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This study evaluated the physiological and biochemical responses of chickpea (Cicer arietinum L.) to foliar application of cineole, carvacrol, and thymol at concentrations of 500 and 1000 ppm. Carvacrol at 1000 ppm significantly enhanced fresh biomass (+15.4%) and aerial biomass (+46.2%), whereas thymol significantly reduced plant height (−20.2%) and overall biomass, yet notably increased chlorophyll content (+23.3%) and vitamin C levels (+41.4%) at the same concentration. Cineole significantly improved antioxidant capacity by increasing total phenolic content (+15.5% at 1000 ppm) and total flavonoid content (+19.1% at 500 ppm), but simultaneously decreased soluble protein synthesis and chlorophyll content (−39% at 500 ppm). Mineral analysis showed notable increases in calcium content following treatment with cineole (+30.5% at 1000 ppm) and carvacrol (+32% at 500 ppm), while thymol at 1000 ppm significantly reduced phosphorus, potassium, manganese, iron, copper, and zinc accumulation. Molecular docking and dynamic simulations revealed strong interactions of thymol and carvacrol with essential enzymes, specifically ascorbate peroxidase and phenylalanine ammonia-lyase, which are involved in antioxidant and phenolic metabolism pathways. These molecular interactions suggest potential contributions of thymol and carvacrol to plant stress resilience mechanisms, although further experimental validation is needed to confirm their roles in vivo. These findings emphasize the importance of optimizing monoterpene concentrations, indicating that carefully calibrated treatments could effectively enhance chickpea growth, nutritional quality, and stress tolerance within sustainable agricultural practices.

Inducible nitric oxide synthase (iNOS) remains a demanding metallo-enzyme target because the catalytic heme shapes both geometry and electrostatics at the binding site. We evaluated the dietary flavonol glycoside isorhamnetin-3-O-glucoside (I3OG) against mouse (3E6T) and human (3E7G) iNOS oxygenase domains using a heme-aware, auditably validated docking workflow. we centered the docking grids at the crystallographic Fe position and validated the protocol by re-docking the native co-crystallized inhibitors (3E6T: AR-C118901/1A2; 3E7G: AR-C95791/AT2), reproducing the crystal poses with heavy-atom RMSD = 1.093 Å and 0.327 Å, respectively (≤ 2.0 Å criterion). Explicit-solvent 100-ns MD confirmed stable complexes for both systems; 3E6T showed tighter ligand RMSD, lower pocket Cα-RMSF, and a more persistent H-bond network. MM/GBSA over equilibrated frames (60−100 ns) yielded ΔG_bind ≈ −44.9 ± 3.9 kcal·mol −1 (3E6T) vs −36.1 ± 3.7 kcal·mol −1 (3E7G), with per-residue hot spots matching docking contacts. Principal-component free-energy maps indicated more focused minima for 3E6T and a broader low-energy valley for 3E7G, consistent with the MD metrics. we performed an apo-form heme-cavity test (heme removed, grid kept at Fe; proximal Cys re-protonated) to probe pocket occupancy/flexibility without claiming a catalytic model. Collectively, the heme-centred, co-crystal-validated protocol plus the apo-cavity readout support I3OG as a plausible scaffold for iNOS engagement and provide a transparent template for future metallo-enzyme docking studies.

Background/Objectives: Oncogenic KRAS drives ~30% of solid tumours, yet the only approved G12C-specific drugs benefit ≈ 13% of KRAS-mutant patients, leaving a major clinical gap. We sought mutation-agnostic natural ligands from Ziziphus lotus, whose stereochemically rich phenolics may overcome this limitation by occupying the SI/II (Switch I/Switch II) groove and locking KRAS in its inactive state. Methods: Phytochemical mining yielded five recurrent phenolics, such as (+)-catechin, hyperin, astragalin, eriodictyol, and the prenylated benzoate amorfrutin A, benchmarked against the covalent inhibitor sotorasib. An in silico cascade combined SI/II docking, multi-parameter ADME/T (Absorption, Distribution, Metabolism, Excretion, and Toxicity) filtering, and 100 ns explicit solvent molecular dynamics simulations. Pharmacokinetic modelling predicted oral absorption, Lipinski compliance, mutagenicity, and acute-toxicity class. Results: Hyperin and astragalin showed the strongest non-covalent affinities (−8.6 kcal mol−1) by forging quadridentate hydrogen-bond networks that bridge the P-loop (Asp30/Glu31) to the α3-loop cleft (Asp119/Ala146). Catechin (−8.5 kcal mol−1) balanced polar anchoring with entropic economy. ADME ranked amorfrutin A the highest for predicted oral absorption (93%) but highlighted lipophilic solubility limits; glycosylated flavonols breached Lipinski rules yet remained non-mutagenic with class-5 acute-toxicity liability. Molecular dynamics trajectories confirmed that hyperin clamps the SI/II groove, suppressing loop RMSF below 0.20 nm and maintaining backbone RMSD stability, whereas astragalin retains pocket residence with transient re-orientation. Conclusions: Hyperin emerges as a low-toxicity, mutation-agnostic scaffold that rigidifies inactive KRAS. Deglycosylation, nano-encapsulation, or soft fluorination could reconcile permeability with durable target engagement, advancing Z. lotus phenolics toward broad-spectrum KRAS therapeutics.

