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The development of nanomaterials has been speedily established in recent years, yet nanoparticles synthesized by traditional methods suffer unacceptable toxicity and the sustainability of the procedure for synthesizing such nanoparticles is inadequate. Consequently, green biosynthesis, which employs biopolymers, is gaining attraction as an environmentally sound alternative to less sustainable approaches. Chitosan-encapsulated nanoparticles exhibit exceptional antibacterial properties, offering a wide range of uses. Chitosan, obtained from shrimp shells, aided in the environmentally friendly synthesis of high-purity zinc oxide nanoparticles (ZnO NPs) with desirable features such as the extraction yield (41%), the deacetylation (88%), and the crystallinity index (74.54%). The particle size of ZnO NPs was 12 nm, while that of chitosan–ZnO NPs was 21 nm, and the bandgap energies of these nanomaterials were 3.98 and 3.48, respectively. The strong antibacterial action was demonstrated by ZnO NPs, chitosan–ZnO NPs, and chitosan–ZnO/PVP, particularly against Gram-positive bacteria, making them appropriate for therapeutic use. The photocatalytic degradation abilities were also assessed for all nanoparticles. At a concentration of 6 × 10 –5  M, chitosan removed 90.5% of the methylene blue (MB) dye, ZnO NPs removed 97.4%, chitosan-coated ZnO NPs removed 99.6%, while chitosan–ZnO/PVP removed 100%. In the case of toluidine blue (TB), at a concentration of 4 × 10 –3  M, the respective efficiencies were 96.8%, 96.8%, 99.5%, and 100%, respectively. Evaluation of radical scavenger activity revealed increased scavenging of ABTS and DPPH radicals by chitosan–ZnO/PVP compared to individual zinc oxide or chitosan–ZnO, where the IC50 results were 0.059, 0.092, 0.079 mg/mL, respectively, in the ABTS test, and 0.095, 0.083, 0.061, and 0.064 mg/mL in the DPPH test, respectively. Moreover, in silico toxicity studies were conducted to predict the organ-specific toxicity through ProTox II software. The obtained results suggest the probable safety and the absence of organ-specific toxicity with all the tested samples.

SIRT3 modulates reactive oxygen species and helps to reduce oxidative stress, resulting in a neuroprotective effect in Parkinson’s disease. The work seeks to develop and synthesize novel, effective SIRT3 modulators, which will modify SIRT3 expression and generate the neuroprotective effect by downregulating reactive oxygen species. The synthesis of the new indole-based carboxamide derivatives IMW 1–16 was guided by molecular docking experiments with the SIRT3 wild-type protein. FT-IR, 1 H-NMR, 13 C-NMR, and mass spectrometry analyzed the synthesized compounds. The efficacy of the compounds IMW 1–16 was assessed using in-vitro assays such as the MTT assay, neuroprotection assay, lactate dehydrogenase assay, superoxide dismutase assay, glutathione peroxidase assay, reactive oxygen species estimation, mitochondrial membrane potential, and real-time polymerase chain reaction estimation. The synthesized compounds IMFW-1, IMTW-5, and IM24DCW-16 were determined to have the lowest cytotoxicity and the most neuroprotective effect. They were found to downregulate the lactate dehydrogenase enzyme levels. The compounds efficiently increased the expression of superoxide dismutase and glutathione peroxidase. They were shown to be beneficial in reducing reactive oxygen species levels. The compounds also significantly increased the expression of SIRT3, PGC-1α, and FOXO3, which are crucial for detoxifying reactive oxygen species. The synthesized novel indole-based carboxamide derivatives were effective modulators of SIRT3. Upregulating SIRT3 expression also upregulated other supporting proteins such as PGC-1α, SOD2, GPx, and FOXO3, and these targets have been known to downregulate the reactive oxygen species levels. The study’s findings reveal the therapeutic potential of the developed and synthesized compounds and their involvement in such pathological situations; among all the compounds, IM24DCW-16 was discovered to be the most promising candidate for the modulation of the SIRT3 in PD.

