Physicochemical properties, metabolomic analysis, antioxidant and lipid - lowering activity of a functional beverage based on cocona (Solanum sessiliflorum Dunal) / Propiedades fisicoquímicas, análisis metabolómico, actividad antioxidante e hipolipemiante de una bebida funcional a base de cocona (Solanum sessiliflorum Dunal)

The physicochemical, microbiological and metabolomics analysis, antioxidant and lipid - lowering effect, and shelf life prediction of a functional beverage based on cocona pul p of SRN9 ecotype was to carry out. According to the results obtained, the beverage complies with all the characteristics of the Peruvian technical standard for juices, nectars and fruit beverages NTP 203.110:2009 and is within the limits established by th e sanitary technical standard NTS N° 071 - MINSA/DIGESA - V.01, with a shelf - life period of 4 months and 1 day. The metabolome regarding bioactive compounds showed the presence of 30 compounds, including several glycosylated flavonols, two flavanols, and two s permidines. Likewise, showed a lipid - lowering effect statistically significant (p < 0.05) about the serum levels of total cholesterol and triglycerides, with a mean reduction of 41.52 mg/dL for total cholesterol levels and 130.80 mg/dL for triglyceride lev els. This beverage could be an alternative for the treatment of atherosclerosis and prevention of cardiovascular diseases.

Se rea lizó el análisis fisicoquímico, microbiológico y metabolómico, efecto antioxidante e hipolipemiante, y vida útil de una bebida funcional a base de cocona ecotipo SRN9. De acuerdo a los resultados, la bebida cumple con las características de la norma técnic a peruana para jugos, néctares y bebidas de frutas NTP 203.110:2009 y se encuentra dentro de los límites establecidos por la norma técnica sanitaria NTS N° 071 - MINSA/DIGESA - V.01, con una vida útil de 4 meses y 1 día. Del perfil metabolómico se identificaro n 30 compuestos, entre ellos varios flavonoles glicosilados, dos flavanoles y dos espermidinas. Asimismo, mostró un efecto hipolipemiante estadísticamente significativo (p < 0,05) sobre los niveles séricos de colesterol total y triglicéridos, con una reduc ción media de 41,52 mg/dL y de 130,80 mg/dL para los niveles de colesterol total y de triglicéridos, respectivamente. Esta bebida podría ser una alternativa para el tratamiento de la aterosclerosis y prevención de enfermedades cardiovasculares.

Antihyperglycemic and antihyperlipidemic effects of fruit extract of Hodgsonia heteroclita (Roxb.) Hook. f. & Thomson in diabetic mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Hodgsonia heteroclita has been known as an important traditionally consumed medicinal plant of North-East India known to have antidiabetic properties. This study aims to investigate the effects of the ethanolic fruit extract of Hodgsonia heteroclita against hyperglycemia and hyperlipidemia by using streptozotocin (STZ) treated diabetic mice. MATERIALS AND METHODS: The fruits of H. heteroclita were collected from the various parts of Kokrajhar district, Assam India (Geographic coordinates: 26°24'3.85″ N 90°16'22.30″ E). Basic morphological evaluations were carried out by the Botanical Survey of India, Eastern circle, Shillong, who also certified and identified the plant. Hexane, chloroform, and ethanolic extracts of the fruit of H. heteroclita were investigated for α-amylase inhibition assay as a rapid screening tool for examining anti-diabetic activity. The efficacy of ethanolic extract at a dose of 100, 200, and 300 mg/kg body weight was tested for 21 days in STZ-induced diabetic mice. The body weight, fasting plasma glucose and serum lipids, and hepatic glycogen levels were measured in experimental animals to examine the antihyperglycemic and antihyperlipidemic efficacy of the extract. Both HPTLC and LC-MS analysis was performed to examine the phyotochemicals present in the ethanolic extract of H. heteroclita. RESULTS: It has been observed that treatment with the ethanolic extract dose-dependently reduced the plasma glucose levels, total cholesterol, low density lipoprotein-cholesterol, very low-density lipoprotein-cholesterol, triglyceride, and increased the body weight, liver glycogens and high-density lipoprotein-cholesterol in STZ treated diabetic mice. HPTLC demonstrated the presence of triterpene compounds and LC-MS analysis revealed the presence Cucurbitacin I, Cucurbitacin E, and Kuguacin G as the triterpene phytoconstituents. CONCLUSION: The present study demonstrated that ethanolic fruit extract of H. heteroclita improved both glycemic and lipid parameters in mice model of diabetes.

HPTLC-Bioluminescent Bioautography Screening of Herbal Teas for Adulteration with Hypolipidemic Drugs.