Background: Saffron (Crocus sativus L.) corms, often discarded as agricultural by-products, are a promising and sustainable source of bioactive metabolites with potential therapeutic relevance. However, their anticancer potential remains largely underinvestigated. Objectives: This study aimed to compare the phytochemical composition of hydroethanolic extracts from fresh (HEEF) and stored (HEES) saffron corms and to evaluate their anticancer effectiveness against colorectal cancer cells. Methods: Phytochemical profiling was performed using HPLC-ESI-QTOF-MS/MS. Cytotoxicity against T84 and SW480 colorectal cancer cell lines was determined by the crystal violet assay. Apoptosis-related protein modulation was assessed by Western blotting. Additionally, molecular docking, molecular dynamics simulations, and MM/GBSA calculations were used to investigate ligand–target binding affinities and stability. Results: Both extracts contained diverse primary and secondary metabolites, including phenolic acids, flavonoids, triterpenoids, lignans, anthraquinones, carotenoids, sugars, and fatty acids. HEES showed higher relative abundance of key bioactive metabolites than HEEF, which was enriched mainly in primary metabolites. HEES showed significantly greater dose-dependent cytotoxicity, particularly against SW480 cells after 24 h (IC50 = 34.85 ± 3.35). Apoptosis induction was confirmed through increased expression of caspase-9 and p53 in T84 cells. In silico studies revealed strong and stable interactions of major metabolites, especially 3,8-dihydroxy-1-methylanthraquinone-2-carboxylic acid with COX2 and crocetin with VEGFR2. Conclusions: Stored saffron corms possess a richer bioactive profile and show enhanced anticancer effects in vitro compared with fresh saffron corms, suggesting that they may represent a promising source of compounds for the future development of colorectal cancer therapeutics.

Cedrus atlantica wood tar (CAWT) is traditionally used as a medicinal product, especially in low- and middle-income countries. Despite its traditional use, scientific support for its efficacy remains limited. This study evaluated the biological properties of CAWT using an integrated approach that combined qualitative and quantitative phytochemical analysis, disc diffusion and microdilution tests for antimicrobial assays (disc diffusion and microdilution), antioxidant activity (DPPH and ferric-reducing power assays), in silico ADMET/toxicity, docking, and MD/MMGBSA and provided a balanced comparison with reference antioxidants. This study demonstrated that CAWT is rich in secondary metabolites linked to biological activity, including polyphenols (307.39 ± 58.45 mg GAE/g), tannins (124.42 ± 6.14 mg TAE/g), and flavonoids (15.62 ± 2.53 mg QE/g). For free radical scavenging, CAWT inhibited DPPH with an IC50 of 19.781 ± 2.51 µg/mL and showed ferric-reducing activity with an IC50 of 83.7 ± 2.88 µg/mL for its antimicrobial activity against Pseudomonas aeruginosa; inhibition zones reached 35.66 ± 0.58 mm. In silico analysis, Swiss ADMET and pkCSM predicted ≥94% intestinal absorption, no cytochrome P450 liabilities, and low acute toxicity for six dominant terpenoids. Docking pinpointed trans-cadina-1(6),4-diene and α/β-himachalene as high-affinity ligands of LasR and gyrase B (ΔG ≈ −8 kcal mol−1). A 100 ns GROMACS run confirmed stable hydrophobic locking of the lead LasR complex (RMSD 0.22 nm), while MM/GBSA calculated a dispersion-dominated binding free energy of −37 kcal mol−1. Overall, CAWT showed in vitro antioxidant activity (DPPH and ferric-reducing assays) and inhibitory effects in disc diffusion assays, while in silico predictions for major terpenoids suggested favorable oral absorption and low acute toxicity. However, chemical composition analysis and bio-guided fractionation are necessary to confirm the antimicrobial activity and to validate the compounds responsible for the observed effects.

