scholarly journals Does Dihydromyricetin Impact on Alcohol Metabolism

2020 ◽  
pp. S573-S581
Author(s):  
A SKOTNICOVÁ ◽  
G BOUBÍNOVÁ ◽  
Z BOŠTÍKOVÁ ◽  
Š DUŠKOVÁ ◽  
M ŠULC ◽  
...  
Keyword(s):  
Alcohol Intoxication ◽  
Hepatoprotective Activity ◽  
Alcohol Metabolism ◽  
Primary Hepatocytes ◽  
Health Promoting ◽  
Adh Activity ◽  
Positive Effect

Dihydromyricetin (DHM) is a natural flavonoid showing several health promoting effects such as protective activity during severe alcohol intoxication. The mechanism underlying the effects of DHM on alcohol metabolism is virtually unknown. The present paper is focused on clarifying the role of DHM in the liver alcohol elimination at its molecular level. First, impact of DHM on alcohol dehydrogenase (ADH) activity in vitro and the enzyme induction in vivo was examined. Neither the ADH activity nor the enzyme expression were influenced by DHM. Next, the effect of DHM during alcohol intoxication were studied on primary hepatocytes isolated from EtOH-premedicated and untreated rats. The viability of cells exposed to alcohol, estimated based on the released enzymes, alanine aminotransferase (ALT) and aspartate aminotransferase (AST), was slightly affected by DHM. Although the expected hepatoprotective effect of DHM was not fully achieved, DHM (in a concentration manner) proved to reduce the level of ROS/RNS in hepatocytes. However, no change in the rate of alcohol metabolism in vivo was found when rats were administered with a single or repeated dose of ethanol supplemented with DHM. In conclusion, the proposed positive effect of DHM during alcohol intoxication has not been proven. Moreover, there is no effect of DHM on the alcohol metabolism. The “hoped-for” DHM hepatoprotective activity can be attributed to the reduction of ROS/RNS levels in cells.

scholarly journals Non-alcoholic fatty liver disease in mice with hepatocyte-specific deletion of mitochondrial fission factor

Diabetologia ◽  
2021 ◽  
Author(s):  
Yukina Takeichi ◽  
Takashi Miyazawa ◽  
Shohei Sakamoto ◽  
Yuki Hanada ◽  
Lixiang Wang ◽  
...  
Keyword(s):  
Er Stress ◽  
Mitochondrial Dynamics ◽  
Mitochondrial Fission ◽  
Primary Hepatocytes ◽  
Alcoholic Fatty Liver ◽  
Expression Of Genes ◽  
Specific Deletion

Abstract Aims/hypothesis Mitochondria are highly dynamic organelles continuously undergoing fission and fusion, referred to as mitochondrial dynamics, to adapt to nutritional demands. Evidence suggests that impaired mitochondrial dynamics leads to metabolic abnormalities such as non-alcoholic steatohepatitis (NASH) phenotypes. However, how mitochondrial dynamics are involved in the development of NASH is poorly understood. This study aimed to elucidate the role of mitochondrial fission factor (MFF) in the development of NASH. Methods We created mice with hepatocyte-specific deletion of MFF (MffLiKO). MffLiKO mice fed normal chow diet (NCD) or high-fat diet (HFD) were evaluated for metabolic variables and their livers were examined by histological analysis. To elucidate the mechanism of development of NASH, we examined the expression of genes related to endoplasmic reticulum (ER) stress and lipid metabolism, and the secretion of triacylglycerol (TG) using the liver and primary hepatocytes isolated from MffLiKO and control mice. Results MffLiKO mice showed aberrant mitochondrial morphologies with no obvious NASH phenotypes during NCD, while they developed full-blown NASH phenotypes in response to HFD. Expression of genes related to ER stress was markedly upregulated in the liver from MffLiKO mice. In addition, expression of genes related to hepatic TG secretion was downregulated, with reduced hepatic TG secretion in MffLiKO mice in vivo and in primary cultures of MFF-deficient hepatocytes in vitro. Furthermore, thapsigargin-induced ER stress suppressed TG secretion in primary hepatocytes isolated from control mice. Conclusions/interpretation We demonstrated that ablation of MFF in liver provoked ER stress and reduced hepatic TG secretion in vivo and in vitro. Moreover, MffLiKO mice were more susceptible to HFD-induced NASH phenotype than control mice, partly because of ER stress-induced apoptosis of hepatocytes and suppression of TG secretion from hepatocytes. This study provides evidence for the role of mitochondrial fission in the development of NASH. Graphical abstract

