scholarly journals Cryptotanshinone from the Salvia miltiorrhiza Bunge Attenuates Ethanol-Induced Liver Injury by Activation of AMPK/SIRT1 and Nrf2 Signaling Pathways

2019 ◽  
Vol 21 (1) ◽  
pp. 265 ◽  
Author(s):  
Arulkumar Nagappan ◽  
Ji-Hyun Kim ◽  
Dae Young Jung ◽  
Myeong Ho Jung
Keyword(s):  
Oxidative Stress ◽  
Liver Injury ◽  
Hepatic Steatosis ◽  
Salvia Miltiorrhiza ◽  
Sirtuin 1 ◽  
Hepatoprotective Effect ◽  
Related Factor ◽  
Salvia Miltiorrhiza Bunge ◽  
Antioxidant Genes ◽  
Compound C

Cryptotanshinone (CT), a diterpene that is isolated from Salvia miltiorrhiza Bunge, exhibits anti-cancer, anti-oxidative, anti-fibrosis, and anti-inflammatory properties. Here, we examined whether CT administration possess a hepatoprotective effect on chronic ethanol-induced liver injury. We established a chronic alcohol feeding mouse model while using C57BL/6 mice, and examined the liver sections with hematoxylin-eosin (H&E) and Oil Red O (ORO) staining. Further, we analyzed the lipogenesis, fatty acid oxidation, oxidative stress, and inflammation genes by using quantitative polymerase chain reaction (qPCR) and immunoblotting in in vivo, and in vitro while using HepG2 and AML-12 cells. CT treatment significantly ameliorated ethanol-promoted hepatic steatosis, which was consistent with the decreased hepatic triglyceride levels. Interestingly, CT activated the phosphorylation of AMP-activated protein kinase (AMPK), sirtuin 1 (SIRT1), and nuclear factor E2-related factor 2 (Nrf2) proteins. Importantly, compound C (AMPK inhibitor) significantly blocked the CT-mediated reduction in TG accumulation, but not Ex52735 (SIRT1 inhibitor), which suggested that CT countering ethanol-promoted hepatic steatosis is mediated by AMPK activation. Furthermore, CT significantly inhibited cytochrome P450 2E1 (CYP2E1) and enhanced both the expression of antioxidant genes and hepatic glutathione levels. Finally, CT inhibited the ethanol-induced inflammation in ethanol-fed mice and HepG2 cells. Overall, CT exhibits a hepatoprotective effect against ethanol-induced liver injury by the inhibition of lipogenesis, oxidative stress, and inflammation through the activation of AMPK/SIRT1 and Nrf2 and the inhibition of CYP2E1. Therefore, CT could be an effective therapeutic agent for treating ethanol-induced liver injury.

scholarly journals Bamboo Stems (Phyllostachys nigra variety henosis) Containing Polyphenol Mixtures Activate Nrf2 and Attenuate Phenylhydrazine-Induced Oxidative Stress and Liver Injury

Nutrients ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 114 ◽  
Author(s):  
Ji Hye Yang ◽  
Moon-Hee Choi ◽  
Chang-Su Na ◽  
Sam Seok Cho ◽  
Jae Hoon Kim ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Injury ◽  
Iron Overload ◽  
Liver Damage ◽  
Hepg2 Cells ◽  
Hepatoprotective Effect ◽  
Glutathione Depletion ◽  
Related Factor ◽  
Nrf2 Target Gene ◽  
Phyllostachys Nigra