IMPHY000797 derivatives have been well known for their efficacy in various diseases. Moreover, IMPHY000797 derivatives have been found to modulate such genes involved in multiple neurological disorders. Hence, this study seeks to identify such genes and the probable molecular mechanism that could be involved in the pathogenesis of Parkinson’s disease. The study utilized various biological tools such as DisGeNET, STRING, Swiss target predictor, Cytoscape, AutoDock 4.2, Schrodinger suite, ClueGo, and GUSAR. All the reported genes were obtained using DisGeNET, and further, the common genes were incorporated into the STRING to get the KEGG pathway, and all the data was converted to a protein/pathway network via Cytoscape. The clustering of the genes was performed for the gene-enriched data using two-sided hypergeometrics (p-value). The binding affinity of the IMPHY000797 was verified with the highest regulated 25 proteins via utilizing the “Monte Carlo iterated search technique” and the “ Emodel and Glide score ” function. Three thousand five hundred eighty-three genes were identified for Parkinson’s disease and 31 genes for IMPHY000797 compound, among which 25 common genes were identified. Further, the “FOXO-signaling pathway” was identified to be a modulated pathway. Among the 25 proteins, the highest modulated genes and highest binding affinity were exhibited by SIRT3, FOXO1, and PPARGC1A with the compound IMPHY000797. Further, rat toxicity analysis provided the efficacy and safety of the compound. The study was required to identify the probable molecular mechanism, which needs more confirmation from other studies, which is still a significant hit-back.

Neurodegenerative diseases, such as Alzheimer’s and Parkinson’s, pose a significant global health challenge, emphasizing the need for novel neuroprotective agents. Basil (Ocimum spp.) has been recognized for its therapeutic potential, and numerous studies have reported neuroprotective effects. In this manuscript, we present a computational protocol to extricate the underlying mechanism of action of basil compounds in neuroprotective effects. Molecular docking-based investigation of the chemical interactions between selected bioactive compounds from basil and key neuroprotective targets, including AChE, GSK3β, γ-secretase, and sirtuin2. Our results demonstrate that basil compound myricerone caffeoyl ester possesses a high affinity of −10.01 and −8.85 kcal/mol against GSK3β and γ-secretase, respectively, indicating their potential in modulating various neurobiological processes. Additionally, molecular dynamics simulations were performed to explore the protein–ligand complexes’ stability and to analyze the bound basil compounds’ dynamic behavior. This comprehensive computational investigation enlightens the putative mechanistic basis for the neuroprotective effects of basil compounds, providing a rationale for their therapeutic use in neurodegenerative disorders after further experimental validation.

Epigallocatechin gallate (EGCG) compound (IMPHY000226) has the potential to modulate multiple molecular mechanisms involved in Parkinson’s disease. Multiple targets such as SIRT3, FOXO1, PRKAA1, PPARGC1A, and CREBBP directly regulate reactive oxygen species levels and oxidative stress, suggesting that targeting these genes could help prevent further cellular damage. EGCG targets were identified using Swiss target prediction, revealing 31 targets modulated by EGCG. Specific keywords were used to identify 4663 targets related to PD modulation. The network was constructed and analyzed using the node and edge counts. Clustering analysis identified specific target groups with high edge counts and Kappa scores, indicating potential key players in PD modulation. The targets SIRT3, FOXO1, and PPARGC1A were predicted to have the highest binding energies via dual algorithm-based molecular docking studies. The MD simulation studies were performed for the highest-docked targets, SIRT3, FOXO1, and PPARGC1A, to assess the stability and interactions. The cell viability assays were conducted at various dosage concentrations for EGCG and resveratrol, which provided dose-dependent effects on cell survival. In the toxicity-induced group, the highest % cell viability of 94% and 81% was observed at a dosage of 6.25 µg/mL and 12.5 µg/mL. The toxicity-induced gene expression studies indicated that the EGCG upregulated the targets SOD2, FOXO1, and GPx. EGCG and resveratrol upregulated the targets SOD2, FOXO1, and GPx at a dosage concentration of 12.5 µg/mL. EGCG was found to be more potent than the resveratrol molecule, indicating that EGCG can be used as an anti-Parkinson agent.

