The anti-colorectal cancer effect and metabolites of Agrimonia pilosa Ledeb.

ETHNOPHARMACOLOGICAL RELEVANCE: Agrimonia pilosa Ledeb. (Rosaceae, A. pilosa) has been used in traditional medicine in China, Japan, Korea, and other Asian countries for treatment of acute and chronic enteritis and diarrhea. Secondary metabolites have been isolated and tested for biological activities. It remains unclear in terms of its potential components of anti-colorectal cancer properties. AIM OF THE STUDY: The study aimed to how extracts from A. pilosa and their components influenced tumor microenvironment and the colorectal tumor growth in vivo on AOM/DSS induced colorectal cancer mice, the metabolites of A. pilosa was also been studied. MATERIALS AND METHODS: Different methods have been used to extract different parts of A. pilosa. And the anti-proliferation effect of these extracts on colon cancer cells have been tested. The components of A. pilosa and its metabolites in vivo were analyzed by UPLC-QTOF-MS/MS. The anti-colorectal cancer (CRC) effects of A. pilosa and its components in vivo were studied on AOM/DSS induced CRC mice. The effects of constituents of A. pilosa on the composition of immune cells in tumor microenvironment (TME) were analyzed by flow cytometry. 16 S rDNA technology was used to analyze the effect of administration on the composition of intestinal microflora. Pathological section staining was used to compare the morphological changes and molecular expression of intestinal tissue in different groups. RESULTS: The constituent exists in root of A. pilosa showed the strongest anti-proliferation ability on colon cancer cells in vitro. The extract from the root of A. pilosa could attenuate the occurrence of colorectal tumors induced by AOM/DSS in a concentration-dependent manner. Administration of the extract from the root of A. pilosa could affect the proportion of γδT cells, tumor associated macrophages and myeloid derived suppressor cells in TME, increasing the proportion of anti-tumor immune cells and decrease the immunosuppressive cells in the TME to promote the anti-tumor immune response. The administration of the extract adjusted the composition of gut microbiota and its components Agrimoniin and Agrimonolide-6-o-glucoside showed the strongest anti-CRC effect in vivo with adjusting the gut microbiota differently. CONCLUSIONS: The extract from root of A. pilosa showed anti-colorectal cancer effects in vivo and in vitro, affecting the composition of gut microbiota and the anti-tumor immune response. Within all components of A. pilosa, Agrimoniin and Agrimonolide-6-o-glucoside showed remarkable anti-CRC efficiency in vivo and in vitro. Besides, the metabolites of extract from root of A. pilosa in gastrointestinal tract mainly composed of two parts: Agrimonolide-related metabolites and Urolithins. The extract from root of A. pilosa could contribute to potential drugs for assisting clinical anti-colon cancer therapy.

Plastrum testudinis Ameliorates Oxidative Stress in Nucleus Pulposus Cells via Downregulating the TNF-α Signaling Pathway.

