Protective effect of Rabdosia amethystoides (Benth) Hara extract on acute liver injury induced by Concanavalin A in mice through inhibition of TLR4-NF-κB signaling pathway

Background: CCl4 acute liver injury (ALI) is a classical model for experimental research. However, there are few reports involved in the fundamental research of CCl4-induced ALI Ligustri Lucidi Fructus (LLF) are and its prescription have been used to treat hepatitis illness clinically. LLF and its active ingredients displayed anti-hepatitis effects, but the mechanism of function has not been fully clarified Objective: To investigate the proteomic analysis of CCl4-induced ALI, and examine the effects of active total glycosides (TG) from LLF on ALI of mice4, including histopathological survey and proteomic changes of liver tissues, and delineate the possible underlying mechanism. Methods: CCl4 was used to produce ALI mice model. The model mice were intragastrically administrated with TG and the liver his-topathological changes of mice were examined. At the end of test, mice liver samples were collected, after protein denaturation, re-duction, desalination and enzymatic hydrolysis, identification was carried out by nano LC-ESI-OrbiTrap MS/MS technology. The data was processed by Maxquant software. The differentially-expressed proteins were screened and identified, and their biological information was also analyzed based on GO and KEGG analysis. Key protein expression was validated by Western blot analysis Results: A total of 705 differentially-expressed proteins were identified during the normal, model and administration group. 9 signifi-cant differential proteins were focused based on analysis. Liver protein expression changes of CCl4-induced ALI mice were mainly involved in several important signal channels, namely FoxO signaling pathway, autophagy-animal, insulin signaling pathway. TG has anti-liver damnification effect in ALI mice, the mechanism of which is related to FoxO1 and autophagy pathways Conclusion: CCl4 inhibited expression of insulin-Like growth factor 1 (Igf1) and 3-phosphoinositide-dependent protein kinase 1 (Pdpk1) in liver cells and induced insulin resistance, thus interfered with mitochondrial autophagy and regeneration of liver cells and the metabolism of glucose and lipid, and caused hepatic necrosis in mice. TG resisted liver injury in mice. TG adjusted the expression level of key proteins Igf1 and Pdpk1 after liver injury and improved insulin resistance, thus promoted autophagy and resisted the liver damage

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Lipopolysaccharide/D-galactosamine-induced acute liver injury could be attenuated by dopamine receptor agonist rotigotine via regulating NF-κB signaling pathway

International Immunopharmacology ◽

10.1016/j.intimp.2021.107798 ◽

2021 ◽

Vol 96 ◽

pp. 107798

Author(s):

Shumin Yue ◽

Tian Wang ◽

Yunqi Yang ◽

Yiqian Fan ◽

Lin Zhou ◽

...

Keyword(s):

Liver Injury ◽

Signaling Pathway ◽

Dopamine Receptor ◽

Receptor Agonist ◽

Acute Liver Injury ◽

Dopamine Receptor Agonist

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Fucosterol Protects against Concanavalin A-Induced Acute Liver Injury: Focus on P38 MAPK/NF-κB Pathway Activity

Gastroenterology Research and Practice ◽

10.1155/2018/2824139 ◽

2018 ◽

Vol 2018 ◽

pp. 1-13 ◽

Cited By ~ 10

Author(s):

Wenhui Mo ◽

Chengfen Wang ◽

Jingjing Li ◽

Kan Chen ◽

Yujing Xia ◽

...

Keyword(s):

