Search Results (9,173)

Studies utilizing cell-based systems to investigate plant-based diets for diabetes management are gaining attention due to the adverse effects associated with commercially available drugs. However, the molecular mechanisms underlying the anti-diabetic effects of specific plant-derived products remain inadequately explored. The major aim of our study was to elucidate the molecular mechanisms by which bioactive compounds in the fruit of Solanum spp. influence key proteins associated with type 2 diabetes. The expressions of genes such as glucose transporter protein 4 (GLUT4), myocyte enhancer factor-2 (MEF-2A), and nuclear respiratory factor-1 (NRF-1) were investigated in a palmitate-induced C2C12 cell model of type 2 diabetes mellitus. The structures of these proteins were retrieved from the protein database, while bioactive compounds previously identified in Solanum spp. were obtained from PubChem site. Drug-likeness properties of these compounds (ligands) were assessed. The docked protein-ligand complexes were further analyzed using the Protein-Ligand Profiler web server. Our results showed that the studied compounds from Solanum spp. profoundly upregulated GLUT4 expression (9–19-fold increase) in the C2C12 cell line, thus surpassing the effects of the standard anti-diabetic drug metformin. Additionally, activities of antioxidant enzymes catalase, superoxide dismutase, and glutathione peroxidase were elevated. Molecular docking showed that rutin, an abundant flavonoid from Solanum spp., had the highest binding affinity for the active sites of the target proteins. These findings provide new mechanistic insight into the anti-diabetic effects of Solanum spp., primarily due to its high rutin content, which plays a major role in the plant’s glucose-regulating and antioxidant actions. Our findings underscore the potential use of Solanum spp. as an affordable functional food for managing type 2 diabetes, especially in developing countries with limited resources for purchasing drugs. Although promising, our findings should be further validated by clinical studies. Full article

The objective of this study is to evaluate, for the first time, the chemical composition and the antioxidant, enzyme inhibitory, photoprotective and antibacterial properties of the Tamarix boveana essential oil (EO) as well as its organic extracts. The analysis of the EO obtained from the aerial parts of T. boveana was carried out employing the technique of gas chromatography with flame ionization detection (GC-FID) and mass spectrometry (GC-MS). Forty-four constituents were identified, constituting 91.18% of the oil, with the major compounds being γ-cadinene (9.41%), β-caryophyllene (6.71%), limonene (6.5%), p-cymene (6.16%), copaene (4.37%), terpinen-4-ol (4.23%), δ-cadinene (4.21%) and γ-terpinene (4.11%). The antioxidant activity of T. boveana essential oil and organic extracts (hydroalcoholic, CHCl₃, AcOEt, n-BuOH) was evaluated by different tests, including DPPH, ABTS, phenanthroline, SNP and ferric reducing power. The findings indicated that T. boveana essential oil possesses moderate antioxidant capacity, with IC₅₀ values of 223.59 ± 1.01 μg/mL according to the DPPH test. The extracts and essential oil also demonstrated notable inhibitory impacts against α-amylase and butyrylcholinesterase. Antimicrobial activity was determined regarding four bacterial strains, determining the minimum inhibitory concentrations (MICs) and bactericidal concentrations (MBCs). The geometry and electronic properties of the main EO compounds were determined using density functional theory (DFT) calculations. Furthermore, docking studies were conducted to investigate the interaction and binding affinity of these molecules with the active sites of BuChE and α-amylase enzymes. The results highlight the value of Tamarix boveana as a medicinal plant and indicate its effectiveness as an important source of bioactive compounds for many uses. Full article

