our knowledge, limited information exists on the composition of its non-volatile extracts. Herein, the phytochemical investigation of the EtOH extract of P. atriplicifolia aerial parts was performed, guided by an analytical approach based on LC-(-)ESI/QExactive/MS/MS. This led to the identification of phenolics, flavonoids, diterpenes (mainly carnosic acid derivatives), and triterpenes. Structural elucidation was performed via NMR and HRMSMS analysis. Furthermore, considering the occurrence of diterpenes closely related to carnosic acid and carnosol, known for their antioxidant properties, the antioxidant activity of the extract (0.5–5.0 μg/mL) and selected pure compounds (0.5–25 μM; compounds 5, 7, 9, 10, 12, 16) was evaluated in Caco-2 intestinal cells, showing significant reduction in free radical levels. The quantitative results highlighted that the above cited compounds occurred in concentrations ranging from 1.73 to 520.21 mg/100 g aerial parts, with carnosol (12) exhibiting the highest concentration (520.21 mg/100 g aerial parts), followed by 1α-hydroxydemethylsalvicanol (9) (91.73 mg/100 g aerial parts) and carnosic acid (16) (88.16 mg/100 g aerial parts). Full article

This study aimed to quantitatively and qualitatively evaluate the content of carnosic acid (CA), 12-O-methyl-carnosic acid (12MCA), carnosol (CS), rosmanol (RO) and 7-O-methyl-epi-rosmanol (7MER) in 61 Lamiaceae plants growing in Greece, using ¹H-qNMR spectroscopy as a simple, rapid and direct method without sample deterioration. For this purpose, methanol extracts from 18 genera (e.g., Salvia, Mentha, Melissa, Ocimum) were analyzed using isolated and fully characterized metabolites, previously identified by our group, as standards. At least one of the target compounds was detected in 22 species, predominantly belonging to the genus Salvia. Notably, 7MER and RO were not detected in any extract. CA, CS and 12MCA were exclusively found in Salvia species, with S. somalensis, S. officinalis and S. fruticosa emerging as the richest sources of these diterpenes. Among them, S. somalensis showed the highest concentration of CA (>30 mg/g), while 12MCA was most abundant in S. microphylla. These results highlight Salvia as the most promising genus for the accumulation of bioactive abietane-type diterpenes. The implementation of ¹H-qNMR for such chemical profiling provides a reliable approach toward the phytochemical standardization of plant extracts, supporting their further use in nutraceutical or pharmaceutical formulations. Full article

Sterile alpha and Toll/interleukin receptor motif-containing protein 1 (SARM1) is a nicotinamide adenine dinucleotide (NAD⁺) hydrolase involved in axonal degeneration and neuronal cell death. SARM1 plays a pivotal role in triggering the neurodegenerative processes that underlie peripheral neuropathies, traumatic brain injury, and neurodegenerative diseases. Importantly, SARM1 knockdown or knockout prevents the degeneration; as a result, SARM1 has been attracting attention as a potent therapeutic target. In recent years, the development of several SARM1 inhibitors derived from synthetic chemical compounds has been reported; however, no dietary ingredients with SARM1 inhibitory activity have been identified. Therefore, we here focused on dietary ingredients and found that carnosol, an antioxidant contained in rosemary, inhibits the NAD⁺-cleavage activity of SARM1. Purified carnosol inhibited the enzymatic activity of SARM1 and suppressed neurite degeneration and cell death induced by the anti-cancer medicine vincristine (VCR). Carnosol also inhibited VCR-induced hyperalgesia symptoms, suppressed the loss of intra-epidermal nerve fibers in vivo, and reduced the blood fluid level of phosphorylated neurofilament-H caused by an axonal degeneration event. These results indicate that carnosol has a neuroprotective effect via SARM1 inhibition in addition to its previously known antioxidant effect via NF-E2-related factor 2 and thus suppresses neurotoxin-induced peripheral neuropathy. Full article

Ferruginol, tanshinones and carnosol are considered privileged natural products due to their demonstrated diverse biological activities with relevance to cancer research. Globally, cancer continues to be a major contributor to mortality rates, making these compounds potentially valuable molecular scaffolds for further development as potential anticancer agents. In this work, a focused library of ferruginol, tanshinone IIA, and carnosol analogues was studied to examine their effectiveness against various solid tumor models. The compounds were efficiently synthesized from either methyl 12-hydroxy-dehydroabietate or 12-hydroxydehydroabietylamine in 1–3 step processes with good chemical yields. The compounds that were synthesized underwent a methodical evaluation using multiple biological tests (including viability assays, clonogenic assays, and mitochondrial membrane polarization measurements) to determine their ability to inhibit in vitro the growth of three breast cancer cell linages. It was determined that while most compounds exhibited biological activity, compounds 10 and 11 demonstrated significant efficacy against triple negative breast cancer cells. These compounds continue to show promising biological activity, suggesting that additional studies to understand their mechanisms of action would be valuable. Full article

