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Introduction: Frankincense has demonstrated promising in vitro anticancer activity. However, its conventional delivery methods face significant challenges due to limited oral bioavailability. To address these limitations, this study focuses on developing optimized nanoemulsions (NEs) of Frankincense oil (FO) to enhance its therapeutic efficacy. Methods: Frankincense resins were extracted and characterized using gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS), identifying key metabolites including isopinocarveol, α-thujene, p-cymene, carvone, germacrene A, and various methyl esters. FO-based nanoemulsions (FO-NEs) were prepared and optimized using a 3-factor, 3-level Box-Behnken Design (BBD), with 10% FO (v/v), 40% surfactant (cremophor EL), and co-surfactant (Transcutol P). The optimized FO-NEs were evaluated for particle size, polydispersity index (PDI), zeta potential, and morphology using scanning electron microscopy (SEM) and atomic force microscopy (AFM). Cytotoxicity, wound healing, mitochondrial membrane potential (MMP), and reactive oxygen species (ROS) assays were performed against breast cancer (MDA-MB-231, MDA-MB-231-TR) and lung cancer (A549, A549-TR, H1299) cell lines. Results: The optimized FO-NEs exhibited an average particle size of 65.1 ± 4.21 nm, a PDI of 0.258 ± 0.04, and a zeta potential of −22.3 ± 1.2 mV. SEM and AFM confirmed the spherical morphology of the FO-NEs. In vitro cytotoxicity studies revealed enhanced anticancer activity of FO-NEs (IC50 = 13.2 μg/mL) compared to free FO (IC50 = 22.5 μg/mL) against resistant breast cancer MDA-MB-231-TR cells. FO-NEs significantly improved cancer cell internalization, disrupted mitochondrial membrane potential, and increased ROS generation, leading to enhanced cytotoxic effects. Discussion: The results demonstrate that nanoemulsion-based delivery significantly enhances the bioactivity and cellular uptake of frankincense oil compared to its free form. FO-NEs exhibit potent anticancer activity, particularly against drug-resistant cancer cell lines, suggesting their potential as a viable strategy for improving the therapeutic efficacy of frankincense in cancer treatment. [ABSTRACT FROM AUTHOR]

Introduction: Alzheimer's disease (AD) is a neurodegenerative disorder that significantly impacts the cognitive function and memory of a person. Despite the significant research efforts, the ability to completely prevent or effectively treat AD and its related dementias remains limited. Protein kinases are integral to AD pathology and represent promising targets for therapeutic intervention. Methods: A series of pyrimidine-based compounds 4-(4-(arylsulfonyl)piperazin-1-yl)-6-(thiophen-3-yl)pyrimidine derivatives (8 - 14) were synthesized and characterised. ATPase inhibition was carried out against the MARK4 enzyme. Molecular docking and molecular dynamics (MD) simulation at 500 ns was carried out against MARK4 (PDB: 5ES1). The drug-likeness feature and toxicity of the molecules were evaluated using QikProp and other tools. Results: Compounds were synthesized following a multi-step approach and characterized using multi-nuclear magnetic resonance (1H/13C-NMR) and mass spectrometry. ATPase inhibition assay of the compounds against MARK4 showed an IC50 value in the micromolar (μM) range. The results of the docking studies were consistent with the in-vitro experiments and identified (9) and (14) as the candidates with the highest affinity towards MARK4. MD simulation further supported these results, showing that the binding of ligands stabilises the target protein. Conclusion: Using experimental and theoretical approaches, we demonstrated that the reported class of pyrimidine derivatives are an excellent starting point for developing the next-generation anti-AD drugs. [ABSTRACT FROM AUTHOR]

