scholarly journals Herbal SGR Formula Prevents Acute Ethanol-Induced Liver Steatosis via Inhibition of Lipogenesis and Enhancement Fatty Acid Oxidation in Mice

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Ping Qiu ◽  
Xiang Li ◽  
De-song Kong ◽  
Huan-zhou Li ◽  
Cong-cong Niu ◽  
...  
Keyword(s):  
Side Effects ◽  
Regulatory Element ◽  
Liver Steatosis ◽  
Adenosine Monophosphate ◽  
Toxicity Tests ◽  
Acid Oxidation ◽  
Protective Effects ◽  
Histopathological Changes ◽  
Acute Ethanol ◽  
Underlying Mechanisms

Our previous study indicated that herbal SGR formula partially attenuates ethanol-induced fatty liver, but the underlying mechanisms remain unclear. In the present study, mice were pretreated with SGR (100 and 200 mg/kg/d bw) for 30 d before being exposed to ethanol (4.8 g/kg bw). The biochemical indices and histopathological changes were examined to evaluate the protective effects and to explore potential mechanisms by investigating the adiponectin, tumor necrosis factor-α(TNF-α), peroxisome proliferators-activated receptor-α(PPAR-α), sterol regulatory element binding protein-1c (SREBP-1c), adenosine monophosphate-activated protein kinase (AMPK), and so forth. Results showed that SGR pretreatment markedly inhibited acute ethanol-induced liver steatosis, significantly reduced serum and hepatic triglyceride (TG) level, and improved classic histopathological changes. SGR suppressed the protein expression of hepatic SREBP-1c and TNF-αand increased adiponectin, PPAR-α, and AMPK phosphorylation in the liver. Meanwhile, acute toxicity tests showed that no death or toxic side effects within 14 days were observed upon oral administration of the extracts at a dose of 16 g/kg body wt. These results demonstrate that SGR could protect against acute alcohol-induced liver steatosis without any toxic side effects. Therefore, our studies provide novel molecular insights into the hepatoprotective effect of SGR formula, which may be exploited as a therapeutic agent for ethanol-induced hepatosteatosis.

scholarly journals Hypothalamic AMPK as a Mediator of Hormonal Regulation of Energy Balance

2018 ◽  
Vol 19 (11) ◽  
pp. 3552 ◽  
Author(s):  
Baile Wang ◽  
Kenneth Cheng
Keyword(s):  
Energy Balance ◽  
Hormonal Regulation ◽  
Energy Homeostasis ◽  
Adenosine Monophosphate ◽  
Acid Oxidation ◽  
Peripheral Tissues ◽  
Adaptive Thermogenesis ◽  
Increase Food Intake ◽  
Regulatory Effects ◽  
Underlying Mechanisms

As a cellular energy sensor and regulator, adenosine monophosphate (AMP)-activated protein kinase (AMPK) plays a pivotal role in the regulation of energy homeostasis in both the central nervous system (CNS) and peripheral organs. Activation of hypothalamic AMPK maintains energy balance by inducing appetite to increase food intake and diminishing adaptive thermogenesis in adipose tissues to reduce energy expenditure in response to food deprivation. Numerous metabolic hormones, such as leptin, adiponectin, ghrelin and insulin, exert their energy regulatory effects through hypothalamic AMPK via integration with the neural circuits. Although activation of AMPK in peripheral tissues is able to promote fatty acid oxidation and insulin sensitivity, its chronic activation in the hypothalamus causes obesity by inducing hyperphagia in both humans and rodents. In this review, we discuss the role of hypothalamic AMPK in mediating hormonal regulation of feeding and adaptive thermogenesis, and summarize the diverse underlying mechanisms by which central AMPK maintains energy homeostasis.

scholarly journals Ruscogenin Ameliorates Experimental Nonalcoholic Steatohepatitis via Suppressing Lipogenesis and Inflammatory Pathway

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Hung-Jen Lu ◽  
Thing-Fong Tzeng ◽  
Shorong-Shii Liou ◽  
Chia Ju Chang ◽  
Cheng Yang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Nonalcoholic Steatohepatitis ◽  
Hepg2 Cells ◽  
Inflammatory Responses ◽  
Smooth Muscle Actin ◽  
Liver Steatosis ◽  
Acid Oxidation ◽  
Mrna Levels ◽  
Protective Effects ◽  
Triglyceride Accumulation

