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Antifibrotic Mechanism of Pinocembrin: Impact on Oxidative Stress, Inflammation and TGF-β /Smad Inhibition in Rats.
Ann Hepatol. 2018 Mar 01; 17(2):307-317.AH

Abstract

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 upregulated 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-κB (NF-κB) 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 celular antioxidant defenses, activating Nrf2-mediated HO-1 expression and modulating NF-κB and TGF-β1/Smad signaling pathway.

Authors+Show Affiliations

Pharmacist at Central Administration for Pharmaceutical Affairs, Ministry of Health, Cairo, Egypt.Pharmacology & Toxicology Department, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.Pharmacology & Toxicology Department, Faculty of Pharmacy, Egyptian Russian University, Cairo, Egypt.Pharmacology & Toxicology Department, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29469035

Citation

Said, Marwa M., et al. "Antifibrotic Mechanism of Pinocembrin: Impact On Oxidative Stress, Inflammation and TGF-β /Smad Inhibition in Rats." Annals of Hepatology, vol. 17, no. 2, 2018, pp. 307-317.
Said MM, Azab SS, Saeed NM, et al. Antifibrotic Mechanism of Pinocembrin: Impact on Oxidative Stress, Inflammation and TGF-β /Smad Inhibition in Rats. Ann Hepatol. 2018;17(2):307-317.
Said, M. M., Azab, S. S., Saeed, N. M., & El-Demerdash, E. (2018). Antifibrotic Mechanism of Pinocembrin: Impact on Oxidative Stress, Inflammation and TGF-β /Smad Inhibition in Rats. Annals of Hepatology, 17(2), 307-317. https://doi.org/10.5604/01.3001.0010.8661
Said MM, et al. Antifibrotic Mechanism of Pinocembrin: Impact On Oxidative Stress, Inflammation and TGF-β /Smad Inhibition in Rats. Ann Hepatol. 2018 Mar 1;17(2):307-317. PubMed PMID: 29469035.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Antifibrotic Mechanism of Pinocembrin: Impact on Oxidative Stress, Inflammation and TGF-β /Smad Inhibition in Rats. AU - Said,Marwa M, AU - Azab,Samar S, AU - Saeed,Noha M, AU - El-Demerdash,Ebtehal, PY - 2018/2/23/entrez PY - 2018/2/23/pubmed PY - 2019/4/23/medline KW - CCl4 KW - HO-1 KW - NF-κB KW - Nrf2 KW - Pinocembrin SP - 307 EP - 317 JF - Annals of hepatology JO - Ann Hepatol VL - 17 IS - 2 N2 - 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 upregulated 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-κB (NF-κB) 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 celular antioxidant defenses, activating Nrf2-mediated HO-1 expression and modulating NF-κB and TGF-β1/Smad signaling pathway. SN - 1665-2681 UR - https://www.unboundmedicine.com/medline/citation/29469035/Antifibrotic_Mechanism_of_Pinocembrin:_Impact_on_Oxidative_Stress_Inflammation_and_TGF_β_/Smad_Inhibition_in_Rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1665-2681(19)30163-2 DB - PRIME DP - Unbound Medicine ER -