Muscular dystrophies (MDs) are an array of inherited disorders characterized by progressive muscle weakness and degeneration. This review explores the genetic foundation, pathophysiological mechanisms, current treatments, and therapeutic potential of medicinal plants for MDs. Although gene therapy, exon-skipping, and stem cell therapies are substantial advancements, they encounter obstacles regarding immune responses, long-term efficacy, and delivery efficiency. A promising complementary approach to conventional MD therapies is presented by natural compounds from medicinal plants. Recent studies and historical use underscore the multi-targeted effects of phytochemicals, such as resveratrol, withaferin A, ginsenosides, curcumin, and epigallocatechin gallate, on muscle regeneration, oxidative stress, and inflammation. These compounds have demonstrated potential in pre-clinical studies to enhance muscle function, reduce inflammation, and reduce oxidative stress. Despite their potential, the utilization of medicinal plants in MD treatment is impeded by regulatory hurdles, potential side effects, variability in bioactive compound concentration, and standardization issues. To address these challenges, it is necessary to implement rigorous clinical trials, standardization protocols, and comprehensive quality control measures. Future research should focus on elucidating the molecular mechanisms of plant-derived compounds, improving biotechnological production techniques, and integrating these treatments into personalized, comprehensive treatment plans. Advances in synthetic biology, genomics, metabolomics, and nanoformulations have the potential to improve the efficacy and safety of phytomedicine in the treatment of MD. Implementing evidence-based integrative approaches can enhance holistic care, improve patient outcomes, and facilitate acceptance of medicinal plant-based therapies in clinical practice. [ABSTRACT FROM AUTHOR]

The growing global demand for renewable energy sources has pushed renewable, green energy sources to the forefront, among which the production of hydrogen gas from water occupies a significant place. To realize this goal, researchers across the globe are developing various systems that could swiftly catalyze the hydrogen evolution reaction (HER) in the highest possible yield. In the present work, the electrocatalytic HER performances of pyridoxal semicarbazone- and thiosemicarbazone-based Cu(II) complexes, i.e., ([Cu(PLSC)Cl2] and [Cu(PLTSC-H)H2O]Br·H2O) are reported. It has been unambiguously demonstrated that the complexes exhibit enviable level of HER catalytic activity. The catalytic activity of the complexes was not only the function of central metal but it was also controlled by the nature of the coordinating ligand.

Muscular dystrophies encompass a heterogeneous group of rare neuromuscular diseases characterized by progressive muscle degeneration and weakness. Among these, Duchenne muscular dystrophy (DMD) stands out as one of the most severe forms. The present study employs an integrative approach combining network pharmacology, quantitative structure-activity relationship (QSAR) modeling, molecular dynamics (MD) simulations, and free energy calculations to identify potential therapeutic targets and natural compounds for DMD. Upon analyzing the GSE38417 dataset, it was found that individuals with DMD exhibited 290 upregulated differentially expressed genes (DEGs) compared to healthy controls. By utilizing gene ontology (GO) and protein-protein interaction (PPI) network analysis, this study provides insights into the functional roles of the identified DEGs, identifying ten hub genes that play a critical role in the pathology of DMD. These key genes include DMD, TTN, PLEC, DTNA, PKP2, SLC24A, FBXO32, SNTA1, SMAD3, and NOS1. Furthermore, through the use of ligand-based pharmacophore modeling and virtual screening, three natural compounds were identified as potential inhibitors. Among these, compounds 3874518 and 12314417 have demonstrated significant promise as an inhibitor of the SMAD3 protein, a crucial factor in the fibrotic and inflammatory mechanisms associated with DMD. The therapeutic potential of the compounds was further supported by molecular dynamics simulation and Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) analysis. These findings suggest that the compounds are viable candidates for experimental validation against DMD. [ABSTRACT FROM AUTHOR]

