The saponins in different parts of Gynostemma pentaphyllum were analyzed via UPLC-Q-TOF-MS~E. A total of 46 saponins were identified, and the underground part had 26 saponins more than the aboveground part, most of which were trisaccharide saponins. The rat model of hyperlipidemia was established with high-fat diet. This study explored the lipid-lowering activity of total saponins in the underground part of G. pentaphyllum, so as to provide a theoretical basis for the comprehensive utilization of the underground part of G. pentaphyllum. A total of 99 healthy SD rats were randomly assigned into a blank group, a model group, a positive drug group, an aboveground total saponins group, and low-, medium-, and high-dose underground total saponins groups. Except the blank group, the other groups were fed with high-fat diet for 6 weeks. Then, the blood was collected from the orbital cavity to determine whether the modeling was successful according to the serum levels of total cholesterol(TC) and triglyceride(TG). After intragastric administration of the corresponding agents for 30 continuous days, the physical state of the rats were observed, and the body weight and liver specific gravity were measured. Furthermore, the levels of TC, TG, low-density lipoprotein cholesterol(LDL-C), high-density lipoprotein cholesterol(HDL-C), alanine transaminase(ALT), aspartate transaminase(AST), bilirubin, and total bile acids in serum, as well as the levels of superoxide dismutase(SOD), malondialdehyde(MDA), peroxidase proliferator-activated receptor(PPAR-γ) in the liver tissue, were determined. The pathological changes of liver was observed via HE staining. The results showed that the aboveground total saponins and medium-and high-dose underground total saponins can treat hepatocyte steatosis, lower TC, TG, LDL-C, ALT, AST, total bilirubin, MDA, and PPAR-γ levels, and increase HDL-C and SOD levels in the model rats. The effect tended to be more obvious with the increase in dosage. Therefore, the total saponins in the underground part of G. pentaphyllum have good pharmacological effect of reducing blood lipid, which provides a theoretical basis for the comprehensive utilization of the underground part of G. pentaphyllum.
Alanine Transaminase/analysis* ; Animals ; Aspartate Aminotransferases/analysis* ; Bile Acids and Salts/blood* ; Bilirubin/blood* ; Cholesterol, LDL/blood* ; Diet, High-Fat/adverse effects* ; Gynostemma/chemistry* ; Hypolipidemic Agents/therapeutic use* ; Lipoproteins, HDL/blood* ; Liver/metabolism* ; Malondialdehyde/analysis* ; Peroxisome Proliferator-Activated Receptors/analysis* ; Rats ; Rats, Sprague-Dawley ; Saponins/therapeutic use* ; Superoxide Dismutase ; Triglycerides/blood* ; Trisaccharides/therapeutic use*

Stearoyl-CoAdesaturase-1 (SCD-1) is a key regulator of monounsaturated fatty acid synthesis. It plays a vital role in lipid synthesis and metabolism. Ca²⁺ is an important cation in the body and plays an important role in the organism. The aims of this study were to investigate the correlation of SCD-1 gene overexpression with lipid indexes and calcium ion level. The pcDNA3.1 (+) + SCD-1 +Flag eukaryotic expression vector and cultured duck uterine epithelial cells were co-transfected. The overexpression of SCD-1 gene was measured using the Flag Label Detection Kit. Ca ions and lipid contents were detected through Fluo-3/AM Calcium Ion Fluorescence Labeling method and Lipid Measuring Kit, respectively. SCD-1 gene overexpression was negatively correlated with triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C), and positively correlated with Ca ion, total cholesterol (TC), very low-density lipoprotein cholesterol (VLDL-C) and low density lipoprotein cholesterol (LDL-C) levels. Meanwhile, Ca ion was positively correlated with TG, LDL-C and HDL-C contents, and negatively correlated with TC and VLDL-C levels. Overexpression of SCD-1 gene could regulate Ca ion secretion, as well as lipid synthesis and transport in duck uterine epithelial cells.
Animals ; Calcium ; metabolism ; Coenzyme A Ligases ; genetics ; Ducks ; Epithelial Cells ; chemistry ; enzymology ; Gene Expression ; Ions ; Lipids ; genetics ; Triglycerides ; metabolism