This study was designed to investigate the hepatoprotective effect of bamboo stems using in vitro and in vivo experimental liver damage models. Ethyl acetate fraction of 80% ethanol extract of Phyllostachys nigra stem (PN3) containing polyphenols had a higher NQO1-ARE reporter gene activity as monitored by the activity of the NF-E2-related factor (Nrf2) antioxidant pathway in cells in comparison to extracts from other species and under other conditions. The Nrf2 was translocated from the cytosol to the nucleus in response to PN3, followed by induction of the Nrf2 target gene expression, including HO-1, GCL, and NQO-1 in HepG2 cells. Phosphorylation of Nrf2 in HepG2 cells was enhanced in PN3, which was mediated by PKCδ, ERK, and p38 MAPK. Consequently, PN3 inhibited arachidonic acid (AA) + iron-induced reactive oxygen species generation and glutathione depletion, and, thus, highlighted their role in cytotoxicity. Treatment with major polyphenols of PN3, including catechin, chlorogenic acid, caffeic acid, and p-coumaric acid, also improved AA + iron-mediated oxidative stress and, thus, improved cell viability. Treatment with phenylhydrazine in mice, i.e., the iron overload liver injury model, increased plasma alanine aminotransferase and aspartate aminotransferase levels and changed histological features in mice—a response that was almost completely blocked by PN3 administration. Moreover, PN3 extract mitigated phenylhydrazine-induced oxidative stress and inflammatory responses. Conclusively, PN3 can exert a hepatoprotective effect against iron overload-induced acute liver damage due to its antioxidant properties.

The hepatoprotective effect of aqueous extracts of Penthorum chinense Pursh against acute alcohol-induced liver injury is associated with ameliorating hepatic steatosis and reducing oxidative stress

2015 ◽  
Vol 6 (5) ◽  
pp. 1510-1517 ◽  
Author(s):  
Yi-Wei Cao ◽  
Yun Jiang ◽  
Da-Yong Zhang ◽  
Xiao-Jing Zhang ◽  
Yuan-Jia Hu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Injury ◽  
Hepatic Steatosis ◽  
Folk Medicine ◽  
Hepatoprotective Effect ◽  
Aqueous Extracts ◽  
Health Food ◽  
Penthorum Chinense Pursh ◽  
Penthorum Chinense

Aqueous extracts ofPenthorum chinensePursh, a health food and folk medicine, protects against acute alcohol-induced liver injury.

Melatonin protection against burn-induced liver injury. A review

Open Medicine ◽  
2014 ◽  
Vol 9 (1) ◽  
pp. 148-158 ◽  
Author(s):  
Ganka Bekyarova ◽  
Maria Tzaneva ◽  
Minka Hristova ◽  
Krasimir Hristov
Keyword(s):  
Oxidative Stress ◽  
Endothelial Dysfunction ◽  
Liver Injury ◽  
Inflammatory Response ◽  
Hepatic Injury ◽  
Clinical Problem ◽  
Related Factor ◽  
Burn Wound ◽  
Antioxidant Genes ◽  
Microcirculatory Disorders

AbstractSevere thermal injury may be complicated by dysfunction of organs distant from the original burn wound, including the liver, and represents a serious clinical problem. Although pathophysiology of burn-induced liver injury remains unclear, increasing evidence implicate activation of inflammatory response, oxidative stress, endothelial dysfunction and microcirculatory disorders as the main mechanisms of hepatic injury. Several studies suggest melatonin as a multifunctional indolamine that counteracts some of the pathophysiologic steps and displays significant beneficial effects against burn-induced cellular injury. This review summarizes the role of melatonin in restricting the burn-induced hepatic injury and focuses on its effects on oxidative stress, inflammatory response, endothelial dysfunction and microcirculatory disorders as well as on signaling pathways such as regulation of nuclear erythroid 2-related factor 2 (Nrf2) and nuclear factor-kappaB (NF-kB). Further studies are necessary to elucidate the modulating effect of melatonin on the transcription factor responsible for the regulation of the pro-inflammatory and antioxidant genes involved in burn injuries.

scholarly journals Gomisin N Alleviates Ethanol-Induced Liver Injury through Ameliorating Lipid Metabolism and Oxidative Stress

2018 ◽  
Vol 19 (9) ◽  
pp. 2601 ◽  
Author(s):  
Arulkumar Nagappan ◽  
Dae Jung ◽  
Ji-Hyun Kim ◽  
Hoyoung Lee ◽  
Myeong Jung
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Fatty Acid ◽  
Liver Injury ◽  
Hepatic Steatosis ◽  
Fatty Acid Oxidation ◽  
Acid Oxidation ◽  
Antioxidant Genes ◽  
Gomisin N