Centaurium erythraea Rafn (“Gosset El Haya”) has long been prized in North African folk medicine, yet Moroccan chemobiological data remain scarce. Ethanol extracts of northern Moroccan aerial parts were profiled by high-performance liquid chromatography (HPLC) and found rich in phenolics, dominated by 4-hydroxybenzoic acid (57.8%) and naringin (10.3%). The extract exhibited strong antioxidant power in the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging assay, with a half-maximal inhibitory concentration (IC50) of ≈74 µg mL−1, and a total antioxidant capacity (TAC) of ≈201 µg mL−1 and selective antimicrobial activity, sharply inhibiting Aspergillus niger, Penicillium digitatum, and Rhodotorula glutinis while sparing Staphylococcus aureus. In-silico absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiling predicted good oral bioavailability for low-molecular-weight acids and aglycones, low toxicity across all metabolites, but absorption liabilities for bulky glycosides. Molecular docking against A. niger esterase (1UKC), C. glabrata lanosterol 14-α-demethylase CYP51 (5JLC), and P. digitatum ethylene-forming oxidoreductase (9EIR) corroborated bioassays: rutin and naringin bound more tightly than fluconazole (ΔG ≈ −9.1 to −10.0 kcal mol−1), whereas quercetin and catechin offered balanced affinity pharmacokinetic profiles. Robust radical scavenging, targeted antifungal potency, and favorable in-silico pharmacokinetics thus position Moroccan C. erythraea as a promising, though standardization-dependent, source of nutraceutical, medicinal, and food-preservation agents. These results support the valorisation of Centaurium erythraea as a promising source for health promotion and green technology applications through its antioxidant, antimicrobial, and drug-like properties.

Centaurium erythraea Rafn (“Gosset El Haya”) has long been prized in North African folk medicine, yet Moroccan chemobiological data remain scarce. Ethanol extracts of northern Moroccan aerial parts were profiled by high-performance liquid chromatography (HPLC) and found rich in phenolics, dominated by 4-hydroxybenzoic acid (57.8%) and naringin (10.3%). The extract exhibited strong antioxidant power in the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging assay, with a half-maximal inhibitory concentration (IC50) of ≈74 µg mL−1, and a total antioxidant capacity (TAC) of ≈201 µg mL−1 and selective antimicrobial activity, sharply inhibiting Aspergillus niger, Penicillium digitatum, and Rhodotorula glutinis while sparing Staphylococcus aureus. In-silico absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiling predicted good oral bioavailability for low-molecular-weight acids and aglycones, low toxicity across all metabolites, but absorption liabilities for bulky glycosides. Molecular docking against A. niger esterase (1UKC), C. glabrata lanosterol 14-α-demethylase CYP51 (5JLC), and P. digitatum ethylene-forming oxidoreductase (9EIR) corroborated bioassays: rutin and naringin bound more tightly than fluconazole (ΔG ≈ −9.1 to −10.0 kcal mol−1), whereas quercetin and catechin offered balanced affinity pharmacokinetic profiles. Robust radical scavenging, targeted antifungal potency, and favorable in-silico pharmacokinetics thus position Moroccan C. erythraea as a promising, though standardization-dependent, source of nutraceutical, medicinal, and food-preservation agents. These results support the valorisation of Centaurium erythraea as a promising source for health promotion and green technology applications through its antioxidant, antimicrobial, and drug-like properties.

Stinging nettle (Urtica dioica) remains under‐characterized despite its widespread ethnomedicinal use. Here, we combine quantitative phytochemistry, validated rodent pharmacology, and multi‐target molecular modeling to explore the analgesic and anti‐inflammatory potential of a Moroccan ecotype. HPLC‐PDA analysis of the hydro‐ethanolic extract (yield 14.8%) identified 15 phenolics, dominated by chlorogenic acid (26.5%), caffeic acid (18.8%), and p‐coumaric acid (12.8%). In vivo, the polyphenolic fraction (100 mg/kg, p.o.) significantly reduced acetic‐acid writhing and carrageenan paw edema by 52% and 73%, respectively, and decreased both neurogenic and inflammatory phases of the formalin assay by over 59%. Similar efficacy was observed with the crude extract at 400 mg/kg, and acute oral toxicity tests showed no adverse effects up to 4 g/kg. Docking studies to mPGES‐1, TRPV1, and BK2R revealed binding energies as low as −10.5 kcal/mol, highlighting rutin, hyperoside, and chlorogenic acid as promising lead compounds. ADME/Tox profiling indicated high oral developability for apigenin and a broad safety margin for all leads. Overall, these findings position U. dioica extracts as mechanistically validated phytopharmaceutical candidates for pain and inflammation management, supporting their potential for clinical development. The hydro‐ethanolic extract of Urtica dioica (yield 14.8%) contained 15 phenolics, mainly chlorogenic, caffeic, and p‐coumaric acids. The polyphenolic fraction (100 mg/kg, p.o.) significantly reduced acetic‐acid writhing (52%) and carrageenan‐induced edema (73%) without toxicity up to 4 g/kg. Docking studies showed strong affinities of rutin, hyperoside, and chlorogenic acid for mPGES‐1, TRPV1, and BK2R, supporting U. dioica as a safe, mechanistically validated candidate for pain and inflammation management.