The aim of this paper was to investigate the molecular mechanism of Calculus Bovis Sativus( CBS) in alleviating lipid accumulation in vitro by serum pharmacology. The CBS-containing serum of mice was obtained by serum pharmacology method to evaluate its effect on the proliferation of LO2 hepatocytes. The lipid reducing effects of CBS-containing serum through Nrf2 was evaluated by fructose-induced LO2 hepatocyte steatosis model,nuclear factor erythroid 2 related factor 2( Nrf2) agonist oltipraz combined intervention,cell oil red O staining and intracellular triglyceride( TG) content. The effects of CBS-containing serum on lipid peroxidation and hepatocytes apoptosis were evaluated by reactive oxygen species( ROS) and apoptosis assay,respectively. Real-time quantitative polymerase chain reaction( PCR) was used to detect the relative expression of lipid synthesis-related genes and apoptosis-related genes.RESULTS:: showed that CBS drug-containing serum had no significant effect on LO2 hepatocyte proliferation. As compared with the model group,CBS-containing serum could effectively reduce the formation of lipid droplets in fructose-induced LO2 hepatocytes,significantly reduce intracellular TG and ROS levels,and significantly reduce hepatocyte apoptosis rate( P < 0. 05). As compared with the model group,carbohydrate responsive element binding protein( ChREBP),sterol regulatory element binding protein-1 c( SREBP-1 c),fatty acid synthase( FAS),acetyl-CoA carboxylase 1( ACC1),stearoyl-CoA desaturase 1( SCD1),Bax and caspase-3 mRNA levels were significantly reduced in CBS drug-containing serum treatment group( P<0. 05). All of the above effects could be reversed by oltipraz.In conclusion,CBS-containing serum can significantly inhibit the fructose-induced LO2 liver fat deposition,and the mechanism may be related to reducing intracellular ROS level through the Nrf2 pathway and improving intracellular peroxidation state to reduce apoptosis.
Animals ; Apoptosis ; Cattle ; Cells, Cultured ; Fatty Liver ; Fructose ; Gallstones ; chemistry ; Hepatocytes ; cytology ; metabolism ; Lipid Metabolism ; Lipid Peroxidation ; Liver ; Medicine, Chinese Traditional ; Mice ; Reactive Oxygen Species ; metabolism ; Serum ; chemistry ; Sterol Regulatory Element Binding Protein 1 ; metabolism ; Triglycerides

Antrodia camphorata, a well-known and highly valued edible medicinal mushroom with intriguing activities like liver protection, has been traditionally used for the treatment of alcoholic liver disease. A. camphorata shows highly medicinal and commercial values with the demand far exceeds the available supply. Thus, the petri-dish cultured A. camphorata (PDCA) is expected to develope as a substitute. In this paper, nineteen triterpenes were isolated from PDCA, and thirteen of them were the unique anthroic acids in A. camphorata, including the main content antcin K, which suggested that PDCA produced a large array of the same anthroic acids as the wild one. Furthermore, no obvious acute toxicity was found suggesting the edible safety of PDCA. In mice alcohol-induced liver injury model, triglyceride (TG), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and malondialdehyde (MDA) had been reduced by the PDCA powder as well as the main content antcin K, which indicated that the PDCA could protect alcoholic liver injury in mice model and antcin K could be the effective component responsible for the hepatoprotective activities of PDCA against alcoholic liver diseases.
Alanine Transaminase ; blood ; Aldehyde Dehydrogenase ; blood ; Animals ; Antrodia ; chemistry ; Aspartate Aminotransferases ; blood ; Biological Products ; chemistry ; pharmacology ; therapeutic use ; Chemical and Drug Induced Liver Injury ; etiology ; prevention & control ; Cholestenes ; chemistry ; pharmacology ; therapeutic use ; Cholesterol, VLDL ; blood ; Disease Models, Animal ; Ethanol ; toxicity ; Female ; Fruiting Bodies, Fungal ; chemistry ; Liver ; drug effects ; metabolism ; pathology ; Liver Diseases, Alcoholic ; prevention & control ; Male ; Malondialdehyde ; blood ; Mice ; Molecular Structure ; Triglycerides ; blood ; Triterpenes ; chemistry ; pharmacology ; therapeutic use

OBJECTIVEAnabasis aretioides (Coss & Moq.), a Saharan plant belonging to Chenopodiaceae family, is widely distributed in semi-desert areas from the Tafilalet region of Morocco. This plant is extensively used by local population against diabetes and cardiovascular disorders. The purpose of the study was to investigate the effect of the aqueous A. aretioides extract on lipid metabolism in normal and streptozotocin (STZ)-induced diabetic rats and to identify the polyphenolic compounds present. In addition, the in vitro antioxidant activity of the aqueous A. aretioides extract was also evaluated.