The overexpression of atypical protein kinase C-iota (PKC-ι) is a biomarker for carcinogenesis in various cell types, such as glioma, ovarian, renal, etc., manifesting as a potential drug target. In previous in vitro studies, ICA-1S and ICA-1T, experimental candidates for inhibiting PKC-ι, have demonstrated their specificity and promising efficacy against various cancers. Moreover, the in vivo studies have demonstrated low toxicity levels in acute and chronic murine models. Despite these prior developments, the binding affinities of the inhibitors were never thoroughly explored from a biophysical perspective. Here, we present the biophysical characterizations of PKC-ι in combination with ICA-1S/1T. Various methods based on molecular docking, light scattering, intrinsic fluorescence, thermal denaturation, and heat exchange were applied. The biophysical characteristics including particle sizing, thermal unfolding, aggregation profiles, enthalpy, entropy, free energy changes, and binding affinity (K_d) of the PKC-ι in the presence of ICA-1S were observed. The studies indicate the presence of domain-specific stabilities in the protein–ligand complex. Moreover, the results indicate a spontaneous reaction with an entropic gain, resulting in a possible entropy-driven hydrophobic interaction and hydrogen bonds in the binding pocket. Altogether, these biophysical studies reveal important insights into the binding interactions of PKC-ι and its inhibitors ICA-1S/1T. Full article

The tomato leafminer (Tuta absoluta), a globally invasive pest, poses a major economic threat to tomato production. Although chemical control remains the primary management method, sustainable alternatives are urgently needed. Sex pheromone communication is critical for moth courtship and mating, with pheromone-binding proteins (PBPs) playing a key role in this process. In this study, we identified a PBP gene, TabsPBP2, from the T. absoluta transcriptome. Real-time quantitative PCR (RT-qPCR) revealed that TabsPBP2 is highly expressed in the antennae, with a strong male-biased expression pattern. Ligand-binding assays demonstrated that TabsPBP2 has the highest affinity for the sex pheromones (3E, 8Z, 11Z)-tetradecatrienyl acetate (TDTA) and (3E, 8Z)-tetradecadienyl acetate (TDDA). It also demonstrated a moderate-to-strong binding affinity to several tomato volatiles, including 2-carene, myrcene, α-pinene, cis-3-hexen-l-ol, methyl salicylate, sabinene, and α-terpinene. Molecular docking suggested that hydrophobic interactions predominantly stabilize the TabsPBP2–ligand complexes, with PHE118, PHE12, LEU90, LEU68, and ALA73 identified as key interacting residues. Electroantennogram (EAG) and Y-tube olfactometer assays confirmed that TDTA and TDDA act as strong attractants for male T. absoluta. This study enhances our understanding of the pheromone recognition in T. absoluta and provides a foundation for developing novel, pheromone-based pest control strategies. Full article

Breast cancer, a highly prevalent malignancy among women, continues to pose a significant global health challenge, as conventional therapies are often limited by adverse effects. This study developed and evaluated nanostructured lipid carriers (NLCs) encapsulating fatty acid amides (FAAs) semi-synthesized from andiroba oil and combined with silk fibroin (SF) as a novel therapeutic strategy. Methods: FAAs were synthesized via direct amidation and characterized by GC-MS, FT-IR, and ¹³C NMR. These fatty acid amides were then incorporated into NLCs containing SF. The formulation was evaluated for its physicochemical stability, cell selectivity, and cytotoxicity against 4T1 murine breast cancer cells and healthy human fibroblasts. Results: The NLC-FAA/SF formulation exhibited physicochemical stability (average particle size: 136.9 ± 23.6 nm; zeta potential: −8.3 ± 12.0 mV; polydispersity index: 0.19 ± 0.04), indicating a monodisperse and stable system. In vitro cytotoxicity assays demonstrated high selective activity against 4T1 murine breast cancer cells (IC₅₀ = 0.18 ± 0.06 μg/mL) and negligible toxicity to healthy human fibroblasts. Molecular docking studies revealed favorable interactions between the FAAs and cannabinoid receptors CB1 and CB2, with unsaturated FAAs showing higher binding scores and stability, suggesting their potential as cannabinoid receptor ligands. These findings highlight NLC-FAA/SF as a promising, selective, and effective nanoplatform for breast cancer treatment, warranting further investigation into its mechanism of action and in vivo efficacy. Full article

