Comprehensive Study of Biogenic AgNPs and Ocimum araratum Extract with Pronounced Hypolipidemic and Antioxidant Effects

Abelyan, Narek

doi:10.5281/zenodo.17566001

Comprehensive Study of Biogenic AgNPs and Ocimum araratum Extract with Pronounced Hypolipidemic and Antioxidant Effects

Abelyan, Narek

Publisher: Zenodo
DOI: 10.5281/zenodo.17566001
Repository: zenodo.org
Language: en

Abstract

Comprehensive Study of Biogenic AgNPs and Ocimum araratum Extract with Pronounced Hypolipidemic and Antioxidant Effects Narek Abelyan1, Ashkhen Hovhannisyan1 1. Department of Medical Biochemistry and Biotechnology, Russian-Armenian University, 0051, Yerevan, Armenia Abstract Given the high prevalence of metabolic disorders and associated pathologies, the search for effective natural agents capable of modulating lipid metabolism and reducing oxidative stress remains a highly relevant challenge. In this study, it was found that biogenic silver nanoparticles (AgNPs), stabilized in a 50% ethanolic extract of Ocimum araratum, exhibit a pronounced hypolipidemic and oxidative stress-reducing effect. This effect was confirmed in vivo using a model of Wistar albino rats, demonstrating a significant reduction in blood lipid levels. To elucidate the molecular mechanisms of action of both the extract and the synthesized nanoparticles, mass spectrometric analysis of the extract was performed, identifying key bioactive components, including rosmarinic and chicoric acids. Using molecular modeling and structural similarity analysis with known compounds from chemical databases, potential protein targets involved in lipid metabolism and oxidative stress regulation were predicted. Aldose reductase - a key enzyme in metabolic processes - was identified as the primary target. Molecular docking and conformational analysis revealed that the main extract components, chicoric acid and rosmarinic acid, interact with key amino acid residues within the aldose reductase binding site that are also targeted by known inhibitors, with binding energies of –9.3 kcal/mol and –10.5 kcal/mol, respectively. Compared to the binding energies of established aldose reductase inhibitors (approximately –10 kcal/mol), these findings suggest a high potential for effective inhibition. This effect was further confirmed by in vitro assays, which fully supported the predictions. These findings indicate that the primary inhibitory effect is attributed to the major components of the extract. However, further studies using molecular modeling showed that silver nanoparticles may exert an additional enhancing effect by interacting with regions near the enzyme’s active site, leading to structural denaturation and inactivation of aldose reductase. Thus, biogenic silver nanoparticles derived from O. araratum extract, along with the extract itself, demonstrate potential as natural agents with significant hypolipidemic and antioxidant activity.

Full text

Comprehensive Study of Biogenic AgNPs and Ocimum araratum Extract with Pronounced Hypolipidemic and Antioxidant Effects Narek Abelyan1, Ashkhen Hovhannisyan1 1. Department of Medical Biochemistry and Biotechnology, Russian-Armenian University, 0051, Yerevan, Armenia Abstract Given the high prevalence of metabolic disorders and associated pathologies, the search for effective natural agents capable of modulating lipid metabolism and reducing oxidative stress remains a highly relevant challenge. In this study, it was found that biogenic silver nanoparticles (AgNPs), stabilized in a 50% ethanolic extract of Ocimum araratum, exhibit a pronounced hypolipidemic and oxidative stress-reducing effect. This effect was confirmed in vivo using a model of Wistar albino rats, demonstrating a significant reduction in blood lipid levels. To elucidate the molecular mechanisms of action of both the extract and the synthesized nanoparticles, mass spectrometric analysis of the extract was performed, identifying key bioactive components, including rosmarinic and chicoric acids. Using molecular modeling and structural similarity analysis with known compounds from chemical databases, potential protein targets involved in lipid metabolism and oxidative stress regulation were predicted. Aldose reductase - a key enzyme in metabolic processes - was identified as the primary target. Molecular docking and conformational analysis revealed that the main extract components, chicoric acid and rosmarinic acid, interact with key amino acid residues within the aldose reductase binding site that are also targeted by known inhibitors, with binding energies of –9.3 kcal/mol and –10.5 kcal/mol, respectively. Compared to the binding energies of established aldose reductase inhibitors (approximately –10 kcal/mol), these findings suggest a high potential for effective inhibition. This effect was further confirmed by in vitro assays, which fully supported the predictions. These findings indicate that the primary inhibitory effect is attributed to the major components of the extract. However, further studies using molecular modeling showed that silver nanoparticles may exert an additional enhancing effect by interacting with regions near the enzyme’s active site, leading to structural denaturation and inactivation of aldose reductase. Thus, biogenic silver nanoparticles derived from O. araratum extract, along with the extract itself, demonstrate potential as natural agents with significant hypolipidemic and antioxidant activity.