Multidrug-resistant (MDR) Salmonella remains a significant global health threat. This study aimed to explore the potential of essential oil components as novel inhibitors of the Salmonella MDR efflux pumps AcrAB and AcrD. Salmonella isolates were characterized for serotype, antibiotic resistance, and efflux pump activity. Essential oil components were screened for inhibitory effects using phenotypic and genotypic methods. In silico docking and molecular dynamics simulations were conducted to investigate binding interactions and stability. Salmonella Typhimurium was the predominant serotype with high MDR rates. Efflux pump activity was prevalent. Cumin and cinnamon oils demonstrated promising inhibitory effects on these pumps. Molecular docking simulations revealed strong binding affinities of analyzed compounds to the AcrAB and AcrD binding pocket. The 2-methyl-1-(p-tolyl)propan-2-ol exhibited higher stability within the AcrAB binding pocket compared to (1S,3R,5R)-1-isopropyl-4-methylenebicyclo[3.1.0]hexan-3-ol within the AcrD binding pocket. Treatment with these oils significantly downregulated efflux pump genes (robA, acrB, mdtB, acrF, acrD, soxS, mdsB, marA). The novel approach of combining in silico and molecular dynamics simulations with precise gene expression analysis provides a valuable framework for future studies aimed at combating MDR Salmonella efflux pumps.

Alzheimer’s disease (AD) is a significant health challenge in the 21st century. In spite of the approval of many new disease-modifying therapies for AD, the clinical advantages of these new treatments are less certain. Aim: This investigation was intended to determine the potential neuroprotective impact of morin hydrate (MH), zeolite clinoptilolite (ZC), and/or physical and mental activities (PhM) on an aluminum chloride (AlCl₃)-induced AD rat model. Methods: Male Sprague Dawley rats were randomly allocated into seven groups. Group I was the control group. Groups II–VII were treated with AlCl₃ for 5 weeks. Groups III–VII were tested for the effects of MH, ZC, and/or PhM. Biochemical, brain histopathological, and behavioral studies were performed. Results: PhM, MH, and ZC combined therapy exhibited a significant neuroprotective effect demonstrated by corrected catecholamines and tau and β-amyloid levels, as well as the antioxidant and anti-ferroptotic effects probably through Nrf2/HO-1/GPX4 and ACSL4 signaling pathways. In addition, combined therapy counteracted the inflammatory responses through modulating the TLR4/NF-κβ/NLRP3 inflammasome expression. Moreover, combined therapy groups showed the maximum improvement of both APOE4/LRP1 and Wnt3/β-catenin/GSK-3β signaling expressions. Conclusion: This research highlights the neuroprotective impact of MH and ZC plus PhM against AlCl₃-induced AD via modulation of Nrf2/HO-1/GPX4, TLR4/NF-κβ/NLRP3, APOE4/LRP1, and Wnt3/β-catenin/GSK-3β signaling pathways. It is the first to point out the inclusion of ferroptosis-Nrf2/inflammasomes cross-talk in the neuroprotection mechanism of MH/ZC against the AlCl₃-mediated AD model.

Cisplatin (CDDP) is a widely used chemotherapeutic agent, but its off-target toxicity, including testicular damage, limits clinical use. Bioactive compounds may help mitigate chemotherapy-induced reproductive toxicity. This study investigates thymol’s role in modulating ferritinophagy to preserve reproductive function and steroidogenesis. Male Wistar rats were randomized to control, CDDP, thymol, or CDDP + thymol groups. Thymol (60 mg/kg) was given orally for 14 days, and CDDP (8 mg/kg) was administered intraperitoneally on day 7. Testicular function was assessed through hormonal analysis, sperm evaluation, and histopathology. Ferritinophagy, oxidative stress, and inflammatory markers were assessed to elucidate thymol’s chemoprotective mechanisms. Thymol co-administration preserved steroidogenesis, restored sperm quality, and maintained testicular architecture in CDDP-treated rats. Thymol suppressed ferritinophagy, reducing iron overload and mitigating reactive oxygen species (ROS)-induced cellular damage. Additionally, thymol activated the Keap1/Nrf2/HO-1 pathway, enhancing antioxidant defenses while downregulating inflammatory mediators (TNF-α, IL-6). Additionally, thymol enhanced CDDP’s selectivity toward cancer cells while reducing its toxicity to normal cells. This study provides evidence that thymol modulates ferritinophagy to attenuate CDDP-induced testicular toxicity, helping preserve reproductive function via regulation of iron homeostasis. These findings highlight thymol’s potential as an adjunct therapy to mitigate chemotherapy-associated reproductive damage while maintaining CDDP’s anticancer efficacy.