The main goal of this study was to assess the bioactive and polysaccharide compositions, along with the antioxidant and antibacterial potentials, of five seaweeds collected from the northeastern coast of Algeria. Through Fourier transform infrared spectroscopy analysis and X-ray fluorescence spectroscopy, the study investigated the elemental composition of these seaweeds and their chemical structure. In addition, this study compared and identified the biochemical makeup of the collected seaweed by using cutting-edge methods like tandem mass spectrometry and ultra-high-performance liquid chromatography, and it searched for new sources of nutritionally valuable compounds. According to the study’s findings, Sargassum muticum contains the highest levels of extractable bioactive compounds, showing a phenolic compound content of 235.67 ± 1.13 µg GAE·mg−1 and a total sugar content of 46.43 ± 0.12% DW. Both S. muticum and Dictyota dichotoma have high concentrations of good polyphenols, such as vanillin and chrysin. Another characteristic that sets brown algae apart is their composition. It showed that Cladophora laetevirens has an extracted bioactive compound content of 12.07% and a high capacity to scavenge ABTS+ radicals with a value of 78.65 ± 0.96 µg·mL−1, indicating high antioxidant activity. In terms of antibacterial activity, S. muticum seaweed showed excellent growth inhibition. In conclusion, all five species of seaweed under investigation exhibited unique strengths, highlighting the variety of advantageous characteristics of these seaweeds, especially S. muticum.

No drug on the market, as a single entity, participates in different pathways involved in the pathology of Alzheimer’s disease. The current study is aimed at the exploration of multifunctional chalcone derivatives which can act on multiple targets involved in Alzheimer’s disease. A series of novel aminoethyl-substituted chalcones have been developed using in silico approaches (scaffold morphing, molecular docking, and ADME) and reported synthetic methods. The synthesized analogs were characterized and evaluated biologically using different in vitro assays against AChE, AGEs, and radical formation. Among all compounds, compound PS-10 was found to have potent AChE inhibitory activity (IC50 = 15.3 nM), even more than the standard drug (IC50 = 15.68 nM). Further, the in vivo evaluation of PS-10 against STZ-induced dementia in rats showed memory improvement (Morris Water Maze test) in rats. Also, PS-10 inhibited STZ-induced brain AChE activity and oxidative stress, further strengthening the observed in vitro effects. Further, the molecular dynamic simulation studies displayed the stability of the PS-10 and AChE complex. The novel aminoethyl-substituted chalcones might be considered potential multifunctional anti-Alzheimer’s molecules.

Mulberry or Morus alba fruits, belonging to the Moraceae family, are well recognized for their distinct taste and high nutritional content. Nevertheless, studies revealing the toxic effects of fruits are scanty. This study aimed to examine the adverse effects of methanolic fruit extract (MFME) derived from M. alba on mice following OECD 425 guidelines. The female Swiss albino mice were divided into two distinct categories. One group was designated as the control group (administered vehicle), while the other was assigned as the test group (administered 2000 mg/kg MFME orally). Subsequently, behavioral changes were monitored daily, and body weights, relative organ weights, and biochemical and hematological parameters were measured. Additionally, liver, kidney, heart, brain, and ovary assessments were conducted on the 14th day to detect any signs of toxicity. A histopathological investigation was conducted on the anesthetized animals’ vital organs (heart, liver, kidney, brain, and ovary). The study’s findings indicate that the oral administration of MFME did not result in any mortality. Additionally, no significant changes were seen in behavior, food and water intake, biochemical parameters, hematological investigations, and organ weights. Furthermore, the histological analysis revealed no notable pathological alterations in the separated essential organs of mice treated with MFME. The results of this study indicate that the oral administration of MFME is deemed safe up to the maximum test dosage of 2000 mg/kg.