scholarly journals Pomegranate as a natural source of phenolic antioxidants

2020 ◽  
Vol 9 ◽  
Author(s):  
Fellipe Lopes De Oliveira ◽  
Thaise Yanka Portes Arruda ◽  
Renan Da Silva Lima ◽  
Sabrina Neves Casarotti ◽  
Maressa Caldeira Morzelle
Keyword(s):  
Antioxidant Activity ◽  
Chronic Diseases ◽  
Biological Effects ◽  
Meat Products ◽  
Phenolic Antioxidants ◽  
Antioxidant Compounds ◽  
Health Promoting

Pomegranate, a recognized source of phenolic compounds, has been associated with health-promoting benefits, mostly due to its antioxidant activity. Ellagic and gallic acids, anthocyanins, and ellagitannins are the main phenolics in pomegranate, showing antioxidant activity. For this reason, pomegranate has been used in foods, such as meat products, as an attempt to retard lipid oxidation and increase shelf-life. In recent years, in vitro, in vivo, and human studies reported the antioxidant activity of pomegranate, especially its peels, with reduced incidence of chronic diseases (e.g., cardiovascular ailments, cancer, neurodegenerative disease, type 2 diabetes, chronic kidney disease). This review aims to present the main antioxidant compounds on pomegranate and their biological effects, the antioxidant activity of pomegranate-based foods, the application of pomegranate as a natural antioxidant food additive, the role of pomegranate in the prevention and management of chronic diseases, as well as the trends and prospects regarding the application of pomegranate in innovative food and health.

Antagonists of the antidiuretic activity of vasopressin

1988 ◽  
Vol 254 (2) ◽  
pp. F165-F177 ◽  
Author(s):  
L. B. Kinter ◽  
W. F. Huffman ◽  
F. L. Stassen
Keyword(s):  
Water Excretion ◽  
Water Handling ◽  
Water Salt ◽  
Renal Responses ◽  
Renal Water Excretion ◽  
Adh Activity ◽  
Stimulation Of

Competitive antagonists of the antidiuretic (ADH) activity of vasopressin were first described some six years ago. When studied in vitro, ADH antagonists displace vasopressin from specific renal binding sites and antagonize, in a competitive fashion, vasopressin stimulation of adenylate cyclase and transepithelial water, salt, and urea fluxes. When studied in vivo, the ADH antagonists increase renal water excretion and antagonize, in a competitive fashion, the ADH activity of vasopressin. Marked species heterogeneity is apparent with ADH antagonists in vivo, and inconsistencies between in vitro and in vivo findings within the same species are reported. Other renal responses associated with administration of ADH antagonists include changes in renal hemodynamics and renal salt and urea excretion. The effects on salt excretion appear to be limited to those species in which vasopressin stimulation of epithelial salt reabsorption has been demonstrated. In summary, the role of vasopressin as the principal factor regulating renal water handling is supported by experience with ADH receptor antagonists. However, that experience also indicates the emerging significance of autocoids, and other synergistic factors, to affect ADH receptor/effector mechanisms and to modulate renal ADH responses.

scholarly journals Preparation and characterization of Pomegranate for Cough Treatment

2021 ◽  
Vol 9 (12) ◽  
pp. 2227-2233
Author(s):  
Mr. Chate Mahesh Madhukar
Keyword(s):  
Health Management ◽  
Neuroprotective Effect ◽  
Health Benefits ◽  
In Vivo Studies ◽  
Promoting Effect ◽  
Health Promoting ◽  
Anti Oxidant

