Targeted delivery of nutraceuticals derived from food for the treatment of obesity and its related complications.

Nutraceuticals which are abundant in foods have attracted much attention due to their bioactive activities of anti-obesity, anti-hyperlipidemia and anti-atherosclerosis. Unfortunately, the poor bioavailability severely undermines their envisioned benefits. Therefore, there is an urgent need to develop suitable delivery systems to promote the benefits of their biological activity. Targeted drug delivery system (TDDS) is a novel drug delivery system that can selectively concentrate drugs on targets in the body, improve the bioavailability of agents and reduce side effects. This emerging drug delivery system provides a new strategy for the treatment of obesity with nutraceuticals and would be a promising alternative to be widely used in the food field. This review summarizes the recent studies on the application in the targeted delivery of nutraceuticals for treating obesity and its related complications, especially the available receptors and their corresponding ligands for TDDS and the evaluation methods of the targeting ability.

Mechanism insight on licorice flavonoids release from Carbopol hydrogels: Role of "release steric hindrance" and drug solubility in the release medium.

The present study was to systematically evaluate different licorice flavonoids (LFs) compounds release behaviors from the single payload hydrogel and LFs extracts hydrogels based on the drug solubility in the release medium (DSRM), intermolecular strength of the hydrogel and the "release steric hindrance" (RSH). Two kinds of LFs (LFs 1: LFs 2 = 5:1, W/W) hydrogels were prepared with Carbopol 940 (CBP) as the thickener, and ten LFs single payload hydrogels were prepared according to the actual content in the LFs 1 extracts. The drug release mechanisms were confirmed by in vitro release experiments and molecular dynamic simulation analysis, and evaluated using novel indicators of ERLFs 1/Sin (the enhancement ratio (ER) of drug release percent of LFs 1-CBP hydrogel to the single payload hydrogel), ERLFs 2/ LFs 1 (ER of drug release percent of LFs 2-CBP hydrogel to LFs 1-CBP hydrogel) and ERrelease medium (ER of drug release percent in different release medium). We found that LFs 1-CBP possessed a significantly higher intermolecular strength and RSH than LFs 2-CBP, resulting in a higher viscosity, which had a positive correlation with the payload content and a negative correlation with the drug release percent. Therefore, the ERLFs 2/ LFs 1 values of ten LFs compounds were all higher than 1. For liquiritigenin and retrochalcone with higher DSRM, they displayed similar ERLFs 1/ Sin, ERLFs 2/ LFs 1 and ERrelease medium values (≈1). For formononetin, licoflavone A and licochalcone A with low DSRM, they exhibited ERLFs 1/Sin values >1. The low DSRM was the decisive factor to restrict their release from the single payload hydrogel. The presence of glycyrrhizin acid (GA) in the LFs could facilitate their release from the LFs extracts hydrogel. For isoliquiritin, isoliquiritigenin and glabridin with a lower content in the LFs extracts, they exhibited ERLFs 1/Sin values <1. The RSH predominantly restricted its release. The study provided guidelines for the reasonable design of LFs extracts hydrogel in pharmaceutical topical formulations.

Skin microbiome reconstruction and lipid metabolism profile alteration reveal the treatment mechanism of Cryptotanshinone in the acne rat.

BACKGROUND: Acne has become one of the most prevalent skin disorders, affecting mostly young people's physical and mental health globally. Cryptotanshinone (CPT) is a potential drug for acne, but its mechanism of acne treatment has not been thoroughly studied on the microbiota. Till date, only a few studies are directed to the impact of acne therapy on skin microbiota and lipid metabolites. PURPOSE: The action mechanism of CPT treatment of acne was investigated by the strategy of microbiome integration with lipidomics. METHODS: The 16Sr DNA sequencing was used to detect skin microbiota composition, and absolute quantitative lipidomics was utilized to identify lipid metabolites profiles levels. Four key proteins of the glycolysis pathway were detected with the immunochemistry method. Antibacterial analysis was used to evaluate CPT treatment of acne. RESULTS: CPT significantly inhibited Staphylococcus epidermidis and Staphylococcus aureus. Combination of the skin microbiome and lipidomics analysis, 29 types of differentially expressed flora (DEFs) and 782 differentially expressed lipid metabolites (DELMs) were significantly altered, especially Staphylococcus, Corynebacterium, Ralstonia, Enhydrobacter, Burkholderia, and Streptococcus. Cer was mainly regulated by Staphylococcus and Corynebacterium, whereas TG and DG were mainly regulated by Ralstonia, Enhydrobacter, Burkholderia, and Streptococcus. The glycolysis pathway was significantly regulated by Staphylococcus on CPT treatment of acne. The energy metabolism, lipid metabolism, immune system, glycan biosynthesis, and metabolism could be reversed by CPT. CONCLUSION: CPT might help acne rats rebuild their skin microbiota and alter lipid metabolism signatures. Furthermore, since skin microbes and skin lipid metabolites have a close correlation and are both regulated by CPT, the findings potentially provide a research foundation for the discovery of biomarkers of skin microbiome imbalance and targeted treatment of acne development mechanisms.

