Avaliação do metoxieugenol e do extrato de Baccharis anomala DC. no tratamento de fibrose hepática

Abstract

Liver fibrosis is a disease that has its development linked to chronic liver damage, often due to viral infections, alcohol and drugs abuse toxins or metal accumulation. Chronic liver damage leads to a continuous inflammatory process that can result in activation of hepatic stellate cells. The activated phenotype of hepatic stellate cells disrupts the balance between synthesis and degradation of extracellular matrix elements, and this process is responsible for initiating the fibrotic process. The progression of liver fibrosis is often detected in late stages of disease and may result in the last stage of chronic liver disease, known as cirrhosis, leading to the risk of liver failure. Currently, liver fibrosis has no well-established treatment, however, the first goal for therapy is to identify and remove the cause of chronic damage and to use therapies capable of reducing activation, proliferation or even inducing apoptosis in hepatic stellate cells. In addition, molecules with an antioxidant effect have shown good effects in decreasing oxidative stress damage. Thus, the search for new candidates for the treatment of liver fibrosis is necessary, and for this, the investigation of molecules from natural and renewable sources seems to be promising, since it is currently known that the secondary metabolites of many plant species have high applicability for the development of new drugs. Thus, the present study investigated the effects of two treatments that have in common, their natural source and their phytochemical composition, mainly composed of phenolic compounds. In the first in vitro and in vivo study, the methoxyeugenol molecule demonstrated a modulatory effect on activated hepatic stellate cells, reducing its activation markers (Col-1, α-SMA and 7 TGF-β e) and inducing to its quiescent phenotype. Also, the treatment was able to activate the PPAR-γ transcription factor, and when in the presence of its inhibitor, GW9662, the effect of methoxyeugenol was suppressed, showing the interaction of PPAR-γ activation in the observed effects. Furthermore, it showed hepatoprotective effect in vivo in mice, attenuating the development of fibrosis and decreasing the activation of NF-kB-mediated inflammatory pathways. In the second in vivo study, treatment with B.anomala extract decreases oxidative stress damage (TBARS and DCFH-DA), reduced activation of pro-inflammatory genes (TNF-α, NF-kB, IL-6 and iNOS ) and protected the animals' livers from the development of fibrosis. The main components of the extract identified by HPLC were caffeic, gallic and coumaric phenolic acids.