scholarly journals Ginsenoside Re Improves Inflammation and Fibrosis in Hepatic Tissue by Upregulating PPARγ Expression and Inhibiting Oxidative Stress in db/db Mice

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Yichuan Jiang ◽  
Dayun Sui ◽  
Min Li ◽  
Huali Xu ◽  
Xiaofeng Yu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Adjunctive Treatment ◽  
Hepatic Tissue ◽  
Peroxisome Proliferator ◽  
Obvious Effect ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ginsenoside Re ◽  
Nonalcoholic Fatty Liver ◽  
Main Component ◽  
Pparγ Expression

Ginsenoside Re (Re) is the main component of “Zhenyuan Capsule” (ZYC), which was wildly used in clinic in China for adjunctive treatment of coronary heart disease (CHD) and type II diabetes (T2DM). Nonalcoholic fatty liver disease (NAFLD) is one of the most important complications of T2DM, as well as an important risk factor of CHD. The aim of the present study was to investigate the effects of Re on NAFLD in db/db mice, one of the most recognized gene deficient animal models on T2DM. Sixteen db/db mice and sixteen wild-type mice were divided into four groups and orally administered Re or placebo in equal volume. According to the results, Re showed no obvious effect on blood glucose, lipids, or body weight of db/db mice. Histology pictures of hepatic tissue showed that Re did not improve steatosis, too. However, some evidence suggested that hepatic injury in db/db mice was attenuated by Re administering. Collagen deposition and aminotransferase elevation were significantly downregulated in the DB + Re group compared to those in the DB Group. The mechanisms of the protect effects of Re represented in db/db mice with NAFLD might be inhibiting oxidative stress and the reupregulation of peroxisome proliferator-activated receptor γ (pparγ) expression. The results of this study indicated that ZYC might be able to help T2DM patients with NAFLD to control the progress of NAFLD as an alternation of thiazolidinediones, synthetic agonists of PPARγ, whose side effects and adverse events should not be ignored.

Natural Aldose Reductase Inhibitor: A Potential Therapeutic Agent for Non-alcoholic Fatty Liver Disease

2020 ◽  
Vol 21 (6) ◽  
pp. 599-609 ◽  
Author(s):  
Longxin Qiu ◽  
Chang Guo
Keyword(s):  
Oxidative Stress ◽  
Liver Disease ◽  
Fatty Liver ◽  
Aldose Reductase ◽  
Fatty Liver Disease ◽  
Acid Oxidation ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Alcoholic Fatty Liver ◽  
Nonalcoholic Fatty Liver

Aldose reductase (AR) has been reported to be involved in the development of nonalcoholic fatty liver disease (NAFLD). Hepatic AR is induced under hyperglycemia condition and converts excess glucose to lipogenic fructose, which contributes in part to the accumulation of fat in the liver cells of diabetes rodents. In addition, the hyperglycemia-induced AR or nutrition-induced AR causes suppression of the transcriptional activity of peroxisome proliferator-activated receptor (PPAR) α and reduced lipolysis in the liver, which also contribute to the development of NAFLD. Moreover, AR induction in non-alcoholic steatohepatitis (NASH) may aggravate oxidative stress and the expression of inflammatory cytokines in the liver. Here, we summarize the knowledge on AR inhibitors of plant origin and review the effect of some plant-derived AR inhibitors on NAFLD/NASH in rodents. Natural AR inhibitors may improve NAFLD at least in part through attenuating oxidative stress and inflammatory cytokine expression. Some of the natural AR inhibitors have been reported to attenuate hepatic steatosis through the regulation of PPARα-mediated fatty acid oxidation. In this review, we propose that the natural AR inhibitors are potential therapeutic agents for NAFLD.

scholarly journals The Mitochondrial Trigger in an Animal Model of Nonalcoholic Fatty Liver Disease

Genes ◽  
2021 ◽  
Vol 12 (9) ◽  
pp. 1439
Author(s):  
Guglielmina Chimienti ◽  
Antonella Orlando ◽  
Francesco Russo ◽  
Benedetta D’Attoma ◽  
Manuela Aragno ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Animal Model ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Mitochondrial Oxidative Stress ◽  
Nonalcoholic Fatty Liver