Danhong injection represses diabetic retinopathy and nephropathy advancement in diabetic mice by upregulating microRNA-30d-5p and targeting JAK1.

Danhong injection (DHI) restrains diabetic retinopathy and nephropathy (DR and DN) advancement in diabetic mice. However, the downstream mechanism of its modulation is not fully studied. Diabetic model mice (db/db mice) were intravenously injected with DHI and corresponding virus particles. MiR-30d-5p and JAK1 were detected. The body weight and fasting blood glucose mice were measured every 4 weeks. The renal tissues and serum of mice were collected, and the contents of creatinine and blood urea nitrogen were biochemically analyzed. IL-6, IFN-γ and TNF-α were detected by ELISA, with the pathological conditions of renal tissues in mice by He staining, and the adjustment conditions by TUNEL. Human retinal pigment epithelium (ARPE-19) cells were selected to induce DR model in vitro by high glucose, and exposed to DHI for treatment. The corresponding plasmids were transfected, and miR-30d-5p and JAK1 were detected, with the proliferation ability by plate cloning, apoptosis by flow cytometry, and cell migration ability by Transwell. The angiogenesis ability of cells was assessed by tube formation assay. The targeting relationship between miR-30d-5p and JAK1 was detected. The results manifested that miR-30d-5p was declined in DR and DN, while JAK1 expression was elevated. DHI was able to improve DR and renal injury. DHI could regulate the miR-30d-5p-JAK1 axis in vivo, and miR-30d-5p targeted and regulated JAK1. Upregulation of miR-30d-5p or inhibition of JAK1 could improve DR and renal injury. The results implies that DHI can repress the development of DR and DN by elevating miR-30d-5p and targeting JAK1.

Protective mechanism of mung bean coat against hyperlipidemia in mice fed with a high-fat diet: insight from hepatic transcriptome analysis.

Mung bean coat (MBC) is a good source of dietary fibre and phenolic compounds with medical properties, and can alleviate metabolic diseases. In the present study, the effects of MBC on high fat diet (HFD)-induced hyperlipidemia mice were evaluated, and the underlying mechanisms of MBC against hyperlipidemia from hepatic transcriptional analysis were explored. Four groups of mice were fed a normal control diet or a HFD with or without MBC supplementation (6%, w/w) for 12 weeks. The results demonstrated that MBC supplementation could effectively alleviate HFD-induced obese symptoms, such as body weight gain and white adipose tissue accumulation. Notably, the serum lipid profiles, including total triglyceride, total cholesterol, and low-density lipoprotein cholesterol, were significantly lowered, accompanied by a significant improvement in hepatic steatosis. RNA-sequencing analysis indicated 1126 differential expression genes responding to MBC supplementation, and the PPAR signaling pathway was significantly enriched. Furthermore, MBC supplementation could significantly upregulate the transcriptional expression of lipid transformation (lipidolysis)-related genes (Cpt1b, Cyp7a1, and PPAR-α) and downregulate the transcriptional expression of lipid synthesis-related genes (Scd1, Cd36, and PPAR-γ) to protect against the HFD-induced hyperlipidemia, and they were confirmed by qRCR and western blotting validation. Taken together, the present study provides valuable information for understanding the curative effects and action mechanism of MBC in alleviating hyperlipidemia, and thus may contribute to the development and application of MBC as functional foods or dietary supplement to protect against hyperlipidemia.