Background: Controlled non-enzymatic glycation reactions are common under normal physiological conditions. However, during elevated blood glucose conditions, the glycation reactions are accelerated, leading to the formation of toxic compounds such as advanced glycation end products (AGEs). Several natural products are now being investigated as protective agents against glycation to preserve blood protein structure and functions. Methods: Human serum albumin (HSA) was glycated with 0.05 M α-D-glucose alone or in the presence of Zingiber officinale Roscoe (ginger) extract (0.781–100 μg/mL) for 10 weeks, and biochemical, biophysical, and computational analyses were carried out. Results: HSA glycated for 10 weeks (G-HSA-10W) resulted in significant production of ketoamines, carbonyl compounds, and AGE pentosidine. Notable structural alterations were observed in G-HSA-10W, ascertained by ultraviolet (UV), fluorescence, and circular dichroism (CD) studies. Antioxidant, anti-glycating, AGEs inhibitory, and antibacterial effects of ginger extracts were observed and attributed to the presence of various phytochemicals. Molecular docking studies suggested that the compounds 8-shagaol and gingerol exhibited strong and multiple interactions with HSA. Molecular simulation analysis suggests HSA attains a high degree of conformational stability with the compounds gingerol and 8-shogaol. Conclusions: These findings showed that ginger extract has an antioxidant function and can prevent glycation-induced biochemical and biophysical alterations in HSA. Thus, aqueous ginger extract can be utilized to combat glycation and AGE-related health issues, especially diabetes, neurological disorders, inflammatory diseases, etc. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a progressive neurodegenerative condition that leads to the gradual decline of neuronal cells. Despite significant interest and investment, complete prevention or treatment for AD and related dementia is still limited. The human acetylcholinesterase (hAChE) enzyme is a promising target for combating AD as it plays a crucial role in metabolising the neurotransmitter acetylcholine, which is essential for cognitive function and memory. The present study employed a multi-step approach, beginning with molecular docking to virtually screen 73 531 compounds from the PubChem library. Subsequently, we used Glide extra precision molecular docking to narrow down the list to three compounds (PubChem CID: 73058259, 141100002, and 44285707). The pharmacological and ADMET properties of the top three compounds were determined using multiple tools. The molecular dynamics (MD) simulation study at 500 ns revealed that all the ligands formed stable complexes with AChE. The trajectories of the ligands were stable, similar/better to the reference compound (donepezil), and identified compounds have drug-like features. This study presents the unique findings of structural and molecular features of new hAChE inhibitors and their dynamics, which have not been studied before. These insights could pave the way for developing more effective treatments for neurological conditions. [ABSTRACT FROM AUTHOR]

The layered double hydroxide (LDH) of FeMgAl and its composite with the rice husk biochar (FeMgAl/RHB) was tried for the first time for removing heavy metal ions of lead (Pb2+) and cadmium (Cd2+) in batch tests. Scanning electron microscopy and Fourier transform infrared spectroscopy demonstrated that FeMgAl/LDH was successfully synthesized and integrated into RHB. Furthermore, the presence of Cd2+ and Pb2+ was confirmed by energy‐dispersive X‐ray spectroscopy, exhibiting an effective adsorption process. The equilibrium contact time was estimated at 15 and 60 min, for Pb2+ and Cd2+, respectively, with high removal efficiencies and adsorption capacities upon immediate contact. Within the observed range (0–100 mg·L−1) of initial metal concentrations, the removal efficiencies decreased constantly using both adsorbents, while 50 or 60 mg·L−1 of Pb2+ and Cd2+, respectively, was estimated as the optimum values due to a steady increase in the adsorption capacities with composite adsorbent presenting a better efficiency, twice of the metal uptake capacity compared with FeMgAl/LDH. The lowest used amount of each adsorbent (0.05 g) exhibited highest adsorption capacity which decreased with increasing amount of adsorbent (up to 0.8 g), whereas the removal efficiencies increased for both heavy metal ions. A solution of pH value 0.7–0.8 was estimated as an optimum value with a uniform increasing pattern of adsorption capacities and percentage removal of both heavy metal ions using the FeMgAl/LDH as well as the composite adsorbent. A perfect fitting of the adsorption data was seen using the pseudo‐second‐order kinetic model, suggesting the chemical sorption to be the control mechanism of adsorption. The fitting of the Langmuir and Temkin isotherm models proposed a monolayer as well as heterogeneous adsorption system. The same was further confirmed based on the reasonable fit of both (Sips and Redlich–Peterson) three‐parameter isotherms in addition to a physical adsorption system, as suggested by the Dubinin–Radushkevich isotherm model. [ABSTRACT FROM AUTHOR]