BackgroundPlastrum testudinis (PT), a widely used traditional Chinese medicine, exerts protective effects against bone diseases such as intervertebral disc degeneration (IDD). Despite its effectiveness, the molecular mechanisms underlying the effects of PT on IDD remain unclear. Methods In this study, we used a comprehensive strategy combining bioinformatic analysis with experimental verification to investigate the possible molecular mechanisms of PT against IDD. We retrieved targets for PT and IDD, and then used their overlapped targets for protein-protein interaction (PPI) analysis. In addition, we used Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses to investigate the anti-IDD mechanisms of PT. Moreover, in vivo and in vitro experiment validations including hematoxylin-eosin (HE) and safranine O-green staining, senescence-associated ß-galactosidase (SA-ß-gal) assay, cell immunofluorescence staining, intracellular ROS measurement and Western blot analysis were performed to verify bioinformatics findings. Results We identified 342 and 872 PT- and IDD-related targets (32 overlapping targets). GO enrichment analysis yielded 450 terms related to oxidative stress and inflammatory response regulation. KEGG analysis identified 48 signaling pathways, 10 of which were significant; the TNF-α signaling pathway had the highest p-value, and prostaglandin G/H synthase 2 (PTGS2), endothelin-1 (EDN1), TNF-α, JUN and FOS were enriched in this pathway. Histopathological results and safranin O/green staining demonstrated that PT attenuated IDD, and SA-ß-gal assay showed that PT ameliorated nucleus pulposus cell (NPC) senescence. An ROS probe was adopted to confirm the protective effect of PT against oxidative stress. Western blot analyses confirmed that PT downregulated the protein expression of PTGS2, EDN1, TNF-α, JUN and FOS in the TNF-α signaling pathway as well as cellular senescence marker p16, proinflammatory cytokine interleukin-6 (IL6), while PT upregulated the expression of NPC-specific markers including COL2A1 and ACAN in a concentration-dependent manner. Conclusions To the best of our knowledge, this study is the first to report that PT alleviates IDD by downregulating the protein expression of PTGS2, EDN1, TNF-α, JUN and FOS in the TNF-α signaling pathway and upregulating that of COL2A1 and ACAN, thus suppressing inflammatory responses and oxidative stress in NPCs.

Peptide photowrapping of gold-silica nanocomposites for constructing MMP-responsive drug capsules for chemo-photothermal therapy.

A multifunctional undecapeptide, YYDPLGLADYY, was designed and synthesized for the photowrapping of silica-coated gold nanorods. The obtained nanocapsules, bearing a well-defined core-shell structure, were able to encapsulate a therapeutic drug, respond to an MMP-upregulated tumor microenvironment, and achieve NIR-triggered anticancer chemo-photothermal therapy with favorable efficacy.

[Energy and nutrients intake from complementary foods of children aged 6-23 months in China in 2019-2021].

OBJECTIVE: To describe the energy and nutrients intake from complementary foods of children aged 6-23 months in different areas of China. METHODS: The data was from the National Special Program for Science & Technology Basic Resources Investigation-China Children's Nutrition and Health System Survey and Application of 0-18 Years Old Children. Children aged 6-23 months(n=546) were included in the current study. Demographic characteristics, socioeconomic status and birth status were collected through questionnaire survey. We used 24-hour weighted dietary record method to collect the intake of complementary foods. Energy, protein, fat, carbohydrate, calcium, iron, zinc, selenium, potassium, vitamin A, vitamin B_1, vitamin B_2 and vitamin C intakes were calculated by using Chinese Food Composition Database. RESULTS: For children aged 6-8 months, 9-11 months, 12-17 months and 18-23 months, the energy intake from complementary foods was 156.1, 258.0, 388.7 and 581.1 kcal, respectively. The protein intake was 5.1, 10.1, 15.0 and 21.7 g, respectively. The fat intake was 3.3, 6.7, 9.5 and 15.9 g, respectively. The calcium intake was 38.7, 54.8, 78.6 and 106.9 mg, respectively. The iron intake was 1.3, 2.2, 3.5 and 5.3 mg, respectively. The zinc intake was 0.7, 1.4, 2.0 and 2.9 mg, respectively. The vitamin A intake was 83.7, 100.3, 157.4 and 180.4 µgRAE, respectively. The vitamin B_1 intake was 0.1, 0.2, 0.2 and 0.3 mg, respectively. The vitamin B_2 intake was 0.1, 0.1, 0.2 and 0.3 mg, respectively. The vitamin C intake was 1.8, 6.3, 9.5 and 19.2 mg, respectively. Compared with the World Health Organization recommended value of nutrients density, the density of protein from complementary foods for children aged 6-23 months was higher(2.6-3.8 mg/100 kcal vs.0.9-1.0 mg/100 kcal). The density of iron(1.0, 0.9 mg/100 kcal vs.4.5, 3.0 mg/100 kcal) and zinc(0.5, 0.5 mg/100 kcal vs.1.6, 1.1 mg/100 kcal) was lower for children aged 6-8 months and 9-11 months, respectively. CONCLUSION: The main issues of complementary food for children in China were high protein for children aged 6-23 months and low iron and zinc for infants aged 6-11 months.

