iridoids and Obesity

Cancer cells exhibit enhanced proliferation rate and a resistance to apoptosis. Epidemiological studies suggest that olive oil intake is associated with a reduced risk of cancer. Olive oil, olives, and olive leaves contain many polyphenols, including oleuropein. Recently, several studies have demonstrated that oleuropein inhibits proliferation and induces apoptosis in different cancer cell lines. In addition, anticancer effects of oleuropein have been seen in animal studies. These effects are associated with oleuropein's ability to modulate gene expression and activity of a variety of different signaling proteins that play a role in proliferation and apoptosis. This article summarizes the existing in vitro and in vivo studies focusing on the anticancer effects of oleuropein and its effects on key signaling molecules. © 2017 BioFactors, 43(4):517-528, 2017.

Topics: Animals; Anthocyanins; Antineoplastic Agents; Apoptosis; Cell Line, Tumor; Cell Proliferation; Humans; Iridoid Glucosides; Iridoids; Obesity

Topics: Adipokines; Animals; Anthocyanins; Aorta; Atherosclerosis; Cardiovascular Diseases; Cholesterol, Dietary; Cornus; Humans; Iridoids; Liver; Liver X Receptors; Male; Metabolic Syndrome; Obesity; Plant Extracts; PPAR alpha; PPAR gamma; Rabbits; Triglycerides

More than 17 million people in the US provide uncompensated care for adults with physical or cognitive limitations. Such caregiving is associated with worse mental and physical health, yet little research has investigated how publicly funded home care might ameliorate these harms.. To investigate the association between Medicaid home care services and family caregivers' health.. This longitudinal cohort study used data from the 1996 to 2017 Medical Expenditures Panel Survey. Data on all household members were collected in 5 interviews over 2 years. Person-level difference-in-difference models were used to isolate within-person changes associated with new onset of Medicaid home care. The Medical Expenditures Panel Survey longitudinal data sets included 331 202 individuals (approximately 10% excluded owing to loss to follow-up). Adult (age ≥21 years) members of households that contained at least 1 person with limited activities of daily living were included in our study. The analysis itself was performed from March to August of 2020.. New onset of regular (≥1 time per month) Medicaid home care in the household.. Self-rated mental and physical health (planned prior to beginning the study).. In this cohort study, Medicaid home care was associated with improvement in caregiver self-rated mental health, but not with any short-term change in self-rated physical health. When evaluating the social value of home care programs, policy makers should consider spillover benefits to caregivers.. For all treatment-naïve patients, TBR

Topics: Activities of Daily Living; Adult; Air Pollution, Indoor; Animals; Anti-Bacterial Agents; Anti-Infective Agents; Anti-Inflammatory Agents; Antioxidants; Azithromycin; Canada; Carbon; Caregivers; Chlorine; Cohort Studies; Corn Oil; COVID-19 Drug Treatment; Daphnia; Dust; Ecosystem; Electrodes; Environmental Monitoring; Fatty Acids; Female; Flavonoids; Fluorides; Glycosides; Greece; Groundwater; Hippocampus; Home Care Services; Humans; Infant; Inflammation; Iridoids; Lamiaceae; Longitudinal Studies; Male; Medicaid; Memory; Metals, Heavy; Methanol; Mice; Microplastics; Middle Aged; N-Methylaspartate; Neural Networks, Computer; Nitrates; Nitrogen Oxides; Nylons; Obesity; Oleic Acid; Olive Oil; Oxidation-Reduction; Phosphorus; Place Cells; Plant Components, Aerial; Plant Extracts; Plastics; Polyesters; Polyurethanes; Prevalence; Quinic Acid; Reactive Oxygen Species; Receptors, N-Methyl-D-Aspartate; Risk Assessment; Sodium Chloride; Soil; Soil Pollutants; Stachys; Staphylococcus aureus; Stearic Acids; Superoxide Dismutase; U937 Cells; United States; Water; Water Pollutants, Chemical; Young Adult