Teas based on nutraceutical herbs are an effective tool against hyperlipidemia. However, the adulteration with chemical drugs is frequently detected. By coupling bioluminescent bioautography with high performance thin-layer chromatography (HPTLC), we developed a facile method suitable for screening hypolipidemic drugs (ciprofibrate and bezafibrate) adulteration in five different herbal teas (lotus leaf, Apocynum, Ginkgo biloba, Gynostemia and chrysanthemum). First, the sensitivity of a bioluminescent bacteria to the analyte was evaluated on different HPTLC layer materials, revealing that the best performance was achieved on the silica gel layer. On this basis, sample extracts were separated on silica gel plates via a standardized HPTLC procedure, forming a selective detection window for the targeted compound. Then, the separation results were rapidly visualized by the bioluminescence inhibition of bacteria cells within 6 min after dipping. The observed inhibition displayed an acceptable limit of detection (<20 ng/zone or 2 mg/kg) and linearity (R2 ≥ 0.9279) within a wide concentration range (50-1000 ng/zone). Furthermore, the optimized method was performed with artificially adulterated samples and the recovery rates were determined to be within the range of 71% to 91%, bracing its practical reliability. Showing superiorly high simplicity, throughput and specificity, this work demonstrated that the analytical method jointly based on HPTLC and bioautography was an ideal tool for screening bioactive compounds in complex biological matrix.

In-silico HMG-CoA reductase-inhibitory and in-vivo anti-lipidaemic/anticancer effects of carotenoids from Spondias mombin.

OBJECTIVES: Inhibition of HMG-CoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase, the rate rate-determining enzyme for the biogenesis of cholesterol is known to show antineoplastic effects. Therefore, this study investigates the in-silico HMG-CoA reductase (HMGCR)-inhibitory and in-vivo anti-lipidaemic/anticancer effects of carotenoids from Spondias mombin. METHODS: Carotenoids from S. mombin leaves were characterized with the aid of liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS). The characterized phytochemicals were obtained from PubChem. They were docked into the orthosteric site of human HMGCR (Protein Data Bank code 1HW8) using AutoDock 4.0 suites. DMBA (7,12-dimethylbenz[a]anthracene) model of breast cancer was treated with the carotenoids extract from S. mombin (100 mg/kg and 200 mg/kg doses) to assess its anti-lipidaemic cum anticancer effects. KEY FINDINGS: Carotenoids from S. mombin; beta-carotene-15,15'-epoxide, astaxanthin and 7,7',8,8'-tetrahydro-ß-ß-carotene demonstrate HMGCR inhibition. They form hydrophobic interactions with key residues within the catalytic domain of HMGCR. The carotenoids extract exhibits anti-lipidaemic/anticancer effects, lowering serum triglyceride, LDL and cholesterol concentration. It increases HDL concentration and downregulates the expression of HMGR, AFP, CEACAM-3, BRCA-1 and HIF-1 mRNAs. CONCLUSION: Carotenoids from S. mombin demonstrate HMG-CoA reductase (HMGCR) inhibition, anti-lipidaemic, and anticancer effects. The inhibition of HMGCR by the carotenoids extract further poses it as a potential anti-hypercholesterolaemia compounds.

Urinary metabolomics analysis of the protective effects of Daming capsule on hyperlipidemia rats using ultra-high-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry.

Hyperlipidemia is recognized as one of the most important risk factors for morbidity and mortality due to cardiovascular diseases. Daming capsule, a Chinese patent medicine, has shown definitive efficacy in patients with hyperlipidemia. In this study, serum biochemistry and histopathology assessment were used to investigate the lipid-lowering effect of Daming capsule. Furthermore, urinary metabolomics based on ultra high performance liquid chromatography with quadrupole time-of-flight mass spectrometry was conducted to identify the urinary biomarkers associated with hyperlipidemia and discover the underlying mechanisms of the antihyperlipidemic action of Daming capsule. After 10 weeks of treatment, Daming capsule significantly lowered serum lipid levels and ameliorated hepatic steatosis induced by a high-fat diet. A total of 33 potential biomarkers associated with hyperlipidemia were identified, among which 26 were robustly restored to normal levels after administration of Daming capsule. Pathway analysis revealed that the lipid-lowering effect of Daming capsule is related to the regulation of multiple metabolic pathways including vitamin B and amino acid metabolism, tricarboxylic acid cycle, and pentose phosphate pathway. Notably, the study demonstrates that metabolomics is a powerful tool to elucidate the multitarget mechanism of traditional Chinese medicines, thereby promoting their research and development.

Characterization of insoluble dietary fiber from three food sources and their potential hypoglycemic and hypolipidemic effects.