METHODSThe effect of an aerial part aqueous extract (APAE) of A. aretioides (5 mg/kg of lyophilized A. aretioides APAE) on plasma lipid profile was investigated in normal and STZ-induced diabetic rats (n = 6) after once daily oral administration for 15 days. The aqueous extract was tested for its 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging activity. Polyphenolic compounds in the extracts were definitively characterized by high-performance liquid chromatography-diode array detection-electrospray ionization-mass spectrometry.

RESULTSIn diabetic rats, oral administration of A. aretioides APAE provoked a significant decrease in both plasma cholesterol and triglyceride levels from the first to the second week (P < 0.01). A significant decrease on plasma triglyceride levels was also observed in normal rats (P < 0.01), where the reduction was 53%. In addition, the phytochemical analysis revealed the presence of 12 polyphenolic compounds. Moreover, according to the DPPH radical-scavenging activity, the aqueous extract showed an in vitro antioxidant activity.

CONCLUSIONAqueous A. aretioides APAE exhibits lipid-lowering and in vitro antioxidant activities. Many polyphenols were present in this extract and these phytoconstituents may be involved in the pharmacological activity of this plant.

Animals ; Antioxidants ; administration & dosage ; Chenopodiaceae ; chemistry ; Cholesterol ; blood ; Chromatography, High Pressure Liquid ; Diabetes Mellitus, Experimental ; blood ; drug therapy ; Humans ; Hypolipidemic Agents ; administration & dosage ; chemistry ; Male ; Phytochemicals ; administration & dosage ; chemistry ; Plant Extracts ; administration & dosage ; chemistry ; Polyphenols ; administration & dosage ; chemistry ; Rats ; Rats, Wistar ; Streptozocin ; Tandem Mass Spectrometry ; Triglycerides ; blood

BACKGROUND/OBJECTIVES: Ginger, a root vegetable, is known to have antioxidant and antiobesity effects. Preparation, such as by steaming, can affect the chemical composition of prepared root vegetables or herbs and can change their functional activities. In the present study, we investigated the protective effects of steamed ginger against oxidative stress and steatosis in C57BL/6J mice fed a high-fat diet. MATERIALS/METHODS: The levels of polyphenols and flavonoids in two different extracts of steamed ginger, i.e., water extract (SGW) and ethanolic extract (SGE); as well, their antioxidant activities were examined. Forty male C57BL/6J mice were fed a normal diet (ND, n = 10), high-fat diet (HFD, 60% fat, w/w, n = 10), HFD supplemented with 200 mg/kg of SGE or garcinia (GAR) by weight (SGED or GARD, respectively, n = 10) for 12 weeks. Serum chemistry was examined, and the expressions of genes involved in lipid metabolism were determined in the liver. Histological analysis was performed to identify lipid accumulations in epididymal fat pads and liver. RESULTS: The SGE had higher contents of polyphenols and flavonoids and higher DPPH and ABTS⁺ free radical scavenging activities compared to those of SGW. Treatment with SGE or GAR significantly decreased the HFD-induced weight gain. Both SGE and GAR significantly reduced the high serum total cholesterol (TC), triglyceride (TG) and low-density lipoprotein levels induced by HFD. Compared to ND, HFD significantly increased hepatic TC and TG levels. SGE or GAR supplementation significantly decreased the increase of hepatic lipids by HFD. Interestingly, SGE had a more significant effect in reducing hepatic TC and TG levels than GAR. Furthermore, hepatic genes involved in lipogenesis and lipolysis were altered in both the SGED and GARD groups. CONCLUSIONS: The present study indicates that steamed ginger supplementation can decrease plasma TC and TG and can inhibit liver steatosis by regulating the expressions of hepatic genes.
Adipose Tissue ; Animals ; Chemistry ; Cholesterol ; Diet ; Diet, High-Fat* ; Ethanol ; Fatty Liver ; Flavonoids ; Garcinia ; Ginger* ; Humans ; Lipid Metabolism ; Lipogenesis ; Lipolysis ; Lipoproteins ; Liver ; Male ; Mice* ; Obesity* ; Oxidative Stress ; Plasma ; Polyphenols ; Steam* ; Triglycerides ; Vegetables ; Water ; Weight Gain