Liver Injury ◽

P38 Mapk ◽

Concanavalin A ◽

Molecular Mechanisms ◽

Therapeutic Agent ◽

Acute Liver Injury ◽

Biological Activities ◽

Hepatic Necrosis ◽

Protective Effects ◽

Eisenia Bicyclis

Objective. Fucosterol is derived from the brown alga Eisenia bicyclis and has various biological activities, including antioxidant, anticancer, and antidiabetic properties. The aim of this study was to investigate the protective effects of fucosterol pretreatment on Concanavalin A- (ConA-) induced acute liver injury in mice, and to understand its molecular mechanisms. Materials and Methods. Acute liver injury was induced in BALB/c mice by ConA (25 mg/kg), and fucosterol (dissolved in 2% DMSO) was orally administered daily at doses of 25, 50, and 100 mg/kg. The levels of hepatic necrosis, apoptosis, and autophagy associated with inflammatory cytokines were measured at 2, 8, and 24 h. Results. Fucosterol attenuated serum liver enzyme levels and hepatic necrosis and apoptosis induced by TNF-α, IL-6, and IL-1β. Fucosterol also inhibited apoptosis and autophagy by upregulating Bcl-2, which decreased levels of functional Bax and Beclin-1. Furthermore, reduced P38 MAPK and NF-κB signaling were accompanied by PPARγ activation. Conclusion. This study showed that fucosterol could alleviate acute liver injury induced by ConA by inhibiting P38 MAPK/PPARγ/NF-κB signaling. These findings highlight that fucosterol is a promising potential therapeutic agent for acute liver injury.

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Mechanism of KLF4 Protection against Acute Liver Injury via Inhibition of Apelin Signaling

Oxidative Medicine and Cellular Longevity ◽

10.1155/2019/6140360 ◽

2019 ◽

Vol 2019 ◽

pp. 1-10 ◽

Cited By ~ 2

Author(s):

Weitao Ji ◽

Hongyun Shi ◽

Hailin Shen ◽

Jing Kong ◽

Jiayi Song ◽

...

Keyword(s):

Liver Injury ◽

Signaling Pathway ◽

Acute Liver Injury ◽

Control Group ◽

Necrosis Factor Alpha ◽

Protein Levels ◽

Klf4 Expression ◽

Mrna And Protein Expression

Krüppel-like factor 4 (KLF4) is a key transcription factor that regulates genes involved in the proliferation or differentiation in different tissues. Apelin plays roles in cardiovascular functions, metabolic disease, and homeostatic disorder. However, the biological function of apelin in liver disease is still ongoing. In this study, we investigated the mechanism of KLF4-mediated protection against acute liver injury via the inhibition of the apelin signaling pathway. Mice were intraperitoneally injected with carbon tetrachloride (CCl4; 0.2 mL dissolved in 100 mL olive oil, 10 mL/kg) to establish an acute liver injury model. A KLF4 expression plasmid was injected through the tail vein 48 h before CCl4 treatment. In cultured LX-2 cells, pAd-KLF4 or siRNA KLF4 was overexpressed or knockdown, and the mRNA and protein levels of apelin were determined. The results showed that the apelin serum level in the CCl4-injected group was higher than that of control group, and the expression of apelin in the liver tissues was elevated while KLF4 expression was decreased in the CCl4-injected group compared to the KLF4-plasmid-injected group. HE staining revealed serious hepatocellular steatosis in the CCl4-injected mice, and KLF4 alleviated this steatosis in the mice injected with KLF4 plasmid. In vitro experiments showed that tumor necrosis factor-alpha (TNF-α) could downregulate the transcription and translation levels of apelin in LX-2 cells and also upregulate KLF4 mRNA and protein expression. RT-PCR and Western blotting showed that the overexpression of KLF4 markedly decreased basal apelin expression, but knockdown of KLF4 restored apelin expression in TNF-α-treated LX-2 cells. These in vivo and in vitro experiments suggest that KLF4 plays a key role in inhibiting hepatocellular steatosis in acute liver injury, and that its mechanism might be the inhibition of the apelin signaling pathway.

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Polydeoxyribonucleotide Exerts Protective Effect Against CCl4-Induced Acute Liver Injury Through Inactivation of NF-κB/MAPK Signaling Pathway in Mice

International Journal of Molecular Sciences ◽

10.3390/ijms21217894 ◽

2020 ◽

Vol 21 (21) ◽

pp. 7894 ◽

Cited By ~ 2

Author(s):

Il-Gyu Ko ◽

Jun-Jang Jin ◽

Lakkyong Hwang ◽

Sang-Hoon Kim ◽

Chang-Ju Kim ◽

...

