Antifibrotic effects of gallic acid on hepatic stellate cells: In vitro and in vivo mechanistic study

Abstract

Few studies reported the antifibrotic effects of gallic acid (GA) despite its known hepatoprotective and antioxidant activities. Accordingly, this study investigated the antifibrotic effects of GA through clarifying its mechanisms on hepatic stellate cells' (HSCs) activation, proliferation and/or apoptosis. In vitro effects of GA on HSC-T6 activation/proliferation, morphology and safety on hepatocytes were assessed. In vivo, hepatic fibrosis was induced via chronic thioacetamide (TAA)-intoxication. TAA-intoxicated rats were treated with silyamrin or GA. At end of experiment, liver functions, hepatic MDA, GSH, PDGF-BB, TGF-β1, TIMP-1 and hydroxyproline were determined. Histological analysis and Sirius red staining of hepatic sections, expressions of alpha-smooth muscle actin (α-SMA), proliferating cellular nuclear antigen (PCNA) and caspase-3 were examined. In vitro, GA resulted in a concentration and time-dependent inhibition in HSCs activation, proliferation (IC50= 45 and 19 μg/mL at 24 and 48 h respectively); restored the quiescent morphology of some activated HSCs plus its safety on hepatocytes. In vivo, GA reduced ALT, AST, MDA, PDGF-BB levels, collagen deposition and fibrosis score (S1 vs S4); increased caspase-3 expression and restored GSH stores, TGF-β1 level, α-SMA and PCNA expressions. In conclusion, GA counteracted the progression of hepatic fibrosis through reduction of HSCs proliferation/activation mutually with their apoptosis induction.

Polyphenols from Tamarix nilotica: LC–ESI-MSn Profiling and In Vivo Antifibrotic Activity

“…The underlying mechanism could be—at least partly—due to restraining of the oxidative stress through GSH replenishment along with inhibiting the inflammatory response. These findings stands in line with previous reports that confirms the antifibrotic activity of quercetin [ 49 , 50 ], kaempferol [ 51 ], gallic acid [ 52 ] or falvonoids [ 53 ]. In addition to the earlier report which refer the in vivo hepatoprotective properties of T. nilotica flowers to its phenolic constituents [ 8 ].…”

Characterizations and Assays of α-Glucosidase Inhibition Activity on Gallic Acid Cocrystals: Can the Cocrystals be Defined as a New Chemical Entity During Binding with the α-Glucosidase?

“…Gallic acid (GA) is a phenolic compound that exists in Chinese gallnut, dogwood, pomegranate, palmate-leaf rhubarb, peony bark, tea and other plants. GA possesses various pharmacological activities, including anti-inflammatory, antioxidant, antibacterial and antiviral properties [9][10][11][12][13] and provides broad application prospects for diseases, such as cardiovascular [14] and neurological [15] diseases, diabetes [16], liver fibrosis [17] and tumors [18]. Furthermore, it was reported that GA showed an obvious inhibitory activity on α-amylase and α-glucosidase, the latter being a target protein in hypoglycemic mechanisms [19].…”

Salacia chinensis L. Stem Extract Exerts Antifibrotic Effects on Human Hepatic Stellate Cells through the Inhibition of the TGF-β1-Induced SMAD2/3 Signaling Pathway

“…However, the Thai traditional formulation for hepatic fibrosis treatment contains Salacia chinensis L. stem water extraction, in which gallic acid was found to be a main component. Moreover, the recent publication revealed the effects of gallic acid on hepatic fibrosis by increasing HSCs apoptosis and reducing hepatocyte oxidative stress [30]. These results suggest that the antifibrotic activities of Salacia chinensis L. stem water extract possibly come from gallic acid.…”