Identification of the antibacterial mechanism of cryptotanshinone on methicillin-resistant Staphylococcus aureus using bioinformatics analysis.

Cryptotanshinone (CT) is an extract from the traditional Chinese medicine Salvia miltiorrhiza, which inhibits the growth of methicillin-resistant Staphylococcus aureus (MRSA) in vitro. This study aims to determine the antibacterial mechanisms of CT by integrating bioinformatics analysis and microbiology assay. The microarray data of GSE13203 was retrieved from the Gene Expression Omnibus (GEO) database to screen the differentially expressed genes (DEGs) of S. aureus strains that were treated with CT treatment. Gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were used to identify the potential target of CT. Data mining on the microarray dataset indicated that pyruvate kinase (PK) might be involved in the antimicrobial activities of CT. The minimum inhibition concentrations (MICs) of CT or vancomycin against the MRSA strain ATCC43300 and seven other clinical strains were determined using the broth dilution method. The effects of CT on the activity of PK were further measured. In vitro tests verified that CT inhibited the growth of an MRSA reference strain and seven other clinical strains. CT hampered the activity of the PK of ATCC43300 and five clinical MRSA strains. CT might hinder bacterial energy metabolism by inhibiting the activity of PK.

Dietary supplementation with mung bean coat alleviates the disorders in serum glucose and lipid profile and modulates gut microbiota in high-fat diet and streptozotocin-induced prediabetic mice.

As amajor by-product of mung bean processing, mung bean coat (MBC), which is rich in polyphenols and dietary fiber, is deemed to be mainly responsible for the health benefits of mung bean. However, its beneficial effects on the hyperglycemia, hyperlipidemia, and gut microbiota composition in prediabetic mice is not fully understood. The objective of this study was to investigate the efficacy of MBC in alleviating high-fat diet and streptozotocin-induced prediabetes. Herein, compared with the model control, dietary supplementation with MBC (3%, w/w) for 12 weeks significantly decreased the fasting blood glucose (24.60%), total cholesterol (15.72%), triglyceride (14.41%), and low-density lipoprotein cholesterol (22.45%). Furthermore, the improvements in glucose tolerance were reflected in the reduction of the area under the curve (AUC) and incremental AUC by approximately 23.08% and 51.18%, respectively. 16S rRNA gene sequencing of fecal microbiota suggested that MBC promoted the enrichment of beneficial bacteria (Roseburia and Bifidobacterium) and the production of short-chain fatty acids. All of the results from this study provided a scientific reference for avoiding the functional ingredients waste of MBC and expanding its application value.

Inhibitory effect of chloroform extracts from Citrus aurantium L. var. amara Engl. on fat accumulation.

BACKGROUND: Excess lipid accumulation can accelerate the development of various metabolic diseases. Blossoms of Citrus aurantium L. var. amara Engl. (CAVA) have been reported to possess inhibitory capacities on lipid deposition. However, the constituents responsible for the observed bioactivity and the underlying mechanisms are still not clearly understood. PURPOSE: To screen constituents from blossoms of CAVA with inhibitory effects on lipid accumulation and to explore the action mechanism. METHODS: The chloroform (CHL) extracts are prepared from blossoms of CAVA by fractional extraction and are characterized using LC-MS assay. 3T3-L1 preadipocytes are induced with differentiation medium (DMI) and treated with CHL extracts. High fat diet (HFD)-induced obese mice are further established and administrated with CHL extracts for 12 weeks. Hematoxylin and eosin (HE) staining, Oil Red O staining, ELISA, RT-qPCR, western blot and 16S rRNA gene sequence methods are employed. RESULTS: 14 compounds are identified in CHL extracts and trigonelline hydrochloride, nobiletin and 7-demethylsuberosin are most abundant. CHL extracts treatment significantly inhibit differentiation of 3T3-L1 cells by regulating expression of preadipocyte factor-1 (Pref-1), fatty acid synthase (FAS) and CCAAT/enhancer binding protein α (C/EBPα). CHL extracts intervention also significantly attenuate features of obesity and improved plasma biochemical profiles in HFD-fed mice. HFD-triggered hepatic steatosis and epididymal adipose tissues (EATs) hypertrophy are also reversed by CHL extracts administration through enhancing antioxidant responses and modulating lipogenesis and energy expenditure-related genes and proteins. 16S rRNA gene sequence data further show that CHL extracts enhance the diversity of gut microbiota. CHL extracts at lower concentrations reduce the ratio of Firmicutes to Bacteroidetes and the abundance of Erysipelotrichaceae. CHL extracts at higher doses markedly increase the abundance of Lachnospiraceae. CONCLUSION: These findings suggest that CHL extracts probably suppress lipid accumulation through inhibiting differentiation of 3T3-L1 cells and attenuating metabolic syndromes in HFD-fed mice.