The escalating global challenges of antimicrobial resistance (AMR) and cancer necessitate innovative therapeutic solutions from natural sources. This study investigated the multifaceted therapeutic potential of pigment-enriched plant extracts. We screened diverse plant extracts for antimicrobial and antibiofilm activity against multidrug-resistant bacteria and fungi. Hibiscus sabdariffa emerged as the most promising, demonstrating potent broad-spectrum antimicrobial and significant antibiofilm activity. Sub-inhibitory concentrations of H. sabdariffa robustly downregulated essential bacterial virulence genes and suppressed aflatoxin gene expression. Comprehensive chemical profiling via HPLC identified major anthocyanin glucosides, while GC-MS revealed diverse non-pigment bioactive compounds, including fatty acids and alcohols. Molecular docking suggested favorable interactions of key identified compounds (Cyanidin-3-O-glucoside and 1-Deoxy-d-arabitol) with E. coli outer membrane protein A (OmpA), indicating potential antiadhesive and antimicrobial mechanisms. Furthermore, H. sabdariffa exhibited selective cytotoxicity against MCF-7 breast cancer cells. These findings establish H. sabdariffa pigment-enriched extract as a highly promising, multi-functional source of novel therapeutics, highlighting its potential for simultaneously addressing drug resistance and cancer challenges through an integrated chemical, biological, and computational approach.

Introduction: Alzheimer’s disease (AD) is a devastating neurodegenerative malady marked by cognitive dysfunction and increased deposition of amyloid-beta and hyperphosphorylated tau proteins. Aluminum-associated neurotoxicity is well-documented and manifests itself in the form of cognitive dysfunction. Nutraceuticals, such as pomegranate extract (POM) or physical activity (PHA), have been recognized to exert beneficial actions on human wellbeing. This study aimed to mechanistically scrutinize the effects of POM and PHA either separately or in combination on AlCl ₃ -induced AD in rats. Methods: Sixty adult male Wistar rats were randomly assigned into five groups: control, AlCl ₃ , AlCl ₃ + PHA, AlCl ₃ + POM, and AlCl ₃ + COMB (POM + PHA) and treated for 5 weeks. Results: PHA and POM, either alone or in combination, exhibited a significant boost in memory and cognitive abilities, evidenced by the significant improvements in behavioral outcomes, elevations in monoamine (DA, NE, 5-HT), LRP1, and neprilysin levels, and reductions in acetylcholinesterase (ACHE) activity, APOE4 levels, and AD markers, relative to the AlCl ₃ -intoxicated group. All treatments significantly ameliorated AlCl ₃ -induced perturbations in antioxidant, neurotrophic, autophagic, inflammatory, endoplasmic reticulum (ER) stress, and apoptotic parameters, along with histopathological and immunohistochemical findings. These effects were demonstrated by the significant increase in antioxidant (Nrf2/HO-1/TAC/SOD), neurotrophic (PI3K/AKT/CREB/BDNF/TrKB), and autophagic (AMPK/SIRT-1/Beclin-1) markers, with significant reduction in neuroinflammatory (P38 MAPK/JNK/NF-κB/JAK-2/STAT-3/TNF-α/IL-1β), ER stress (PERK/CHOP/GRP78), and apoptotic (BAX/P53/caspase-3) markers, relative to the AlCl ₃ -intoxicated group. Interestingly, the combination exerted more favorable actions in all measured parameters and histological findings than the solo-treated groups. Conclusion: This study revealed the superiority of the combined therapy, compared to solo treatments, in alleviation of AlCl ₃ -induced AD in rats, via adjustment of the Nrf2/HO-1, P38 MAPK/JNK/NF-κB/JAK-2/STAT-3, PI3K/AKT/GSK-3β/CREB, AMPK/SIRT-1, PERK/CHOP, and apoptotic hubs.