Dietary fiber is an important nutrient for improving human health and controlling calorie intake, and is used to produce functional foods. In this study, insoluble dietary fiber (IDF) from three sources (enoki mushrooms, carrots, and oats) was characterized and their hypoglycemic and hypolipidemic effects were determined with in vitro and in vivo models. The results of Scanning electron microscopy (SEM) showed that the IDF from the three sources have different morphologies. The Fourier transform infrared spectroscopy (FT-IR) results showed that the IDF samples from the three sources have similar active groups, but the X-ray diffraction (XRD) and thermogravimetric analysis/differential scanning calorimetry (TGA/DSC) results indicated that oat IDF mainly contained cellulose, and enoki mushroom IDF and carrot IDF contained hemicelluloses and cellulose. Among three IDF, carrot IDF had stronger water holding capacity, swelling capacity, and adsorption capacity of oil and cholate; enoki mushroom IDF had stronger glucose adsorption capacity and the ability to inhibit fat digestion; while oat IDF had stronger cholesterol adsorption capacity. None of the three IDF showed significant inhibition on starch digestion. Results from mouse feeding studies showed that IDF from three sources all improved glucose tolerance and inhibited the rise of blood lipid after the fat loading. Thus, this study demonstrated the functional significance of the IDF from three sources, which provides a reference for their application in functional food products aiming at maintaining healthy glucose and blood lipid levels.

Simultaneous determination and quantitation of hypolipidemic drugs in fingerprints by UPLC-Q-TRAP/MS.

An ultra-performance liquid chromatography tandem triple quadrupole compound linear ion trap mass spectrometry (UPLC-Q-TRAP/MS) method was developed and validated for the detection of hypolipidemic drugs in fingerprints. 13 hypolipidemic drugs were well separated by the gradient elution of 0.01% formic acid in water and methanol at a flow rate of 0.4 mL/min within 11 min. The analytes were detected in positive (ESI+) and negative (ESI-) modes and scanned using scheduled multiple reaction monitoring-information dependent acquisition-enhanced product ion (SMRM-IDA-EPI) for best selectivity and sensitivity. The calibration curves showed good linearity in the range of 0.050-50.000 ng/patch with coefficients (r2) higher than 0.9904 for all analytes. Meantime, the LODs and LLOQs were in ranges of 0.001-0.034 and 0.003-0.050 ng/patch. The accuracies, intra-day and inter-day precision ranged from -13.3 to 0.3%, 1.1-10.4% and 3.7-14.5%, respectively. The recoveries ranged from 79.9 to 114.8%, while the absolute and relative matrix effects were in the range of 83.0-107.2% and 2.2-9.7%. By comparing the non-spiked fingerprints from healthy volunteers with the fingerprints obtained from patients, demonstrated that the method was competent for determination and quantitation of hypolipidemic drugs in fingerprints.

Screening of hypolipidemic active components in Jiang-Zhi-Ning and its preliminary mechanism research based on "active contribution value" study.

ETHNOPHARMACOLOGICAL RELEVANCE: Jiang-Zhi-Ning (JZN) is a traditional Chinese medicine formula, which has the effect of lowering blood lipid level and softening blood vessels. It is clinically used in the treatment of hyperlipidemia with significant curative effect. AIM OF THE STUDY: This study aims to screen the active components of JZN that are responsible for its blood lipids lowering effect and lay the foundation for elucidating pharmacodynamic material basis of the hypolipidemic effect of the formula. MATERIALS AND METHODS: The hyperlipidemia model was used to evaluate the efficacy of the JZN effective extraction with the TC and TG of rat plasma as evaluation index. Then the established ultra-high performance liquid chromatography coupled with electrospray ionization-quadrupole-time of flight-mass spectrometry (UPLC-ESI-Q-TOF-MSn) method was utilized to analyze the components of JZN effective extraction and the absorbed components in rat plasma, the potential active components were screened by using the combined analysis results of in vivo and in vitro component identification. Then an established ultra-high performance liquid chromatography-triple quadrupole mass spectrometry (UPLC-QqQ-MSn) method was used to determine the content of potential active components and its natural ratio in JZN effective extraction, and a potential active components combination (PACC) was formed accordingly. Then a HepG2 cell hyperlipidemia model induced by sodium oleate was used to study the hypolipidemic activity of PACC by detecting the content of TG level in the model. Meanwhile, the real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to conduct preliminary research on its hypolipidemic mechanism. Then combined with the concept of "combination index" in the "median-effect principle", to calculate the half inhibitory concentration (IC50) values of PACC and each monomer component on inhibiting the TG level in the cell model. Subsequently, the "activity contribution study" was carried out, and the components with the sum of the "activity contribution value" of 85% were finally selected as the hypolipidemic active components of JZN. RESULTS: The pharmacodynamics results showed that JZN effective extraction has displayed a good hypolipidemic effect. 45 components were identified in vitro, 108 components were identified from rat plasma, and 17 potential active components were screened out. The content determination result showed that the ratio of each potential active components in PACC as following: cassiaside C: rubrofusarin-6-O-gentiobioside: aurantio-obtusin-6-O-glucoside: hyperoside: isoquercitrin: quercetin-3-O-glucuronide: (E)-2,3,5,4'-tetrahydroxystilbene-2-O-glucoside: rutin: emodin-8-O-glucoside: astragalin: armepavine: N-nornuciferine: coclaurine: O-nornuciferine: nuciferine: N-norarmepavine: higenamine = 3.30: 16.06: 9.15: 23.94: 98.40: 417.45: 189.68: 8.62: 1.28: 5: 3.51: 14.57: 1.06: 1.35: 1: 5.64: 6.06, and the activity study results showed that it has displayed a good hypolipidemic activity. Finally, the hypolipidemic active components screened out by the "activity contribution study" were: quercetin-3-O-glucuronide, (E)-2,3,5,4'-tetrahydroxystilbene-2-O-glucoside, isoquercitrin, O-nornuciferine, hyperoside and rubrofusarin-6-O-gentiobioside. CONCLUSIONS: A scientific and rational approach of screening the hypolipidemic active ingredients of JZN has been developed in the current study. In addition, the research revealed the blood lipid lowering mechanism of those ingredients, which provide a solid basis for further elucidating the hypolipidemic pharmacodynamic material basis and action mechanism of JZN.

