Antifibrotic effect of Pluchea sagitallis (Lam.) cabrera aqueous extract in grx cell lineage

Authors

  • Fabiana Garbachi de Oliveira Mendes Ouri Laboratório de Pesquisa em Biofísica Celular e Inflamação Cellular Biophysics and Inflammation Laboratory, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Brazil.
  • Paula Bacaicoa Caruso Laboratório de Pesquisa em Biofísica Celular e Inflamação Cellular Biophysics and Inflammation Laboratory, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Brazil.
  • Gabriela Viegas da Silva Laboratório de Pesquisa em Biofísica Celular e Inflamação Cellular Biophysics and Inflammation Laboratory, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Brazil.
  • Henrique Dias Laboratório de Pesquisa em Biofísica Celular e Inflamação Cellular Biophysics and Inflammation Laboratory, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Brazil.
  • Juliana Romeu Marques Laboratório de Pesquisa em Biofísica Celular e Inflamação Cellular Biophysics and Inflammation Laboratory, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Brazil.
  • Fernanda Bordignon Nunes 1- Laboratório de Pesquisa em Biofísica Celular e Inflamação Cellular Biophysics and Inflammation Laboratory, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Brazil. 2- Departamento de Ciências Básicas da Saúde, Universidade Federal de Ciências da Saúde de Porto Alegre, Brazil
  • Pedro Maria de Abreu Ferreira Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Brazil.
  • Jarbas Rodrigues de Oliveira Laboratório de Pesquisa em Biofísica Celular e Inflamação, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Avenida Ipiranga 6681, prédio 12, bloco C, sala 221, CEP 90619-900, Porto Alegre, Rio Grande do Sul, Brazil.

Keywords:

hepatic fibrosis, hepatic stellate cell, Pluchea sagitallis

Abstract

Liver fibrosis is a complex disease that is caused by inappropriate tissue repair due to the deposition of connective tissue. When a chronic lesion affects the liver, regenerative response fails and hepatocytes are replaced with abundant extracellular matrix (ECM). The imbalance between production and degradation of ECM will result in the accumulation of proteins that change normal liver architecture, and thus its functionality. The main source of ECM is the activated hepatic stellate cell (HSC). In order, to clarify possible therapeutic approaches to the disease, this work aimed to evaluate the possible antifibrotic action of Pluchea sagitallis (Lam.) Cabrera on an activated HSC immortalized lineage (GRX). Our results demonstrated that the P. sagittalis aqueous extract at 0.039 and 0.078 mg/mL concentrations was able to reduce cell growth and proliferation. Regarding to oxidative stress evaluation, there was no statistically significant difference between the treated group and the control. Staining with OilRed-O (ORO) showed a statistically significant increase in intracellular lipid content after 5 days of treatment, exerting in vitro effect on the GRX phenotypic change of activated towards the quiescent state. These results were confirmed by colorimetric quantification of lipid content. Regarding the TGF-β1 and collagen production, there were no statistically significant differences observed between the groups. In conclusion, the P. sagittalis aqueous extract reduces the growth and proliferation of GRX cells and induces the reversal of activated towards a quiescent phenotype. There was no decrease in cell proliferation either by necrosis or by apoptosis via activation of the senescence. Thus, our data suggest that the extract showed an antifibrotic effect, possibly by activating phenotype reversal.

References

Bissell DM, Roulot D, George J. Transforming growth

factor beta and the liver. Hepatology;2001(34):859–67.

Bitencourt S, de Mesquita FC, Caberlon E, da Silva GV,

Basso BS, Ferreira GA, de Oliveira JR. Capsaicin induces de-differentiation of activated hepatic stellate cell.

Biochem Cell Biol 2012;.

Borojevic R, Monteiro AN. Vinhas SA, Domont GB,

Moura˜o PA, Emonard H, Grimaldi G, Grimaud JA. Establishment of a continuous cell line from fibrotic schistosomal granulomas in mice livers. vol. 1985;.

Bradford MM. A rapid and sensitive method for

the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal

Biochem;1976(72):248–54.

Co´rdova WHP, Mesa. LG, Hill ALP. Metabo´litos secundarios y actividad antimicrobiana de Pluchea carolinensis.

Revista Cubana de Farma´cia;2006(40).

Co´rdova WHP, Tabart J. Quesada AG, Sipel A, Hill ALP,

Kevers C, Dommes J. Antioxidant capacity of three Cuban

species of the genus Pluchea. Cass( Asteraceae) Journal of

Food Biochemistry;2010(34):249–261.

Duval F. Moreno-Cuevas JE, Gonza´lez-Garza MT,

Rodr´ıguez-Montalvo C, Cruz-Vega DE. Liver fibrosis and

protection mechanisms action of medicinal plants targeting

apoptosis of hepatocytes and hepatic stellate cells;.

Duval F. Moreno-Cuevas JE, Gonza´lez-Garza MT,

Rodr´ıguez-Montalvo C, Cruz-Vega DE. Protective mechanisms of medicinal plants targeting hepatic stellate cell

activation and extracellular matrix deposition in liver fibrosis. Chin Med;2014(9):27–10.