Foxtail Millet Improves Blood Glucose Metabolism in Diabetic Rats through PI3K/AKT and NF-κB Signaling Pathways Mediated by Gut Microbiota.

Foxtail millet (FM) is receiving ongoing increased attention due to its beneficial health effects, including the hypoglycemic effect. However, the underlying mechanisms of the hypoglycemic effect have been underexplored. In the present study, the hypoglycemic effect of FM supplementation was confirmed again in high-fat diet and streptozotocin-induced diabetic rats with significantly decreased fasting glucose (FG), glycated serum protein, and areas under the glucose tolerance test (p < 0.05). We employed 16S rRNA and liver RNA sequencing technologies to identify the target gut microbes and signaling pathways involved in the hypoglycemic effect of FM supplementation. The results showed that FM supplementation significantly increased the relative abundance of Lactobacillus and Ruminococcus_2, which were significantly negatively correlated with FG and 2-h glucose. FM supplementation significantly reversed the trends of gene expression in diabetic rats. Specifically, FM supplementation inhibited gluconeogenesis, stimulated glycolysis, and restored fatty acid synthesis through activation of the PI3K/AKT signaling pathway. FM also reduced inflammation through inhibition of the NF-κB signaling pathway. Spearman's correlation analysis indicated a complicated set of interdependencies among the gut microbiota, signaling pathways, and metabolic parameters. Collectively, the above results suggest that the hypoglycemic effect of FM was at least partially mediated by the increased relative abundance of Lactobacillus, activation of the PI3K/AKT signaling pathway, and inhibition of the NF-κB signaling pathway.

Hypoglycemic Effect of Prolamin from Cooked Foxtail Millet (Setaria italic) on Streptozotocin-Induced Diabetic Mice.

Millet proteins have been demonstrated to possess glucose-lowering and lipid metabolic disorder modulation functions against diabetes; however, the molecular mechanisms underlying their anti-diabetic effects remain unclear. The present study aimed to investigate the hypoglycemic effect of prolamin from cooked foxtail millet (PCFM) on type 2 diabetic mice, and explore the gut microbiota and serum metabolic profile changes that are associated with diabetes attenuation by PCFM. Our diabetes model was established using a high-fat diet combined with streptozotocin before PCFM or saline was daily administrated by gavage for 5 weeks. The results showed that PCFM ameliorated glucose metabolism disorders associated with type 2 diabetes. Furthermore, the effects of PCFM administration on gut microbiota and serum metabolome were investigated. 16S rRNA gene sequencing analysis indicated that PCFM alleviated diabetes-related gut microbiota dysbiosis in mice. Additionally, the serum metabolomics analysis revealed that the metabolite levels disturbed by diabetes were partly altered by PCFM. Notably, the decreased D-Glucose level caused by PCFM suggested that its anti-diabetic potential can be associated with the activation of glycolysis and the inhibition of gluconeogenesis, starch and sucrose metabolism and galactose metabolism. In addition, the increased serotonin level caused by PCFM may stimulate insulin secretion by pancreatic ß-cells, which contributed to its hypoglycemic effect. Taken together, our research demonstrated that the modulation of gut microbiota composition and the serum metabolomics profile was associated with the anti-diabetic effect of PCFM.

A comparison between whole mung bean and decorticated mung bean: beneficial effects on the regulation of serum glucose and lipid disorders and the gut microbiota in high-fat diet and streptozotocin-induced prediabetic mice.

