The irrational use of antibiotics has favored the emergence of resistant bacteria, posing a serious threat to global health. To counteract antibiotic resistance, this research seeks to identify novel antimicrobials derived from essential oils that operate through several mechanisms. It aims to evaluate the quality and composition of essential oils from Origanum compactum and Origanum elongatum; test their antimicrobial activity against various strains; explore their synergies with commercial antibiotics; predict the efficacy, toxicity, and stability of compounds; and understand their molecular interactions through docking and dynamic simulations. The essential oils were extracted via hydrodistillation from the flowering tops of oregano in the Middle Atlas Mountains in Morocco. Gas chromatography combined with mass spectrometry (GC-MS) was used to examine their composition. Nine common antibiotics were chosen and tested alone or in combination with essential oils to discover synergistic effects against clinically important and resistant bacterial strains. A comprehensive in silico study was conducted, involving molecular docking and molecular dynamics simulations (MD). O. elongatum oil includes borneol (8.58%), p-cymene (42.56%), thymol (28.43%), and carvacrol (30.89%), whereas O. compactum oil is mostly composed of γ-terpinene (22.89%), p-cymene (15.84%), thymol (10.21%), and (E)-caryophyllene (3.63%). With O. compactum proving to be the most potent, these essential oils showed antibacterial action against both Gram-positive and Gram-negative bacteria. Certain antibiotics, including ciprofloxacin, ceftriaxone, amoxicillin, and ampicillin, have been shown to elicit synergistic effects. To fight resistant bacteria, the essential oils of O. compactum and O. elongatum, particularly those high in thymol and (E)-caryophyllene, seem promising when combined with antibiotics. These synergistic effects could result from their ability to target the same bacterial proteins or facilitate access to target sites, as suggested by molecular docking simulations. Molecular dynamics simulations validated the stability of the examined protein–ligand complexes, emphasizing the propensity of substances like thymol and (E)-caryophyllene for particular target proteins, opening the door to potentially effective new therapeutic approaches against pathogens resistant to multiple drugs.

Honey, with its varied and extensive characteristics, is a complex and diverse biological substance that has been used since ancient times. The aim of this study is to thoroughly characterize the physicochemical, phytochemical, and biological properties of four floral honey varieties from the Fez-Meknes region in Morocco, with the goal of promoting the valorization of Moroccan honey in skincare and cosmetic products. The analyses of their physicochemical characteristics encompass various parameters such as pH, acidity, density, water content, Brix index, conductivity, ash content, hydroxymethylfurfural (HMF) content, and color. The levels of polyphenols range from 22.1 ± 0.4 to 69.3 ± 0.17 mg GAE/100 g of honey, measured using the Folin–Ciocalteu method for polyphenol quantification. Additionally, the estimation of flavonoid quantities in 100 g of honey, conducted using the aluminum trichloride method, reveals values ranging from 3.6 ± 0.2 to 7.2 ± 0.6 mg QE. Furthermore, it is noteworthy that honey exhibits high levels of glucose and relatively low concentrations of proteins. The quantitative evaluation of antioxidant effects, carried out through the 2,2-diphenyl-1-picrylhydrazyl free-radical-scavenging method and the ferric-reducing antioxidant power (FRAP) method, highlights the strong antioxidant capacity of multifloral honey, characterized by low inhibitory concentration values (IC₅₀ = 30.43 mg/mL and EC₅₀ = 16.06 mg/mL). Moreover, all honey varieties demonstrate antibacterial and antifungal properties, with multifloral honey standing out for its particularly pronounced antimicrobial activity. The correlation analyses between phytochemical composition and antioxidant and antibacterial activities reveal an inverse relationship between polyphenols and IC₅₀ (DPPH) and EC₅₀ (FRAP) concentrations of honey. The correlation coefficients are established at R² = −0.97 and R² = −0.99, respectively. Additionally, a significant negative correlation is observed between polyphenols, flavonoids, and antifungal power (R² = −0.95 and R² = −0.96). In parallel, a marked positive correlation is highlighted between antifungal efficacy, DPPH antioxidant activity (R² = 0.95), and FRAP (R² = 0.92). These results underscore the crucial importance of phytochemical components in the beneficial properties of honey, meeting international quality standards. Consequently, honey could serve as a natural alternative to synthetic additives.

Background/Objectives: Teucrium polium L. is widely used in traditional medicine and has been proposed as a source of antimicrobial adjuvants in the context of antimicrobial resistance. Here, we characterized the essential oil (EO) and polar extracts of T. polium and evaluated their antioxidant activity, antimicrobial potency against clinical multidrug-resistant (MDR) isolates, and the interaction of the EO with conventional antibiotics using a chequerboard assay (FICI); further, we investigated in silico molecular interactions with some targets related to resistance. Methods/Results: The EO, which was hydrodistilled and subsequently analyzed by GC–MS, is characterized by dominant limonene content (24.13%) and contents of oxygenated sesquiterpenes such as β-eudesmol (10.48%) and α-muurolol (8.10%). HPLC/UV–ESI–MS characterization of the extracts (decoction and Soxhlet) demonstrated that they were rich in polyphenolic compounds and flavonoids, which matched the standard phytochemical characteristics of this species. The extracts exhibited significant reducing capabilities, and the hydroethanolic extract exhibited the highest antioxidant activity (DPPH IC₅₀ = 15.41 μg/mL; FRAP EC₅₀ = 30.65 μg /mL), while the EO revealed at most moderate capacity in these tests. In antimicrobial assays, the EO inhibited fungi more effectively than the extracts (MIC of 1.17 mg/mL against Aspergillus niger; 4.69 mg/mL against Candida spp.), while antibacterial MICs for both the EO and extracts were generally high (up to 50 mg/mL). Combination testing nevertheless identified synergistic or additive effects of the EO with selected antibiotics, notably with ceftazidime against ESBL-producing Escherichia coli (FICI = 0.141) and Staphylococcus aureus (FICI = 0.039) and with amikacin against Klebsiella pneumoniae (FICI = 0.313); the EO–ceftriaxone pairing against ESBL E. coli was additive (FICI = 0.516). Docking simulations further supported these observations by showing the favorable predicted binding of oxygenated sesquiterpenes, most notably β-eudesmol and α-muurolol (up to −8.6 kcal/mol), to resistance-related targets such as RND efflux pumps, β-lactamases, and porins. Conclusions: Taken together, the in vitro and in silico data suggest that T. polium could be explored as a natural antimicrobial option and as an adjuvant to enhance antibiotic activity against multidrug-resistant pathogens.