Postmenopausal women, who have reduced circulating estrogen levels, are more prone to develop obesity and related metabolic diseases than premenopausal women. The absence of safe and effective treatments for postmenopausal obesity has changed the focus to natural products as alternative remedies. Total salvianolic acids (TSA) are the major water-soluble ingredients of Danshen. Salvianolic acid (SA) is the major constituent of the TSA. Salvianolic acids, including TSA and SA, are widely used in traditional Chinese medicine. In the present study, ovariectomized rats and LO2 cells were used to study the effects of salvianolic acids on body weight gain and hepatic steatosis. Salvianolic acids reduced ovariectomy (OVX)-induced body weight gain, attenuated the expressions of hepatic lipogenic genes, such as sterol regulatory element binding protein (SREBP)1, fatty acid synthase (FAS), and stearoyl-CoA desaturase (SCD)1, and decreased the liver triglyceride (TG) and total cholesterol (TC). For the molecular mechanisms, OVX and high glucose-induced phosphorylation of signal transducer and activator of transcription (STAT)-3 was inhibited by salvianolic acids treatment. In LO2 cells, inhibition of STAT-3 by siRNA attenuated the increased expression of SREBP1 and TG induced by high glucose. Salvianolic acids reduced the upregulation of SREBP1 and TG induced by high glucose in LO2 cells. In conclusion, these findings illustrated that salvianolic acids markedly alleviated the lipid metabolism disorders and protected against the postmenopausal obesity. The underlying mechanism was probably associated with the regulation of STAT-3 signaling.
Alkenes ; administration & dosage ; Animals ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Humans ; Lipid Metabolism ; drug effects ; Liver ; drug effects ; metabolism ; Obesity ; drug therapy ; genetics ; metabolism ; Ovariectomy ; Polyphenols ; administration & dosage ; Postmenopause ; drug effects ; genetics ; metabolism ; Rats ; STAT3 Transcription Factor ; genetics ; metabolism ; Salvia miltiorrhiza ; chemistry ; Signal Transduction ; drug effects ; Sterol Regulatory Element Binding Protein 1 ; genetics ; metabolism ; Triglycerides ; metabolism

Farnesoid X receptor (FXR) is a member of the nuclear receptor superfamily of ligand-activated transcription factors. As a metabolic regulator, FXR plays key roles in bile acid and cholesterol metabolism and lipid and glucose homeostasis. Therefore, FXR is a potential drug target for several metabolic syndromes, especially those related to lipidemia disorders. In the present study, we identified small molecule SIPI-7623, a derivative of an extract from Oriental wormwood (Artemisia capillaris), and found that it specifically upregulated the expression of cholesterol-7-alpha-hydroxylase (CYP7A1), downregulated the expression of sterol-regulatory element-binding protein 1c (SREBP-1c) in the liver, and inhibited the expression of ileal bile acid binding-protein (IBABP) in the ileum of rats. We found that inhibition of FXR by SIPI-7623 decreased the level of cholesterol and triglyceride. SIPI-7623 reduced the levels of cholesterol and triglyceride in in vitro HepG2 cell models, ameliorated diet-induced atherosclerosis, and decreased the serum lipid content on rats and rabbits model of atherosclerosis in vivo. Furthermore, SIPI-7623 decreased the extent of atherosclerotic lesions. Our resutls demonstrated that antagonism of the FXR pathway can be employed as a therapeutic strategy to treat metabolic diseases such as hyperlipidemia and atherosclerosis. In conclusion, SIPI-7623 could be a promising lead compound for development of drugs to treat hyperlipidemia and atherosclerosis.
Animals ; Artemisia ; chemistry ; Atherosclerosis ; drug therapy ; genetics ; metabolism ; Cholesterol ; metabolism ; Cholesterol 7-alpha-Hydroxylase ; genetics ; metabolism ; Drugs, Chinese Herbal ; administration & dosage ; Humans ; Hyperlipidemias ; drug therapy ; genetics ; metabolism ; Hypolipidemic Agents ; administration & dosage ; Liver ; drug effects ; metabolism ; Male ; Rabbits ; Rats ; Rats, Sprague-Dawley ; Receptors, Cytoplasmic and Nuclear ; antagonists & inhibitors ; genetics ; metabolism ; Sterol Regulatory Element Binding Protein 1 ; genetics ; metabolism ; Triglycerides ; metabolism

