Animal models for liver disease – A practical approach for translational research

Benzothiadiazole-based non-fullerene acceptors

Purpose
Liver fibrosis is a worldwide health issue. Development of effective new drugs for treatment of this disease is of great importance. This study investigated the therapeutic effects of ferulic acid on liver fibrosis in vitro and in vivo.

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Ferulic acid attenuates liver fibrosis and hepatic stellate cell activation via inhibition of TGF-β/Smad signaling pathway.

Phenylpropanoids and their derivatives are plant secondary metabolites widely present in fruits, vegetables, cereal grains, beverages, spices and herbs. They are known to have multifaceted effects which include antimicrobial, antioxidant, anti-inflammatory, antidiabetic, anticancer activities and as well as exhibits renoprotective, neuroprotective, cardioprotective and hepatoprotective effects. Owing to their antioxidant, antimicrobial and photoprotective properties, these compounds have wide application in the food (preservation, packaging films and edible coating), pharmaceutical, cosmetic and other industries such as textile (colorant), biofuel (antioxidant additive) and sensors (sensing biologically relevant molecules). Phenylpropanoids are present in commercially available dietary supplements and skin care products. In this review, we have presented the current knowledge on the biosynthesis, occurrence, biological activities of phenylpropanoids and their derivatives, along with the mechanism of action and their potential applications in various industries.

Phenylpropanoids and its derivatives: biological activities and its role in food, pharmaceutical and cosmetic industries.

Methyl ferulic acid attenuates liver fibrosis and hepatic stellate cell activation through the TGF-β1/Smad and NOX4/ROS pathways.

Hepatoprotective effects of Methyl ferulic acid on alcohol-induced liver oxidative injury in mice by inhibiting the NOX4/ROS-MAPK pathway.

The present study aimed to investigate the hepatoprotective effects of methyl ferulic acid (MFA) against oxidative stress and apoptosis in acute liver injury induced by carbon tetrachloride (CCl4) in rats, as well as the underlying mechanisms. Sprague Dawley rats were treated with CCl4 after oral administration of MFA (25, 50, and 100 mg/kg) or dimethyl diphenyl bicarboxylate (200 mg/kg) for 7 days. The hepatoprotective effects of MFA were determined by analyzing serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities as well as changes of oxidant parameters. Histopathological analysis was performed to determine the degree of hepatic injury. The mechanisms were investigated by detecting the levels of NADPH oxidase (NOX) trans-membrane subunit NOX4, its ligand p22phox, as well as caspase3, cleaved caspase3, B-cell lymphoma (Bcl)-2, Bcl-2-associated X protein (Bax), tumor necrosis factor (TNF)-α, interleukin (IL)-1, reactive oxygen species (ROS), thiobarbituric acid-reactive substances (TBARS), total anti-oxidant capacity (TAC), phosphorylated J-Jun N-terminal kinase (p-JNK) and p-p38 mitogen-activated protein kinase (MAPK) using semi-quantitative polymerase chain reaction, western blot analysis and colorimetric assays. MFA treatment significantly decreased serum enzymatic activities of ALT and AST. MFA markedly increased activities of liver superoxide dismutase, catalase and glutathione peroxidase, and reduced the malondialdehyde concentration. Histopathological examination demonstrated that MFA reduced lipid degeneration, cytoplasmic vacuolization, necrosis and inflammatory cell infiltration in the liversof CCl4-treated rats. MFA treatment markedly inhibited the expression of inflammatory factors TNF-α and IL-1β. Mechanistic study revealed that MFA decreased the TAC and the levels of ROS and TBARS. Furthermore, MFA treatment led to a reduction of the mRNA and protein expression of NOX4 and p22phox, as well as the protein levels of caspase3, cleaved caspase-3 and Bax, and an upregulation of p-JNK, p-p38 MAPK and Bcl-2 proteins in the liver. The present study demonstrated that MFA has hepatoprotective effects against CCl4-induced acute liver damage. MFA has anti-oxidant, anti-inflammatory and anti-apoptotic activities and was able to modulate the NOX4/p22phox/ROS-JNK/p38 MAPK signaling pathway.

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Hepatoprotective effect of methyl ferulic acid against carbon tetrachloride-induced acute liver injury in rats.

Methyl ferulic acid attenuates ethanol-induced hepatic steatosis by regulating AMPK and FoxO1 Pathways in Rats and L-02 cells.

The aim of the present study was to assess the molecular mechanism of ethanol‑induced oxidative stress‑mediated apoptosis in L‑02 liver cells in order to elucidate novel pathways associated with alcoholic liver disease. L‑02 cells were treated with 400 mM ethanol with or without inhibitors. The cell viability was measured by an MTT assay. Cell apoptosis was assessed by flow cytometry and a single‑stranded DNA (ssDNA) assay. Intracellular reactive oxygen species (ROS) production of L‑02 cells was determined using the 2',7'‑dichlorofluorescein‑diacetate dye. The protein expression of c‑Jun N‑terminal kinase (JNK), phosphorylated (p)‑JNK, P38, p‑P38, NADPH oxidase (NOX)1, NOX4, p22phox, B‑cell lymphoma 2 (Bcl‑2) and Bcl‑2‑associated X protein were measured by western blot analysis. The mRNA expression of NOX1, NOX4 and p22phox was measured by reverse transcription polymerase chain reaction analysis. The results indicated that after treatment with various concentrations of ethanol for the indicated durations, L‑02 cells were displayed a significant decrease in cell viability in a dose‑and time‑dependent manner. Ethanol‑induced apoptosis and cell death of L‑02 cells was accompanied by the generation of ROS, elevated expression of NOX, as well as phosphorylation of JNK and P‑38. In addition, increased expression of Bcl‑2 was induced by 400 mM ethanol. Furthermore, treatment with NOX inhibitor attenuated the ethanol‑induced a decrease in cell viability, and an increase in apoptosis and Bcl‑2 expression. In conclusion, ethanol induced apoptosis in the L‑02 hepatocyte cell line via generation of ROS and elevated expression of NOX4. This indicated that activation of JNK and p38 in the mitogen‑activated protein kinase pathway promotes apoptosis in L‑02 cells.

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Li Li

Papers

Methyl ferulic acid attenuates liver fibrosis and hepatic stellate cell activation through the TGF-β1/Smad and NOX4/ROS pathways.

Hepatoprotective effects of Methyl ferulic acid on alcohol-induced liver oxidative injury in mice by inhibiting the NOX4/ROS-MAPK pathway.

Hepatoprotective effect of methyl ferulic acid against carbon tetrachloride-induced acute liver injury in rats.

Methyl ferulic acid attenuates ethanol-induced hepatic steatosis by regulating AMPK and FoxO1 Pathways in Rats and L-02 cells.

NOX4/ROS mediate ethanol‑induced apoptosis via MAPK signal pathway in L‑02 cells.