Aedes aegypti, also known as the yellow fever mosquito, presents a major public health challenge, highlighting the need for effective biorational agents for mosquito control. Here, we investigated the synergistic effects of essential oil mixtures derived from Hypenia irregularis that is a mint-family shrub native to Brazil’s Cerrado biome, known as “alecrim do Cerrado”, in combination with essential oils from noni (Morinda citrifolia), Brazilian mint (“salva-do-Marajó”, Hyptis crenata), and lemongrass (Cymbopogon citratus) against Ae. aegypti. We conducted phytochemical analyses and assessed larvicidal, repellent, and oviposition deterrent activities. Using in silico methods, we predicted molecular interactions between key essential oil components and physiological targets involved in repellent action (odorant-binding protein AeagOBP1 and olfactory receptor Or31) and larvicidal activity (GABA and octopamine receptors, TRP channels, and acetylcholinesterase [AChE]). Major compounds identified included octanoic acid (23%; Hipe. irregularis × M. citrifolia), 2,5-dimethoxy-p-cymene (21.9%; Hipe. irregularis × Hypt. crenata), and citral (23.0%; Hipe. irregularis × C. citratus). Although individual oils showed strong larvicidal activity (Hipe. irregularis LC₅₀ = 2.35 µL/mL; Hypt. crenata = 2.37 µL/mL; M. citrifolia and C. citratus = 2.71 µL/mL), their mixtures did not display synergistic effects. Similarly, repellency and oviposition deterrence were comparable to DEET for individual oils but were not enhanced in mixtures. Notably, the Hipe. irregularis × C. citratus essential oil blend reduced oviposition deterrence. Molecular docking confirmed strong binding of major oil components to AeagOBP1 and Or31, supporting their role in repellency. For larvicidal effects, AChE showed the highest predicted binding affinity. Overall, our findings suggest that H. irregularis, Hypt. crenata, C. citratus, and M. citrifolia (alone or in 1:1 mixture) are promising, sustainable agents for A. aegypti control. Full article

Normal proliferation of ovarian granulosa cells is essential for follicular development. The results of this study showed that ADAMTS1 was primarily localized in the cytoplasm of granulosa cells in sheep ovarian follicles, as revealed by immunohistochemistry and immunofluorescence staining. Knockdown and overexpression experiments of ADAMTS1 in granulosa cells demonstrated that the number of EdU-positive cells significantly decreased in the knockdown group (p < 0.05), while the expression levels of Bax (p < 0.05), Bax/Bcl2 (p < 0.01), and caspase3 (p < 0.05) were significantly upregulated, indicating that knockdown of ADAMTS1 markedly inhibited granulosa cell proliferation. In contrast, overexpression of ADAMTS1 significantly promoted cell proliferation. Transcriptome sequencing revealed that PSAT1 and SLC6A9 were significantly downregulated in the knockdown group and significantly upregulated in the overexpression group, which was confirmed by Quantitative Polymerase Chain Reaction (Q-PCR) (p < 0.05). KEGG enrichment analysis showed that PSAT1 was significantly enriched in the glycine, serine and threonine metabolism and vitamin B6 metabolism pathways. Molecular docking analysis indicated a stable binding interface between ADAMTS1 and PSAT1. Based on these findings, we speculate that ADAMTS1 may regulate amino acid metabolism in ovarian granulosa cells by modulating the expression of SLC6A9, which in turn affects PSAT1 in the glycine, serine, and threonine metabolism and vitamin B6 metabolism pathways, thereby influencing granulosa cell proliferation. Full article

Carboxymethyl cellulose (CMC) films, derived from sugarcane bagasse agricultural waste (SCB) incorporated with Betalains-nitrogen-doped carbon dots (Betalains-N–CQDs), derived from beet root waste (BR), offer a sustainable, smart and naked-eye sensor for strawberry packaging due to their excellent fluorescent and shape memory properties. These CMC-Betalains-N–CQDs aim to enhance strawberry preservation and safety by enabling visual detection of common food contaminants such as bacteria, fungi and Pb(II). Crucially, the CMC-Betalains-N–CQD film also exhibits excellent shape memory properties, capable of fixing various shapes under alkaline conditions and recovering its original form in acidic environments, thereby offering enhanced physical protection for delicate produce like strawberries. Optical studies reveal the Betalains-N–CQDs’ pH-responsive fluorescence, with distinct emission patterns observed across various pH levels, highlighting their potential for sensing applications. Scanning Electron Microscopy (SEM) confirms the successful incorporation of Betalains-N–CQDs into the CMC matrix, revealing larger pores in the composite film that facilitate better interaction with analytes such as bacteria. Crucially, the CMC-Betalains-N–CQD film demonstrates significant antibacterial activity against common foodborne pathogens like Escherichia coli, Staphylococcus aureus, and Candida albicans, as evidenced by inhibition zones and supported by molecular docking simulations showing strong binding interactions with bacterial proteins. Furthermore, the film functions as a fluorescent sensor, exhibiting distinct color changes upon contact with different microorganisms and Pb(II) heavy metals, enabling rapid, naked-eye detection. The film also acts as a pH sensor, displaying color shifts (brown in alkaline, yellow in acidic) due to the betalains, useful for monitoring food spoilage. This research presents a promising, sustainable, and multifunctional intelligent packaging solution for enhanced food safety and extended shelf life. Full article