Ferris H, Zheng L. Plant Sources of Chinese Herbal Remedies: Effects on Pratylenchus vulnus and Meloidogyne javanica. J Nematol;1999(31):241–63.

Filippi-Chiela EC, Oliveira MM, Jurkovski B, CallegariJacques SM, da Silva VD, Lenz G. Nuclear morphometric

analysis (NMA): screening of senescence, apoptosis and

nuclear irregularities. PLoS One;2012(7):10–1371.

Friedman SL. Molecular regulation of hepatic fibrosis,

an integrated cellular response to tissue injury. J Biol

Chem;2000(275):2247–50.

Friedman SL. Hepatic fibrosis-overview.

Toxicology;2008(254):120–9.

Friedman SL. Hepatic stellate cells: protean, multifunctional, and enigmatic cells of the liver. Physiol

Rev;2008(88):125–72.

Guimara˜es EL. Franceschi MF, Grivicich I, Dal-Pizzol

F, Moreira JC, Guaragna RM, Borojevic R, Margis R,

Guma FC. Relationship between oxidative stress levels

and activation state on a hepatic stellate cell line. Liver

Int;2006(26):477–85.

Halliwell B, Whiteman M. Measuring reactive species

and oxidative damage in vivo and in cell culture: how

should you do it and what do the results mean? Br J

Pharmacol;142(231-55):10–1038.

Kissmann KG, Groth D. Plantas Infestantes e Nocivas.

BASF Brasileira S/A 2ª. 1992;2.

Lotersztajn S, Julien B. Clere FT, Grenard P, Mallat AH.

Hepatic fibrosis: Molecular mechanisms and drug targets.

Annu harmacol Toxicol;2005(45):605–28.

McCuskey RS. Functional morphology of the liver with

emphasis on microvasculature. In: Tavaloni N, Berk PD

eds. Hepatic transport and bile secretion: physiology and

pathophysiology. New York: Raven Press Ltd.1993;1-10;.

Neuman MG. Apoptosis in diseases of the liver. vol. 2001;.

Pe´rez-Garc´ıa F, Mar´ın E. Adzet T, Can˜igueral S. Activity of plant extracts on the respiratory burst and the stress

protein synthesis. Phytomedicine;2001(8):31–8.

Pe´rez-Garc´ıa F, Mar´ın E. Can˜igueral S, Adzet T. Antiinflammatory action of Pluchea sagittalis: involvement of

an antioxidant mechanism. Life Sci;1996(59):2033–40.

Ram´ırez-Zacar´ıas JL, Castro-Mun˜ozledo F, Kuri-Harcuch

W. Quantitation of adipose conversion and triglycerides

by staining intracytoplasmic lipids with Oil red O. Histochemistry; 1992.

Reyes-Trejo B, Joseph-Nathan P. Modhephene derivates

from Pluchea sericea. Phytochemistry;1999(51):75–78.

Rockey D. The cellular pathogenesis of portal hypertension: stellate cell contractility, endothelin, and nitric oxide.

Hepatology;1997(25):2–5.

Souza IC, Martins LA. Coelho BP, Grivicich I, Guaragna

RM, Gottfried C, Borojevic R, Guma FC. Resveratrol inhibits cell growth by inducing cell cycle arrest in activated

hepatic stellate cells. Mol Cell Biochem;.

Spiller F. Anti-inflammatory effects of red pepper (Capsicum baccatum) on carrageenan- and antigen-induced inflammation. J Pharm Pharmacol;2007(60).

Vicente CP, Fortuna VA, Margis R. Trugo L, Borojevic R.

Retinol uptake and metabolism, and cellular retinol binding protein expression in an in vitro model of hepatic stellate cells. Mol Cell Biochem;1998(187):11–21.

Winau F. Quack C, Darmoise A, Kaufmann SH. Starring stellate cells in liver immunology. Curr Opin

Immunol;2008(20):68–74.

Ye Y, Dan Z. All-trans retinoic acid diminishes collagen

production in a hepatic stellate cell line via suppression

of active protein-1 and c-Jun N-terminal kinase signal. J

Huazhong Univ Sci Technolog Med Sci;2010(30):726–33

Downloads

Published

31-03-2018

How to Cite

1.
Fabiana Garbachi de Oliveira Mendes Ouri, Paula Bacaicoa Caruso, Gabriela Viegas da Silva, Henrique Dias, Juliana Romeu Marques, Fernanda Bordignon Nunes, Pedro Maria de Abreu Ferreira, Jarbas Rodrigues de Oliveira. Antifibrotic effect of Pluchea sagitallis (Lam.) cabrera aqueous extract in grx cell lineage. ijp [Internet]. 2018 Mar. 31 [cited 2024 Oct. 22];10(1):30-8. Available from: https://ijp.arjournals.org/index.php/ijp/article/view/587

Issue

Section

Original Research Articles