Nowadays, the pharmacological effects of Plantaginis semen was getting more and more attention because of the great effect of treating diuresis, hypertension, hyperlipidemia, and hyperglycemia. According to the Chinese Pharmacopoeia, Plantaginis semen is the seed of Plantago asiatica L. or P. depressa Willd. This was verified by examining chemical composition differences in a preliminary experiment, predicting their differences in pharmacology.. In this study, we aimed to compared the the differences in main components and anti-obesity effects of Plantago asiatica L. seed extract (PASE) and P. depressa Willd. seed extract (PDSE).. The ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) analysis was used to characterize and compare the differences chemical constituents of PASE and PDSE. The difference therapeutic effects between PASE and PDSE on obesity and associated metabolic disorders was investigated by high-fat (HF) diet induced mice model.. The fingerprint of Plantaginis semen were established by screening and identified 15 main components, including iridoids, phenethanol glycosides, flavonoids, guanidines, and fatty acids. Pentahydroxy flavanone was observed only in PDSE but not in PASE. The quantitative analysis results indicated that the main bioactive components in PASE were geniposidic acid and acteoside; their concentrations were three times higher in PASE than in PDSE. In anti-obesity effects, the result show the levels of fasting blood glucose were improved in both PASE and PDSE when compared with the HF group, while the PASE is show a significant effect then the PDSE group and improved the glucose tolerance but not in PDSE. The results also displayed that the Plantaginis semen did not modify food intake or body weight but decreased abdominal white/brown adipocyte size, serum total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-c), hepatic TG and TC, fecal TG and TC concentrations when compared with the HF group. Among these indicators, serum TG, liver TG, fecal TC and TG levels were significantly improved in PASE compared with PDSE. The results indicated that PASE treatment more effectively improved lipid and glucose metabolism in HF diet-induced obese mice than did PDSE.. As Plantaginis semen sources, P. asiatica L. seeds demonstrated more bioactive components and favorable metabolic disorder treatment outcomes than did P. depressa Willd. seeds.

Topics: Adipocytes; Animals; Anti-Obesity Agents; Body Weight; Cholesterol, LDL; Diet, High-Fat; Hyperlipidemias; Iridoid Glucosides; Iridoids; Male; Mice, Inbred C57BL; Obesity; Plant Extracts; Plantago; Seeds; Triglycerides

Topics: Animals; Beverages; Chromatography, Liquid; Diet, High-Fat; Gas Chromatography-Mass Spectrometry; Hyperlipidemias; Iridoid Glucosides; Iridoids; Male; Mice; Mice, Inbred ICR; Obesity; Olea; Phenylethyl Alcohol; Plant Leaves; Tandem Mass Spectrometry

To investigate the effects of genipin on promoting brown adipose tissue activation and white adipose tissue browning.. The male C57BL/6J mice were divided into three groups: normal control group, genipin group and cold-stimulus group.Genipin group were treated consecutively with genipin at a dose of 15 mg/kg once a day for 9 days, normal control group were treated with the saline.The mice with cold-stimulus were exposed to 4℃ environment for 5 days.Daily food amount and body weight were measured.Morphological changes were observed in the subscapular region, inguinal region and epididymis around the adipose tissue.The expression of uncoupling protein 1 (UCP1) was determined by real-time PCR and Western blot respectively.. The wet weight of white fat in genipin-treated mice was decreased by 16% , and 28% in that of cold-stimulus mice, compared with the normal control group (P＜0.05).After treatments of genipin and cold-stimulus, the color of white adipose tissues was darker, and the size of lipid droplets in adipocytes was smaller, whereas the number was increased.Compared with the normal control group, UCP1 expression was increased obviously in fat tissues, including the subcutaneous and visceral white adipose tissues, and brown adipose tissue after treated with genipin and cold-stimulus (P＜0.05).. Genipin promoted activation of brown adipose tissue and browning of white adipose tissue by upregulating UCP1 expression, which could contribute to the loss of body weight against obesity.