[Dietary micronutrient intake of children aged 2-5 years in China in 2019-2021].

OBJECTIVE: To describe dietary intake of calcium, iron, zinc, selenium, vitamin A, vitamin B_1, vitamin B_2 and vitamin C and compare the intake between urban and rural areas among preschool children aged 2-5 years based on the data from the National Nutrition and Health Systematic Survey for Children 0-17 Years of Age in China. METHODS: Children from 14 provinces were selected by multi-stage stratified random cluster sampling, and the dietary data of preschool children aged 2-5 years were recorded using the 3 day 24-hour weighted food records method. SAS 9.4 was used to calculate dietary intake of these micronutrients based on the Chinese Food Composition Table and to compare the intake between urban and rural areas. The risk of insufficient or excessive intake of micronutrients among Chinese children aged 2-5 years was assessed according to the Chinese Dietary Reference Intakes(DRIs) 2013 edition. RESULTS: A total of 820 children aged 2 to 5 years were selected. The median daily dietary calcium intake of children aged 2-5 years in China was 433.7, 338.9, 356.4 and 347.4 mg, respectively. The median daily dietary intake of vitamin B_1 of children aged 2-5 years was 0.5 mg for all age groups. The median daily dietary vitamin B_2 intake of children aged 2-5 years was 0.7, 0.6, 0.6 and 0.6 mg, respectively. The median daily dietary intake of vitamin C of children aged 2-5 years was 37.9, 37.4, 44.0 and 40.0 mg, respectively. The median daily dietary selenium intake of children aged 2-5 years was 17.1, 20.5, 22.7 and 22.3 µg, respectively. Dietary calcium intake for aged 2-5 years, dietary vitamin B_2 intake for aged 2-4 years, dietary iron, selenium, zinc and vitamin B_1 intake for aged 2-3 years was significantly greater in urban children than rural children. Among all nutrients, the proportion of dietary calcium intakes below the estimated average requirement(EAR) was the highest in aged 2-5 years(61.4%, 76.4%, 91.4% and 91.5%, respectively). The proportions of dietary vitamin B_1, vitamin C and selenium intake lower than EAR of children aged 2-5 years in China were 52.4%-63.2%, 42.8%-50.2% and 46.6%-58.7%, respectively. COUCLUSION: The dietary calcium intake of children aged 2-5 years in China remains insufficient for these children, especially for rural children. Dietary vitamin B_1, vitamin C and selenium intake should be improved.

Research on the Mechanism of Kaempferol for Treating Senile Osteoporosis by Network Pharmacology and Molecular Docking.

Kaempferol (KP), as a natural anti-inflammatory compound, has been reported to have curative effects on alleviating senile osteoporosis (SOP), which is an inflammation-related musculoskeletal disease, but the molecular mechanisms remain unclear due to scanty relevant studies. We predicted the targets of KP and SOP, and the common targets of them were subsequently used to carry out PPI analysis. Moreover, we adopted GO and KEGG enrichment analysis and molecular docking to explore potential mechanisms of KP against SOP. There were totally 152 KP-related targets and 978 SOP-related targets, and their overlapped targets comprised 68 intersection targets. GO enrichment analysis showed 1529 biological processes (p < 0.05), which involved regulation of inflammatory response, oxidative stress, regulation of bone resorption and remodeling, osteoblast and osteoclast differentiation, etc. Moreover, KEGG analysis revealed 146 items including 44 signaling pathways (p < 0.05), which were closely linked to TNF, IL-17, NF-kappa B, PI3K-Akt, MAPK, estrogen, p53, prolactin, VEGF, and HIF-1 signaling pathways. By means of molecular docking, we found that kaempferol is bound with the key targets' active pockets through some connections such as hydrogen bond, pi-alkyl, pi-sigma, pi-pi Stacked, pi-pi T-shaped, and van der Waals, illustrating that kaempferol has close combination with the key targets. Collectively, various targets and pathways involve in the process of kaempferol treatment against SOP through regulating inflammatory response, oxidative stress, bone homeostasis, etc. Moreover, our study first reported that kaempferol may regulate core targets' expression with involvement of inflammatory response, oxidative stress, and bone homeostasis, thus treating SOP.

