Antifibrotic Mechanism of Pinocembrin: Impact on Oxidative Stress, Inflammation and TGF-β /Smad Inhibition in Rats
| Autor: | Natali Vega-Magaña, Jorge Segura-Ortega, José Sergio Zepeda-Nuño, Vidal Delgado-Rizo, Susana del Toro-Arreola, Leonel García-Benavides, Miriam Ruth Bueno-Topete, Jorge Gutierrez-Franco, Marta Escarra-Senmarti, Adelaida Sara Minia Zepeda Morales, Jesse Haramati |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cirrhosis Specialties of internal medicine Inflammation Mucin 2 03 medical and health sciences 0302 clinical medicine Cholestasis Pinocembrin Medicine Mesenteric lymph nodes Intestinal permeability Hepatology Tight junction business.industry General Medicine medicine.disease Molecular biology Small intestine 030104 developmental biology medicine.anatomical_structure RC581-951 CCl4 NF-kB Nrf2 HO-1 030220 oncology & carcinogenesis medicine.symptom business |
| Zdroj: | Annals of Hepatology, Vol 17, Iss 2, Pp 307-317 (2018) |
| ISSN: | 1665-2681 |
| Popis: | Introduction. The present study aimed to elucidate the potential antifibrotic effects of pinocembrin (PIN), a flavanone found abundantly in honey and propolis, by studying its effect on different oxidative stress, inflammatory and fibrosis markers in an experimental model of CCl4-induced liver fibrosis.Material and methods. PIN (20 mg/kg) was given orally 3 times/week for 6 consecutive weeks alternating with CCl4 (0.5 mL/kg, 1:1 mixture with corn oil, i. p.) twice weekly. Different hepatotoxicity indices, oxidative stress, inflammatory and liver fibrosis markers were assessed.Results. PIN significantly restored liver transaminases and total cholesterol to normal levels. Also, PIN ameliorated oxidative stress injury evoked by CCl4 as evidenced by inhibition of reduced glutathione depletion and lipid peroxidation as well as elevation of antioxidant enzyme superoxide dismutase (SOD). Further, PIN up-regulated the nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2), thereby inducing the expression and activity of the cytoprotective enzyme hemeoxygenase-1 (HO-1). Moreover, PIN alleviated pro-inflammatory cytokines such as TNF-α via inhibiting nuclear factor-KB (nF-kB) activation. As markers of fibrosis, collagen and α-SMA expression increased markedly in the CCl4 group and PIN prevented these alterations. In addition, PIN down-regulated TGFβ1 and p-Smad2/3, thereby inhibiting TGFβ1/Smad signaling pathway.Conclusion. These results suggest that PIN possess potent antifibrotic effects that can be explained on its antioxidant properties. It ameliorates oxidative stress and inflammation during induction of fibrogenesis via its ability to augment cellular antioxidant defenses, activating Nrf2-mediated HO-1 expression and modulating NF-KB and TGF-β1/Smad signaling pathway. |
| Databáze: | OpenAIRE |
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