The aim of this study is to investigate the beneficial effects of whole mung bean (WMB) and decorticated mung bean (DMB) on the regulation of serum glucose and lipid disorders in high-fat diet (HFD) and streptozotocin (STZ)-induced prediabetic mice, and to further explore their gut microbiota modulatory effects. In the present study, the ability of mung bean-based diets to combat prediabetes-related metabolic disorders was determined by assessing the changes in the physiological, biochemical, and histological parameters, and the gut microbiota composition of prediabetic mice. The supplementation of both WMB and DMB can effectively alleviate HFD and STZ-induced impaired glucose tolerance (P < 0.05), which was accompanied by improvements in pancreatic ß-cell damage and hepatic steatosis. However, only WMB supplementation significantly decreased the fasting blood glucose and fasting serum insulin levels by sensitizing insulin action (P < 0.05), and reduced the serum lipid profiles and glycosylated serum protein levels (P < 0.05). Furthermore, high-throughput pyrosequencing of the 16S rRNA gene revealed that WMB and DMB supplementation could prevent HFD and STZ-induced gut microbiota dysbiosis, especially for the enrichment of some benign bacteria, such as Bifidobacterium and Akkermansia, and the reduction of some harmful bacteria (Staphylococcus and Enterococcus). Overall, although decortication processing had an impact on the beneficial effects of mung bean, it did not cause the loss of all health benefits.

Whole mung bean (Vigna radiata L.) supplementation prevents high-fat diet-induced obesity and disorders in a lipid profile and modulates gut microbiota in mice.

PURPOSE: Obesity, a strong risk factor for metabolic disorder, has become a major impediment for public health globally. The objective of this study was to assess the anti-obesity effect of mung bean, and the relationship between the gut microbiota modulatory effects of mung bean and the prevention of obesity. METHODS: Thirty-two four-week-old male C57BL/6 J mice were divided into four groups: normal chow diet (NCD), high-fat diet (HFD), a high-fat diet supplemented with 30% whole mung bean flour (HFD-WMB), and a high-fat diet supplemented with 30% decorticated mung bean flour (HFD-DMB). The ability of a mung bean-based diet to combat obesity-related metabolic disorder was determined by assessing the changes in physiological, histological, biochemical parameters, and gut microbiota composition of mice with HFD-induced obesity at 12 weeks. RESULTS: Both of WMB and DMB supplementation can effectively alleviate HFD-induced lipid metabolic disorders, which was accompanied by a reduction in hepatic steatosis. However, the only supplementation with WMB significantly reduced HFD-induced body weight gain, fat accumulation, and adipocyte size, and ameliorated the glucose tolerance and insulin resistance by sensitizing insulin action. Furthermore, high-throughput pyrosequencing of 16S rRNA revealed that WMB and DMB supplementation could normalize HFD-induced gut microbiota dysbiosis. Especially, WMB and DMB supplementation significantly promoted the relative abundance of Akkermansia and Bifidobacterium, respectively, and both of them significantly restored the relative abundance of several HFD-dependent taxa back to normal status in this study. Spearman's correlation analysis revealed that those genera are closely correlated with obesity-related indices. CONCLUSIONS: Although WMB showed better beneficial effects on HFD-induced obesity in comparison with DMB, DMB still retained some health benefits. Moreover, the alleviation of HFD-induced changes by mung bean supplementation was, at least, partially conciliated by structural modulation of gut microbiota.

Mechanisms of white mustard seed (Sinapis alba L.) volatile oils as transdermal penetration enhancers.

We investigated the transdermal drug permeation enhancement properties and associated mechanisms of white mustard (Sinapis alba L.) seed volatile oil (SVO). Using gas chromatography-mass spectrometry, we showed that SVO was composed primarily of allylisothiocyanate and isothiocyanatocyclopropane. Compared with azone, SVO had better penetration-enhancing effects on three model drugs (5-Fluorouracil, Osthole, and Paeonol), with each having different oil-water partition coefficients. Histopathology showed that SVO did not induce skin irritation when the concentration was lower than 2% (v/v), and it induced less irritation than azone. According to attenuated total reflection-Fourier transform infrared spectroscopy and transmission electron microscopy, SVO induced skin lipid structural disorder and increased the distance between the stratum corneum, which is beneficial to the penetration of drugs. Cellular experiments showed that SVO inhibited Ca2+-ATPase activity, increased intracellular Ca2+ concentration, and changed the membrane potential in HaCaT cells, which promoted drug transfer into the skin. Our findings reveal that SVO is a safe and efficient natural product that has great potential as skin penetration enhancer.

