This research investigated the antihypertensive effects of tamarind products and compared their potentials based on an animal model’s data verified by molecular docking, multitarget interactions, and dynamic simulation assays. GC-MS-characterized tamarind products were administered to cholesterol-induced hypertensive albino rat models. The two-week-intervened animals were dissected to collect their serum and organs and respectively subjected to analyses of their hypertension-linked markers and tissue architectures. The lead biometabolites of tamarinds interacted with eight target receptors in the molecular docking and dynamic simulation studies and with multitarget in the network pharmacological analyses. The results show that the serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), C-reactive protein (CRP), troponin I, and lipid profiles were maximally reinstated by the phenolic-enriched ripened sour tamarind extract compared to the sweet one, but the seed extracts had a smaller influence. Among the tamarind’s biometabolites, ϒ-sitosterol was found to be the best ligand to interact with the guanylate cyclase receptor, displaying the best drug-likeliness with the highest binding energy, −9.3 Kcal. A multitargeted interaction-based degree algorithm and a phylogenetic tree of pathways showed that the NR3C1, REN, PPARG, and CYP11B1 hub genes were consistently modulated by ϒ-sitosterol to reduce hypertension and related risk factors. The dynamic simulation study showed that the P-RMSD values of ϒ-sitosterol–guanylate cyclase were stable between 75.00 and 100.00 ns at the binding pocket. The findings demonstrate that ripened sour tamarind extract may be a prospective antihypertensive nutraceutical or supplement target affirmed through advanced preclinical and clinical studies.

Background : Propolis is a natural resinous mixture produced by bees. It provides beneficial effects on human health in the treatment/management of many diseases. The present study was performed to demonstrate the anti-Acanthamoeba activity of ethanolic extracts of Propolis samples from Iran. The interactions of the compounds and essential proteins of Acanthamoeba were also visualized through docking simulation. Methods: The minimal inhibitory concentrations (MICs) of Propolis extract against Acanthamoeba trophozoites and cysts was determined in vitro. In addition, two-fold dilutions of each of agents were tested for encystment, excystment and adhesion inhibitions. Three major compounds of Propolis extract such as chrysin, tectochrysin and pinocembrin have been selected in molecular docking approach to predict the compounds that might be responsible for encystment, excystment and adhesion inhibitions of A. castellanii. Furthermore, to confirm the docking results, molecular dynamics (MD) simulations were also carried out for the most promising two ligand-pocket complexes from docking studies. Results : The minimal inhibitory concentrations (MICs) 62.5 and 125 µg/mL of the most active Propolis extract were assessed in trophozoites stage of Acanthamoeba castellanii ATCC30010 and ATCC50739, respectively. At concentrations lower than their MICs values (1/16 MIC), Propolis extract revealed inhibition of encystation. However, at 1/2 MIC, it showed a potential inhibition of excystation and anti-adhesion. The molecular docking and dynamic simulation revealed the potential capability of Pinocembrin to form hydrogen bonds with A. castellanii Sir2 family protein (AcSir2), an encystation protein of high relevance for this process in Acanthamoeba. Conclusions : The results provided a candidate for the development of therapeutic drugs against Acanthamoeba infection. In vivo experiments and clinical trials are necessary to support this claim.

Helicobacter pylori infection causes gastritis, peptic ulcer disease, mucosa-associated lymphoid tissue lymphoma, and gastric cancer and can also promote thrombosis. It is estimated that approximately 4.5 billion individuals are infected, thus rendering H. pylori the most prevalent microbial pathogen. Currently established regimes for antibiotic treatment are massively challenged by increasing drug resistance and the development of novel antimicrobial therapies is urgently required. The antibiotic capreomycin is clinically used against multiple drug-resistant strains of Mycobacterium tuberculosis. It targets the complex between TlyA, a hemolysin- and RNA-binding protein, and the bacterial rRNA. In this study we have explored the possible antibacterial effects of capreomycin against several strains of H. pylori and found only moderate activity which was comparable to metronidazole-resistant strains. Molecular docking of capreomycin to TlyA proteins from H. pylori and M. tuberculosis identified several residues within TlyA which interact with the drug; however, binding affinities of H. pylori TlyA for capreomycin appear to be higher than those of Mycobacterium TlyA. The data suggest that capreomycin may warrant further investigations into its potential use as antibiotic against H. pylori.

Background and Aim: Malaria continues to pose a global health challenge, exacerbated by the emergence of drug-resistant strains of Plasmodium falciparum. This study aimed to evaluate the anti-Plasmodium potential of Propolis extracts collected from various Iranian regions and to characterize the molecular interactions of their bioactive phytochemicals with P. falciparum lactate dehydrogenase (PfLDH), a key enzyme in parasite glycolysis. Materials and Methods: The anti-Plasmodium activity of ethanol-extracted Propolis was assessed against P. falciparum NF54 using the SYBR Green I fluorescence assay. Gas chromatography-mass spectrometry (GC-MS) analysis identified major phytochemicals in the most active extract. Molecular docking and 100-ns molecular dynamic (MD) simulations were performed to evaluate the binding affinity and stability of selected compounds (tectochrysin and galangin) against PfLDH in both holo (Protein Data Bank [PDB] ID: 1LDG) and apo (PDB ID: 2X8L) forms. Results: Propolis collected from Kermanshah city exhibited the highest anti-Plasmodium activity (IC50 = 6.69 ± 1.44 μg/mL). GC-MS analysis identified tectochrysin and galangin as major constituents. Molecular docking revealed strong binding affinities of tectochrysin (−7.8 kcal/mol) and galangin (−7.5 kcal/mol) to PfLDH, surpassing the binding energies of standard antimalarial drugs (chloroquine and quinine). MD simulations confirmed the stability of tectochrysin and galangin within the PfLDH active sites, with favorable root mean square deviation, root mean square fluctuation, gyration, solvent-accessible surface area, molecular surface area, and polar surface area profiles, indicating persistent and stable protein-ligand interactions throughout the simulation. Conclusion: The findings support the promising anti-Plasmodium potential of Propolis-derived compounds, particularly tectochrysin and galangin, as novel PfLDH inhibitors. Their potential applicability in transdisciplinary anti-parasitic therapy across human and veterinary medicine warrants further in vivo validation and clinical investigations. Keywords: anti-malarial candidates, galangin, lactate dehydrogenase, molecular docking, molecular dynamics, Plasmodium falciparum, Propolis extract, tectochrysin