Serum metabonomics coupled with HPLC-LTQ/orbitrap MS and multivariate data analysis on the ameliorative effects of Bidens bipinnata L. in hyperlipidemic rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Hyperlipidemia (HLP) is a prevalence chronic cardiovascular disease, which is treated by traditional Chinese medicine (TCM) in China. More and more attention has been paid to the application of metabolomics in the study of TCM. Bidens bipinnata L. (BBL), a folk medicine in contemporary China, has the efficacy in the treatment of hyperlipidemia (HLP) in China. However, little is known of the underlying mechanism of BBL. This research aimed to investigate ameliorative effects of BBL on hyperlipidemic rats and explore the mechanism by metabolomics method. MATERIALS AND METHODS: Hyperlipidemic rats were established by high fat diet (HFD). Biochemical assay was used to evaluate the efficacy of BBL. A metabolomics approach based on high performance liquid chromatography-linear ion trap/orbitrap high-resolution mass spectrometry (HPLC-LTQ/orbitrap MS) was performed to analyze the serum biomarkers from model group, control group and BBL group. Principle component analysis (PCA) and partial least-squares discriminate analysis (PLS-DA) were utilized to identify differences of metabolic profiles in rats among the three groups. In order to identify possible pathways that were affected by HLP, the identified endogenous metabolites were analyzed by using MetaboAnalyst. In the network pharmacology study, our research group found that PPAR signaling pathway was the most important pathway of BBL in the treatment of HLP. Then, it was found that changes in the major metabolic pathways would affect the PPAR signaling pathway through comprehensive analysis based on KEGG database. Therefore, the expression of key genes in the PPAR signaling pathway was detected by real-time quantitative fluorescence PCR (RT-qPCR). RESULTS: Six metabolites, which showed a significantly restoring trend from HLP to normal condition, were regarded as potential biomarkers of BBL treatment. The levels of phosphorylcholine, mevalonic acid and leukotriene B4 (LTB4) increased significantly (P < 0.01) in hyperlipidemic rats, while the levels of linoleic acid, arachidonic acid (AA) and lysophosphatidylcholine (18:0) (Lyso PC (18:0)) decreased significantly (P < 0.01) in comparison with control rats. Those endogenous metabolites were chiefly involved in linoleic acid metabolism, AA metabolism and terpenoid backbone biosynthesis. According to the results of RT-qPCR analysis, the mRNA expressions of PPAR α, PPAR ß and PPARγ in model group were difference compared with control group. And the expression difference could be regulated closer to normal level after BBL intervention. CONCLUSIONS: The results of biochemical assay, serum metabolic pattern and RT-qPCR analysis showed that BBL could exert a significant improvement on lipid levels, liver function, renal function, as well as the mRNA expression level of PPAR signaling pathway.

Sustainable environment-friendly quantitative determination of three anti-hyperlipidemic statin drugs and ezetimibe in binary mixtures by first derivative Fourier transform infrared (FTIR) spectroscopy.