Network Pharmacology Integrated with Molecular Docking Explores the Mechanisms of Naringin against Osteoporotic Fracture by Regulating Oxidative Stress.

Naringin (NG), as the most abundant component of Drynariae Rhizoma (Chinese name: Gusuibu), has been proved to be an antioxidant flavonoid on promoting osteoporotic fracture (OF) healing, but relevant research is scanty on the underlying mechanisms. We adopted target prediction, protein-protein interaction (PPI) analysis, Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and molecular docking to establish a system pharmacology database of NG against OF. Totally 105 targets of naringin were obtained, including 26 common targets with OF. A total of 415 entries were obtained through GO Biological Process enrichment analysis (P < 0.05), and 37 entries were obtained through KEGG pathway enrichment analysis with seven signaling pathways included (P < 0.05), which were primarily concerned with p53, IL-17, TNF, estrogen, and PPAR signaling pathways. According to the results of molecular docking, naringin is all bound in the active pockets of the core targets with 3-9 hydrogen bonds through some connections such as hydrophobic interactions, Pi-Pi stacked interactions, and salt bridge, demonstrating that naringin binds tightly to the core targets. In general, naringin may treat OF through multiple targets and multiple pathways via regulating oxidative stress, etc. Notably, it is first reported that NG may regulate osteoclast differentiation and oxidative stress through the expression of the core targets so as to treat OF.

Network pharmacology integrated with experimental validation reveals the regulatory mechanism of plastrum testudinis in treating senile osteoporosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Plastrum testudinis (PT) has been used in traditional Chinese medicine to treat bone diseases such as senile osteoporosis (SOP) for thousands of years. However, the underlying mechanisms remain largely unknown. AIM OF THE STUDY: This study aims to investigate the possible molecular mechanism of PT in the treatment of SOP using an integrated strategy of network pharmacology and experimental validation. MATERIALS AND METHODS: The compounds of PT and its targets were identified through the BATMAN-TCM database. The SOP-related targets were retrieved from the GeneCards database. Protein-protein interaction information was obtained by inputting the intersection targets into the STRING database. Cytoscape software was used to construct a protein-protein interaction network and a PT-compound-target-SOP network. Using Cytoscape and R software, we conducted GO function and KEGG pathway enrichment analyses. We also conducted in vivo and in vitro experiments to verify the network pharmacology findings. RESULTS: In total, 6 active compounds and 342 targets of PT were screened, of which 57 common targets were related to SOP. The GO biological process enrichment analysis identified 880 entries, mainly relating to the regulation of hormone response, the cell apoptotic process, the apoptotic signaling pathway, NF-kappaB transcription factor activity, fatty acid transportation, osteoclast differentiation, macrophage activation, and inflammatory response. The KEGG pathway enrichment analysis identified 52 entries, including 14 related signaling pathways, which mainly involved the TNF, MAPK, IL-17, AGE-RAGE, estrogen, relaxin, and other signaling pathways. Our in vivo experiments confirmed that PT alleviates SOP, while the in vitro experiments demonstrated that PT exerts a suppressive effect on osteoclast differentiation and bone resorption in a concentration-dependent manner. Furthermore, we observed that PT downregulates the expression of osteoclast-specific genes, including C-FOS, TNF, and BDNF, in the MAPK signaling pathway. CONCLUSION: Through network pharmacology and experimental validation, this study is the first to report that PT downregulates the expression of osteoclast-specific genes, including C-FOS, TNF, and BDNF, in the MAPK signaling pathway, thus exerting a suppressive effect on osteoclast differentiation and bone resorption, which may be the molecular mechanism for PT treatment of SOP.