Background: The increasing number of resistant bacterial strains is reducing the effectiveness of antimicrobial drugs in preventing infections. It has been shown that resistant strains invade living organisms and cause a wide range of illnesses, leading to a surprisingly high death rate. Objective: The present study aimed to identify novel dihydropteroate synthase (DHPS) inhibitors from Stenotrophomonas maltophilia using structure-based computational techniques. Methodology: This in silico study used various bioinformatics and cheminformatics approaches to find new DHPS inhibitors. It began by retrieving the crystal structure via PDB ID: 7L6P, followed by energy minimization. The DHPS enzyme was virtually screened against the CHEMBL library to target S. maltophilia through enzyme inhibition. Then, absorption, distribution, metabolism, and excretion (ADME) analysis was performed to select the top hits. This process identified the top-10 hits. Additionally, imidazole (control) was used for comparative assessment. Furthermore, a 100 ns molecular dynamics simulation and post-simulation analyses were conducted. The docking results were validated through binding free energy calculations and entropy energy estimation approaches. Results: The docking results prioritized 10 compounds based on their binding scores, with a maximum threshold of −7 kcal/mol for selection. The ADME assessment shortlisted 3 out of 10 compounds: CHEMBL2322256, CHEMBL2316475, and CHEMBL2334441. These compounds satisfied Lipinski’s rule of five and were considered drug-like. The identified inhibitors demonstrated greater stability and less deviation compared to the control (imidazole). The average RMSD stayed below 2 Å, indicating overall stability without major deviations in the DHPS–ligand complexes. Post-simulation analysis assessed the stability and interaction profiles of the complexes under physiological conditions. Hydrogen bonding analysis showed the control to be more stable than the three tested complexes. Increased salt bridge interactions suggested stronger electrostatic stabilization, while less alteration of the protein’s secondary structure indicated better structural compatibility. These findings support the potential of these novel ligands as potent DHPS inhibitors. Binding energy estimates showed that CHEMBL2322256 was the most stable, with scores of −126.49 and −124.49 kcal/mol. Entropy calculations corroborated these results, indicating that CHEMBL2322256 had an estimated entropy of 8.63 kcal/mol. Conclusions: The newly identified compounds showed more promising results compared to the control. While these compounds have potential as innovative drugs, further research is needed to confirm their effectiveness as anti-DHPS agents against antibiotic resistance and S. maltophilia infections. Full article

Background: Anaplastic lymphoma kinase (ALK) is a validated oncogenic driver in non-small cell lung cancer and other malignancies, making it a clinically relevant target for small-molecule inhibition. Methods: Here, we report a computational discovery pipeline integrating structure-based virtual screening, machine learning-guided prioritization, molecular dynamics simulations, and binding free energy analysis to identify potential ALK inhibitors from a natural product-derived subset of the ZINC20 database. We trained and benchmarked eleven machine learning models, including tree-based, kernel-based, linear, and neural architectures, on curated bioactivity datasets of ALK inhibitors to capture nuanced structure-activity relationships and prioritize candidates beyond conventional docking metrics. Results: Six compounds were shortlisted based on binding affinity, solubility, bioavailability, and synthetic accessibility. Molecular dynamics simulations over 100 ns revealed stable ligand engagement, with limited conformational fluctuations and consistent retention of the protein’s structural integrity. Key catalytic residues, including GLU105, MET107, and ASP178, displayed minimal fluctuation, while hydrogen bonding and residue interaction analyses confirmed persistent engagement across all ligand-bound complexes. Binding free energy estimates identified ZINC3870414 and ZINC8214398 as top-performing candidates, with ΔG_total values of –46.02 and –46.18 kcal/mol, respectively. Principal component and dynamic network analyses indicated that these compounds restrict conformational sampling and reorganize residue communication pathways, consistent with functional inhibition. Conclusions: These results highlight ZINC3870414 and ZINC8214398 as promising scaffolds for further optimization and support the utility of integrating machine learning with dynamic and network-based metrics in early-stage kinase inhibitor discovery. Full article