Topics: Adipose Tissue, Brown; Adipose Tissue, White; Animals; Cholagogues and Choleretics; Iridoids; Male; Mice; Mice, Inbred C57BL; Obesity; Uncoupling Protein 1; Up-Regulation

Hyperlipidemia is a chronic disorder which plays an important role in the development of cardiovascular diseases, type 2 diabetes, atherosclerosis, hypertension, and nonalcoholic fatty liver disease. Genipin (GNP) is a metabolite from genipioside, which is an active component of the traditional Chinese medicine Gardenia jasminoides Ellis, and has been recognized as a beneficial compound against metabolic disorders. However, whether it can correct overnutrition-induced dyslipidemia is still unknown. In this study, the effects of GNP on attenuating hyperlipidemia and hepatic lipid accumulation were investigated using normal and obese mice induced with a high-fat diet (HFD) and primary hepatocytes treated with free fatty acids. We also sought to identify potential targets of GNP to mediate its effects in the liver. We found that obese mice treated with GNP showed a decrease in the body weight, serum lipid levels, as well as hepatic lipid accumulation. Besides, GNP regulated hepatic expression levels of lipid metabolic genes, which are important in maintaining systemic lipid homeostasis. At the molecular level, GNP increased the expression levels of miR-142a-5p, which bound to 3' untranslated region of Srebp-1c, an important regulator of lipogenesis, which thus led to the inhibition of lipogenesis. Collectively, our data demonstrated that GNP effectively antagonized HFD-induced hyperlipidemia and hepatic lipid accumulation in mice. Such effects were achieved by regulating miR-142a-5p/SREBP-1c axis.

Topics: Animals; Anti-Obesity Agents; Cells, Cultured; Computational Biology; Diet, High-Fat; Dose-Response Relationship, Drug; Fatty Acids, Nonesterified; Gene Expression Regulation; Genes, Reporter; Hyperlipidemias; Insulin Resistance; Iridoids; Lipid Metabolism; Lipotropic Agents; Liver; Male; Mice, Inbred C57BL; MicroRNAs; Non-alcoholic Fatty Liver Disease; Obesity; Random Allocation; Sterol Regulatory Element Binding Protein 1

Genipin is the major active component of Gardeniae fructus and has been shown to ameliorate diabetes and insulin resistance in rat models. In this study, we first investigated the effect of genipin on obesity and the related lipid metabolism mechanisms in diet-induced obese rats. Our results showed that genipin reduced body weight, food intake, and visceral fat mass; ameliorated dyslipidemia, glucose intolerance, insulin intolerance, adipocyte hypertrophy, and hepatic steatosis; and reduced serum tumor necrosis factor-α level in diet-induced obese rats. Quantitative real-time reverse-transcription polymerase chain reaction results further illustrated that genipin promoted lipolysis and β-oxidation of fatty acid by upregulating gene expressions of hormone-sensitive lipase and adipose triglyceride lipase in white adipose tissue (WAT) and peroxisome proliferator-activated receptor-α and carnitine palmitoyltransferase 1α in hepatic tissue. Moreover, genipin promoted browning of WAT by upregulating the mRNA and protein levels of uncoupling protein 1 and PRD1-BF1-RIZ1 homologous domain containing 16 in WAT. Additionally, genipin inhibited gene expressions of activin receptor-like kinase 7, tumor necrosis factor-α, and interlukin-6 in WAT. These results indicated that genipin had a potential therapeutic role in obesity, in which regulation of lipid mobilization and browning of WAT were involved.

Topics: Adipose Tissue, White; Animals; Diet; Disease Models, Animal; Iridoids; Lipid Mobilization; Male; Obesity; Rats

Our previous study found that geniposide, an agonist of glucagon-like peptide-1 receptor (GLP-1R), protected against cardiac hypertrophy via the activation of AMP-activated protein kinase

Topics: AMP-Activated Protein Kinases; Animals; Anti-Inflammatory Agents; Cardiomegaly; Diet, High-Fat; Heart; Inflammation; Iridoids; Male; Mice; Mice, Inbred C57BL; Myocytes, Cardiac; Obesity; Signal Transduction; Sirtuin 1