FTIR spectrometry is considered a sustainable green analytical chemistry procedure. Its use in quantitative analysis of pharmaceutical compounds in their raw resources and in their dosage forms is growing currently. The current research offers an environment-friendly, speedy, cost-effective, reliable and easy method for the simultaneous estimation of anti-hyperlipidemic drugs. No sample preparation was required except for grinding and mixing with KBr for making pellets used for acquisition of the FT-IR spectra. First-derivative FTIR spectroscopy is used to assess quantitatively atorvastatin (ATR), rosuvastatin (RSV) and simvastatin (SMV) in their binary mixtures with ezetimibe (EZT). For the first mixture, EZT and ATR were determined at 1733.18 cm-1 and 1647.74 cm-1, respectively. In the second mixture, the zero-crossing wave numbers selected for the determination of EZT and RSV were 1733.18 cm-1 and 955.69 cm-1, correspondingly. Whereas, the third mixture was quantified at the wavenumbers of 1520.93 and 3569.68 cm-1 for EZT and SMV, respectively. Validation of the procedure has been performed complying with recommendations of the International Conference of Harmonization (ICH) presenting linearity, accuracy, precision, robustness and selectivity. The linear range for all drugs was 2-30 mg/g. It was found that the LOD was 0.607, 0.311, 0.491 and 0.395 mg/g and the LOQ was found to be 1.839, 0.942, 1.490 and 1.190 mg/g for EZT, ATR, RSV, and SMV, correspondingly. The proposed technique was found to be accurate and precise in terms of percentage error and percentage relative standard deviation among intraday and interday measurements. It was also found selective through comparison of the results of standard drugs with results of binary mixtures and of pharmaceutical tablets. It was found robust through making slight variations in the working conditions and the results obtained remained statistically equivalent. The technique was applied effectively for the estimation of the binary mixtures under study in their tablets. Comparing the found outcomes to those of reference derivative UV spectrophotometric methods gave no significant difference between them. Analytical eco-scale and the scale of Green Analytical Procedure Index (GAPI) are the two scales utilized for evaluation of the greenness of the technique and it was found to be excellent green.

Anti-hyperglycemic and anti-hyperlipidemic effects of a special fraction of Luohanguo extract on obese T2DM rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Luohanguo (LHG), a traditional Chinese medicine, could clear heat, moisten the lung, soothe the throat, restore the voice, and lubricate intestine and open the bowels. LHG has been utilized for the treatment of sore throats and hyperglycemia in folk medicine as a homology of medicine and food. The hypoglycemic pharmacology of LHG has attracted considerable attention, and mogrosides have been considered to be active ingredients against diabetes mellitus. We have found that these mogrosides could be metabolized into their secondary glycosides containing 1-3 glucose residues in type 2 diabetes mellitus (T2DM) rats in previous studies. These metabolites may be the antidiabetic components of LHG in vivo. Thus far, no reports have been found on reducing blood glucose of mogrosides containing 1-3 glucose residues. AIMS OF THE STUDY: The aim of this study was to confirm that mogrosides containing 1-3 glucose residues were the active components of LHG for antidiabetic effects and to understand their potential mechanisms of action. MATERIALS AND METHODS: First, the special fraction of mogrosides containing 1-3 glucose residues was separated from a 50% ethanol extract of LHG, and the chemical components were identified by ultra-performance liquid chromatography (UPLC) and named low-polar Siraitia grosvenorii glycosides (L-SGgly). Second, the antidiabetic effects of L-SGgly were evaluated by HFD/STZ-induced (high-fat diet and streptozocin) obese T2DM rats by indexing fasting blood glucose (FBG), fasting insulin (FINS), and insulin resistance, and then compared with other fractions in the separation process. The changes in serum lipid levels were also detected. Finally, possible mechanisms of antidiabetic activity of L-SGgly were identified as increasing GLP-1 levels and activating liver AMPK in T2DM rats. RESULTS: The chemical analysis of L-SGgly showed that they contain 11-oxomogroside V, mogroside V, mogroside III, mogroside IIE, mogroside IIIA1, mogroside IIA1, and mogroside IA1, respectively. The total content of the mogrosides in L-SGgly was 54.4%, including 15.7% mogroside IIA1 and 12.6% mogroside IA1. L-SGgly showed excellent effects on obese T2DM rats compared with the other fractions of LHG extract, including significantly reducing the levels of FBG (p < 0.001) and modifying insulin resistance (p < 0.05). Meanwhile, they could significantly decrease the content of triglyceride (p < 0.01), total cholesterol (p < 0.01), low-density lipoprotein cholesterol (p < 0.01) and free fatty acid (p < 0.001) and increase the content of high-density lipoprotein cholesterol (p < 0.001) in serum of T2DM rats. Moreover, L-SGgly can significantly increase (p < 0.01) GLP-1 levels and decrease (p < 0.01) IL-6 levels in T2DM rat serum. AMPK-activating activity in T2DM rats was also upregulated by L-SGgly, but no statistical significance was shown. CONCLUSION: L-SGgly, fractions separated from LHG extract, were verified to have obvious anti-hyperglycemic and anti-hyperlipidemic effects on T2DM rats. Furthermore, L-SGgly regulated insulin secretion in T2DM rats by increasing GLP-1 levels. These findings provide an explanation for the antidiabetic role of LHG.

The nutraceutical potential of Lepidium sativum L. seed flavonoid-rich extract in managing metabolic syndrome components.