Prostate cancer is one of the most prevalent cancer types diagnosed in older men. Investigations into traditional medicines like Rosmarinus officinalis L., popularly known as rosemary, are a current research interest due to its anti-cancer properties. This study investigates the cytotoxicity of aqueous and ethanolic rosemary leaf extracts in DU-145 cells and the interaction of its active metabolites with key prostate cancer targets using an in silico approach. The water extract of rosemary leaves showed greater cytotoxicity than the ethanol extract, with IC₅₀ values of 1.4140 ± 0.1138 mg/mL and 1.8666 ± 0.0367 mg/mL, respectively; the highest cytotoxic effects for both extracts were observed at 5 mg/mL. These findings indicate significant cytotoxic differences based on concentration and solvent. Network pharmacology identified 37 genes linked to prostate adenocarcinoma, highlighting key genes like EGFR, TP53, ERBB2, IGFBP3, MMP-2, MMP-9, HDAC6, PDGFRB, and FGFR1. Molecular dynamics simulations and binding energy calculations revealed strong interactions between carnosol and rosmarinic acid with these targets, with TP53–carnosol showing the most stable conformation. Rosmarinic acid was identified as a promising candidate due to its low toxicity. This study demonstrates the potential anti-prostate cancer properties of rosemary leaf extracts for further investigations on the development of drugs against prostate cancer. Full article

Rosmarinic acid (RA) is a bioactive phenolic compound prevalent in various medicinal plants, renowned for its significant pharmacological properties. This study aims to optimise the extraction conditions of this compound from Rosmarinus officinalis L. using the response surface methodology (RSM) with a three-variable, three-level Box–Behnken design. Optimising the parameters for supercritical CO₂ (scCO₂) extraction focused on pressure (150 to 350 bar), temperature (40 to 80 °C), and co-solvent weight percentage (5 to 15% ethanol), evaluating their impact on overall yield and RA content. The optimal conditions determined were a pressure of 150 bar, a temperature of 80 °C, and 15% ethanol, yielding a total extract of 21.86 ± 1.55%, with an RA content of 3.43 ± 0.13 mg/g dry matter (DM). Scanning electron microscopy revealed that the scCO₂ treatment induced microcracks on the surface of the rosemary powder, enhancing the fluid’s ability to penetrate the plant matrix. By employing the combined scCO₂-Soxhlet method, the RA content increased to 5.78 mg/g DM. Furthermore, the final extract obtained using the Soxhlet post-scCO₂ treatment contained only trace amounts of carnosic acid (0.38 ± 0.10 mg/g DM) and carnosol (0.38 ± 0.20 mg/g DM), compared to the crude extract obtained solely with Soxhlet, which exhibited significantly higher concentrations of 8.45 ± 2.98 mg/g DM of carnosol and 16.67 ± 0.94 mg/g DM of carnosic acid. This work highlighted an innovative extraction strategy based on the coupling of scCO₂ and Soxhlet, which significantly increased RA content while reducing concentrations of other compounds such as CA and CAR. This approach makes it possible to produce RA-enriched extracts, offering considerable potential for future large-scale applications and commercialisation. Full article

Background/Objectives: The present study focused on the formulation and evaluation of novel topical systems containing Salvia officinalis (sage), emphasizing their antioxidant and anti-inflammatory properties. Sage, rich in carnosol, offers considerable therapeutic potential, yet its low water solubility limits its effectiveness in traditional formulations. The aim of our experimental work was to improve the solubility and thus bioavailability of the active ingredient by developing self-nano/microemulsifying drug delivery systems (SN/MEDDSs) with the help of Labrasol and Labrafil M as the nonionic surfactants, Transcutol HP as the co-surfactant, and isopropyl myristate as the oily phase. Methods: The formulations were characterized for droplet size, zeta potential, polydispersity index (PDI), encapsulation efficacy, and stability. The composition exhibiting the most favorable characteristics, with particle sizes falling within the nanoscale range, was incorporated into a cream and a gel, which were compared for their textural properties, carnosol penetration, biocompatibility and efficacy. Results: Release studies conducted using Franz diffusion cells demonstrated that the SNEDDS-based cream achieved up to 80% carnosol release, outperforming gels. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) test and enzyme-linked immunosorbent assays (ELISA) showed strong efficacy, with an in vivo carrageenan-induced rat paw edema model revealing that the SNEDDS-based cream significantly reduced inflammation. Conclusions: These findings highlight the potential of SNEDDS-enhanced topical formulations in improving therapeutic outcomes. Further research is warranted to confirm their long-term safety and efficacy. Full article

