Marina Rigotti, Laura Ferrazzi Finger, Júlia Maiara dos Santos, Luciana Bavaresco Andrade Touguinha, Adriano Costa De Camargo, Alina Concepción-Alvarez, Raquel Bridi, Michel Mansur Machado, Lucielli Savegnago, Catia Santos Branco
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Molecular docking was performed with target proteins involved in depression-related toll-like receptor (TLR) signaling pathways. The bioaccessibility, antioxidant activity, total polyphenol content of GSE were evaluated across all digestive stages, and BV-2 microglial cells were exposed to the final digestion metabolites. The significant compounds catechin and rutin exhibited molecular affinity with the proteins AKT1 and MAPK8, suggesting an anti-inflammatory effect of GSE. Bioaccessibility assays revealed a reduction of phenolic compounds during the gastric and duodenal digestion phases, which were reestablished to levels like the control in the jejunal and ileal phases. The digested extract (concentrations ≤ 50 µg/mL; 24 h) was non-cytotoxic to BV-2 cells and did not alter the production of nitric oxide (NO) or reactive oxygen species (ROS) (<i>p</i> > 0.05). These results suggest that GSE may be a promising candidate for modulating inflammation-related conditions. Additionally, in vivo toxicity assessments using the <i>Artemia salina</i> model indicated that the extract is safe for in vivo applications.</p></div>","PeriodicalId":656,"journal":{"name":"Journal of Pharmaceutical Innovation","volume":"20 4","pages":""},"PeriodicalIF":2.7000,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Exploring the Anti-Inflammatory Effects of Grape Seed Extract on Depressive Disorder: A Preclinical and Network Pharmacology Approach\",\"authors\":\"Marina Rigotti, Laura Ferrazzi Finger, Júlia Maiara dos Santos, Luciana Bavaresco Andrade Touguinha, Adriano Costa De Camargo, Alina Concepción-Alvarez, Raquel Bridi, Michel Mansur Machado, Lucielli Savegnago, Catia Santos Branco\",\"doi\":\"10.1007/s12247-025-10034-3\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Grape seed extract (GSE) is a biotechnological input known for its anti-inflammatory and neuroprotective properties. 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Exploring the Anti-Inflammatory Effects of Grape Seed Extract on Depressive Disorder: A Preclinical and Network Pharmacology Approach
Grape seed extract (GSE) is a biotechnological input known for its anti-inflammatory and neuroprotective properties. This study aimed to chemically characterize GSE and evaluate their effects on targets associated with the gut-brain axis in depression using in silico methods. Phenolic bioaccessibility and in vitro and in vivo safety profiles were also assessed. Network pharmacology (NP) was employed to identify the properties and potential targets of GSE’s main bioactive compounds, which were identified via High-Performance Liquid Chromatography with Diode-Array Detection (HPLC-DAD). Molecular docking was performed with target proteins involved in depression-related toll-like receptor (TLR) signaling pathways. The bioaccessibility, antioxidant activity, total polyphenol content of GSE were evaluated across all digestive stages, and BV-2 microglial cells were exposed to the final digestion metabolites. The significant compounds catechin and rutin exhibited molecular affinity with the proteins AKT1 and MAPK8, suggesting an anti-inflammatory effect of GSE. Bioaccessibility assays revealed a reduction of phenolic compounds during the gastric and duodenal digestion phases, which were reestablished to levels like the control in the jejunal and ileal phases. The digested extract (concentrations ≤ 50 µg/mL; 24 h) was non-cytotoxic to BV-2 cells and did not alter the production of nitric oxide (NO) or reactive oxygen species (ROS) (p > 0.05). These results suggest that GSE may be a promising candidate for modulating inflammation-related conditions. Additionally, in vivo toxicity assessments using the Artemia salina model indicated that the extract is safe for in vivo applications.
期刊介绍:
The Journal of Pharmaceutical Innovation (JPI), is an international, multidisciplinary peer-reviewed scientific journal dedicated to publishing high quality papers emphasizing innovative research and applied technologies within the pharmaceutical and biotechnology industries. JPI''s goal is to be the premier communication vehicle for the critical body of knowledge that is needed for scientific evolution and technical innovation, from R&D to market. Topics will fall under the following categories:
Materials science,
Product design,
Process design, optimization, automation and control,
Facilities; Information management,
Regulatory policy and strategy,
Supply chain developments ,
Education and professional development,
Journal of Pharmaceutical Innovation publishes four issues a year.