Galangin Reverses Hepatic Fibrosis by Inducing HSCs Apoptosis <i>via</i> the PI3K/Akt, Bax/Bcl-2, and Wnt/β-Catenin Pathway in LX-2 Cells

Abstract

Hepatic fibrosis (HF) is a common disease, with currently no available treatment.Galangin, a natural flavonoid extracted from Alpinia officinaruim Hance, has multiple effects demonstrated in previous studies. The aim of the present study was to explore the anti-fibrogenic effect of galangin in vitro, and research its potential molecular mechanisms. LX-2 cells were chosen as an in vitro HF model, and were treated with galangin in different concentrations. Cell viability was analyzed using Cell Counting Kit-8 (CCK-8) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, cell apoptosis was measured using flow cytometry, and the anti-fibrogenic effect of galangin was determined using quantitative reverse transcription polymerase chain reaction (RT-qPCR), immunofluorescence, and western blotting. The results show that the proliferation of LX-2 cells was efficiently inhibited by galangin, and apoptosis was induced in a dose-dependent manner. Both the mRNA and protein expression of α-SMA and collagen I were markedly downregulated. Galangin also inhibited the PI3K/Akt and Wnt/β-catenin signaling pathways and increased the Bax/Bcl-2 ratio. The results of this study suggest that galangin has an anti-fibrogenic effect and may represent a promising agent in the treatment of hepatic fibrosis.

Galangin inhibits neointima formation induced by vascular injury via regulating the PI3K/AKT/mTOR pathway

“…Galangin is an extract of the ginger plant galangal, in which the main chemical component is 3,5,7-trihydroxyflavone, a polyphenolic compound. 2 Previous studies have shown that galangin has the ability to inhibit cell proliferation, 3 promote apoptosis, 4 inhibit cell metastasis, 5 and induce cell autophagy 6 as well as provide anti-inflammatory 7 and antioxidant effects. 8 In terms of mechanisms, galangin has reversed liver fibrosis by inhibiting the activation of the PI3K/AKT signaling pathway; 4 galangin has also alleviated rheumatoid arthritis by inhibiting the activation of the PI3K/AKT signaling pathway.…”

“…2 Previous studies have shown that galangin has the ability to inhibit cell proliferation, 3 promote apoptosis, 4 inhibit cell metastasis, 5 and induce cell autophagy 6 as well as provide anti-inflammatory 7 and antioxidant effects. 8 In terms of mechanisms, galangin has reversed liver fibrosis by inhibiting the activation of the PI3K/AKT signaling pathway; 4 galangin has also alleviated rheumatoid arthritis by inhibiting the activation of the PI3K/AKT signaling pathway. 9 The PI3K/AKT signaling pathway plays an important role in the process of neointimal hyperplasia after vascular injury.…”

Galangin delivered by retinoic acid-modified nanoparticles targeted hepatic stellate cells for the treatment of hepatic fibrosis

“…47,48 Based on our previous study, GA is highly effective against HF, as the inhibition of aHSC in vitro was initiated at the concentration of 6 mg mL −1 . 24 The capacity of GA-NPs and RA-GA-NPs was approximately 240 mg. This capacity could meet the requirement for drug administration and avoid toxicity induced by an overdose.…”

“…22,23 Our earlier studies also revealed that GA shows anti-brotic activity in LX-2 cells by inhibiting the PI3K/Akt pathway and its downstream pathways. 24 However, aer oral administration, GA exhibits low bioavailability due to its water-soluble hydrophobicity; this limits its clinical application.…”

Small-molecule natural products for reversing liver fibrosis based on modulation of HSCs activation: an update

“…(3) Inhibition of HSCs through induction of autophagy and natural killer cell-mediated killing: Dihydromyricetin (DHM) [228] . (4) Reverse LF by inducing HSC apoptosis through Wnt/β-linked protein, Bax/Bcl-2 as well as PI3K/Akt pathways: Galangin [229] . (5) Inhibiting HSC activation by targeting the miR-181b/PTEN axis: Liquiritigenin (LQ) [230] .…”