Nonalcoholic fatty liver disease (NAFLD) is the leading liver chronic disease featuring hepatic steatosis. Mitochondrial β-oxidation participates in the derangement of lipid metabolism at the basis of NAFLD, and mitochondrial oxidative stress contributes to the onset of the disease. We evaluated the presence and effects of mitochondrial oxidative stress in the liver from rats fed a high-fat plus fructose (HF-F) diet inducing NAFLD. Supplementation with dehydroepiandrosterone (DHEA), a multitarget antioxidant, was tested for efficacy in delaying NAFLD. A marked mitochondrial oxidative stress was originated by all diets, as demonstrated by the decrease in Superoxide Dismutase 2 (SOD2) and Peroxiredoxin III (PrxIII) amounts. All diets induced a decrease in mitochondrial DNA content and an increase in its oxidative damage. The diets negatively affected mitochondrial biogenesis as shown by decreased peroxisome proliferator-activated receptor-γ co-activator-1α (PGC-1α), mitochondrial transcription factor A (TFAM), and the COX-IV subunit from the cytochrome c oxidase complex. The reduced amounts of Beclin-1 and lipidated LC3 II form of the microtubule-associated protein 1 light chain 3 (LC3) unveiled the diet-related autophagy’s decrease. The DHEA supplementation did not prevent the diet-induced changes. These results demonstrate the relevance of mitochondrial oxidative stress and the sequential dysfunction of the organelles in an obesogenic diet animal model of NAFLD.

scholarly journals Loss of Hepatocyte-Specific PPARγ Expression Ameliorates Early Events of Steatohepatitis in Mice Fed the Methionine and Choline-Deficient Diet

PPAR Research ◽  
2020 ◽  
Vol 2020 ◽  
pp. 1-13 ◽  
Author(s):  
Jose Cordoba-Chacon
Keyword(s):  
Fatty Acid ◽  
Molecular Mechanisms ◽  
Fatty Acid Uptake ◽  
Peroxisome Proliferator ◽  
Acid Uptake ◽  
Deficient Diet ◽  
Peroxisome Proliferator Activated Receptor ◽  
Nonalcoholic Fatty Liver ◽  
Cd36 Expression ◽  
Pparγ Expression

The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing worldwide. To date, there is not a specific and approved treatment for NAFLD yet, and therefore, it is important to understand the molecular mechanisms that lead to the progression of NAFLD. Methionine- and choline-deficient (MCD) diets are used to reproduce some features of NAFLD in mice. MCD diets increase the expression of hepatic peroxisome proliferator-activated receptor gamma (PPARγ, Pparg) and the fatty acid translocase (CD36, Cd36) which could increase hepatic fatty acid uptake and promote the progression of NAFLD in mice and humans. In this study, we assessed the contribution of hepatocyte-specific PPARγ and CD36 expression to the development of early events induced by the MCD diet. Specifically, mice with adult-onset, hepatocyte-specific PPARγ knockout with and without hepatocyte CD36 overexpression were fed a MCD diet for three weeks. Hepatocyte PPARγ and/or CD36 expression did not contribute to the development of steatosis induced by the MCD diet. However, the expression of inflammatory and fibrogenic genes seems to be dependent on the expression of hepatocyte PPARγ and CD36. The expression of PPARγ and CD36 in hepatocytes may be relevant in the regulation of some features of NAFLD and steatohepatitis.

scholarly journals Growth Hormone Inhibits Apoptosis in Human Colonic Cancer Cell Lines: Antagonistic Effects of Peroxisome Proliferator Activated Receptor-γ Ligands

Endocrinology ◽  
2004 ◽  
Vol 145 (7) ◽  
pp. 3353-3362 ◽  
Author(s):  
Fausto Bogazzi ◽  
Federica Ultimieri ◽  
Francesco Raggi ◽  
Dania Russo ◽  
Renato Vanacore ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Colonic Cancer ◽  
Cancer Cell Lines ◽  
Peroxisome Proliferator ◽  
Signal Transducer ◽  
Peroxisome Proliferator Activated Receptor ◽  
Antiapoptotic Effect ◽  
Pparγ Expression ◽  
Colonic Cells

Abstract GH has antiapoptotic effects on several cells. However, the antiapoptotic mechanisms of GH on colonic mucosa cells are not completely understood. Peroxisome proliferator activated receptor-γ (PPARγ) activation enhances apoptosis, and a link between GH and PPARγ in the colonic epithelium of acromegalic patients has been suggested. We investigated the effects of GH and of PPARγ ligands on apoptosis in colonic cancer cell lines. Colonic cells showed specific binding sites for GH, and after exposure to 0.05–50 nm GH, their apoptosis reduced by 45%. The antiapoptotic effect was due to either GH directly or GH-dependent local production of IGF-1. A 55–85% reduction of PPARγ expression was observed in GH-treated cells, compared with controls (P < 0.05). However, treatment of the cells with 1–50 μm ciglitazone (cig), induced apoptosis and reverted the antiapoptotic effects of GH by increasing the programmed cell death up to 3.5-fold at 30 min and up to 1.7-fold at 24 h. Expression of Bcl-2 and TNF-related apoptosis-induced ligand was not affected by either GH or cig treatment, whereas GH reduced the expression of Bax, which was increased by cig treatment. In addition, GH increased the expression of signal transducer and activator of transcription 5b, which might be involved in the down-regulation of PPARγ expression. In conclusion, GH may exert a direct antiapoptotic effect on colonic cells, through an increased expression of signal transducer and activator of transcription 5b and a reduction of Bax and PPARγ. The reduced GH-dependent apoptosis can be overcome by PPARγ ligands, which might be useful chemopreventive agents in acromegalic patients, who have an increased colonic polyps prevalence.

