iridoids and Hyperlipidemias

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

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

The aim of the present study was to investigate the antiobesity effect of oleuropein on high-fat diet (HFD) induced body weight gain and visceral adiposity in mice, and to explore the underlying mechanisms involved.. C57BL/6N mice were fed with a normal diet, HFD (40% fat of total energy), and HFD-supplemented with 0.03% oleuropein for 10 wk. Oleuropein significantly reduced HFD-induced body weight gain and visceral adiposity. Oleuropein also significantly reversed the HFD-induced elevations of adipogenic related gene expression involved in WNT10b- and galanin-mediated signalings in adipose tissue of mice. Consistent with in vivo findings, oleuropein dose-dependently suppressed lipid accumulation in 3T3-L1 cells during preadipocyte differentiation. Additionally, exposure of the 3T3-L1 preadipocytes to oleuropein resulted in a marked attenuation of the secreted frizzled-related protein 2 (WNT inhibitor) or galnon (galanin receptor agonist) induced cellular lipid accumulation.. This study demonstrated the oleuropein-reduced body weight gain and visceral adiposity in HFD-fed mice. The protective effect of oleuropein against HFD-induced adiposity in mice appeared to be mediated through the upregulation of genes involved in WNT10b-mediated signaling and downregulation of genes involved in galanin-mediated signaling cascades.

Topics: 3T3-L1 Cells; Adiposity; Animals; Cell Differentiation; Diet, High-Fat; Dose-Response Relationship, Drug; Galanin; Gene Expression Regulation; Hyperlipidemias; Iridoid Glucosides; Iridoids; Membrane Proteins; Mice; Mice, Inbred C57BL; Mice, Obese; Signal Transduction; Weight Gain; Wnt Proteins

Insulin resistance (IR) increases with age and plays a key role in the pathogenesis of type 2 diabetes mellitus. Oxidative stress and mitochondrial dysfunction are supposed to be major factors leading to age-related IR. Genipin, an extract from Gardenia jasminoides Ellis fruit, has been reported to stimulate insulin secretion in pancreatic islet cells by regulating mitochondrial function. In this study, we first investigated the effects of genipin on insulin sensitivity and the potential mitochondrial mechanisms in the liver of aging rats. The rats were randomly assigned to receive intraperitoneal injections of either 25mg/kg genipin or vehicle once daily for 12days. The aging rats showed hyperinsulinemia and hyperlipidemia, and insulin resistance as examined by the decreased glucose decay constant rate during insulin tolerance test (kITT). The hepatic tissues showed steatosis and reduced glycogen content. Hepatic malondialdehyde level and mitochondrial reactive oxygen species (ROS) were higher, and levels of mitochondrial membrane potential (MMP) and ATP were lower as compared with the normal control rats. Administration of genipin ameliorated systemic and hepatic insulin resistance, alleviated hyperinsulinemia, hyperglyceridemia and hepatic steatosis, relieved hepatic oxidative stress and mitochondrial dysfunction in aging rats. Furthermore, genipin not only improved insulin sensitivity by promoting insulin-stimulated glucose consumption and glycogen synthesis, inhibited cellular ROS overproduction and alleviated the reduction of levels of MMP and ATP, but also reversed oxidative stress-associated JNK hyperactivation and reduced Akt phosphorylation in palmitate-treated L02 hepatocytes. In conclusion, genipin ameliorates age-related insulin resistance through inhibiting hepatic oxidative stress and mitochondrial dysfunction.

Topics: Adenosine Triphosphate; Age Factors; Aging; Animals; Antioxidants; Cell Line; Dose-Response Relationship, Drug; Enzyme Activation; Fatty Liver; Hepatocytes; Hyperinsulinism; Hyperlipidemias; Hypoglycemic Agents; Insulin Resistance; Iridoids; JNK Mitogen-Activated Protein Kinases; Liver; Male; Malondialdehyde; Membrane Potential, Mitochondrial; Mitochondria, Liver; Oxidative Stress; Palmitic Acid; Phosphorylation; Proto-Oncogene Proteins c-akt; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species

We have investigated antihyperlipidaemic effect of swertiamarin (50 mg/kg, oral once) isolated from the perennial herb Enicostemma littorale Blume in poloxamer 407 (P-407)-induced hyperlipidaemic rats. Rats were made hyperlipidaemic by intraperitoneal administration of P-407 (400 mg/kg). Serum lipid levels such as total cholesterol, triglycerides and low-density lipoprotein cholesterol increased significantly (P < 0.001) compared with normal control rats. All these changes were significantly prevented in the rats treated with swertiamarin. Serum high-density lipoprotein (HDL) cholesterol was found to be reduced in the P-407 control rats. However, administration of swertiamarin significantly (P < 0.01) increased HDL levels and it showed a significant lipid-lowering effect, as well as a high antiatherogenic potential. Overall swertiamarin is an effective lipid-lowering lead compound and can be useful for preventing atherosclerosis.

Topics: Animals; Glucosides; Hyperlipidemias; Hypolipidemic Agents; Iridoid Glucosides; Iridoids; Male; Poloxamer; Pyrones; Rats; Rats, Wistar