The Protective Effect of Cordycepin on D-Galactosamine/Lipopolysaccharide-Induced Acute Liver Injury

Li, Jin; Zhong, Liping; Zhu, Haibo; Wang, Fengzhong

doi:10.1155/2017/3946706

Cited by 26 publications

(24 citation statements)

References 34 publications

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“…D-gal can cause liver cell necrosis and lead to ALF, as well as abnormally elevated serum TNF-α, which then triggers the cascade of inflammatory mediators and is closely related to the pathophysiology of ALF[ 28 , 29 ]. In our study, a strong inflammatory response was observed, as evidenced by markedly increased levels of TNF-α, IL-1β, IL-6, and endotoxin, all of which were positively correlated with the dose of D-gal.…”

Section: Discussionmentioning

confidence: 99%

Novel D-galactosamine-induced cynomolgus monkey model of acute liver failure

Feng

Cai

et al. 2017

WJG

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AIMTo establish a simplified, reproducible D-galactosamine-induced cynomolgus monkey model of acute liver failure having an appropriate treatment window.METHODSSixteen cynomolgus monkeys were randomly divided into four groups (A, B, C and D) after intracranial pressure (ICP) sensor implantation. D-galactosamine at 0.3, 0.25, 0.20 + 0.05 (24 h interval), and 0.20 g/kg body weight, respectively, was injected via the small saphenous vein. Vital signs, ICP, biochemical indices, and inflammatory factors were recorded at 0, 12, 24, 36, 48, 72, 96, and 120 h after D-galactosamine administration. Progression of clinical manifestations, survival times, and results of H&E staining, TUNEL, and Masson staining were recorded.RESULTSCynomolgus monkeys developed different degrees of debilitation, loss of appetite, and jaundice after D-galactosamine administration. Survival times of groups A, B, and C were 56 ± 8.7 h, 95 ± 5.5 h, and 99 ± 2.2 h, respectively, and in group D all monkeys survived the 144-h observation period except for one, which died at 136 h. Blood levels of ALT, AST, CK, LDH, TBiL, Cr, BUN, and ammonia, prothrombin time, ICP, endotoxin, and inflammatory markers [(tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6)] significantly increased compared with baseline values in different groups (P < 0.05). Pathological results showed obvious liver cell necrosis that was positively correlated with the dose of D-galactosamine.CONCLUSIONWe successfully established a simplified, reproducible D-galactosamine-induced cynomolgus monkey model of acute liver failure, and the single or divided dosage of 0.25 g/kg is optimal for creating this model.

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Section: Discussionmentioning

confidence: 99%

Novel D-galactosamine-induced cynomolgus monkey model of acute liver failure

Feng

Cai

et al. 2017

WJG

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“…IMM-H007 or M1 was found to activate cellular AMPK by interacting with the γ subunit, but not by changing the cellular energy state 7 . In our previous study, cordycepin was found to protect against GalN/LPS-induced acute liver failure 11 . Therefore, we speculated that M1 might have the similar beneficial effects on fulminant hepatitis.…”

Section: Introductionmentioning

confidence: 87%

AMP-activated protein kinase agonist N6-(3-hydroxyphenyl)adenosine protects against fulminant hepatitis by suppressing inflammation and apoptosis

Chen

Zhong

et al. 2018

Cell Death Dis

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Both AMP-activated protein kinase (AMPK) agonist and inhibitor have been reported to protect against fulminant hepatitis, implying that AMPK may play a complicated role in the development of fulminant hepatitis. In this study, we exploited whether the novel AMPK agonist N6-(3-hydroxyphenyl)adenosine (named as M1) exerted protective effects on fulminant hepatitis and whether its beneficial effects were AMPK-dependent. Results showed that intraperitoneal injection of M1 improved liver function, ameliorated liver injury and finally raised the survival rate in d-galactosamine/lipopolysaccharide (GalN/LPS)-treated mice. These beneficial effects of M1 may attribute to the suppression of pro-inflammatory cytokines production and the prevention of hepatocyte apoptosis. Furthermore, M1 pretreatment mitigated LPS-stimulated TLR4 expression and NFκB activation in murine peritoneal macrophages and prevented actinomycin D (Act D)/tumor necrosis factor α (TNFα)-induced apoptosis by promoting protective autophagy in primary hepatocytes. Additionally, M1-induced AMPK activation was responsible both for its anti-inflammatory action in macrophages and for its anti-apoptotic action in hepatocytes. To our surprise, compared with the control AMPKα1lox/lox/AMPKα2lox/lox mice, liver-specific AMPKα1 knockout (AMPKα1LS−/−) mice were more sensitive to GalN/LPS administration but not AMPKα2LS−/−mice, and the beneficial effects of M1 on acute liver failure and the production of pro-inflammatory factors were dampened in AMPKα1LS−/− mice. Therefore, our study may prove that M1 could be a promising therapeutic agent for fulminant hepatitis, and targeting AMPK may be useful therapeutically in the control of LPS-induced hepatotoxicity.

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“… 2016 ; Li et al. 2017 ), and mangiferin (Pan et al. 2016 ) can inhibit hepatic injury induced by GalN/LPS.…”

Section: Immunological Liver Injurymentioning

confidence: 99%

Molecular mechanism and research progress on pharmacology of traditional Chinese medicine in liver injury

Zhang

Wang

Zhong

et al. 2018

Pharmaceutical Biology

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Context: Liver disease is a common threat to human health, caused by a variety of factors that damage the liver. Recent studies have shown that active ingredients (for example: flavonoids, saponins, acids, phenols, and alkaloids) from Traditional Chinese Medicine (TCM) can have hepatoprotective benefits, which represents an attractive source of drug discovery for treating liver injury.Objective: We reviewed recent contributions on the chemically induced liver injury, immunological liver damage, alcoholic liver injury, and drug-induced liver injury, in order to summarize the research progress in molecular mechanism and pharmacology of TCM, and provides a comprehensive overview of new TCM treatment strategies for liver disease.Materials and methods: Relevant literature was obtained from scientific databases such as Pubmed, Web of Science. and CNKI databases on ethnobotany and ethnomedicines (from January 1980 to the end of May 2018). The experimental studies involving the antihepatic injury role of the active agents from TCM and the underlying mechanisms were identified. The search terms included ‘liver injury’ or ‘hepatic injury’, and ‘traditional Chinese medicine’, or ‘herb’.Results: A number of studies revealed that the active ingredients of TCM exhibit potential therapeutic benefits against liver injury, while the underlying mechanisms appear to contribute to the regulation of inflammation, oxidant stress, and pro-apoptosis signaling pathways.Discussion and conclusions: The insights provided in this review will help further exploration of botanical drugs in the development of liver injury therapy via study on the effective components of TCM.

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The Protective Effect of Cordycepin on D-Galactosamine/Lipopolysaccharide-Induced Acute Liver Injury

Cited by 26 publications

References 34 publications

Novel D-galactosamine-induced cynomolgus monkey model of acute liver failure

Novel D-galactosamine-induced cynomolgus monkey model of acute liver failure

AMP-activated protein kinase agonist N6-(3-hydroxyphenyl)adenosine protects against fulminant hepatitis by suppressing inflammation and apoptosis

Molecular mechanism and research progress on pharmacology of traditional Chinese medicine in liver injury

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