The aim of the study was to investigate the protective effects of ruscogenin, a major steroid sapogenin in Ophiopogon japonicus, on experimental models of nonalcoholic steatohepatitis. HepG2 cells were exposed to 300 μmol/l palmitic acid (PA) for 24 h with the preincubation of ruscogenin for another 24 h. Ruscogenin (10.0 μmol/l) had inhibitory effects on PA-induced triglyceride accumulation and inflammatory markers in HepG2 cells. Male golden hamsters were randomly divided into five groups fed a normal diet, a high-fat diet (HFD), or a HFD supplemented with ruscogenin (0.3, 1.0, or 3.0 mg/kg/day) by gavage once daily for 8 weeks. Ruscogenin alleviated dyslipidemia, liver steatosis, and necroinflammation and reversed plasma markers of metabolic syndrome in HFD-fed hamsters. Hepatic mRNA levels involved in fatty acid oxidation were increased in ruscogenin-treated HFD-fed hamsters. Conversely, ruscogenin decreased expression of genes involved in hepatic lipogenesis. Gene expression of inflammatory cytokines, chemoattractive mediator, nuclear transcription factor-(NF-)κB, andα-smooth muscle actin were increased in the HFD group, which were attenuated by ruscogenin. Ruscogenin may attenuate HFD-induced steatohepatitis through downregulation of NF-κB-mediated inflammatory responses, reducing hepatic lipogenic gene expression, and upregulating proteins inβ-oxidation pathway.

scholarly journals Extracts of Vine Tea Improve Diet-Induced Non-Alcoholic Steatohepatitis Through AMPK-LXRα Signaling

2021 ◽  
Vol 12 ◽  
Author(s):  
Yu-jun Chen ◽  
Hai-yan Song ◽  
Zi-wei Zhang ◽  
Qian Chen ◽  
Zhi-peng Tang ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Liver Lipid ◽  
Adenosine Monophosphate ◽  
Antagonistic Effect ◽  
Tunel Staining ◽  
Acid Oxidation ◽  
Protective Effects ◽  
Alcoholic Steatohepatitis ◽  
Acid Diet

Chinese vine tea can improve glucose and lipid metabolic disorders. However, its protective effects in non-alcoholic steatohepatitis (NASH) and its underlying molecular mechanisms remain unclear. Liver X receptor α (LXRα) inhibition and adenosine monophosphate-(AMP)-activated protein kinase (AMPK) activation can enhance control of NASH. AMPK activators have also been shown to inactivate LXRα. Here, the anti-NASH effects of vine tea extract (VTE) dosed at 1 g.100 g−1 diet were investigated using NASH mice challenged with a methionine and choline-deficient l-amino acid diet (MCDD) and a high-fat diet (HFD). Pharmacological mechanisms of VTE were explored using TUNEL staining, AMPK inhibition, Western blot, reporter assays, qRT-PCR analyses, and immunofluorescence. VTE treatment improved fatty liver in HFD-induced mice, while it alleviated the progression of NASH including protecting against liver lipid accumulation, steatosis, endoplasmic reticulum stress, apoptosis, inflammation, and functional injury in MCDD-fed mice. VTE reduced the action of hepatic lipogenic genes, F4/80, pro-inflammatory cytokines, CHOP, and cleaved Caspase-3 expression, while promoting expression of fatty acid oxidation genes CPT1α, ß. VTE also enhanced AMPK and blocked LXRα signaling in mouse livers. In vitro results indicated that VTE increased AMPK phosphorylation and reduced LXRα activity in HepG2 cells. Conversely, the antagonistic effect of VTE on LXRα was decreased through AMPK inhibition. Our data suggests that VTE may improve diet-induced NASH, which involves the pharmacological modulation of the AMPK-LXRα signaling pathway.

The effects of dietary methionine restriction on the function and metabolic reprogramming in the liver and brain – implications for longevity

2019 ◽  
Vol 30 (6) ◽  
pp. 581-593 ◽  
Author(s):  
Dušan Mladenović ◽  
Tatjana Radosavljević ◽  
Dragan Hrnčić ◽  
Aleksandra Rasic-Markovic ◽  
Olivera Stanojlović
Keyword(s):  
Growth Factor ◽  
Life Span ◽  
De Novo ◽  
Regulatory Element ◽  
Adenosine Monophosphate ◽  
Metabolic Reprogramming ◽  
Fibroblast Growth Factor 21 ◽  
Acid Oxidation ◽  
Peripheral Tissues ◽  
Methionine Restriction