Mung Bean (Vigna radiata L.): Bioactive Polyphenols, Polysaccharides, Peptides, and Health Benefits.

Mung bean (Vigna radiata L.) is an important pulse consumed all over the world, especially in Asian countries, and has a long history of usage as traditional medicine. It has been known to be an excellent source of protein, dietary fiber, minerals, vitamins, and significant amounts of bioactive compounds, including polyphenols, polysaccharides, and peptides, therefore, becoming a popular functional food in promoting good health. The mung bean has been documented to ameliorate hyperglycemia, hyperlipemia, and hypertension, and prevent cancer and melanogenesis, as well as possess hepatoprotective and immunomodulatory activities. These health benefits derive primarily from the concentration and properties of those active compounds present in the mung bean. Vitexin and isovitexin are identified as the major polyphenols, and peptides containing hydrophobic amino acid residues with small molecular weight show higher bioactivity in the mung bean. Considering the recent surge in interest in the use of grain legumes, we hope this review will provide a blueprint to better utilize the mung bean in food products to improve human nutrition and further encourage advancement in this field.

Altered metabolites in guinea pigs with allergic asthma after acupoint sticking therapy: New insights from a metabolomics approach.

BACKGROUND: Clinical evidence gathered in Chinese communities suggested that acupoint sticking therapy could be an alternative treatment for asthma-related diseases. However, its underlying mechanism is still poorly understood. AIM/HYPOTHESIS: In this study, we aimed to investigate the mechanism of the anti-inflammatory effect of acupoint sticking application with 'Treatment of Winter Disease in Summer' (TWDS) prescription by using metabolomics. METHODS: Allergic asthma in guinea pig was sensitized and challenged by ovalbumin (OVA). Histopathological evaluation of the lung tissue was performed by hematoxylin and eosin (H&E) staining and Masson's trichrome staining. The levels of Th2 cytokine and IgE level in serum were measured using enzyme-linked immunoassay (ELISA). The mRNA expression levels of IL-4, IL-5, IL-13 and orosomucoid-like 3 (ORMDL3) were measured using quantitative reverse transcription polymerase chain reaction (RT-qPCR). Proteins of NF-κB signaling pathway were measured using western blot. The serum metabolomics profiles were obtained by using ultra-performance liquid chromatography combined with electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC-ESI-QTOF-MS). RESULTS: The overall results confirmed that AST with TWDS prescription had a significant protective effect against OVA-induced allergic asthma in guinea pig. This treatment not only attenuated airway inflammation and collagen deposition in the airway, but also decreased the levels of IL-4, IL-5, IL-13 and IgE in serum. In addition, metabolomics results indicated that metabolisms of phospholipid, sphingolipid, purine, amino acid and level of epinephrine were restored back to the normal control level. Moreover, results of the gene expression of ORMDL3 in lung tissues indicated that AST using TWDS could alter the sphingolipid metabolism. Further western blotting analysis also showed that its anti-inflammatory mechanism was by decreasing the phosphorylation of p65 and IκB. CONCLUSION: The study demonstrated that metabolomics provides a better understanding of the actions of TWDS acupoint sticking therapy on OVA-induced allergic asthma.

Simultaneous determination of wogonin, oroxylin a, schisandrin, paeoniflorin and emodin in rat serum by HPLC-MS/MS and application to pharmacokinetic studies.

Wogonin and oroxylin A in Scutellariae Radix, schisandrin in Chinensis Fructus, paeoniflorin in Moutan Cortex and emodin in Polygoni Cuspidate Rhizome et Radix are anti-inflammatory active compounds. A method for simultaneous determination of the five compounds in rat was developed and validated using high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS). The separation was performed on a Symmetry C18 column (4.6 × 50 mm, 3.5 µm) with acetonitrile and 0.1% formic acid aqueous solution as the mobile phases. The detection was performed using multiple-reaction monitoring with electrospray ionization source in positive-negative ion mode. The calibration curves showed good linearity (r ≥ 0.9955). The lower limit of quantification (LLOQ) was 5 ng/mL for wogonin and schisandrin, 10 ng/mL for oroxylin A and emodin, and 15 ng/mL for paeoniflorin, respectively. The relative standard deviations of intraday and interday precisions were <11.49 and 14.28%, respectively. The extraction recoveries and matrix effects were acceptable. The analytes were stable under the experiment conditions. The validated method has been successfully applied to pharmacokinetic studies of the five compounds in rats after oral administration of Hu-gan-kan-kang-yuan capsule. This paper would be a valuable reference for pharmacokinetic studies of Chinese medicine preparations containing the five compounds.