A Tale of Two Diseases: Exploring Mechanisms Linking Diabetes Mellitus with Alzheimer’s Disease

2021 ◽  
pp. 1-17
Author(s):  
Jessica Lynn ◽  
Mingi Park ◽  
Christiana Ogunwale ◽  
George K. Acquaah-Mensah
Keyword(s):  
Diabetes Mellitus ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Glycogen Synthase ◽  
Mammalian Target Of Rapamycin ◽  
Insulin Receptors ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Main Component ◽  
The Impact

Dementias, including the type associated with Alzheimer’s disease (AD), are on the rise worldwide. Similarly, type 2 diabetes mellitus (T2DM) is one of the most prevalent chronic diseases globally. Although mechanisms and treatments are well-established for T2DM, there remains much to be discovered. Recent research efforts have further investigated factors involved in the etiology of AD. Previously perceived to be unrelated diseases, commonalities between T2DM and AD have more recently been observed. As a result, AD has been labeled as “type 3 diabetes”. In this review, we detail the shared processes that contribute to these two diseases. Insulin resistance, the main component of the pathogenesis of T2DM, is also present in AD, causing impaired brain glucose metabolism, neurodegeneration, and cognitive impairment. Dysregulation of insulin receptors and components of the insulin signaling pathway, including protein kinase B, glycogen synthase kinase 3β, and mammalian target of rapamycin are reported in both diseases. T2DM and AD also show evidence of inflammation, oxidative stress, mitochondrial dysfunction, advanced glycation end products, and amyloid deposition. The impact that changes in neurovascular structure and genetics have on the development of these conditions is also being examined. With the discovery of factors contributing to AD, innovative treatment approaches are being explored. Investigators are evaluating the efficacy of various T2DM medications for possible use in AD, including but not limited to glucagon-like peptide-1 receptor agonists, and peroxisome proliferator-activated receptor-gamma agonists. Furthermore, there are 136 active trials involving 121 therapeutic agents targeting novel AD biomarkers. With these efforts, we are one step closer to alleviating the ravaging impact of AD on our communities.

scholarly journals Estimating Drug Efficacy with a Diet-Induced NASH Model in Chimeric Mice with Humanized Livers

Biomedicines ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1647
Author(s):  
Keishi Kisoh ◽  
Go Sugahara ◽  
Yuko Ogawa ◽  
Suzue Furukawa ◽  
Yuji Ishida ◽  
...  
Keyword(s):  
Drug Development ◽  
Drug Efficacy ◽  
Developed Countries ◽  
Liver Disorder ◽  
New Drugs ◽  
Peroxisome Proliferator ◽  
Chimeric Mice ◽  
Peroxisome Proliferator Activated Receptor ◽  
Nonalcoholic Fatty Liver ◽  
Nash Model

Nonalcoholic fatty liver disease/steatohepatitis (NAFLD/NASH) is the most common liver disorder in developed countries. Although many new therapeutics for NASH are present in the drug development pipeline, there are still no approved drugs. One of the reasons that makes NASH drug development challenging is the lack of appropriate animal NASH models that resolve issues arising from inter-species differences between humans and rodents. In the present study, we developed a choline-deficient, L-amino-acid-defined, high-fat-diet (CDAHFD)-induced human NASH model using human liver chimeric mice. We demonstrated human hepatocyte injury by an elevation of plasma human alanine aminotransferase 1 in mice fed CDAHFD. Histological analysis showed that CDAHFD feeding induced similar histological changes to human NASH patients, including ballooning, inflammation, apoptosis, regeneration of human hepatocytes, and pericellular and perisinusoidal fibrosis. The chimeric mice fed CDAHFD were treated with a peroxisome-proliferator-activated receptor α/δ agonist, Elafibranor. Elafibranor ameliorated steatosis, ballooning of hepatocytes, and preserved fibrosis progression. We developed a novel humanized NASH model that can elucidate pathophysiological mechanisms and predict therapeutic efficacy in human NASH. This model will be useful in exploring new drugs and biomarkers in the early stages of human NASH.

Sign in / Sign up

Export Citation Format

Share Document