Rheumatoid arthritis (RA) is a chronic inflammatory disease mainly affecting the synovial joints. A highly potent antagonist of C-C chemokine receptor 5 (CCR5), maraviroc (MVC), plays an essential role in treating several infectious diseases but has not yet been evaluated for its potential effects on RA development. This study focused on evaluating the therapeutic potential of MVC on collagen-induced arthritis (CIA) in DBA/1J mice. Following CIA induction, animals were treated intraperitoneally with MVC (50 mg/kg) daily from day 21 until day 35 and evaluated for clinical score and histopathological changes in arthritic inflammation. We further investigated the effect of MVC on Th9 (IL-9, IRF-4, and GATA3) and Th17 (IL-21R, IL-17A, and RORγT) cells, TNF-α, and RANTES in CD8+ T cells in the spleen using flow cytometry. We also assessed the effect of MVC on mRNA and protein levels of IL-9, IL-17A, RORγT, and GATA3 in knee tissues using RT-PCR and western blot analysis. MVC treatment in CIA mice attenuated the clinical and histological severity of inflammatory arthritis, and it substantially decreased IL-9, IRF4, IL-21R, IL-17A, RORγT, TNF-α, and RANTES production but increased GATA3 production in CD8+ T cells. We further observed that MVC treatment decreased IL-9, IL-17A, and RORγt mRNA and protein levels and increased those of GATA3. This study elucidates the capacity of MVC to ameliorate the clinical and histological signs of CIA by reducing pro-inflammatory responses, suggesting that MVC may have novel therapeutic uses in the treatment of RA.

This study explores the potential of Ailanthus excelsa Roxb. for managing obesity by evaluating its effects on key metabolic enzymes. We evaluated a hydroalcoholic extract and its fractions for their ability to modulate important metabolic enzymes, porcine pancreatic lipase , HMG-CoA reductase , α-glucosidase , and α-amylase activities. Our methodology integrated in vitro enzymatic assays with cluster analysis (MCODE, ClueGO, and Cluepedia) and network pharmacology to elucidate interactions between metabolites and target enzymes. Protein-protein interaction (PPI) analysis, consisting of a network with 51 nodes and 264 edges, was performed using the CytoNCA plugin to calculate topological parameters. Key targets were identified based on degree centrality, including ADIPOQ , PPARA , PPARG , IL6 , TNF , and AKT1 . Cluster analysis of the PPI networks, conducted using the MCODE plugin, highlighted a top cluster with a high score of 22.82. Network pharmacology has identified key targets associated with obesity, including HK1 , HK2 , PIK3CA , AKT1 , MTOR , CD36 , ACACB , SLC2A4 , CPTIA , INSR , ACACA , FASN , and ADIPOQ . These targets are linked to highly modulated metabolic pathways. Isoquercetin shows significant binding affinities: − 7.11 for HMG-CoA Reductase (PDB ID: 1HW9), -9.96 for lipase (PDB ID: 1LPB), − 8.96 for α-amylase , and − 10.41 for α-Glucosidase (PDB ID: 3A47). The ethyl acetate fractions exhibit notable inhibition of Porcine Pancreatic lipase (IC 50 : 56.25 ± 4.85 µg/mL) and HMG-CoA reductase (IC 50 : 108.27 ± 3.38 µg/mL), α-glucosidase (IC 50 : 117.08 ± 3.28 µg/mL), and α-amylase (IC 50 : 125.93 ± 2.29 µg/mL). Moreover, metabolites showed stronger binding affinities to all four enzymes than reference molecules. By integrating in vitro assays with molecular modeling , this study highlights the promising potential of A. excelsa and its fractions in obesity management, offering valuable insights into its therapeutic applications.