Crotalaria juncea L. (Fabaceae: Faboideae), traditionally used as green manure due to its nitrogen-fixing capacity, also exhibits therapeutic potential for conditions such as anemia and psoriasis. However, its cosmetic applications remain largely unexplored. This study examined the phytochemical profiles and biological activities of ethanolic extracts from the root, flower, and leaf of C. juncea, focusing on their potential use in cosmetic formulations. Soxhlet extraction with 95% ethanol was employed. Among the extracts, the leaf showed the highest total flavonoid content, while the root contained the highest total phenolic content. The root extract demonstrated the strongest antioxidant activity, as assessed by DPPH, FRAP, and lipid peroxidation assays, along with significant anti-tyrosinase and anti-aging effects via collagenase and elastase inhibition. LC-MS/QTOF analysis identified genistein and kaempferol as the major bioactive constituents in the root extract. Molecular docking confirmed their strong interactions with enzymes associated with skin aging. Additionally, the root extract exhibited notable anti-inflammatory activity. These results suggest that C. juncea root extract is a promising multifunctional natural ingredient for cosmetic applications due to its antioxidant, anti-tyrosinase, anti-aging, and anti-inflammatory properties. Full article

Background/Objectives: Annona muricata (AM), commonly known as soursop or guanabana, has long been used in traditional medicine for its purported anticancer properties. However, scientific studies evaluating its potential enhancing or additive effects with conventional antineoplastic drugs (ADs) remain limited. This study aimed to assess the cytotoxic effects of an aqueous AM infusion alone and in combination with standard ADs in cancer cell lines, while also evaluating its safety in healthy cells. Additionally, we explored the potential molecular interactions of AM metabolites with therapeutic targets using silico modeling. Methods: An AM infusion (125 and 250 µg/mL) was tested on two cancer cell lines—MDA-MB-231 (human triple-negative breast cancer) and TC-1 (murine HPV16-positive cancer)—as well as healthy human leukocytes and a non-tumorigenic mouse lung cell line. Cell viability was assessed using the Alamar Blue™ assay. The combined effects of AM with multiple first-line ADs were evaluated. In silico molecular docking was performed with Molegro Virtual Docker to assess the interaction of AM metabolites (quercetin and hyperoside) with the A2B adenosine receptor. Additionally, the physicochemical properties of 13 AD were analyzed to explore correlations with cytotoxic outcomes. Results: AM infusion alone exhibited low cytotoxicity in both cancer and healthy cell types. However, when combined with ADs, it enhanced cytotoxic effects in cancer cells while sparing healthy cells at the evaluated concentrations. Docking studies revealed strong interactions between quercetin and hyperoside (major metabolites in the AM infusion) and the A2B receptor, supporting a possible mechanistic explanation for the observed effects. Conclusions: AM infusion may act as a chemical modulator, potentiating the effects of conventional ADs in cancer cells while preserving normal cell viability. These findings encourage further preclinical exploration of AM as a complementary agent in integrative oncology. Full article