Oleuropein is the pungent principle of raw olives. Oleuropein aglycone (OA) is a major phenolic compound in extra virgin olive oil and the absorbed form of oleuropein. We aimed to determine the mechanism underlying the nutritional effects of oleuropein and OA on interscapular brown adipose tissue (IBAT) in rats with high-fat (HF) diet-induced obesity by examining the agonistic activity of oleuropein and OA toward the transient receptor potential ankyrin 1 (TRPA1) and vanilloid 1 (TRPV1). Four-week-old male Sprague-Dawley rats were fed an HF (palm oil 30% wt:wt) diet alone or with oleuropein (HF-O, 1 g/kg diet) for 28 days. In rats fed HF-O compared to HF, urinary noradrenaline, adrenaline and UCP1 levels in IBAT were significantly higher, whereas plasma leptin levels and the total weight of the abdominal cavity adipose tissue were significantly lower. In anaesthetized 7-week-old male Sprague-Dawley rats, the OA (3.8 mg of intravenous injection)-induced increase in plasma noradrenaline secretion was suppressed by TRPA1 or TRPV1 antagonist and by a β2- or β3-adrenoceptor antagonist. Furthermore, OA-activated rat and human TRPV1s expressed on HEK293 cells at the same level as zingerone (pungent component in ginger). OA also activated humanTRPA1, and its potency was approximately 10-fold stronger than that for TRPV1. These findings suggest that OA is the agonist of both TRPA1 and TRPV1 and that OA enhances UCP1 expression in IBAT with a concomitant decrease in the visceral fat mass of HF-diet-induced obese rats through enhanced noradrenaline secretion via β-adrenergic action following TRPA1 and TRPV1 activation.

Topics: Acetates; Adipose Tissue, Brown; Animals; Catecholamines; Cyclopentane Monoterpenes; Diet, High-Fat; Epinephrine; HEK293 Cells; Humans; Iridoid Glucosides; Iridoids; Male; Norepinephrine; Obesity; Pyrans; Rats, Sprague-Dawley; Signal Transduction; TRPA1 Cation Channel; TRPV Cation Channels; Uncoupling Protein 1

Oleuropein, which is the major compound of olive leaves, has been reported to exert several pharmacological properties, including anti-cancer, antidiabetic and anti-atherosclerotic activities. The objective of this study was to evaluate the effect of oleuropein on adiponectin level in high cholesterol diet (HCD) induced obesity in rat and the molecular mechanism underlying its activation. Our results showed that orally administered oleuropein (50 mg/kg) by gavage for 8 weeks decreased the body weight, adipose tissue mass and triglyceride and attenuated steatosis in liver. Moreover, the effect of oleuropein on adiponectin, an important hormone with fatty-acid oxidation properties, was evaluated and our data illustrated that oleuropein supplementation increased serum adiponectin concentration. The effects of oleuropein on protein expression related to lipogenic genes were investigated and our results showed that its administration significantly inhibited peroxisome proliferator-activated receptor γ (PPARγ), sterol regulatory element-binding protein-1c (SREBP-1c) and fatty-acid synthase (FAS). In addition, oleuropein stimulated the HCD-induced inhibition of AMP-activated protein kinase (AMPK) in epididymal adipose tissues. These results suggest that oleuropein exerts anti-obesity effects in HCD rats by activating AMPK and suppressing PPAR γ (Peroxisome proliferator-activated receptor γ) expression in adipose tissues. These data provide that oleuropein has important implications for preventing obesity.

Topics: Adiponectin; AMP-Activated Protein Kinases; Animals; Anti-Obesity Agents; Anticholesteremic Agents; Cholesterol; Enzyme Activation; Iridoid Glucosides; Iridoids; Lipid Metabolism; Lipids; Male; Obesity; PPAR gamma; Rats; Rats, Wistar; Sterol Regulatory Element Binding Protein 1

The effect of the extract of Ligustrumn lucidum fruits (LFE) and its major secoiridoid (LFS), (8-E)-nüzhenide, on obesity was investigated using high fat-diet (HFD)-induced C58BL/6J obese mice. LFE and LFS were administered at the doses of 300 mg/kg and 30 mg/kg, respectively, for 6 weeks. The anti-obesity activity was evaluated by measuring body weight, epididymal fat and metabolic plasma parameters. On Day 42, the body weight of the LFS-treated group was significantly lower compared with the HFD-treated group. Body weight gain was also reduced by 23.2% and 32.0% in the LFE- and LFS-treated groups, respectively, compared with the HFD group. In addition, the weight of the epididymal fat in the mice was significantly decreased in the HFD+LFS group. The food efficiency ratios (FERs) of the HFD+LFE and HFD+LFS groups were also lower compared with the HFD group with the same food intake. Metabolic parameters that had increased in the HFD group were decreased in the HFD+LFE and HFD+LFS groups. In particular, the increased triglyceride values were significantly reduced in the HFD+LFS group. These results show that treatment with LFE and LFS decreased HFD-induced obesity, mainly by improving metabolic parameters, such as fats and triglycerides. Therefore, LFE and LFS have potential benefits in regulation of obesity.

