Anti-alcohol liver disease effect ofGentianae macrophyllaeextract through MAPK/JNK/p38 pathway

Abstract

Objectives The hepatoprotective effect of Gentianae macrophyllae root extract (GME) on alcoholic liver disease (ALD) was evaluated through ethanol induced ALD animal model. Methods Mice were randomly divided into control normal group (10 mice), ethanol‐induced ALD model group (10 mice) and GME plus ethanol group (30 mice). Mice in model group were given intragastric administration with 50% (v/v) ethanol aqueous solution (200 μl for each) once daily for 19 days. Mice in control normal group received equal volumes of water. Mice in GME plus ethanol group were given intragastric administration with 50% (v/v) ethanol aqueous solution (200 μl for each) once daily at 10:00 a.m., after 1 h, mice in GME group sequentially were treated with 20, 40 and 100 mg/kg of GME by gastric gavage for 19 days. the average food and water consumed by the mice in every group were recorded every 2 days and body weight of every mouse in every group was measured every 2 days. Key findings Results showed that GME significantly improved alcohol induced liver injury in a dose‐dependent manner. The impaired hepatic tissue structure was repaired and the collagen deposition declined after GME administration. Meanwhile, the level of malonaldehyde (MDA), Aspartate transaminase (AST) and alanine transaminase (ALT) (indicators of liver damage) in blood serum were significantly controlled by GME with a dose‐dependent manner, moreover, body weight and liver index were also improved after administration of GME. Pro‐inflammatory cytokines including MCP‐1, TNF‐α, IL‐1 and IL‐6 were detected through RT‐PCR and ELISA in experiment and GME can significantly inhibit the expression of TNF‐α, IL‐1 and IL‐6 but have no effect on MCP‐1. In order to explore the mechanism of GME on ALD, MAPKs pathway was examined and results indicated that GME attenuated ALD through inhibiting the phosphorylation of JNK and P38 and further suppressing the initiation of inflammation. Conclusions GME attenuated ALD through inhibiting the phosphorylation of JNK and P38 and further suppressing the initiation of inflammation.

RETRACTED: microRNA-155 Modulates Hepatic Stellate Cell Proliferation, Apoptosis, and Cell Cycle Progression in Rats With Alcoholic Hepatitis via the MAPK Signaling Pathway Through Targeting SOCS1

“…Moreover, another critical finding of this study is that miR-155 activated the MAPK signaling pathway via SOCS1 to promote AH progression. It was previously reported that, through the inhibition of the phosphorylation of JNK and p38, Gentianae macrophyllae root extract (a constituent of traditional Chinese medicine) helped to attenuate alcoholic liver disease by constraining inflammation responses (Cui et al, 2019). Others have shown that miR-155 is involved in the mediation of inflammatory response and the MAPK signaling pathway (Zhu et al, 2012).…”

Taxifolin, a novel food, attenuates acute alcohol-induced liver injury in mice through regulating the NF-κB-mediated inflammation and PI3K/Akt signalling pathways

“…Alcohol dehydrogenase in the cytoplasm of liver cells will metabolize ethanol into acetaldehyde, aldehyde dehydrogenase (ALDH) or other isoenzymes. The lack of acetaldehyde dehydrogenase leads to the accumulation of acetaldehyde, and excess acetaldehyde produces a large amount of reactive oxygen species (ROS), which in turn leads to oxidative stress, hepatic stellate cells (HSCs) and cause severe hepatotoxicity (Cui et al 2019). In addition, the hepatocytes were directly stimulated by the ethanol and acetaldehyde accumulated in the liver, which can cause degeneration and necrosis of liver cells, and aggravate hepatocyte apoptosis (Li et al 2017).…”

“…In recent years, the active ingredients in natural medicinal plants have performed well in liver protection. For example, maltol treats CCl 4 -induced acute liver injury by inhibiting apoptosis and inflammatory response (Liu et al 2018); the mechanism of garlic protective polysaccharide on liver protective activity is detected by inhibiting TNF-a, TGF-b1 and core proteoglycan (Wang et al 2018); Gentian leaf extract can exert anti-inflammatory activity by inhibiting the translocation of NF-jB transcription activity (Cui et al 2019); Green tea extract can reduce liver inflammation by regulating Toll-like receptor (TLR) 2/3 (Wang et al 2017).…”

“… 2018 ); Gentian leaf extract can exert anti-inflammatory activity by inhibiting the translocation of NF-κB transcription activity (Cui et al. 2019 ); Green tea extract can reduce liver inflammation by regulating Toll-like receptor (TLR) 2/3 (Wang et al. 2017 ).…”

Effect of fucoidan on ethanol-induced liver injury and steatosis in mice and the underlying mechanism

“…KCs play an important role in inflammation and hepatic homeostasis. Activated KCs are important in the pathogenesis and the progression of ALD as they induce an inflammatory cascade and release interleukin-1β (IL-1β), IL-6, IL-18, and other pro-inflammatory cytokines to aggravate liver damage (8,9). Chronic alcohol consumption may have an additional impact on the endoplasmic reticulum and mitochondria (10).…”