Abstract Methionine is an essential sulphur-containing amino acid involved in protein synthesis, regulation of protein function and methylation reactions. Dietary methionine restriction (0.12–0.17% methionine in food) extends the life span of various animal species and delays the onset of aging-associated diseases and cancers. In the liver, methionine restriction attenuates steatosis and delays the development of non-alcoholic steatohepatitis due to antioxidative action and metabolic reprogramming. The limited intake of methionine stimulates the fatty acid oxidation in the liver and the export of lipoproteins as well as inhibits de novo lipogenesis. These effects are mediated by various signaling pathways and effector molecules, including sirtuins, growth hormone/insulin-like growth factor-1 axis, sterol regulatory element binding proteins, adenosine monophosphate-dependent kinase and general control nonderepressible 2 pathway. Additionally, methionine restriction stimulates the synthesis of fibroblast growth factor-21 in the liver, which increases the insulin sensitivity of peripheral tissues. In the brain, methionine restriction delays the onset of neurodegenerative diseases and increases the resistance to various forms of stress through antioxidative effects and alterations in lipid composition. This review aimed to summarize the morphological, functional and molecular changes in the liver and brain caused by the methionine restriction, with possible implications in the prolongation of maximal life span.

scholarly journals Anti-Adipogenic Effect of Neferine in 3T3-L1 Cells and Primary White Adipocytes

Nutrients ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1858
Author(s):  
Miey Park ◽  
Jinyoung Han ◽  
Hae-Jeung Lee
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Synthase ◽  
Binding Protein ◽  
Regulatory Element ◽  
Antioxidant Properties ◽  
Adenosine Monophosphate ◽  
Sirtuin 1 ◽  
Acid Oxidation ◽  
Peroxisome Proliferator ◽  
Dependent Manner

Neferine, an alkaloid component extracted from lotus seed embryos, is known for its anti-inflammatory, anticancer, and antioxidant properties. However, the anti-adipogenic activity of neferine has not been thoroughly investigated. In this study, neferine was found to inhibit lipid accumulation in a dose-dependent manner during the differentiation of 3T3-L1 cells without inducing cytotoxicity. Real-time polymerase chain reaction and immunoblot analysis revealed the downregulation in the expression of peroxisome proliferator activated receptor gamma (PPARγ), CCAAT/enhancer-binding protein alpha (C/EBPα), sterol regulatory element-binding protein-1c (SREBP-1c), and fatty acid synthase (FAS) and the upregulation in carnitine palmitoyltransferase-1 (CPT-1) and sirtuin 1 (SIRT1) levels following neferine treatment. Furthermore, neferine increased the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC), which is an important regulator of fatty acid oxidation. Our result indicates that neferine attenuates adipogenesis and promotes lipid metabolism by activating AMPK-mediated signaling. Therefore, neferine may serve as a therapeutic candidate for obesity treatment.

scholarly journals Resveratrol alleviates alcoholic fatty liver in mice

2008 ◽  
Vol 295 (4) ◽  
pp. G833-G842 ◽  
Author(s):  
Joanne M. Ajmo ◽  
Xiaomei Liang ◽  
Christopher Q. Rogers ◽  
Brandi Pennock ◽  
Min You
Keyword(s):  
Fatty Liver ◽  
Regulatory Element ◽  
Protective Action ◽  
Liver Steatosis ◽  
Sirtuin 1 ◽  
Acid Oxidation ◽  
Signaling System ◽  
Alcoholic Fatty Liver ◽  
Ampk Signaling ◽  
Resveratrol Treatment

Alcoholic fatty liver is associated with inhibition of sirtuin 1 (SIRT1) and AMP-activated kinase (AMPK), two critical signaling molecules regulating the pathways of hepatic lipid metabolism in animals. Resveratrol, a dietary polyphenol, has been identified as a potent activator for both SIRT1 and AMPK. In the present study, we have carried out in vivo animal experiments that test the ability of resveratrol to reverse the inhibitory effects of chronic ethanol feeding on hepatic SIRT1-AMPK signaling system and to prevent the development of alcoholic liver steatosis. Resveratrol treatment increased SIRT1 expression levels and stimulated AMPK activity in livers of ethanol-fed mice. The resveratrol-mediated increase in activities of SIRT1 and AMPK was associated with suppression of sterol regulatory element binding protein 1 (SREBP-1) and activation of peroxisome proliferator-activated receptor γ coactivator α (PGC-1α). In parallel, in ethanol-fed mice, resveratrol administration markedly increased circulating adiponectin levels and enhanced mRNA expression of hepatic adiponectin receptors (AdipoR1/R2). In conclusion, resveratrol treatment led to reduced lipid synthesis and increased rates of fatty acid oxidation and prevented alcoholic liver steatosis. The protective action of resveratrol is in whole or in part mediated through the upregulation of a SIRT1-AMPK signaling system in the livers of ethanol-fed mice. Our study suggests that resveratrol may serve as a promising agent for preventing or treating human alcoholic fatty liver disease.