Keyword(s):

Liver Injury ◽

Protective Effect ◽

Inflammatory Cytokines ◽

Intraperitoneal Injection ◽

Acute Liver Injury ◽

Adenosine A2a Receptor ◽

Liver Index ◽

A2a Receptor ◽

Adenosine A2a ◽

Pro Inflammatory Cytokines

Acute liver injury (ALI) causes life-threatening clinical problem, and its underlying etiology includes inflammation and apoptosis. An adenosine A2A receptor agonist, polydeoxyribonucleotide (PDRN), exhibits anti-inflammatory and anti-apoptotic effects by inhibiting the secretion of pro-inflammatory cytokines. In the current study, the protective effect of PDRN against carbon tetrachloride (CCl4)-induced ALI was investigated using mice. For the induction of ALI, mice received intraperitoneal injection of CCl4 twice over seven days. Mice from the PDRN-treated groups received an intraperitoneal injection of 200 μL saline containing PDRN (8 mg/kg), once a day for seven days, starting on day 1 after the first CCl4 injection. In order to confirm that the action of PDRN occurs through the adenosine A2A receptor, 8 mg/kg 3,7-dimethyl-1-propargylxanthine (DMPX), an adenosine A2A receptor antagonist, was treated with PDRN. Administration of CCl4 impaired liver tissue and increased the liver index and histopathologic score. The expression of pro-inflammatory cytokines was increased, and apoptosis was induced by the administration of CCl4. Administration of CCl4 activated nuclear factor-kappa B (NF-κB) and facilitated phosphorylation of signaling factors in mitogen-activated protein kinase (MAPK). In contrast, PDRN treatment suppressed the secretion of pro-inflammatory cytokines and inhibited apoptosis. PDRN treatment inactivated NF-κB and suppressed phosphorylation of signaling factors in MAPK. As a result, liver index and histopathologic score were reduced by PDRN treatment. When PDRN was treated with DMPX, the anti-inflammatory and anti-apoptotic effect of PDRN disappeared. Therefore, PDRN can be used as an effective therapeutic agent for acute liver damage.

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Protective effect of Schisandra chinensis total lignans on acute alcoholic-induced liver injury related to inhibiting CYP2E1 activation and activating the Nrf2/ARE signaling pathway

Revista Brasileira de Farmacognosia ◽

10.1016/j.bjp.2019.01.008 ◽

2019 ◽

Vol 29 (2) ◽

pp. 198-205 ◽

Cited By ~ 4

Author(s):

Lianlin Su ◽

Ping Li ◽

Tulin Lu ◽

Chunqin Mao ◽

De Ji ◽

...

Keyword(s):

Liver Injury ◽

Protective Effect ◽

Signaling Pathway ◽

Schisandra Chinensis

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The Late-Stage Protective Effect of Mito-TEMPO against Acetaminophen-Induced Hepatotoxicity in Mouse and Three-Dimensional Cell Culture Models

Antioxidants ◽

10.3390/antiox9100965 ◽

2020 ◽

Vol 9 (10) ◽

pp. 965

Author(s):

Mohammad Abdullah-Al-Shoeb ◽

Kenta Sasaki ◽

Saori Kikutani ◽

Nanami Namba ◽

Keiichi Ueno ◽

...

Keyword(s):

Oxidative Stress ◽

Cell Culture ◽

Liver Injury ◽

Protective Effect ◽

Acute Liver Injury ◽

Three Dimensional ◽

3D Cell Culture ◽

Cell Culture Model ◽

Culture Model ◽

Apap Hepatotoxicity

An overdose of acetaminophen (APAP), the most common cause of acute liver injury, induces oxidative stress that subsequently causes mitochondrial impairment and hepatic necroptosis. N-acetyl-L-cysteine (NAC), the only recognized drug against APAP hepatotoxicity, is less effective the later it is administered. This study evaluated the protective effect of mitochondria-specific Mito-TEMPO (Mito-T) on APAP-induced acute liver injury in C57BL/6J male mice, and a three dimensional (3D)-cell culture model containing the human hepatoblastoma cell line HepG2. The administration of Mito-T (20 mg/kg, i.p.) 1 h after APAP (400 mg/kg, i.p.) injection markedly attenuated the APAP-induced elevated serum transaminase activity and hepatic necrosis. However, Mito-T treatment did not affect key factors in the development of APAP liver injury including the activation of c-jun N-terminal kinases (JNK), and expression of the transcription factor C/EBP homologous protein (CHOP) in the liver. However, Mito-T significantly reduced the APAP-induced increase in the hepatic oxidative stress marker, nitrotyrosine, and DNA fragmentation. Mito-T markedly attenuated cytotoxicity induced by APAP in the HepG2 3D-cell culture model. Moreover, liver regeneration after APAP hepatotoxicity was not affected by Mito-T, demonstrated by no changes in proliferating cell nuclear antigen formation. Therefore, Mito-T was hepatoprotective at the late-stage of APAP overdose in mice.

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