Bacterial quorum sensing (QS) is a critical communication process that regulates gene expression in response to population density, influencing activities such as biofilm formation, virulence, and antibiotic resistance. This study investigates the inhibitory effects of five phytochemicals—apigenin, carnosol, chlorogenic acid, quercetin, and rosmarinic acid—on the S-ribosylhomocysteinase (LuxS) enzyme, a key player in AI-2 signaling across both Gram-positive and Gram-negative bacteria. Using molecular docking studies, we identified that these phytochemicals interact with the LuxS enzyme, with apigenin, carnosol, chlorogenic acid, and rosmarinic acid binding within the substrate-binding pocket and exhibiting binding scores below −7.0 kcal/mol. Subsequent in vitro assays demonstrated that these compounds inhibited AI-2 signaling and biofilm formation in Escherichia coli MG1655 in a concentration-dependent manner. Notably, carnosol and chlorogenic acid showed the most potent effects, with IC₅₀ values of approximately 60 μM. These findings suggest that these phytochemicals may serve as potential QS inhibitors, providing a foundation for developing new anti-pathogenic agents to combat bacterial infections without promoting antibiotic resistance. Further studies are warranted to explore the therapeutic applications of these compounds in both clinical and agricultural settings. Full article

The objective of this study was the optimization of the extraction process and the qualitative and quantitative determination of the bioactive metabolites: 12-O-methylcarnosic acid (12MCA), carnosic acid (CA), carnosol (CS), 7-O-methyl-epi-rosmanol (7MER) and rosmanol (RO) in infusions, decoctions, turbulent flow extracts, tinctures and oleolites from three Salvia species: Salvia officinalis L. (common sage, SO), Salvia fruticosa Mill. (Greek sage, SF) and Salvia rosmarinus Spenn (syn Rosmarinus officinalis L.) (rosemary, SR), using Quantitative Proton Nuclear Magnetic Resonance Spectroscopy (¹H-qNMR). Regarding the aqueous extracts, decoctions appeared to be richer sources of the studied metabolites than infusions among the three plants. For SR, the turbulent flow extraction under heating was the most efficient one. The optimum time for the preparation of decoctions was found to be 5 min for SF and SO and 15 min for SR. It is noteworthy that SR tinctures were not stable in time due to decomposition of the abietane-type diterpenes CA and CS because of the polar solvent used for their preparation. Contrary to this finding, the oleolites of SR appeared to be very stable. Olive oil as a solvent for extraction was very protective for the contained abietane-type diterpenes. A preliminary stability study on the effect of the storage time of the SF on the abietane-type diterpenes content showed that the total quantity of abietanes decreased by 16.51% and 40.79% after 12 and 36 months, respectively. The results of this investigation also demonstrated that ¹H-qNMR is very useful for the analysis of sensitive metabolites, like abietane-type diterpenes, that can be influenced by solvents used in chromatographic analysis. Full article

The influence of incorporation of post-distillation solid wastes of the aromatic plants (SWAP), oregano, rosemary, lemon balm, and spearmint into wheat breads at 1% and 2% levels on their physicochemical and sensorial properties, and antioxidant and volatile profiles were investigated. SWAP breads had darker crumbs and crust and greener crumbs compared to the control, but rather similar loaf specific volume and textural attributes (crust puncture test and crumb Texture Profile Analysis). Although the mold growth on bread crumb surface was not inhibited by SWAP presence, LC-DAD-MS revealed a large increase in terpenoids, like carnosic acid (all SWAP), carnosol (rosemary) and carvacrol (oregano), phenolic (rosmarinic and salvianolic) acids and flavonoids in bread with SWAP inclusion, leading to enhanced antioxidant capacity (ABST, DPPH and FRAP assays). The distinct aromatic plant flavors were detected in the fortified breads by trained assessors and confirmed by SPME-GC/MS volatile analysis, showing high levels of terpenoids in SWAP breads, like carvacrol (oregano), caryophyllene (rosemary and lemon balm), and carvone (spearmint), and rendering the 2% fortification unacceptable by consumers. Nevertheless, breads with 1% oregano or rosemary waste had similar control overall acceptability scores, indicating that SWAP can be a promising ingredient for developing antioxidant-enriched wheat breads. Full article

Some of the properties that have been attributed to honey are antioxidant, anti-inflammatory, and antimicrobial effects, especially due to its content of bioactive compounds, mainly phenolic compounds (PCs), whose content varies greatly depending on the variety, origin, agronomic conditions, harvest season, and climate. The aim of the present study is to characterise 21 honeys from Sierra Nevada (Granada). High-performance liquid chromatography coupled to quadrupole-time of flight mass spectrometry (HPLC-ESI-QTOF-MS) was used. Mass accuracy and true isotopic patterns in both MS and MS/MS spectra enabled the tentative identification of 58 PCs, including flavonoids, phenolic acids and derivatives. The average content of PCs was 83.01 ± 16.36 µg/g, with flavonoids accounting for more than 85%. The most abundant compounds were naringenin (16.88 ± 3.15 µg/g), pinocembrin (12.33 ± 2.92 µg/g), chrysin (12.21 ± 2.09 µg/g), carnosol (9.52 ± 2.90 µg/g), galangin (5.41 ± 1.68 µg/g), and apigenin (5.24 ± 0.89 µg/g). Due to this interesting composition, more studies are necessary to determine if the extreme environmental conditions of Sierra Nevada cause abiotic stress in the plants located there, fostering this concentration of PCs. Full article