Abstract: Pomegranates fruits have innumerable health benefits and its implication in diseases cure have been widely recognized since ancient time. Moreover, pomegranate fruits, seeds and peels are intensively used in traditional medicine as a natural therapy. It contains numerous valuable ingredients such as flavonoids, ellagitannin, punicalagin, ellagic acid, vitamins and minerals. The principal constituents including punicalagins and ellagitannin are responsible for immeasurable health benefits due to its strong antioxidant activity. Additionally, constituents of pomegranate show health promoting effect through the modulation of physiological and biochemical pathways. Recent evidences suggested that pomegranates fruits, peels and seeds illustrate therapeutics implications in health management via inhibition of free radical effect and modulation of enzymes activity linked with diseases development and progression. In this review, we summarize the therapeutic role of pomegranate fruits, seeds and peels in the health managements based on in vitro and in vivo studies. Keywords: Pomegranates, Anti-oxidant, Anti-inflammatory effect, Heptoprotective effect, Neuroprotective effect and antimicrobial effects.

Procalcific effect of proprotein convertase subtilisin/kexin type 9 (PCSK9) in chronic kidney disease (CKD)

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
N Ferri ◽  
M.G.P Lupo ◽  
M.R Rattazzi
Keyword(s):  
Colorimetric Assay ◽  
Extracellular Calcium ◽  
Calcium Deposition ◽  
Standard Diet ◽  
Plasma Total Cholesterol ◽  
Calcium Crystals ◽  
Positive Effect

Abstract Aim PCSK9 has been recently associated with a higher rate of calcification in hypercholesterolemic, diabetes and CKD patients. The aim of this study was thus to investigate the role of PCSK9 in VC process, under uremic condition, both on in vivo and in vitro experimental settings. Methods Sprauge Dawley rats were fed a standard diet (SD, n=11) or uremic diet (UD, n=11) for 6 weeks. Calcium crystals in aortas were visualized by von Kossa staining and quantified by a colorimetric assay and plasma total cholesterol determined. Control and PCSK9-overexpressing smooth muscle cells (SMCsPCSK9) were cultured with 2.5% FCS ± Pi for 7 days. Hydroxyapatite deposition by SMCs was measured by a colorimetric assay. The number and the content of pro-calcific extracellular vesicles (EVs) budding from the cells were determined. Results The hyperphosphatemia secondary to CKD lead to rat aortic calcification (+7.3-fold) and a significant increase in TC and PCSK9 levels (+1.4 and +2.7-fold, respectively). Higher expression of PCSK9 was also observed in kidney (+4.8-fold) and liver (+1.5-fold). SMCsPCSK9 showed higher extracellular calcium deposition (+1.4-fold) in response to Pi and increase EVs production (+7-fold). The incubation of control cells with recombinant PCSK9 did not induce extracellular calcium deposition. Conclusions Our study suggest a positive effect of intracellular PCSK9 on vascular calcification in CKD condition. Pro-calcific budding of EVs seems one of the possible mediators of this process. PCSK9 and calcification Funding Acknowledgement Type of funding source: None

scholarly journals In Vitro and In Vivo Experimental Hepatotoxic Models in Liver Research: Applications to the Assessment of Potential Hepatoprotective Drugs

2016 ◽  
pp. S417-S425 ◽  
Author(s):  
H. FARGHALI ◽  
M. KGALALELO KEMELO ◽  
L. WOJNAROVÁ ◽  
N. KUTINOVÁ CANOVÁ
Keyword(s):  
Hepatoprotective Activity ◽  
Sirtuin 1 ◽  
In Vivo Model ◽  
In Vivo Models ◽  
Product Removal ◽  
Liver Injuries