Gomisin N (GN), a lignan derived from Schisandra chinensis, has been shown to possess antioxidant, anti-inflammatory, and anticancer properties. In the present study, we investigated the protective effect of GN against ethanol-induced liver injury using in vivo and in vitro experiments. Histopathological examination revealed that GN administration to chronic-binge ethanol exposure mice significantly reduced ethanol-induced hepatic steatosis through reducing lipogenesis gene expression and increasing fatty acid oxidation gene expression, and prevented liver injury by lowering the serum levels of aspartate transaminase and alanine transaminase. Further, it significantly inhibited cytochrome P450 2E1 (CYP2E1) gene expression and enzyme activity, and enhanced antioxidant genes and glutathione level in hepatic tissues, which led to decreased hepatic malondialdehyde levels. It also lowered inflammation gene expression. Finally, GN administration promoted hepatic sirtuin1 (SIRT1)-AMP-activated protein kinase (AMPK) signaling in ethanol-fed mice. Consistent with in vivo data, treatment with GN decreased lipogenesis gene expression and increased fatty acid oxidation gene expression in ethanol-treated HepG2 cells, thereby preventing ethanol-induced triglyceride accumulation. Furthermore, it inhibited reactive oxygen species generation by downregulating CYP2E1 and upregulating antioxidant gene expression, and suppressed inflammatory gene expression. Moreover, GN prevented ethanol-mediated reduction in SIRT1 and phosphorylated AMPK. These findings indicate that GN has therapeutic potential against alcoholic liver disease through inhibiting hepatic steatosis, oxidative stress and inflammation.

scholarly journals Sanghuangporus sanghuang Mycelium Prevents Paracetamol-Induced Hepatotoxicity through Regulating the MAPK/NF-κB, Keap1/Nrf2/HO-1, TLR4/PI3K/Akt and CaMKKβ/LKB1/AMPK Pathways and Suppressing Oxidative Stress and Inflammation

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 897
Author(s):  
Wen-Ping Jiang ◽  
Jeng-Shyan Deng ◽  
Shyh-Shyun Huang ◽  
Sheng-Hua Wu ◽  
Chin-Chu Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Protein Kinase ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Mitogen Activated Protein Kinase ◽  
Heme Oxygenase 1 ◽  
Molecular Evidence ◽  
Related Factor ◽  
Serum Aminotransferase ◽  
Compound C

Liver damage induced by paracetamol overdose is the main cause of acute liver failure worldwide. In order to study the hepatoprotective effect of Sanghuangporus sanghuang mycelium (SS) on paracetamol-induced liver injury, SS was administered orally every day for 6 days in mice before paracetamol treatment. SS decreased serum aminotransferase activities and the lipid profiles, protecting against paracetamol hepatotoxicity in mice. Furthermore, SS inhibited the lipid peroxidation marker malondialdehyde (MDA), hepatic cytochrome P450 2E1 (CYP2E1), and the histopathological changes in the liver and decreased inflammatory activity by inhibiting the production of proinflammatory cytokines in paracetamol-induced acute liver failure. Moreover, SS improved the levels of glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase in the liver. Significantly, SS diminished mitogen-activated protein kinase (MAPK), Toll-like receptor 4 (TLR4), phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt), and the nuclear factor-kappa B (NF-κB) axis, as well as upregulated the Kelch-like ECH-associated protein 1 (Keap1)/erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway, in paracetamol-induced mice. SS mainly inhibited the phosphorylation of the liver kinase B1 (LKB1), Ca2+/calmodulin-dependent kinase kinase β (CaMKKβ), and AMP-activated protein kinase (AMPK) protein expression. Furthermore, the protective effects of SS on paracetamol-induced hepatotoxicity were abolished by compound C, an AMPK inhibitor. In summary, we provide novel molecular evidence that SS protects liver cells from paracetamol-induced hepatotoxicity by inhibiting oxidative stress and inflammation.

scholarly journals Hepatoprotective Effect of Polysaccharides Isolated from Dendrobium officinale against Acetaminophen-Induced Liver Injury in Mice via Regulation of the Nrf2-Keap1 Signaling Pathway