Pomegranate leaf (PGL) has a definite role in regulating lipid metabolism. However, pharmacokinetic results show the main active ingredient, ellagic acid, in PGL has lower oral bioavailability, suggesting that the lipid-lowering effect of PGL may act through inhibiting lipid absorption in the small intestine. Our results demonstrated that pomegranate leaf and its main active ingredients (i.e., ellagic acid, gallic acid, pyrogallic acid and tannic acid) were capable of inhibiting pancreatic lipase activity in vitro. In computational molecular docking, the four ingredients had good affinity for pancreatic lipase. Acute lipid overload experiments showed that a large dosage of PGL significantly reduced serum total cholesterol (TG) and triglycerides (TC) levels in addition to inhibiting intestinal lipase activity, which demonstrated that PGL could inhibit lipase activity and reduce the absorption of lipids. We also found that PGL could reverse the reduced tight-junction protein expression due to intestinal lipid overload, promote Occludin and Claudin4 expression in the small intestine, and enhance the intestinal mucosal barrier. In conclusion, we demonstrated that PGL can inhibit lipid absorption and reduce blood TG and TC by targeting pancreatic lipase, promoting tight-junction protein expression and thereby preventing intestinal mucosa damage from an overload of lipids in the intestine.
Animals ; Enzyme Inhibitors ; administration & dosage ; chemistry ; Humans ; Hyperlipidemias ; drug therapy ; enzymology ; metabolism ; Intestinal Absorption ; Intestine, Small ; metabolism ; Kinetics ; Lipase ; chemistry ; metabolism ; Lipid Metabolism ; Lythraceae ; chemistry ; Male ; Mice ; Mice, Inbred ICR ; Plant Extracts ; administration & dosage ; chemistry ; Plant Leaves ; chemistry ; Triglycerides ; metabolism

Realgar nanoparticles (NPs) are increasingly used as therapeutic agents for their enhanced anti-proliferation effect and cytotoxicity on cancer cells. However, the alteration of particle size may enhance biological reactivity as well as toxicity. A LC/MS and GC/MS based metabolomics approach was employed to explore the mechanism of realgar NPs-induced hepatotoxicity and identify potential biomarkers. Male Sprague-Dawley rats were administrated intragastrically with realgar or realgar NPs at a dose of 1.0 g·kg·d for 28 days and toxic effects of realgar NPs on liver tissues were examined by biochemical indicator analysis and histopathologic examination. Increased levels of serum enzymes and high hepatic steatosis were discovered in the realgar NPs treated group. Multivariate data analysis revealed that rats with realgar NPs-induced hepatotoxicity could be distinctively differentiated from the animals in the control and realgar treated groups. In addition, 21 and 32 endogenous metabolites were apparently changed in the serum and live extracts, respectively. Realgar NPs might induce free fatty acid and triglyceride accumulation, resulting in hepatotoxicity. In conclusion, the present study represents the first comprehensive LC/MS- and GC/MS-based metabolomics analysis of realgar NPs-induced hepatotoxicity, which may help further research of nanotoxicity.
Animals ; Biomarkers ; blood ; chemistry ; Chromatography, Liquid ; methods ; Fatty Acids ; metabolism ; Gas Chromatography-Mass Spectrometry ; methods ; Liver ; chemistry ; drug effects ; metabolism ; Male ; Mass Spectrometry ; methods ; Metabolomics ; methods ; Nanoparticles ; toxicity ; Rats ; Rats, Sprague-Dawley ; Triglycerides ; metabolism