Lingonberry Anthocyanins Inhibit Hepatic Stellate Cell Activation and Liver Fibrosis via TGFβ/Smad/ERK Signaling Pathway

• DOI: 10.1021/acs.jafc.1c05384
• Publication Date: 2021-11-04T17:14:37Z
• Authors: Guokun Zhang; Yunyao Jiang; Xin Liu; Yongyan Deng; Bin Wei; Liyan Shi
• Keywords: Liver Cirrhosis; 0301 basic medicine; 0303 health sciences; Rats; 3. Good health; Anthocyanins; Transforming Growth Factor beta1; 03 medical and health sciences; Liver; Transforming Growth Factor beta; Hepatic Stellate Cells; Animals; Vaccinium vitis-idaea; Carbon Tetrachloride; Signal Transduction

Phytochemicals from lingonberry have rich pharmacological value and may play an essential role in treating liver diseases. We investigated the regulatory role of lingonberry anthocyanins (LA) on HSC activation in vitro and liver fibrogenesis in vivo. The viability of HSCs treated with LA was significantly reduced in a dose-dependent manner at the concentration of 25-100 μg/mL, in which the monomers of LA also reduced the proliferation of HSCs via IC50 assay. The inducer transforming growth factor β1 (TGFβ1) and the effector α-smooth muscle actin (α-SMA) of HSC activation were all decreased both in protein and RNA levels treated by LA. Moreover, LA alleviated CCl4-induced liver fibrosis in rats, reducing collagen aggregation and production and decreasing the hydroxyproline (HYP) and malondialdehyde (MDA) levels in the liver tissue. Moreover, LA reduced the indexes of serum liver fibrosis and reversed the index of serum liver function in CCl4-induced rats. Furthermore, the antioxidant enzymes, including superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT), in the liver tissue and serum were significantly increased upon treatment with LA. Importantly, LA promoted hepatic parenchymal cell proliferation and inhibited the expression of TGFβ/Smad/extracellular regulated protein kinase (ERK) signaling pathway-related genes. This study demonstrates the anti-liver fibrosis activity of LA and investigates its mechanism, which may provide a novel strategy for treating liver fibrosis using lingonberry.