Protective effects and possible mechanisms of Centella asiatica (L.) urban extract against acute and chronic liver injury: Evidence from in vivo and in vitro studies

2021 ◽  
Author(s):  
Jiabin Lu ◽  
Chao Chen ◽  
Renhua Gai ◽  
Huacheng Qiu ◽  
Yue Wu ◽  
...  
Keyword(s):  
Liver Injury ◽  
Centella Asiatica ◽  
Chronic Liver ◽  
In Vitro Studies ◽  
Protective Effects ◽  
Chronic Liver Injury

scholarly journals Mycelium Polysaccharides from Termitomyces albuminosus Attenuate CCl4-Induced Chronic Liver Injury Via Inhibiting TGFβ1/Smad3 and NF-κB Signal Pathways

2019 ◽  
Vol 20 (19) ◽  
pp. 4872 ◽  
Author(s):  
Zhao ◽  
Li ◽  
Feng ◽  
Zhang ◽  
Yuan ◽  
...  
Keyword(s):  
Liver Injury ◽  
Chronic Liver ◽  
Molar Ratio ◽  
Gas Chromatography Mass Spectrometry ◽  
Signal Pathways ◽  
Chronic Liver Injury ◽  
Potential Health ◽  
Anti Inflammatory

A major fraction (MPT-W), eluted by deionized water, was extracted from mycelium polysaccharides of Termitomyces albuminosus (MPT), and its antioxidant, anti-fibrosis, and anti-inflammatory activities in CCl4-induced chronic liver injury mice, as well as preliminary characterizations, were evaluated. The results showed that MPT-W was a polysaccharide of α- and β-configurations containing xylose (Xyl), fucose (Fuc), mannose (Man), galactose (Gal), and glucose (Glc) with a molar ratio of 0.29:8.67:37.89:35.98:16.60 by gas chromatography-mass spectrometry (GC-MS), Fourier transform infrared (FT-IR) spectroscopy. Its molecular weight (Mw), obtained by high-performance gel permeation chromatography (HPGPC), was 1.30 × 105 Da. The antioxidant assays in vitro showed that MPT-W displayed scavenging free-radical abilities. Based on the data of in vivo experiments, MPT-W could inhibit TGFβ1/Smad3 and NF-κB pathways; decrease the level and activity of cytochrome P4502E1 (CYP2E1), malonaldehyde (MDA) and serum enzyme; activate the HO-1/Nrf2 pathway; and increase antioxidant enzymes to protect the liver in CCl4-induced chronic liver injury mice. Therefore, MPT-W could be a potentially natural and functional resource contributing to antioxidant, hepatoprotective, and anti-inflammatory effects with potential health benefits.

Liver 5-HT7 receptors: A novel regulator target of fibrosis and inflammation-induced chronic liver injury in vivo and in vitro

2017 ◽  
Vol 43 ◽  
pp. 227-235 ◽  
Author(s):  
Beyzagul Polat ◽  
Zekai Halici ◽  
Elif Cadirci ◽  
Emre Karakus ◽  
Yasin Bayir ◽  
...  
Keyword(s):  
Liver Injury ◽  
Chronic Liver ◽  
Chronic Liver Injury

scholarly journals circ-CBFB upregulates p66Shc to perturb mitochondrial dynamics in APAP-induced liver injury

2020 ◽  
Vol 11 (11) ◽  
Author(s):  
Zhecheng Wang ◽  
Yan Zhao ◽  
Ruimin Sun ◽  
Yu Sun ◽  
Deshun Liu ◽  
...  
Keyword(s):  
Liver Injury ◽  
Mitochondrial Dynamics ◽  
Circular Rna ◽  
Protective Effects ◽  
Bioinformatics Analyses ◽  
Hepatocyte Injury ◽  
Rna Immunoprecipitation ◽  
Competitive Endogenous Rna