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Guosheng Lin ◽  
Dandan Luo ◽  
Jingjing Liu ◽  
Xiaoli Wu ◽  
Jinfen Chen ◽  
...  
Keyword(s):  
Liver Injury ◽  
Signaling Pathway ◽  
Nuclear Translocation ◽  
Hepatoprotective Effect ◽  
Dendrobium Officinale ◽  
Regulatory Subunit ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Glutamate Cysteine Ligase ◽  
Nrf2 Signaling Pathway

The effect of polysaccharides isolated from Dendrobium officinale (DOP) on acetaminophen- (APAP-) induced hepatotoxicity and the underlying mechanisms involved are investigated. Male Institute of Cancer Research (ICR) mice were randomly assigned to six groups: (1) control, (2) vehicle (APAP, 230 mg/kg), (3) N-acetylcysteine (100 mg/kg), (4) 50 mg/kg DOP, (5) 100 mg/kg DOP, and (6) 200 mg/kg DOP. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in the serum and glutathione (GSH), malondialdehyde (MDA), catalase (CAT), total antioxidant capacity (T-AOC), myeloperoxidase (MPO), and reactive oxygen species (ROS) levels in the liver were determined after the death of the mice. The histological examination of the liver was also performed. The effect of DOP on the Kelch-like ECH-associated protein 1- (Keap1-) nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway was evaluated using Western blot analysis and real-time polymerase chain reaction (PCR). The results showed that DOP treatment significantly alleviated the hepatic injury. The decrease in ALT and AST levels in the serum and ROS, MDA, and MPO contents in the liver, as well as the increases in GSH, CAT, and T-AOC in the liver, were observed after DOP treatment. DOP treatment significantly induced the dissociation of Nrf2 from the Nrf2−Keap1 complex and promoted the Nrf2 nuclear translocation. Subsequently, DOP-mediated Nrf2 activation triggered the transcription and expressions of the glutamate–cysteine ligase catalytic (GCLC) subunit, glutamate–cysteine ligase regulatory subunit (GCLM), heme oxygenase-1 (HO-1), and NAD(P)H dehydrogenase quinone 1 (NQO1) in APAP-treated mice. The present study revealed that DOP treatment exerted potentially hepatoprotective effects against APAP-induced liver injury. Further investigation about mechanisms indicated that DOP exerted the hepatoprotective effect by suppressing the oxidative stress and activating the Nrf2−Keap1 signaling pathway.

MicroRNA-128-3p aggravates doxorubicin-induced liver injury by promoting oxidative stress via targeting Sirtuin-1

2019 ◽  
Vol 146 ◽  
pp. 104276 ◽  
Author(s):  
Xuerong Zhao ◽  
Yue Jin ◽  
Lei Li ◽  
Lina Xu ◽  
Zeyao Tang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Injury ◽  
Sirtuin 1

scholarly journals Overview of Salvia miltiorrhiza as a Potential Therapeutic Agent for Various Diseases: An Update on Efficacy and Mechanisms of Action

Antioxidants ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 857
Author(s):  
Inyong Jung ◽  
Hyerin Kim ◽  
Seongcheol Moon ◽  
Hyuk Lee ◽  
Bonglee Kim
Keyword(s):  
Oxidative Stress ◽  
Therapeutic Agent ◽  
Salvia Miltiorrhiza ◽  
Cerebrovascular Diseases ◽  
Mechanisms Of Action ◽  
Therapeutic Effects ◽  
Nervous System Diseases ◽  
Salvia Miltiorrhiza Bunge ◽  
Pubmed Central ◽  
Therapeutic Benefits

Salvia miltiorrhiza Bunge (S. miltiorrhiza) is a medicinal herb that has been used for the treatment for various diseases such as cardiovascular and cerebrovascular diseases in East Asia including Korea. Considering its extensive usage as a therapeutic agent for multiple diseases, there is a need to review previous research regarding its therapeutic benefits and their mechanisms. Therefore, we searched PubMed and PubMed Central for articles reporting its therapeutic effects on certain disease groups including cancers, cardiovascular, liver, and nervous system diseases. This review provides an overview of therapeutic benefits and targets of S. miltiorrhiza, including inflammation, fibrosis, oxidative stress, and apoptosis. The findings on multi-functional properties of S. miltiorrhiza discussed in this article support the efficacy of S. miltiorrhiza extract on various diseases, but also call for further research on the multiple mechanisms that mediate its therapeutic effects.