The present study aimed to investigate the phytochemical and pharmacological identities of a Lepidium sativum L. (LS) flavonoid-rich extract and its beneficial effects on metabolic, hormonal, and histological status. Chemical screening, as well as high-performance liquid chromatography with diode-array detection (HPLC-DAD) identified high concentrations of the main flavonoid compounds in LS crude extract such as flavonols (quercetin, kaempferol), flavones (luteolin, apigenin), and especially flavanones (naringin, naringenin). Examinations of the biochemical and histopathological aspects showed the curative effects carried by LS flavonoid-rich extracts on high-fat diet-fed Wistar rats. In this study, we propose that these molecules probably exerted the bioactivity observed in the treated group through improving insulin sensitivity, dyslipidemia, inflammation, and pancreas ß cell integrity. PRACTICAL APPLICATIONS: The LS seed is widely used in traditional medicine to treat hyperglycemia and inflammation. During the traditional mixture preparation, the thermal procedures could impair the bioactions of the most interesting group of LS phytoconstituants, flavonoids. In the present study, we propose an appropriate procedure to preserve those phytochemicals and suggest them as a substitute for the management of metabolic diseases. The dried LS extract showed an incredible set of effective flavonoids, which revealed hypoglycemic, hypolipidemic, anti-inflammatory, cytoprotective, and antidiabetic activities. Thus, LS flavonoids constitute a remarkable product to consider in pharmaceutical industry targeting diabetes and heart diseases. Due to their enormous antioxidant potential, the LS flavonoids could be also used in food engineering and cosmetic preparations. Their practical applications is however often limited by low solubility and stability in lipophilic media. Therefore, a modification of the flavonoid structure is possibly required.

AMPK activation is involved in hypoglycemic and hypolipidemic activities of mogroside-rich extract from Siraitia grosvenorii (Swingle) fruits on high-fat diet/streptozotocin-induced diabetic mice.

Previous studies suggested the anti-diabetic effect of mogrosides in type 1 diabetes. To evaluate the potential effect of mogrosides in type 2 diabetes, we herein investigated the hypoglycemic and hypolipidemic effects and the underlying mechanism of mogroside-rich extract (MGE) using a high-fat diet in combination with streptozotocin (STZ)-induced diabetic model. MGE feeding for 5 weeks did not result in any obvious impact on the body weight and energy intake, but caused a moderate decrease of organ index in diabetic mice. MGE-supplemented diabetic mice showed a notable reduction of fasting blood glucose (FBG), glycated serum protein (GSP), serum insulin, homeostasis model assessment-insulin resistance (HOMA-IR), and serum atherogenic lipid profiles in a dose-dependent manner, whereas significant increases in the anti-atherogenic lipid profile, insulin sensitivity, glucose and insulin tolerance capacity with high dose (300 mg kg-1) MGE were observed (P < 0.01). Besides, hepatocyte polymorphism, lipid accumulation and steatosis were ameliorated and restored to near normal at the high dose. Furthermore, hepatic 5'AMP-activated protein kinase (AMPK) signaling was dose-dependently activated. Accordingly, the mRNA levels of hepatic gluconeogenic and lipogenic genes were downregulated and fat oxidation-associated genes were upregulated. These findings suggest that the hypoglycemic and hypolipidemic activities of MGE are probably attributed to the attenuation of insulin resistance and activation of hepatic AMPK signaling.

[The influence of the drying method for food properties and hypolidemic potential of oyster mushrooms (Pleurotus ostreatus)].

