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Curcumin downregulates Smad pathways and reduces hepatic stellate cells activation in experimental fibrosis.
Ann Hepatol. 2020 Sep - Oct; 19(5):497-506.AH

Abstract

INTRODUCTION AND OBJECTIVES

Curcumin, a polyphenol, is a natural compound that has been widely studied as a hepatoprotector; however, only a few studies have examined its ability to reduce fibrosis in previously established cirrhosis. The objective of this study was to investigate whether curcumin could reduce carbon tetrachloride (CCl4)-induced fibrosis and if so, to determine the action mechanisms involved in the reduction process.

MATERIALS AND METHODS

CCl4 was administered to male Wistar rats (400 mg/kg, three times a week, i. p.) for 12 weeks; curcumin (100 mg/kg body weight twice per day, p. o.) was administered from week 9-12 of CCl4 treatment. Biochemical markers of hepatic injury and oxidative stress were evaluated. Hematoxylin and eosin, Masson's trichrome stains, transmission electron microscopy; immunohistochemistry, and zymography assays were carried out. Moreover, Smad3 and α-SMA mRNA and protein levels were studied. Western blotting by TGF-β, CTGF, Col-I, MMP-13, NF-κB, IL-1, IL-10, Smad7, pSmad3, and pJNK proteins was developed.

RESULTS AND CONCLUSIONS

Curcumin reduced liver damage, oxidative stress, fibrosis, and restored normal activity of MMP-9 and MMP-2. Besides, curcumin restored NF-κB, IL-1, IL-10, TGF-β, CTGF, Col-I, MMP-13, and Smad7 protein levels. On the other hand, curcumin decreased JNK and Smad3 phosphorylation. Furthermore, curcumin treatment decreased α-SMA and Smad3 protein and mRNA levels. Curcumin normalized GSH, and NF-κB, JNK-Smad3, and TGF-β-Smad3 pathways, leading to a decrement in activated hepatic stellate cells, thereby producing its antifibrotic effects.

Authors+Show Affiliations

Laboratory of Experimental Hepatology, Department of Pharmacology, Cinvestav-IPN, Av. Instituto Politécnico Nacional, Mexico City, Mexico.Department of Physiology, Biophysics and Neurosciences, Cinvestav-IPN, Mexico City, Mexico.Department of Infectomics and Molecular Pathogenesis, Cinvestav-IPN, Mexico City, Mexico.School of Higher Education in Medicine-IPN, Mexico City, Mexico.Laboratory of Experimental Hepatology, Department of Pharmacology, Cinvestav-IPN, Av. Instituto Politécnico Nacional, Mexico City, Mexico.Department of Physiology, Biophysics and Neurosciences, Cinvestav-IPN, Mexico City, Mexico.Department of Infectomics and Molecular Pathogenesis, Cinvestav-IPN, Mexico City, Mexico.Laboratory of Experimental Hepatology, Department of Pharmacology, Cinvestav-IPN, Av. Instituto Politécnico Nacional, Mexico City, Mexico. Electronic address: pmuriel@cinvestav.mx.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32673649

Citation

Hernández-Aquino, Erika, et al. "Curcumin Downregulates Smad Pathways and Reduces Hepatic Stellate Cells Activation in Experimental Fibrosis." Annals of Hepatology, vol. 19, no. 5, 2020, pp. 497-506.
Hernández-Aquino E, Quezada-Ramírez MA, Silva-Olivares A, et al. Curcumin downregulates Smad pathways and reduces hepatic stellate cells activation in experimental fibrosis. Ann Hepatol. 2020;19(5):497-506.
Hernández-Aquino, E., Quezada-Ramírez, M. A., Silva-Olivares, A., Ramos-Tovar, E., Flores-Beltrán, R. E., Segovia, J., Shibayama, M., & Muriel, P. (2020). Curcumin downregulates Smad pathways and reduces hepatic stellate cells activation in experimental fibrosis. Annals of Hepatology, 19(5), 497-506. https://doi.org/10.1016/j.aohep.2020.05.006
Hernández-Aquino E, et al. Curcumin Downregulates Smad Pathways and Reduces Hepatic Stellate Cells Activation in Experimental Fibrosis. Ann Hepatol. 2020 Sep - Oct;19(5):497-506. PubMed PMID: 32673649.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Curcumin downregulates Smad pathways and reduces hepatic stellate cells activation in experimental fibrosis. AU - Hernández-Aquino,Erika, AU - Quezada-Ramírez,Marco A, AU - Silva-Olivares,Angélica, AU - Ramos-Tovar,Erika, AU - Flores-Beltrán,Rosa E, AU - Segovia,José, AU - Shibayama,Mineko, AU - Muriel,Pablo, Y1 - 2020/07/14/ PY - 2020/03/02/received PY - 2020/05/06/revised PY - 2020/05/28/accepted PY - 2020/7/17/pubmed PY - 2021/8/24/medline PY - 2020/7/17/entrez KW - CCl(4) KW - Curcumin KW - Fibrosis KW - HSC. KW - Smad KW - TGF-β SP - 497 EP - 506 JF - Annals of hepatology JO - Ann Hepatol VL - 19 IS - 5 N2 - INTRODUCTION AND OBJECTIVES: Curcumin, a polyphenol, is a natural compound that has been widely studied as a hepatoprotector; however, only a few studies have examined its ability to reduce fibrosis in previously established cirrhosis. The objective of this study was to investigate whether curcumin could reduce carbon tetrachloride (CCl4)-induced fibrosis and if so, to determine the action mechanisms involved in the reduction process. MATERIALS AND METHODS: CCl4 was administered to male Wistar rats (400 mg/kg, three times a week, i. p.) for 12 weeks; curcumin (100 mg/kg body weight twice per day, p. o.) was administered from week 9-12 of CCl4 treatment. Biochemical markers of hepatic injury and oxidative stress were evaluated. Hematoxylin and eosin, Masson's trichrome stains, transmission electron microscopy; immunohistochemistry, and zymography assays were carried out. Moreover, Smad3 and α-SMA mRNA and protein levels were studied. Western blotting by TGF-β, CTGF, Col-I, MMP-13, NF-κB, IL-1, IL-10, Smad7, pSmad3, and pJNK proteins was developed. RESULTS AND CONCLUSIONS: Curcumin reduced liver damage, oxidative stress, fibrosis, and restored normal activity of MMP-9 and MMP-2. Besides, curcumin restored NF-κB, IL-1, IL-10, TGF-β, CTGF, Col-I, MMP-13, and Smad7 protein levels. On the other hand, curcumin decreased JNK and Smad3 phosphorylation. Furthermore, curcumin treatment decreased α-SMA and Smad3 protein and mRNA levels. Curcumin normalized GSH, and NF-κB, JNK-Smad3, and TGF-β-Smad3 pathways, leading to a decrement in activated hepatic stellate cells, thereby producing its antifibrotic effects. SN - 1665-2681 UR - https://www.unboundmedicine.com/medline/citation/32673649/Curcumin_downregulates_Smad_pathways_and_reduces_hepatic_stellate_cells_activation_in_experimental_fibrosis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1665-2681(20)30065-X DB - PRIME DP - Unbound Medicine ER -