Effect of foxtail millet protein hydrolysates on lowering blood pressure in spontaneously hypertensive rats.

PURPOSE: The objective of this study was to determine the effect of foxtail millet protein hydrolysates on lowering blood pressure in spontaneously hypertensive rats (SHRs). METHODS: The protein of foxtail millet after extruding or fermenting and the raw foxtail millet was extracted and hydrolyzed by digestive protease to generate angiotensin-converting enzyme (ACE) inhibitory peptides. The potential antihypertensive effect of protein hydrolysates from foxtail millet in SHRs was investigated. RESULTS: After 4 weeks of treatment with 200 mg peptides/kg of body weight of protein hydrolysates, blood pressure was lowered significantly, and the raw and extruded samples were more effective than the fermented samples. The serum ACE activity and angiotensin II levels in the treatment groups were significantly lower than that of the control. The percent heart weight decreased in the treatment groups. CONCLUSION: Thus, ingestion of foxtail millet protein hydrolysates especially for the raw and extruded hydrolysates may ameliorate hypertension and alleviate related cardiovascular diseases.

Developing an Absorption-Based Quality Control Method for Hu-Gan-Kang-Yuan Capsules by UFLC-QTOF-MS/MS Screening and HPLC-DAD Quantitative Determination.

Traditional Chinese Medicine Preparations (TCMPs) contain massive numbers of ingredients responsible for their multiple efficacies. An absorption-based quality control method for complicated TCMPs using Hu-gan-kang-yuan Capsule (HGKYC) as an example was developed. To select proper chemical markers for quality control of HGKYC, an ultra-fast liquid chromatography (UFLC) coupled with electrospray ionization quadrupole time-off light mass spectrometry (UFLC-QTOF-MS/MS) method was used for the rapid separation and structural identification of the constituents in the HGKYC extract and the rat serum after oral administration of HGKYC. As a result, one hundred and seven prototype constituents including flavonoids, organic acid, phenylpropanoids, anthraquinones, saponins, alkaloids, terpenes, phenols and amino acids in HGKYC extract, and 43 compounds found in rat serum after oral administration of HGKYC were unambiguously identified or tentatively characterized by comparing retention times and MS information with those of authentic standards or available literature references. Finally, a simple, low-cost and effective method of simultaneous determination for baicalein, wogonin, paeonol and emodin in HGKYC was developed using high performance liquid chromatography coupled with a diode array detector. In conclusion, an absorption-based quality control pattern was developed and successfully used for evaluating HGKYC.

[Influence of Qingdai compound on expression of bcr/abl and JWA in K562 cells].

To study the effects of Qingdai compound on proliferation and apoptosis of K562 cells, as well as the expression of bcr/abl and JWA mRNA, K562 cells were treated in culture with different concentrations of Qingdai compound (2.5, 5, 7.5, 10 and 20 mg/ml) and harvested at 24 hours. Then morphological changes were observed by light microscopy (LM); expressions of bcr/abl and JWA were detected with semi-quantitative RT-PCR. The results showed that morphological changes were observed as the increment of the Qingdai compound concentration. Inhibition effects on proliferation and apoptosis in K562 cells were seen. A concentration-dependent decreases were found in bcr-abl and JWA mRNA expression of K562 cells. Qingdai compound partially inhibited proliferation and induced apoptosis of K562 cells. Expressions of both bcr/abl and JWA, which took part in cell proliferation and apoptosis, were down-regulated in a dose dependent manner. In conclusion, Qingdai compound can partially inhibit the expressions of bcr/abl and JWA genes in K562 cells, and the clinical effect of Qingdai compound on CML may be associated with apoptosis of leukemic cells.