Anti-liver fibrosis activity of curcumin/chitosan-coated green silver nanoparticles

Abstract Liver fibrosis results from the hepatic accumulation of the extracellular matrix accompanied by a failure of the mechanisms responsible for matrix dissolution. Pathogenesis of liver fibrosis is associated with many proteins from different cell types. In the present study, in silico molecula...

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Main Authors: Alya Elzoheiry, Esraa Ayad, Nahed Omar, Kadry Elbakry, Ayman Hyder
Format: Article
Language:English
Published: Nature Portfolio 2022-11-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-022-23276-9
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author Alya Elzoheiry
Esraa Ayad
Nahed Omar
Kadry Elbakry
Ayman Hyder
author_facet Alya Elzoheiry
Esraa Ayad
Nahed Omar
Kadry Elbakry
Ayman Hyder
author_sort Alya Elzoheiry
collection DOAJ
description Abstract Liver fibrosis results from the hepatic accumulation of the extracellular matrix accompanied by a failure of the mechanisms responsible for matrix dissolution. Pathogenesis of liver fibrosis is associated with many proteins from different cell types. In the present study, in silico molecular docking analysis revealed that curcumin may inhibit the fibrosis-mediating proteins PDGF, PDGFRB, TIMP-1, and TLR-9 by direct binding. Nano-formulation can overcome curcumin problems, increasing the efficacy of curcumin as a drug by maximizing its solubility and bioavailability, enhancing its membrane permeability, and improving its pharmacokinetics, pharmacodynamics and biodistribution. Therefore, green silver nanoparticles (AgNPs) were synthesized in the presence of sunlight by means of the metabolite of Streptomyces malachiticus, and coated with curcumin-chitosan mixture to serve as a drug delivery tool for curcumin to target CCl4-induced liver fibrosis mouse model. Fibrosis induction significantly increased hepatic gene expression of COL1A1, α-SMA, PDGFRB, and TIMP1, elevated hepatic enzymes, increased histopathological findings, and increased collagen deposition as determined by Mason’s trichrome staining. Treatment with naked AgNPs tended to increase these inflammatory effects, while their coating with chitosan, similar to treatment with curcumin only, did not prevent the fibrogenic effect of CCl4. The induction of liver fibrosis was reversed by concurrent treatment with curcumin/chitosan-coated AgNPs. In this nano form, curcumin was found to be efficient as anti-liver fibrosis drug, maintaining the hepatic architecture and function during fibrosis development. This efficacy can be attributed to its inhibitory role through a direct binding to fibrosis-mediating proteins such as PDGFRB, TIMP-1, TLR-9 and TGF-β.
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spelling doaj.art-9fb9c6c7f0b2486b85707e4a1b0c04aa2022-12-22T03:58:05ZengNature PortfolioScientific Reports2045-23222022-11-0112111410.1038/s41598-022-23276-9Anti-liver fibrosis activity of curcumin/chitosan-coated green silver nanoparticlesAlya Elzoheiry0Esraa Ayad1Nahed Omar2Kadry Elbakry3Ayman Hyder4Zoology Department, Faculty of Science, Damietta UniversityZoology Department, Faculty of Science, Damietta UniversityZoology Department, Faculty of Science, Damietta UniversityZoology Department, Faculty of Science, Damietta UniversityFaculty of Science, Damietta UniversityAbstract Liver fibrosis results from the hepatic accumulation of the extracellular matrix accompanied by a failure of the mechanisms responsible for matrix dissolution. Pathogenesis of liver fibrosis is associated with many proteins from different cell types. In the present study, in silico molecular docking analysis revealed that curcumin may inhibit the fibrosis-mediating proteins PDGF, PDGFRB, TIMP-1, and TLR-9 by direct binding. Nano-formulation can overcome curcumin problems, increasing the efficacy of curcumin as a drug by maximizing its solubility and bioavailability, enhancing its membrane permeability, and improving its pharmacokinetics, pharmacodynamics and biodistribution. Therefore, green silver nanoparticles (AgNPs) were synthesized in the presence of sunlight by means of the metabolite of Streptomyces malachiticus, and coated with curcumin-chitosan mixture to serve as a drug delivery tool for curcumin to target CCl4-induced liver fibrosis mouse model. Fibrosis induction significantly increased hepatic gene expression of COL1A1, α-SMA, PDGFRB, and TIMP1, elevated hepatic enzymes, increased histopathological findings, and increased collagen deposition as determined by Mason’s trichrome staining. Treatment with naked AgNPs tended to increase these inflammatory effects, while their coating with chitosan, similar to treatment with curcumin only, did not prevent the fibrogenic effect of CCl4. The induction of liver fibrosis was reversed by concurrent treatment with curcumin/chitosan-coated AgNPs. In this nano form, curcumin was found to be efficient as anti-liver fibrosis drug, maintaining the hepatic architecture and function during fibrosis development. This efficacy can be attributed to its inhibitory role through a direct binding to fibrosis-mediating proteins such as PDGFRB, TIMP-1, TLR-9 and TGF-β.https://doi.org/10.1038/s41598-022-23276-9
spellingShingle Alya Elzoheiry
Esraa Ayad
Nahed Omar
Kadry Elbakry
Ayman Hyder
Anti-liver fibrosis activity of curcumin/chitosan-coated green silver nanoparticles
Scientific Reports
title Anti-liver fibrosis activity of curcumin/chitosan-coated green silver nanoparticles
title_full Anti-liver fibrosis activity of curcumin/chitosan-coated green silver nanoparticles
title_fullStr Anti-liver fibrosis activity of curcumin/chitosan-coated green silver nanoparticles
title_full_unstemmed Anti-liver fibrosis activity of curcumin/chitosan-coated green silver nanoparticles
title_short Anti-liver fibrosis activity of curcumin/chitosan-coated green silver nanoparticles
title_sort anti liver fibrosis activity of curcumin chitosan coated green silver nanoparticles
url https://doi.org/10.1038/s41598-022-23276-9
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