Cranberry (Vacinium macrocarpon) phytochemicals inhibit hepatic stellate cell activation and liver fibrosis

Shi, Liyan; Zhang, Xiuli; Liu, Xin; Jiang, Yunyao; Deng, Yongyan; Liu, Junzhi

doi:10.1016/j.fbio.2021.101176

Cited by 7 publications

(9 citation statements)

References 30 publications

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“…At the same time, it synthesizes a large amount of ECM and expresses the HSC marker α-SMA . In this study, we used the self-activated HSC-T6 line for the in vitro study. ,,, We found that LA can inhibit HSC activation as detected in the high expression levels of α-SMA and TGFβ1 (Figure ), suggesting that there must be one or several monomers that can play a significant role in LA. Thus, the IC50 values of LA monomers between 22.8 and 76.2 are detected (Table ).…”

Section: Discussionmentioning

confidence: 90%

“…The HSCs were cultured in 24-well plates (1 × 10 5 cells/mL, 0.5 mL) treated with LA or silymarin (SL) (Yuanye, Shanghai, China) at different concentrations (25 or 50 μg/mL) for 48 h. Then, the cells were fixed with 4% paraformaldehyde for IF staining performed as previously described. − Fixed cells were permeabilized with 0.3% Triton X-100 (Sigma-Aldrich, USA) for 20 min and then blocked in 3% bovine serum albumin (BSA) for 30 min. Subsequently, the cells were incubated with primary antibodies transforming growth factor-β1 (TGFβ1) and α-smooth muscle actin (α-SMA), respectively, for 12 h at 4 °C.…”

Section: Methodsmentioning

confidence: 99%

“…Tissues (0.1 g) of the liver were homogenized with 1 mL of normal saline and then centrifuged (8000 g ) for 10 min at 4 °C and the supernatant was taken to be tested. The levels of hydroxyproline (HYP) and malondialdehyde (MDA) were detected by the spectrophotometric method according to the instruction manuals of the HYP and MDA assay kits (BC0250 and BC0025, Solarbio, China) …”

Section: Methodsmentioning

confidence: 99%

“…Then, RNA was reverse transcribed to synthesize cDNA. A 20 μL system, including cDNA, primers (Table S2), and SYBR Green (SYBR), was used for qRT-PCR analysis as previously described. − …”

Section: Methodsmentioning

confidence: 99%

“…The levels of hydroxyproline (HYP) and malondialdehyde (MDA) were detected by the spectrophotometric method according to the instruction manuals of the HYP and MDA assay kits (BC0250 and BC0025, Solarbio, China). 20 Activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) in the liver tissues and serum samples were also detected using kits (BC0175, BC1175, and BC0205, Solarbio, China) by the spectrophotometric method according to the instruction manuals.…”

Section: ■ Introductionmentioning

confidence: 99%

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

Zhang

Jiang

Liu

et al. 2021

J. Agric. Food Chem.

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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.

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Section: Discussionmentioning

confidence: 90%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%

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

Zhang

Jiang

Liu

et al. 2021

J. Agric. Food Chem.

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Proanthocyanidins attenuated liver damage and suppressed fibrosis in CCl4-treated rats

Othman

EL-Missiry

Farag

et al. 2022

Environ Sci Pollut Res

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Liver damage and fibrosis are serious health problems without effective treatment. Proanthocyanidins (PAs) are flavonoids with several biological effects. We investigated the potential anti-fibrotic effect of proanthocyanidins on carbon tetrachloride (CCl4)-induced liver injury and fibrosis. Liver fibrosis was induced by oral administration of CCl4 three times a week for 5 and 9 weeks. PAs were daily administered in a dose of 500 mg/kg bw. Animals were divided into five groups: control groups, olive oil-treated group, Pas-treated group, CCl4-treated animals, and PAs + CCl4-treated rats. CCl4 and PAs were administered by gavage. Administration of CCl4 caused a significant elevation in alanine aminotransferase and aspartate aminotransferase activities, the concentration of alpha-2-macroglobulin, and bilirubin concentration. In addition, the protein and apolipoprotein contents were significantly decreased in the serum of CCl4-treated rats. These results were accompanied by histopathological alterations and increased inflammation, apoptosis, and DNA damage. Treatment with PAs caused remarkable regression of fibrosis and alpha-2-macroglobulin with improvement in histological characteristics of the liver after 5 and 9 weeks of intoxication. PAs could also maintain redox balance, evidenced by the prevention of lipid peroxidation and mitigation of the decrease in antioxidants. Treatment of intoxicated rats with PAs resulted in a significant decline in pro-inflammatory cytokines, including IL-6, IL-1β, and TNF-α in serum. This is associated with a remarkable decrease in apoptosis of hepatic cells shown by decreased levels of Bax, caspase-3, and -9, with increased Bcl-2. The protective effect of PAs was also evident by protecting DNA integrity in the intoxicated rats. PAs suppressed hepatic fibrosis, improved liver function and structure via modulating the interdependence between oxidative stress, inflammation, apoptosis, and DNA integrity in CCl4-treated rats.

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An updated review on chemical compositions, biological capabilities, and clinical benefits of cranberries

et al. 2023

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Cranberry (Vacinium macrocarpon) phytochemicals inhibit hepatic stellate cell activation and liver fibrosis

Cited by 7 publications

References 30 publications

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

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

Proanthocyanidins attenuated liver damage and suppressed fibrosis in CCl4-treated rats

An updated review on chemical compositions, biological capabilities, and clinical benefits of cranberries

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