This mini-review highlights our and others’ experience about in vitro and in vivo models that are being used to follow up events of liver injuries under various hepatotoxic agents and potential hepatoprotective drugs. Due to limitations of the outcomes in each model, we focus primarily on two models. First, a developed perfusion method for isolated immobilized hepatocytes that improves the process of oxygenation and helps in end-product removal is of considerable value in improving cell maintenance. This cellular model is presented as a short-term research-scale laboratory bioreactor with various physiological, biochemical, molecular, toxicological and pharmacological applications. Second, the in vivo model of D-galactosamine and lipopolysaccharide (D-GalN/LPS) combination-induced liver damage is described with some details. Recently, we have revealed that resveratrol and other natural polyphenols attenuate D-GalN/LPS-induced hepatitis. Moreover, we reported that D-GalN/LPS down-regulates sirtuin 1 in rat liver. Therefore, we discuss here the role of sirtuin 1 modulation in hepatoprotection. A successful development of pharmacotherapy for liver diseases depends on the suitability of in vitro and in vivo hepatic injury systems. Several models are available to screen the hepatotoxic or hepatoprotective activity of any substance. It is important to combine different methods for confirmation of the findings.

scholarly journals Health promoting and sensory properties of phenolic compounds in food

Revista CERES ◽  
2014 ◽  
Vol 61 (suppl) ◽  
pp. 764-779 ◽  
Author(s):  
Lívia de Lacerda de Oliveira ◽  
Mariana Veras de Carvalho ◽  
Lauro Melo
Keyword(s):  
Phenolic Compounds ◽  
Defense Mechanisms ◽  
Biological Effects ◽  
Food Sources ◽  
In Vivo Studies ◽  
Chemical Structures ◽  
Health Promoting

Phenolic compounds have been extensively studied in recent years. The presence of these compounds in various foods has been associated with sensory and health promoting properties. These products from the secondary metabolism of plants act as defense mechanisms against environmental stress and attack by other organisms. They are divided into different classes according to their chemical structures. The objective of this study was to describe the different classes of phenolic compounds, the main food sources and factors of variation, besides methods for the identification and quantification commonly used to analyze these compounds. Moreover, the role of phenolic compounds in scavenging oxidative stress and the techniques of in vitro antioxidant evaluation are discussed. In vivo studies to evaluate the biological effects of these compounds and their impact on chronic disease prevention are presented as well. Finally, it was discussed the role of these compounds on the sensory quality of foods.

scholarly journals In Vivo and In Vitro Hepatoprotective Effects of Geranium koreanum Methanolic Extract via Downregulation of MAPK/Caspase-3 Pathway

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Md Rashedunnabi Akanda ◽  
In-Shik Kim ◽  
Dongchoon Ahn ◽  
Hyun-Jin Tae ◽  
Weishun Tian ◽  
...  
Keyword(s):  
Molecular Mechanism ◽  
Hepg2 Cells ◽  
Caspase 3 ◽  
Hepatoprotective Activity ◽  
Intracellular Ros ◽  
Mrna And Protein Expression ◽  
Serum Biochemical

Geranium koreanum (GK) is an indigenous Chinese herbal medicine widely used for the treatment of various inflammation and liver disorders. However, the exact mechanism of action of GK remains unknown. This study aimed to investigate the protective effect and related molecular mechanism of GK on NaAsO2-induced cytotoxicity in HepG2 cells and liver damage in mice. The cytoprotective role of GK was assessed on HepG2 cells using MTT assay. Oxidative stress and lactate dehydrogenase levels were measured with ROS and LDH assay. Histopathology and serum enzymes levels were estimated. The molecular mechanism was evaluated by qPCR and immunoblotting to ensure the hepatoprotective role of GK against NaAsO2 intoxication in mice. We found cotreatment with GK significantly attenuated NaAsO2-induced cell viability loss, intracellular ROS, and LDH release. Hepatic histopathology and serum biochemical parameters, ALT, and AST were notably improved by cotreatment with GK. Beside, GK markedly altered both mRNA and protein expression level of MAPK. The proapoptotic and antiapoptotic protein Bax/Bcl-2 ratio was significantly regulated by GK. Moreover, GK remarkably suppressed the postapoptotic transcription protein cleaved caspase-3 expression. The present study reveals that GK possesses hepatoprotective activity which is probably involved in the modulation of the MAPK/caspase-3 pathway.