Cpt1a promoted ROS-induced oxidative stress and inflammation in liver injury via the Nrf2/HO-1 and NLRP3 inflammasome signaling pathway

2020 ◽  
Author(s):  
Xigang Luo ◽  
Dapeng Sun ◽  
Yinxiang Wang ◽  
Fengxiang Zhang ◽  
Yi Wang
Keyword(s):  
Oxidative Stress ◽  
Liver Injury ◽  
Signaling Pathway ◽  
Nlrp3 Inflammasome ◽  
Receptor Protein ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Over Expression ◽  
Vitro Model

Various liver diseases caused by liver damage seriously affect people’s health. The purpose of this study was to clarify that the effects and mechanism of Carnitine palmitoyltransferase 1 (Cpt1a) on oxidative stress and inflammation in liver injury. It was found that the expression of Cpt1a mRNA was up-regulated in model mice of liver injury. So, over-expression of Cpt1a increased reactive oxygen species (ROS) production and malondialdehyde (MDA) levels, and reduced superoxide dismutase (SOD), glutathione (GSH) and glutathione peroxidase (GSH-px) levels in vitro model of liver injury. It was also shown that over-expression of Cpt1a suppressed the Nuclear factor-erythroid-2-related factor 2 (Nrf2)/ heme oxygenase-1 (HO-1) signaling pathway. In summary, these data indicate that Cpt1a promotes ROS-induced oxidative stress in liver injury via the Nrf2/HO-1 and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome signaling pathway.

Epimedium koreanum Ameliorates Oxidative Stress-Mediated Liver Injury by Activating Nuclear Factor Erythroid 2-Related Factor 2

2018 ◽  
Vol 46 (02) ◽  
pp. 469-488 ◽  
Author(s):  
Ji Yun Jung ◽  
Sang Mi Park ◽  
Hae Li Ko ◽  
Jong Rok Lee ◽  
Chung A Park ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Injury ◽  
Hepg2 Cells ◽  
Liver Diseases ◽  
Caspase 3 ◽  
Glutathione Depletion ◽  
Related Factor ◽  
Nuclear Factor ◽  
Nrf2 Activation ◽  
Anti Oxidant

Oxidative stress induced by reactive oxygen species is the main cause of various liver diseases. This study investigated the hepatoprotective effect of Epimedium koreanum Nakai water extract (EKE) against arachidonic acid (AA)[Formula: see text][Formula: see text][Formula: see text]iron-mediated cytotoxicity in HepG2 cells and carbon tetrachloride (CCl4-)-mediated acute liver injury in mice. Pretreatment with EKE (30 and 100[Formula: see text][Formula: see text]g/mL) significantly inhibited AA[Formula: see text][Formula: see text][Formula: see text]iron-mediated cytotoxicity in HepG2 cells by preventing changes in the expression of cleaved caspase-3 and poly(ADP-ribose) polymerase. EKE attenuated hydrogen peroxide production, glutathione depletion, and mitochondrial membrane dysfunction. EKE also increased the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2), transactivated anti-oxidant response element harboring luciferase activity, and induced the expression of anti-oxidant genes. Furthermore, the cytoprotective effect of EKE against AA[Formula: see text][Formula: see text][Formula: see text]iron was blocked in Nrf2 knockout cells. Ultra-performance liquid chromatography analysis showed that EKE contained icariin, icaritin, and quercetin; icaritin and quercetin were both found to protect HepG2 cells from AA[Formula: see text][Formula: see text][Formula: see text]iron via Nrf2 activation. In a CCl4-induced mouse model of liver injury, pretreatment with EKE (300[Formula: see text]mg/kg) for four consecutive days ameliorated CCl4-mediated increases in serum aspartate aminotransferase activity, histological activity index, hepatic parenchyma degeneration, and inflammatory cell infiltration. EKE also decreased the number of nitrotyrosine-, 4-hydroxynonenal-, cleaved caspase-3-, and cleaved poly(ADP-ribose) polymerase-positive cells in hepatic tissues. These results suggest EKE is a promising candidate for the prevention or treatment of oxidative stress-related liver diseases via Nrf2 activation.

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