Polydatin Attenuates Carbachol-induced Contraction of Guinea Pig Gallbladder

2019 ◽  
Vol 18 (1) ◽  
pp. 34-38
Author(s):  
Chen Lei ◽  
Pan Xiang ◽  
Shen Yonggang ◽  
Song Kai ◽  
Zhong Xingguo ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Guinea Pig ◽  
Smooth Muscles ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Dependent Manner ◽  
Underlying Mechanisms ◽  
Dose Dependent

The aim of this study was to determine whether polydatin, a glucoside of resveratrol isolated from the root of Polygonum cuspidatum, warranted development as a potential therapeutic for ameliorating the pain originating from gallbladder spasm disorders and the underlying mechanisms. Guinea pig gallbladder smooth muscles were treated with polydatin and specific inhibitors to explore the mechanisms underpinning polydatin-induced relaxation of carbachol-precontracted guinea pig gallbladder. Our results shown that polydatin relaxed carbachol-induced contraction in a dose-dependent manner through the nitric oxide/cyclic guanosine monophosphate/protein kinase G and the cyclic adenosine monophosphate/protein kinase A signaling pathways as well as the myosin light chain kinase and potassium channels. Our findings suggested that there was value in further exploring the potential therapeutic use of polydatin in gallbladder spasm disorders.

Anthocyanins As Modulators of Cell Redox-Dependent Pathways in Non-Communicable Diseases

2020 ◽  
Vol 27 (12) ◽  
pp. 1955-1996 ◽  
Author(s):  
Antonio Speciale ◽  
Antonella Saija ◽  
Romina Bashllari ◽  
Maria Sofia Molonia ◽  
Claudia Muscarà ◽  
...  
Keyword(s):  
Human Health ◽  
Biological Activities ◽  
Wide Spectrum ◽  
Antioxidant Defenses ◽  
Noncommunicable Diseases ◽  
Protective Effects ◽  
Pathological Conditions ◽  
Chronic Pulmonary Diseases ◽  
Underlying Mechanisms

: Chronic Noncommunicable Diseases (NCDs), mostly represented by cardiovascular diseases, diabetes, chronic pulmonary diseases, cancers, and several chronic pathologies, are one of the main causes of morbidity and mortality, and are mainly related to the occurrence of metabolic risk factors. Anthocyanins (ACNs) possess a wide spectrum of biological activities, such as anti-inflammatory, antioxidant, cardioprotective and chemopreventive properties, which are able to promote human health. Although ACNs present an apparent low bioavailability, their metabolites may play an important role in the in vivo protective effects observed. : This article directly addresses the scientific evidences supporting that ACNs could be useful to protect human population against several NCDs not only acting as antioxidant but through their capability to modulate cell redox-dependent signaling. In particular, ACNs interact with the NF-κB and AP-1 signal transduction pathways, which respond to oxidative signals and mediate a proinflammatory effect, and the Nrf2/ARE pathway and its regulated cytoprotective proteins (GST, NQO, HO-1, etc.), involved in both cellular antioxidant defenses and elimination/inactivation of toxic compounds, so countering the alterations caused by conditions of chemical/oxidative stress. In addition, supposed crosstalks could contribute to explain the protective effects of ACNs in different pathological conditions characterized by an altered balance among these pathways. Thus, this review underlines the importance of specific nutritional molecules for human health and focuses on the molecular targets and the underlying mechanisms of ACNs against various diseases.

scholarly journals Protective Effect of Pyrus ussuriensis Maxim. Extract against Ethanol-Induced Gastritis in Rats

Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 439
Author(s):  
Naila Boby ◽  
Muhammad Aleem Abbas ◽  
Eon-Bee Lee ◽  
Zi-Eum Im ◽  
Walter H. Hsu ◽  
...  
Keyword(s):  
Therapeutic Option ◽  
Adenosine Monophosphate ◽  
Ethanol Ingestion ◽  
Dependent Manner ◽  
Protective Effects ◽  
Gastric Mucosal Lesions ◽  
Cellular Degeneration ◽  
Mucosal Lesions ◽  
Pyrus Ussuriensis Maxim

