Cellular and molecular effects of Baccharis dracunculifolia D.C. and Plectranthus barbatus Andrews medicinal plant extracts on retinoid metabolism in the human hepatic stellate cell LX-2

Caio Mateus Da Silva,Kumiko Koibuchi Sakane,Maria Aparecida Marin Morales,Franco Dani Campos Pereira,Karen C M Moraes,Flávio Henrique Caetano

doi:10.1186/s12906-019-2591-8

Abstract

BackgroundChronic hepatic diseases are serious problems worldwide, which may lead to the development of fibrosis and eventually cirrhosis. Despite the significant number of people affected by hepatic fibrosis, no effective treatment is available. In the liver, hepatic stellate cells are the major fibrogenic cell type that play a relevant function in chronic liver diseases. Thus, the characterization of components that control the fibrogenesis in the hepatic stellate cells is relevant in supporting the development of innovative therapies to treat and/or control liver fibrosis. The present study investigated the effects of Baccharis dracunculifolia D.C. and Plectranthus barbatus Andrews medicinal plant extracts in LX-2 transdifferentiation.MethodsLX-2 is a human immortalized hepatic stellate cell that can transdifferentiate in vitro from a quiescent-like phenotype to a more proliferative and activated behavior, and it provides a useful platform to assess antifibrotic drugs. Then, the antifibrotic effects of hydroalcoholic extracts of Baccharis dracunculifolia and Plectranthus barbatus medicinal plants on LX-2 were evaluated.ResultsThe results in our cellular analyses, under the investigated concentrations of the plant extracts, indicate no deleterious effects on LX-2 metabolism, such as toxicity, genotoxicity, or apoptosis. Moreover, the extracts induced changes in actin filament distribution of activated LX-2, despite not affecting the cellular markers of transdifferentiation. Consistent effects in cellular retinoid metabolism were observed, supporting the presumed activity of the plant extracts in hepatic lipids metabolism, which corroborated the traditional knowledge about their uses for liver dysfunction.ConclusionThe combined results suggested a potential hepatoprotective effect of the investigated plant extracts reinforcing their safe use as coadjuvants in treating imbalanced liver lipid metabolism.

Highlights

Chronic hepatic diseases are serious problems worldwide, which may lead to the development of fibrosis and eventually cirrhosis
Because the Hepatic Stellate Cells (HSC) are extremely responsive to liver injury, the present study investigated cellular and molecular effects of Baccharis dracunculifolia and Plectranthus barbatus leaf extracts in LX-2 cells cultivated under activated conditions
The potential toxicity of B. dracunculifolia and P. barbatus extracts in hepatic stellate cells Thiazolyl Blue Tetrazolium Bromide (MTT) analyses were performed to establish the optimal concentrations of the plant extracts used in the present study

Summary

Introduction

Chronic hepatic diseases are serious problems worldwide, which may lead to the development of fibrosis and eventually cirrhosis. The characterization of components that control the fibrogenesis in the hepatic stellate cells is relevant in supporting the development of innovative therapies to treat and/or control liver fibrosis. Hepatic stellate cells (HSCs) play a key role in the development of fibrosis [6, 7]. In healthy tissues, those cells maintain a quiescent-like phenotype, containing lipid droplets (LDs) that are rich in triglycerides, retinyl esters and cholesterol esters [8,9,10]. The transdifferentiation induces cellular cytoskeleton changes through the development of prominent cytoplasmic fibers and increased cell size [12]. The clarification of molecular routes that support the mechanisms of cellular transdifferentiation could contribute to innovative strategies to treat hepatic fibrosis

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Conclusion