Abstract p66Shc, a master regulator of mitochondrial reactive oxygen species (mtROS), is a crucial mediator of hepatocyte oxidative stress. However, its functional contribution to acetaminophen (APAP)-induced liver injury and the mechanism by which it is modulated remain unknown. Here, we aimed to assess the effect of p66Shc on APAP-induced liver injury and to evaluate if circular RNA (circRNA) functions as a competitive endogenous RNA (ceRNA) to mediate p66Shc in APAP-induced liver injury. p66Shc-, miR-185-5p-, and circ-CBFB-silenced mice were injected with APAP. AML12 cells were transfected with p66Shc, miR-185-5p, and circ-CBFB silencing or overexpression plasmids or siRNAs prior to APAP stimulation. p66Shc was upregulated in liver tissues in response to APAP, and p66Shc silencing in vivo protected mice from APAP-induced mitochondrial dynamics perturbation and liver injury. p66Shc knockdown in vitro attenuated mitochondrial dynamics and APAP-induced hepatocyte injury. Mechanically, p66Shc perturbs mitochondrial dynamics partially by inhibiting OMA1 ubiquitination. miR-185-5p, which directly suppressed p66Shc translation, was identified by microarray and bioinformatics analyses, and its overexpression attenuated mitochondrial dynamics and hepatocyte injury in vitro. Furthermore, luciferase, pull-down and RNA immunoprecipitation assays demonstrated that circ-CBFB acts as a miRNA sponge of miR-185-5p to mediate p66Shc in APAP-induced liver injury. circ-CBFB knockdown also alleviated APAP-induced mitochondrial dynamics perturbation and hepatocyte injury. More importantly, we found that the protective effects of circ-CBFB knockdown on p66Shc, mitochondrial dynamics and liver injury were abolished by miR-185-5p inhibition both in vivo and in vitro. In conclusion, p66Shc is a key regulator of APAP-induced liver injury that acts by triggering mitochondrial dynamics perturbation. circ-CBFB functions as a ceRNA to regulate p66Shc during APAP-induced liver injury, which may provide a potential therapeutic target.

scholarly journals Target prediction of anti-chronic liver injury of Kangxian pill based on network pharmacology

2021 ◽  
Author(s):  
Min Cao ◽  
Yiyang Wang ◽  
Haizhao Liu ◽  
Xueqian Dong ◽  
Mengxue Dong ◽  
...  
Keyword(s):  
Liver Injury ◽  
Protein Expression ◽  
Molecular Mechanisms ◽  
Target Prediction ◽  
Vital Role ◽  
Chronic Liver ◽  
Network Pharmacology ◽  
Chronic Liver Injury ◽  
Tnf Α

Abstract BackgroundThe present study aimed to validate the protect effect of Kangxian pill (KXP) on chronic hepatic injury (CHI) and investigate its potential mechanism by network pharmacology-based prediction and experimental verification in vivo . MethodsThe effect of KXP in the treatment of carbon tetrachloride (CCL 4 )-induced CHI is investigated by calculating liver index, measuring AST and ALT levels and performing HE staining. Targets of active ingredients of KXP were predicted in TCSMP and targets of chronic liver injury were searched in DisGeNET, OMIM and GeneCards databases. We obtain some pivotal targets of KXP for the treatment of CHI by intersecting the targets of KXP and CHI. Subsequently, we performed gene ontology (GO) functional and pathways enrichment analyses, as well as conducted networks based on potential targets to determine the core targets and representative pathways.We further validated expressions of IL-6, IL-1β, TNF-α, Bax, Bcl2, PI3K, Akt, and pAkt according to the potential molecular mechanisms analyzed based on network pharmacology analysis.ResultsThe results showed that the levels of AST and ALT in serum decreased after treatment with KXP. HE staining also revealed that KXP could improve hepatocyte abnormality in vivo . A total of 81 potential targets of KXP in the treatment of CHI were identified through network pharmacology analysis. After integrating potential targets, function enrichment, representative pathways and networks, we identified PI3K, AKT1,BCL2, TNF-α, IL-1β, and IL-6 as potential targets, which may play a vital role in the KXP treatment. The experimental results also showed that KXP could down-regulate the mRNA and protein expression of IL-1β, IL-6, TNF-α and Bax, and up-regulate the PI3K and p-Akt protein expression i n vivo .ConclusionsOur results suggest that KXP could alleviate CHI through regulating inflammation and apoptosis and provide deep insight into the hepato-protective mechanisms.

scholarly journals Raf Kinase Inhibitory Protein Down-Expression Exacerbates Hepatic Fibrosis In Vivo and In Vitro