scholarly journals Prospects for the Use of NF-кb Inhibitors to Stimulate the Functions of Regeneration-Competent Cells of Nerve Tissue and Neuroregeneration in Ethanol-Induced Neurodegeneration

2020 ◽  
Vol 11 (1) ◽  
pp. 8065-8074
Keyword(s):  
Intracellular Signaling ◽  
Alcohol Intoxication ◽  
Growth Potential ◽  
Nerve Tissue ◽  
Competent Cells ◽  
Pharmacological Targets ◽  
Intracellular Signaling Molecules

The implementation of the concept of drug therapy of neurological disorders in chronic alcohol intoxication is, in some cases, unsuccessful. Promising is the search for new pharmacological targets among the intracellular signaling molecules of regenerating-competent cells. In the conditions of in vitro and in vivo modeling of ethanol-induced neurodegeneration, the role of NF-кВ in the realization of the growth potential of neural progenitors and the secretion of neurotrophins by glial elements was studied. The absence of participation of NF-кВ in the regulation of mitotic activity of neural SC (NSC) and of neuronal-committed progenitors (NCP) in their optimal living conditions and in the influence of ethanol in vitro is shown. At the same time, NF-кВ hinders the implementation of the NSC specialization process. The prolonged introduction of ethanol per os mice was accompanied by the appearance of an inhibitory value in NF-кВ in relation to the intensity of progenitors proliferation. The blockade of NF-кВ of NSC and NCP animals with neurodegeneration caused the progression of their cell cycle. The participation of NF-кВ in the secretory function of astrocytes and oligodendrogliocytes has been established. The inactivation of the nuclear transcription factor led to a decrease in their production of neurotrophins, including in the case of ethanol. At the same time, there were no changes from the microglia functioning.

scholarly journals Dicer-dependent production of microRNA221 in hepatocytes inhibits p27 and is required for liver regeneration in mice

2017 ◽  
Vol 312 (5) ◽  
pp. G464-G473 ◽  
Author(s):  
Yuki Oya ◽  
Ryota Masuzaki ◽  
Daisuke Tsugawa ◽  
Kevin C. Ray ◽  
Yongchao Dou ◽  
...  
Keyword(s):  
Liver Regeneration ◽  
Hepatocyte Proliferation ◽  
Inhibitory Effects ◽  
Primary Hepatocytes ◽  
Direct Role ◽  
Targeted Inhibition ◽  
Dependent Mechanism

Dicer processes microRNAs (miRs) into active forms in a wide variety of tissues, including the liver. To determine the role of Dicer in liver regeneration, we performed a series of in vivo and in vitro studies in a murine 2/3 hepatectomy model. Dicer was downregulated after 2/3 hepatectomy, and loss of Dicer inhibited liver regeneration associated with decreased cyclin A2 and miR-221, as well as increased levels of the cell cycle inhibitor p27. In vitro, miR-221 inhibited p27 production in primary hepatocytes and increased hepatocyte proliferation. Specific reconstitution of miR-221 in hepatocyte-specific Dicer-null mice inhibited p27 and restored liver regeneration. In wild type mice, targeted inhibition of miR-221 using a cholesterol-conjugated miR-221 inhibited hepatocyte proliferation after 2/3 hepatectomy. These results identify Dicer production of miR-221 as an essential component of a miRNA-dependent mechanism for suppression of p27 that controls the rate of hepatocyte proliferation after partial hepatectomy. NEW & NOTEWORTHY Our findings demonstrate a direct role for microRNAs in controlling the rate of liver regeneration after injury. By deleting Dicer, an enzyme responsible for processing microRNAs into mature forms, we determined miR-221 is a critical microRNA in the physiological process of restoration of liver mass after injury. miR-221 suppresses p27, releasing its inhibitory effects on hepatocyte proliferation. Pharmaceuticals based on miR-221 may be useful to modulate hepatocyte proliferation in the setting of liver injury.

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