The aim of this research was to study the influence of two drying methods: freeze-drying sublimation and dry-air drying on the selected nutritional properties and hypolipidemic potential of fruiting bodies of oyster mushroom (Pleurotus ostreatus). The criteria for evaluation of the food properties were the color, the morphological structure, regidratation capacity, the total level of soluble proteins, fats, polysaccharides, free amino acids and monosaccharides. Lipid-lowering potential of oyster mushroom was evaluated by the concentration of lovastatin and the level of antioxidant activity. It has been experimentally revealed that the value of optical density of hydro-alcohol extracts of dried oyster mushrooms at a wavelength of 295 nm most clearly characterized its color which intensity was almost twice less in sublimated mushrooms, than шт the sample dried by dry-air method. Histological data showed that dry-air drying lead to the destruction of the mushroom cells and to the formation of a dense layered structure. Sublimation drying preserved the ordered cell structure and provided less deformation and shrinkage of the tissues. Using X-ray microtomography it was reported that freeze-dried mushrooms had uniform pore volume distribution. Dry-air dehydration method lead to the formation of larger cavities. The average percentage of the open pores was: 29.41±0.52% (after dry-air method), 11.10±0.41% (after freeze-drying method). Respectively the number of closed pores, which reflected the true value of porosity, was 0.99±0.01 and 1.75±0.01%. Structural differences of the samples of the dry oyster mushroom combined with their unequal hydration ability. Indicator of rehydration for oyster mushroom dried by sublimation method was 5.4±0.1, and for samples obtained by dry-air method it was 3.2±0.1. Respectively the average time of maximum water absorption was 22.7±1.8 and 45.3±2.9 minutes. It was found that the freeze-drying sublimation conditions were more conducive for the preservation of the biologically active protein and polysaccharide components of oyster mushrooms and on the other hand dry-air drying method increased the nutritional value of oyster mushrooms due to the reactions of polysaccharides autohydrolysis. The number of proteins and polysaccharides of the Oyster mushrooms samples dried by dry-air method and freeze-drying method was 72.0% and 56.0% respectively. Concentrations of free amino acids and glucose in the samples dried by freeze-drying and dry-air methods were 11.60±0.31%; 175.20±6.10 mg% and 7.00±0.28%; 144.0±5.7 mg% respectively. It has been experimentally recorded that the conditions of freeze drying were optimal in terms of ensuring the preservation of the content of natural statin and the antioxidant capacity of oyster mushrooms that provided its hypolipidemic potential. The amount of lovastatin in an the freeze-dried samples was 342±9.0 mg/kg, and was significantly higher than in the samples received by dry-air method - 190±6.0 mg/kg. The level of antioxidant activity of the oyster mushrooms samples were respectively 3.83±0.02 against 2.0±0.03 mmol/100 g. The conducted researches proved that for the production of dry oyster mushroom as a potential biologically active feedstock for the functional food products with lipid-regulating directivity the choice of the drying method had a fundamental importance.

Isolation and identification by high resolution liquid chromatography tandem mass spectrometry of novel peptides with multifunctional lipid-lowering capacity.

This work describes the isolation, characterization, and identification by RP-HPLC-ESI-Q-TOF of novel peptides that interfere in the fat digestion and absorption mechanisms by multiple pathways. Peptides were ultrafiltrated and peptides in the most active fraction were further separated by semipreparative RP-HPLC. Nine different subfractions were obtained observing a high amount of peptides in subfraction F3. Peptides in subfraction F3 could simultaneously reduce the solubility of cholesterol in micelles and inhibit pancreatic cholesterol esterase and pancreatic lipase, even after a simulated gastrointestinal digestion. The identification of lipid-lowering peptides has been scarcely performed and when done, low selectivity or sensitivity of employed identification techniques or conditions did not yield reliable results. Separation and detection of peptides by RP-HPLC-ESI-Q-TOF-MS was optimized and most favorable conditions were employed for the identification of peptides using de novo sequencing. Ten different peptides with 4-9 amino acids were identified. Main feature of identified peptides was the high acidity derived from a high presence of amino acids glutamic acid and aspartic acid in their sequences.

Biological-Profiling-Based Systematic Analysis of Rhizoma Coptidis from Different Growing Regions and Its Anticholesterol Biosynthesis Activity on HepG2 Cells.

Rhizoma Coptidis is a widely cultivated traditional Chinese herb. Although the chemical profiles of Rhizoma Coptidis have been established previously, the biological profiling of Rhizoma Coptidis has not been conducted yet. In this study, we collected Rhizoma Coptidis varieties from four distinct growing regions and performed genome-wide biological response fingerprinting (BioReF) on HepG2 cells using a gene expression array. Similar biological pathways were affected by extracts of all four Rhizoma Coptidis varieties but not by their analogue, Mahoniae Caulis. Among these pathways, the terpenoid backbone biosynthesis pathway was highly enriched, and six genes in the mevalonate (MVA) pathway were all down-regulated. However, the expression, maturation, as well as the specific DNA binding capacity of their coordinate transcription factor, sterol response element binding protein 2 (SREBP2), was not affected by Rhizoma Coptidis extract (RCE) or its typical active alkaloid berberine. Cellular cholesterol content tests further verified the cholesterol-lowering function of RCE in vitro, which supplements evidence for the use of Rhizoma Coptidis in hyperlipidemia treatment. This is the first described example of evaluating the quality of Rhizoma Coptidis with BioReF and a good demonstration of using BioReF to uncover the mechanisms of herbs at a systematic level.

Antimycobacterial and hypolipemiant activities of Bidens odorata (Cavanilles).

