# Baccharis articulata aqueous extract exerts in vitro antifibrotic effect in hepatic stellate cells by attenuating collagen deposition and TGF-ß1 protein expression

## TL;DR

A Brazilian plant extract shows antifibrotic effects in liver cells by reducing collagen and TGF-β1, suggesting potential for treating liver fibrosis.

## Contribution

Demonstrates the antifibrotic potential of Baccharis articulata extract in hepatic stellate cells through TGF-β1 inhibition and lipid accumulation.

## Key findings

- The extract reduced collagen content and TGF-β1 protein expression in hepatic stellate cells.
- Treatment induced lipid accumulation, reverting cells to a quiescent state without cytotoxicity.
- Caffeoylquinic acids in the extract may contribute to antifibrotic effects.

## Abstract

Baccharis articulata (Lam) Pers. is an herb native to southern Brazil and is widely used in local traditional medicine for weight loss and for the treatment of digestive and liver diseases. However, only a few studies have been conducted to scientifically validate the folk use of this plant. This study assessed the in vitro therapeutic effects of an aqueous extract of B. articulata and chlorogenic acid on liver fibrosis in murine hepatic stellate cells (HSC; GRX cell line). The decrease in cell proliferation and cytotoxicity, as well as phenotypic reversion by the presence of lipid droplets and reduction in collagen content after seven days of treatment, were evaluated. The mechanisms responsible for the antifibrotic effects of the extract, including the plasminogen activation system, were assessed. from high-performance liquid chromatography coupled with diode array detector and tandem mass spectrometry (HPLC-DAD-MS/MS) data. Twenty-six metabolites were identified in the extract, including flavonoids, phenylpropanoid derivatives, and diterpenes. Treatment with the extract significantly induced the accumulation of lipids in the cytoplasm of cells, indicating that it could revert the HSC phenotype to a quiescent state with no cytotoxic or antiproliferative effects. These findings may be related to the inhibition of the TGF-β1 pathway, a biomarker of liver fibrosis, upregulation of the plasminogen system, and dose-dependent inhibition of plasmin activity. The presence of caffeoylquinic acids seems to be partially related to the extract effect, as chlorogenic acid displayed antiproliferative activity and reduced collagen content in hepatic stellate cells. Considering the unmet need for antifibrotic therapies, the use of medicinal plants to inhibit the proliferation of activated HSC is promising, and this study indicated that the aqueous extract of B. articulata has potential therapeutic activity against hepatic fibrosis (see also Figure 1(Fig. 1) graphical abstract).