The therapeutic mechanisms of propolis against CCl4-mediated liver injury by mediating apoptosis of activated hepatic stellate cells and improving the hepatic architecture through PI3K/AKT/mTOR, TGF-?/Smad2, Bcl2/BAX/P53 and iNOS signaling pathways

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dc.contributor.authorBadr, Gamal
dc.contributor.authorSayed, Eman Abdo
dc.contributor.authorWaly, Hanan
dc.contributor.authorHassan, Khadiga Abdel-Hameed
dc.contributor.authorMahmoud, Mohamed H.
dc.contributor.authorSelamoglu, Zeliha
dc.date.accessioned2024-11-07T10:39:44Z
dc.date.available2024-11-07T10:39:44Z
dc.date.issued2019
dc.departmentNiğde Ömer Halisdemir Üniversitesi
dc.description.abstractBackground/Aims: Propolis is one of the most promising natural products, exhibiting not only therapeutic but also prophylactic actions. Propolis has several biological and pharmacological properties, including hepatoprotective activities. The present study aimed to investigate the underlying molecular mechanisms of propolis against CCl4-mediated liver fibrosis. Methods: Three groups of male BALB/c mice (n=15/group) were used: group 1 comprised control mice; groups 2 and 3 were injected with CCl4 for the induction of liver fibrosis. Group 3 was then orally supplemented with propolis (100 mg/kg body weight) for four weeks. Different techniques were used to monitor the antifibrotic effects of propolis, including histopathological investigations using H&E, Masson's trichrome and Sirius red staining; Western blotting; flow cytometry; and ELISA. Results: We found that the induction of liver fibrosis by CCl4 was associated with a significant increase in hepatic collagen and ?-smooth muscle actin (?-SMA) expression. Moreover, CCl4-treated mice also exhibited histopathological alterations in the liver architecture. Additionally, the liver of CCl4-treated mice exhibited a marked increase in proinflammatory signals, such as increased expression of HSP70 and increased levels of proinflammatory cytokines and ROS. Mechanistically, the liver of CCl4-treated mice exhibited a significant increase in the phosphorylation of AKT and mTOR; upregulation of the expression of BAX and cytochrome C; downregulation of the expression of Bcl2; a significant elevation in the levels of TGF-? followed by increased phosphorylation of SMAD2; and a marked increase in the expression of P53 and iNOS. Interestingly, oral supplementation of CCl4-treated mice with propolis significantly abolished hepatic collagen deposition, abrogated inflammatory signals and oxidative stress, restored CCl4-mediated alterations in the signaling cascades, and hence repaired the hepatic architecture nearly to the normal architecture observed in the control mice. Conclusion: Our findings revealed the therapeutic potential and the underlying mechanisms of propolis against liver fibrosis. © 2019 The Author(s).
dc.description.sponsorshipNational Institutes of Health, NIH; Assiut University, AU; Deanship of Scientific Research, King Saud University
dc.identifier.doi10.33594/000000140
dc.identifier.endpage322
dc.identifier.issn1015-8987
dc.identifier.issue2
dc.identifier.pmid31343125
dc.identifier.scopus2-s2.0-85070522073
dc.identifier.scopusqualityQ2
dc.identifier.startpage301
dc.identifier.urihttps://doi.org/10.33594/000000140
dc.identifier.urihttps://hdl.handle.net/11480/11148
dc.identifier.volume53
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherCell Physiol Biochem Press GmbH & Co KG
dc.relation.ispartofCellular Physiology and Biochemistry
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.snmzKA_20241106
dc.subjectAntioxidants
dc.subjectInflammation
dc.subjectLiver fibrosis
dc.subjectOxidative stress
dc.subjectPropolis
dc.titleThe therapeutic mechanisms of propolis against CCl4-mediated liver injury by mediating apoptosis of activated hepatic stellate cells and improving the hepatic architecture through PI3K/AKT/mTOR, TGF-?/Smad2, Bcl2/BAX/P53 and iNOS signaling pathways
dc.typeArticle

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