ETHNOPHARMACOLOGICAL RELEVANCE: Bidens odorata Cavanilles is a medicinal and edible plant known as "mozote blanco, aceitilla, acahual, mozoquelite" which is traditionally used in Mexico as a diuretic, hypoglycaemic, anti-inflammatory, antipyretic, antitussive, to treat gastrointestinal disorders, kidney pain, and lung or respiratory diseases. AIM OF THE STUDY: This research study was aimed at phytochemical analysis of aerial extracts of B. odorata for antimycobacterial and lipid-lowering activities. MATERIALS AND METHODS: Compounds 1 (((2R, 3R, 4S, 5S, 6R)-3,4,5-Tryhidroxy-6-(((E)-3-(4-hydroxyphenyl) acryloyl) oxy) tetrahydro-2H-pyran-2-yl) methyl-4-hydroxybenzoate) and 2 (3,5-Dihydroxybenzoic acid) were isolated from B. odorata aerial shoots and their structural elucidation was carried out using 1 and 2D NMR, infrared spectroscopy (IR) and mass spectrometry (ESI-MS). The antimycobacterial activity of various extracts and compounds 1 and 2 was determined using the Microplate Alamar Blue Assay (MABA). The evaluation of the hypolipidemic effect of the ethanolic extract and the glycosylated compound 1 was tested in a murine model of hypercholesterolemia induced by diet and by Triton WR-1339. On the other hand, the LD50 of the ethanolic extract was evaluated in ICR mice by the OECD protocol TG 423. RESULTS: Antimycobacterial assay of hexane, CH2Cl2, EtOAc, ethanolic and aqueous extracts, as well as the new glycosidic compound 1 and benzoic acid derivative 2 isolated from B. odorata showed minimal inhibitory concentrations (MIC) of 100, 12.5, 12.5, 12.5, ≥200, 3.125 and 50 µg/mL, respectively, against Mycobacterium tuberculosis H37Rv. Only hexane and CH2Cl2 extracts were observed to be active against Mycobacterium smegmatis mc2155 at a concentration of 50 and 100 µg/mL, respectively. The ethanolic extract showed lipid-lowering activity at doses of 100 and 1000 mg/kg, while glycosidic compound 1 was active at doses of 50 and 100 mg/kg. In addition, the LD50 of the ethanolic extract was >2000 mg/kg, meaning that this extract does not cause lethality or adverse effects, and no signs of organs alterations or tissue damage were observed. CONCLUSION: The hexane, CH2Cl2, EtOAc, and ethanolic extracts of B. odorata, as well as their components 1 and 2, displayed antimycobacterial activity against M. tuberculosis. Moreover, the ethanolic extract and glycosidic compound 1 showed an important lipid-lowering effect, without lethality or secondary effect. The results of this study support the documented traditional use for B. odorata.

Spectrum-effect relationship between HPLC fingerprints and hypolipidemic effect of Curcuma aromatica.

Curcuma aromatica is used as a traditional Chinese medicine, and it is mainly distributed in Guangxi, China. In this study, 10 batches of C. aromatica were collected from different origins in Guangxi. The fingerprints were established by HPLC technique to investigate the quality stability of C. aromatica. The spectrum-effect relationship between HPLC fingerprints and hypolipidemic effect of C. aromatica was assessed by similarity analysis, gray relational analysis and multiple linear regression analysis. From the results, the similarity values between each batch of C. aromatica and reference fingerprint were >0.880, indicating the good quality stability of the 10 batches of C. aromatica. Twenty common peaks were selected as the fingerprints to evaluate the quality and hypolipidemic effect of C. aromatica. The results of spectrum-effect relationship showed that peaks 10, 18, 13, 15 and 17 in the fingerprints were closely related to hypolipidemic effect. This study successfully established the spectrum-effect relationship between HPLC fingerprints and hypolipidemic effect of C. aromatica, which provided methods for quality control and more effectively studies on bioactive compounds of C. aromatica. It could also provide a new simple and effective method for utilizing the fingerprints to optimize the Chinese prescription and develop traditional Chinese medicine.

Variability in Potency Among Commercial Preparations of Berberine.

Berberine is an isoquinoline alkaloid plant extract that is widely available as a dietary supplement in the United States and has demonstrated efficacy in the treatment of type 2 diabetes mellitus and dyslipidemia. Because of its increased use and purported pharmacological properties, potential variations in product quality could pose a barrier to berberine's safety and effectiveness in clinical practice. Thus, this study evaluated the potency of dietary supplements containing berberine available in the U.S. commercial market. Fifteen unique dietary supplements containing berberine were purchased through U.S. dietary supplement vendors. For each product, berberine was extracted from 3 unique capsules and analyzed by ultra-high-performance liquid chromatography tandem mass spectrometry. Percentage content based on the product label claim was determined for each product. The average berberine content across the products was found to be 75% ± 25% of the product label claim, with product potency ranging from 33% to 100%. Nine of the 15 tested products (60%) failed to meet the potency standards of 90% to 110% of labeled content claim, as commonly required of pharmaceutical preparations by the U.S. Pharmacopeial Convention. Evaluation of the relationship between product cost and the measured potency failed to demonstrate an association between quality and cost. Variability in product quality may significantly contribute to inconsistencies in the safety and effectiveness of berberine. In addition, the quality of the berberine product cannot be inferred from its cost.