Topics: Animals; Body Weight; Diet, High-Fat; Hypoglycemic Agents; Iridoids; Ligustrum; Mice; Mice, Obese; Obesity

Accumulation of visceral fat induces various symptoms of metabolic syndrome such as insulin resistance and abnormal glucose/lipid metabolism and eventually leads to the onset of ischemic cerebrovascular diseases. Geniposide, which is iridoid glycoside from the fruit of Gardenia jasminoides ELLIS, is recognized as being useful against hyperlipidemia and fatty liver. In order to clarify the effect of geniposide on metabolic disease-based visceral fat accumulation and the relevant molecular mechanism, experiments were performed in spontaneously obese Type 2 diabetic TSOD mice and the free fatty acid-treated HepG2 cells. In the TSOD mice, geniposide showed suppression of body weight and visceral fat accumulation, alleviation of abnormal lipid metabolism and suppression of intrahepatic lipid accumulation. In addition, geniposide alleviated abnormal glucose tolerance and hyperinsulinemia, suggesting that geniposide has an insulin resistance-alleviating effect. Next, in order to investigate the direct effect of geniposide on the liver, the effect on the free fatty acid-treated HepG2 fatty liver model was investigated using genipin, which is the aglycone portion of geniposide. Genipin suppressed the intracellular lipid accumulation caused by the free fatty acid treatment and also significantly increased the intracellular expression of a fatty acid oxidation-related gene (peroxisomal proliferator-activated receptor: PPARα). From these results, it was confirmed that geniposide has an anti-obesity effect, an insulin resistance-alleviating effect and an abnormal lipid metabolism-alleviating effect, and the metabolite genipin shows a direct effect on the liver, inducing expression of a lipid metabolism-related gene as one of its molecular mechanisms.

Topics: Adipose Tissue; Animals; Anti-Obesity Agents; Body Weight; Diabetes Mellitus, Type 2; Drug Evaluation, Preclinical; Fatty Acids, Nonesterified; Fatty Liver; Gardenia; Glucose Intolerance; Hep G2 Cells; Humans; Hyperinsulinism; Hypoglycemic Agents; Insulin Resistance; Iridoids; Lipid Metabolism; Liver; Male; Metabolic Diseases; Metabolic Syndrome; Mice; Mice, Obese; Obesity; Phytotherapy; Plant Preparations

Olive oil and its minor constituents have been recommended as important dietary therapeutic interventions in preventive medicine. However, a question remains to be addressed: what are the effects of olive oil and its phenolic compounds on obesity-induced cardiac metabolic changes?. Male Wistar rats were divided into two groups (n = 24/group): (C) receiving standard-chow; (Ob) receiving hypercaloric-chow. After 21 days C and Ob groups were divided into four subgroups (n = 6/group):(C) standard-chow and saline; (C-Olive)standard-chow and olive-oil (3.0 g/kg.day); (C-Oleuropein)standard-chow and oleuropein (0.023 mg/kg/day); (C-Cafeic) standard-chow and cafeic-acid (2.66 mg/kg/day); (Ob)receiving hypercaloric-chow and saline;(Ob-Olive) hypercaloric-chow and olive-oil;(Ob-Oleuropein) hypercaloric-chow and oleuropein;(Ob-Cafeic) hypercaloric-chow and cafeic-acid. Treatments were given twice a week during 21 days.. After 42 days, obesity was evidenced in Ob rats from enhanced body-weight, surface-area, and body-mass-index. Energy-expenditure, oxygen consumption(VO2) and fat-oxidation were lower in Ob-group than in C. Despite no morphometric changes, Ob-Olive, Ob-Oleuropein and Ob-Cafeic groups had higher VO2, fat-oxidation, myocardial beta-hydroxyacyl coenzyme-A dehydrogenase and lower respiratory-quotient than Ob. Citrate-synthase was highest in Ob-Olive group. Myocardial lipid-hydroperoxide(LH) and antioxidant enzymes were unaffected by olive-oil and its compounds in obesity condition, whereas LH was lower and total-antioxidant-substances were higher in C-Olive and C-Oleuropein than in C.. The present study demonstrated for the first time that olive-oil, oleuropein and cafeic-acid enhanced fat-oxidation and optimized cardiac energy metabolism in obesity conditions. Olive oil and its phenolic compounds improved myocardial oxidative stress in standard-fed conditions.