Pyrus ussuriensis Maxim (Korean pear) has been used for hundreds of years as a traditional herbal medicine for asthma, cough, and atopic dermatitis in Korea and China. Although it was originally shown to possess anti-inflammatory, antioxidant, and antiatopic properties, its gastroprotective effects have not been investigated. In the present study, we evaluated the protective effects of Pyrus ussuriensis Maxim extract (PUE) against ethanol-induced gastritis in rats. The bioactive compound profile of PUE was determined by gas chromatography mass spectroscopy (GC-MS) and high-performance liquid chromatography (HPLC). The gastroprotection of PUE at different doses (250 and 500 mg/kg body weight) prior to ethanol ingestion was evaluated using an in vivo gastritis rat model. Several endpoints were evaluated, including gastric mucosal lesions, cellular degeneration, intracellular damage, and immunohistochemical localization of leucocyte common antigen. The gastric mucosal injury and ulcer score were determined by evaluating the inflamed gastric mucosa and by histological examination. To identify the mechanisms of gastroprotection by PUE, antisecretory action and plasma prostaglandin E2 (PGE2), gastric mucosal cyclic adenosine monophosphate (cAMP), and histamine levels were measured. PUE exhibited significant antioxidant effects with IC50 values of 56.18 and 22.49 µg/mL for 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′- azino-di-(3-ethylbenzothiazoline)-6-sulfonic acid (ABTS) inhibition (%), respectively. In addition, GC/MS and HPLC analyses revealed several bioactive compounds of PUE. Pretreatment with PUE significantly (P < 0.05) decreased the ulcer index by preventing gastric mucosal lesions, erosion, and cellular degeneration. An immunohistochemical analysis revealed that PUE markedly attenuated leucocyte infiltration in a dose-dependent manner. The enhancement of PGE2 levels and attenuation of cAMP levels along with the inhibition of histamine release following PUE pretreatment was associated with the cytoprotective and healing effects of PUE. In contrast, the downregulation of the H+/K+ ATPase pathway as well as muscarinic receptor (M3R) and histamine receptor (H2R) inhibition was also involved in the gastroprotective effects of PUE; however, the expression of cholecystokinin-2 receptors (CCK2R) was unchanged. Finally, no signs of toxicity were observed following PUE treatment. Based on our results, we conclude that PUE represents an effective therapeutic option to reduce the risk of gastritis and warrants further study.

scholarly journals Melatonin Successfully Rescues the Hippocampal Molecular Machinery and Enhances Anti-oxidative Activity Following Early-Life Sleep Deprivation Injury

Antioxidants ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 774
Author(s):  
Hung-Ming Chang ◽  
Hsing-Chun Lin ◽  
Hsin-Lin Cheng ◽  
Chih-Kai Liao ◽  
To-Jung Tseng ◽  
...  
Keyword(s):  
Sleep Deprivation ◽  
Early Life ◽  
Cognitive Activity ◽  
Oxidative Activity ◽  
Protective Effects ◽  
Long Term Effects ◽  
Ionic Distribution ◽  
Melatonin Administration ◽  
Molecular Machinery ◽  
Underlying Mechanisms

Early-life sleep deprivation (ESD) is a serious condition with severe cognitive sequelae. Considering hippocampus plays an essential role in cognitive regulation, the present study aims to determine whether melatonin, a neuroendocrine beard with significant anti-oxidative activity, would greatly depress the hippocampal oxidative stress, improves the molecular machinery, and consequently exerts the neuro-protective effects following ESD. Male weanling Wistar rats (postnatal day 21) were subjected to ESD for three weeks. During this period, the animals were administered normal saline or melatonin (10 mg/kg) via intraperitoneal injection between 09:00 and 09:30 daily. After three cycles of ESD, the animals were kept under normal sleep/wake cycle until they reached adulthood and were sacrificed. The results indicated that ESD causes long-term effects, such as impairment of ionic distribution, interruption of the expressions of neurotransmitters and receptors, decreases in the levels of several antioxidant enzymes, and impairment of several signaling pathways, which contribute to neuronal death in hippocampal regions. Melatonin administration during ESD prevented these effects. Quantitative evaluation of cells also revealed a higher number of neurons in the melatonin-treated animals when compared with the saline-treated animals. As the hippocampus is critical to cognitive activity, preserving or even improving the hippocampal molecular machinery by melatonin during ESD not only helps us to better understand the underlying mechanisms of ESD-induced neuronal dysfunction, but also the therapeutic use of melatonin to counteract ESD-induced neuronal deficiency.

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