2016 ◽  
Vol 40 (1-2) ◽  
pp. 49-61 ◽  
Author(s):  
Quanfang Huang ◽  
Chunhong Liang ◽  
Ling Wei ◽  
Jinlan Nie ◽  
Shengjuan Lu ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Liver Injury ◽  
Hepatic Fibrosis ◽  
Chronic Liver ◽  
Chronic Liver Injury ◽  
Inhibitory Protein ◽  
Raf Kinase ◽  
Raf Kinase Inhibitory Protein ◽  
Liver Tissues

Background/Aims: Raf kinase inhibitory protein (RKIP) is closely associated with numerous tumors and participates in their development through regulating the growth, apoptosis, invasion and metastasis of tumor cells. However, the role of RKIP in chronic liver injury and particularly in liver fibrosis is still unclear. Methods: In the present study, hepatic fibrosis was induced by porcine serum (PS) in rats and primary hepatic stellate cells (HSCs) were isolated from rat livers. Moreover, locostatin was used to interfere with RKIP expression. Results: RKIP expression was significantly inhibited by locostatin in both liver tissues of rats and primary HSCs. Down-regulating RKIP expression resulted in serious liver injury, extensive accumulation of collagen, and significant increase in the levels of ALT, AST and TNF-α during liver fibrosis in rats. Moreover, down-regulating RKIP significantly promoted HSCs proliferation and colony formation in vitro. Reduced RKIP significantly increased the production of collagen and the level of α-SMA as well as the expression of MMP-1 and MMP-2 in both liver tissues and primary HSCs. Furthermore, down-regulating RKIP promoted the activation of the ERK and TLR4 signaling pathways. Conclusion: Our findings clearly indicate an inverse correlation between RKIP level and the degree of the liver injury and fibrosis. The decrease in RKIP expression may exacerbate chronic liver injury and liver fibrosis.

Protective effects of isorhamnetin on pulmonary arterial hypertension: in vivo and in vitro studies

2020 ◽  
Vol 34 (10) ◽  
pp. 2730-2744
Author(s):  
Zhi Chang ◽  
Jia‐ling Wang ◽  
Zhi‐cheng Jing ◽  
Ping Ma ◽  
Qing‐bing Xu ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
In Vitro Studies ◽  
Protective Effects ◽  
Pulmonary Arterial

scholarly journals Omeprazole increases survival via different mechanisms in two rat models of liver injury

2021 ◽  
Author(s):  
Masaya Kotsuka ◽  
Yuki Hashimoto ◽  
Richi Nakatake ◽  
Tetsuya Okuyama ◽  
Masahiko Hatta ◽  
...  
Keyword(s):  
Liver Injury ◽  
Mrna Expression ◽  
Rat Hepatocytes ◽  
Protective Effects ◽  
Necrosis Factor Alpha ◽  
Beneficial Effects ◽  
Factor Alpha ◽  
Oxide Synthase

Abstract Omeprazole (OMZ) is a proton pump inhibitor (PPI) that is used to reduce gastric acid secretion, but little is known about its possible liver protective effects. This study investigated whether OMZ has beneficial effects in rat septic models of lipopolysaccharide (LPS)-induced liver injury after D-galactosamine (GalN) treatment and 70% hepatectomy (PH), and to determine the mechanisms of OMZ in an in vitro model of liver injury. In the in vivo models, the effects of OMZ were examined 1 h before treatment. OMZ increased survival and decreased tumor necrosis factor-alpha, inducible nitric oxide synthase, cytokine-induced neutrophil chemoattractant 1, interleukin (IL)-6, and IL-1β mRNA expression, and increased IL-10 mRNA expression in the livers of both GaIN/LPS- and PH/LPS-treated rats. Necrosis and apoptosis were inhibited by OMZ in GaIN/LPS rats, but OMZ had no effects on necrosis in PH/LPS rats. Primary rat hepatocytes were treated with IL1-β in the presence or absence of OMZ (in vitro model). OMZ inhibited iNOS induction partially through suppression of NF-κB signaling in hepatocytes. Furthermore, OMZ inhibited the induction of several inflammatory mediators, resulting in the prevention of LPS-induced liver injury after GalN liver failure and PH, although OMZ showed different doses and mechanisms in the two models.

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