Topics: 3-Hydroxyacyl CoA Dehydrogenases; Animals; Caffeic Acids; Calorimetry; Citrate (si)-Synthase; Iridoid Glucosides; Iridoids; Male; Myocardium; Obesity; Olive Oil; Phenols; Plant Oils; Pyrans; Rats; Rats, Wistar

A subset of neurons in the brain, known as 'glucose-excited' neurons, depolarize and increase their firing rate in response to increases in extracellular glucose. Similar to insulin secretion by pancreatic beta-cells, glucose excitation of neurons is driven by ATP-mediated closure of ATP-sensitive potassium (K(ATP)) channels. Although beta-cell-like glucose sensing in neurons is well established, its physiological relevance and contribution to disease states such as type 2 diabetes remain unknown. To address these issues, we disrupted glucose sensing in glucose-excited pro-opiomelanocortin (POMC) neurons via transgenic expression of a mutant Kir6.2 subunit (encoded by the Kcnj11 gene) that prevents ATP-mediated closure of K(ATP) channels. Here we show that this genetic manipulation impaired the whole-body response to a systemic glucose load, demonstrating a role for glucose sensing by POMC neurons in the overall physiological control of blood glucose. We also found that glucose sensing by POMC neurons became defective in obese mice on a high-fat diet, suggesting that loss of glucose sensing by neurons has a role in the development of type 2 diabetes. The mechanism for obesity-induced loss of glucose sensing in POMC neurons involves uncoupling protein 2 (UCP2), a mitochondrial protein that impairs glucose-stimulated ATP production. UCP2 negatively regulates glucose sensing in POMC neurons. We found that genetic deletion of Ucp2 prevents obesity-induced loss of glucose sensing, and that acute pharmacological inhibition of UCP2 reverses loss of glucose sensing. We conclude that obesity-induced, UCP2-mediated loss of glucose sensing in glucose-excited neurons might have a pathogenic role in the development of type 2 diabetes.

Topics: Adenosine Triphosphate; Animals; Diabetes Mellitus, Type 2; Dietary Fats; Glucose; Homeostasis; Humans; Ion Channels; Iridoid Glycosides; Iridoids; Mice; Mice, Obese; Mice, Transgenic; Mitochondrial Proteins; Neurons; Obesity; Potassium Channels, Inwardly Rectifying; Pro-Opiomelanocortin; Uncoupling Protein 2

Uncoupling protein 2 (UCP2) negatively regulates insulin secretion. UCP2 deficiency (by means of gene knockout) improves obesity- and high glucose-induced beta cell dysfunction and consequently improves type 2 diabetes in mice. In the present study, we have discovered that the small molecule, genipin, rapidly inhibits UCP2-mediated proton leak. In isolated mitochondria, genipin inhibits UCP2-mediated proton leak. In pancreatic islet cells, genipin increases mitochondrial membrane potential, increases ATP levels, closes K(ATP) channels, and stimulates insulin secretion. These actions of genipin occur in a UCP2-dependent manner. Importantly, acute addition of genipin to isolated islets reverses high glucose- and obesity-induced beta cell dysfunction. Thus, genipin and/or chemically modified variants of genipin are useful research tools for studying biological processes thought to be controlled by UCP2. In addition, these agents represent lead compounds that comprise a starting point for the development of therapies aimed at treating beta cell dysfunction.

Topics: Adenosine Triphosphate; Aldehydes; Animals; Drugs, Chinese Herbal; Glucose; Heterocyclic Compounds, 3-Ring; Insulin; Insulin Secretion; Insulin-Secreting Cells; Ion Channels; Iridoid Glycosides; Iridoids; Islets of Langerhans; Male; Membrane Transport Proteins; Mice; Mice, Knockout; Mice, Obese; Mitochondria; Mitochondrial Membranes; Mitochondrial Proteins; Molecular Conformation; Obesity; Potassium Channels; Protons; Pyrans; Uncoupling Protein 2