Amomum villosum, a medicinal and edible plant, has shown promise in improving digestive health; however, the mechanisms underlying its antioxidant and hypoglycemic effects remain unclear. This study aimed to optimize the extraction of A. villosum essential oil (AVEO) and elucidate its bioactive potential. Ultrasound-assisted extraction yielded 3.84% AVEO under optimal conditions. Gas chromatography–mass spectrometry combined with SwissADME analysis identified nine active components, including bornyl acetate, (−)-Spathulenol, and (−)-Pogostol. In vitro assays demonstrated potent α-glucosidase inhibition (IC₅₀: 0.99 mg/mL) and strong free radical scavenging activities against 1,1-diphenyl-2-picrylhydrazyl (IC₅₀: 0.87 mg/mL), hydroxyl (IC₅₀: 0.18 mg/mL), and superoxide anion radicals (IC₅₀: 0.01 mg/mL). A significant positive correlation was observed between its antioxidant and hypoglycemic activities. Network pharmacology identified 11 core targets involved in oxidative stress and glucose metabolism, with functional enrichment pointing to the PPAR and steroid hormone signaling pathways. Molecular docking confirmed stable binding affinities of bornyl acetate, (−)-spathulenol, and (−)-pogostol to JAK2, NCOA2, and PPARA via hydrogen bonding and hydrophobic interactions. These findings provide a mechanistic basis for the dual antioxidant–hypoglycemic effects of AVEO and support its potential application in the development of functional foods and natural therapeutics targeting metabolic disorders. Full article

Background/Objectives: Liver cancer is considered one of the most dangerous types of cancer due to both the patients’ and the physician’s delay in diagnosis. Metal/ligand complexes represent antitumor drugs; however, they have several limitations such as a lack of specificity that results in damage to healthy organs. Therefore, there is a need for a material that improves specificity and decreases side effects. Magnetite nanoparticles (MNPs) show outstanding findings in the targeting and treatment of cancer-diseased organs. Methods: Herein, a metal/ligand palladium complex with antitumor activity was prepared and loaded onto magnetite nanoparticles for the treatment of liver cancer. The proposed structures with the lowest energy geometries were identified by density functional theory (DFT) utilizing the Gaussian09 program. Molecular docking simulation was conducted on an HP Pavilion dv6 Notebook PC equipped with an AMD Phenom™ N930 Quad processor. Afterward, the prepared nano-systems were investigated using FTIR and TEM. In vitro drug release measurement was evaluated in PBS at different time intervals. Eventually, the selectivity of these nano-systems was investigated using an animal rat model. Results: The results showed that MNPs with a crystalline structure and superparamagnetic characteristics (Ms = 71.273 emu/g) were created with a large surface area (63.75 m²/g), and they were validated to be acceptable for drug delivery applications. The palladium complex [Pd(DMEN)Cl₂] loaded onto magnetite released highly in acidic circumstances (pH 4.5), implying that it could be employed for targeted therapy of liver cancer. Conclusions: In vivo investigations in a rat model of liver cancer induced by diethylnitrosamine and thioacetamide (DEN/TAA) showed that the combination of the palladium complex and magnetite demonstrated a potent anticancer therapeutic activity on liver cancer in rats, improving liver function and structure while mitigating inflammation. Full article

Mitochondrial dysfunction is implicated across a spectrum of neurological diseases, yet its causal role and mechanistic specificity remain unclear. This study employed a multi-modal integrative analysis of mitochondrial gene expression in Alzheimer’s Disease (AD), Amyotrophic Lateral Sclerosis (ALS), Multiple Sclerosis (MS), and Parkinson’s Disease (PD) to address these gaps. We combined machine learning for predictive modeling with genetic causal inference methods (Mendelian Randomization, colocalization, PheWAS), followed by drug enrichment analysis and molecular docking. Our machine learning models, particularly Support Vector Machine and Multi-layer Perceptron, effectively classified these conditions, with MS exhibiting the highest predictability (mean Accuracy: 0.758). Causal inference analyses identified specific gene–disease links; for instance, genetically predicted increased expression of PDK1 was causally associated with an elevated risk for both AD (OR = 1.041) and ALS (OR = 1.037), identifying pyruvate metabolism as a shared vulnerability. In contrast, genes like SLC25A38 emerged as highly predictive specifically for PD. We also observed evidence of potential brain–periphery interaction, such as a bidirectional causal relationship between red blood cell indices and MS risk. Finally, drug enrichment analysis highlighted Celecoxib, and subsequent molecular docking predicted a strong binding affinity to PDK1 (docking score S = −6.522 kcal/mol), generating hypotheses for potential metabolic modulation. Taken together, this study provides a computational hypothesis framework suggesting mitochondrial pathways and targets that warrant future biological validation. This study provides specific, genetically supported evidence for the causal role of mitochondrial pathways in neurological diseases and identifies tangible targets for future therapeutic development. Full article