Plastrum testudinis extract suppresses osteoclast differentiation via the NF-κB signaling pathway and ameliorates senile osteoporosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Plastrum testudinis (PT) is a kind of single traditional Chinese medicine that can tonify kidney and strengthen bone. Plastrum testudinis extract (PTE) has been approved to promote the osteogenic differentiation of bone marrow-derived mesenchymal stem cells in vitro. However, the mechanism by which PTE reduces osteoclast differentiation has not yet been reported. AIM OF THE STUDY: To explore the potential of PTE as a therapeutic treatment for bone loss caused by senile osteoporosis (SOP). MATERIALS AND METHODS: We evaluated whether PTE could inhibit RANKL-induced osteoclast differentiation both in vitro and in vivo, and investigated PTE-induced phenotypes of human peripheral blood monocytes. RESULTS: We found that PTE inhibited osteoclast differentiation and bone resorption in vitro in a concentration-dependent manner and that PTE treatment is most effective during the early stages of osteoclastogenesis. Moreover, we found that PTE could block the NF-κB signaling pathway in vitro, leading to the down-regulation of osteoclast-specific genes including C-FOS and NFATC1. The results from our in vivo mouse study suggest that PTE treatment suppresses osteoclast formation and mitigates bone loss caused by SOP. Notably, we also found that PTE inhibited RANKL-induced osteoclast differentiation in human peripheral blood monocytes. CONCLUSION: Our results suggest that PTE treatment suppresses osteoclastogenesis and ameliorates bone loss caused by SOP by selectively blocking the nuclear translocation of NF-κB/p50.

The emerging role of miR-128 in musculoskeletal diseases.

MicroRNA-128 (miR-128) is associated with cell proliferation, differentiation, migration, apoptosis, and survival. Genetic analysis studies have demonstrated that miR-128 participates in bone metabolism, which involves bone marrow-derived mesenchymal stem cells, osteoblasts, osteoclasts, and adipocytes. miR-128 also participates in regeneration of skeletal muscles by targeting myoblast-associated proteins. The deregulation of miR-128 could lead to a series of musculoskeletal diseases. In this review, we discuss recent findings of miR-128 in relation to bone metabolism and muscle regeneration to determine its potential therapeutic effects in musculoskeletal diseases, and to propose directions for future research in this significant field.

Jingui Shenqi Pills Regulate Bone-Fat Balance in Murine Ovariectomy-Induced Osteoporosis with Kidney Yang Deficiency.

Jingui Shenqi Pills (JGSQP) have been a staple of traditional Chinese medicine for thousands of years, used primarily as a treatment for kidney yang deficiency (KYD). In vitro analyses of JGSQP revealed strong induction of osteogenic differentiation and inhibition of adipogenic differentiation in bone-marrow-derived mesenchymal stem/stromal cells. However, the mechanisms by which JGSQP regulate the bone-fat balance in murine ovariectomy-induced osteoporosis with KYD have not been reported. Materials and Methods. Two-month-old female C57BL/6 mice were divided randomly into three groups: those receiving a sham operation (Sham); those undergoing bilateral ovariectomy and selection of KYD syndrome (Model); and those subjected to both bilateral ovariectomy and KYD syndrome selection for 8 weeks, followed by JGSQP treatment for 4 weeks (JGSQP). In the Sham and Model groups, mice were given the same dose of distilled water orally for 4 weeks. Animals from all three groups were euthanised at the 12th week. Vertebral microarchitecture and histomorphology were examined by micro-CT and H&E staining, respectively. In addition, we examined the mRNA expression of Akt, Wnt10b, Osterix (Osx), Fndc5, PPARγ, and Fabp4, as well as the protein of AKT, phosphorylation-AKT (p-AKT), BMP2, COL1A1, and FNDC5. Results. JGSQP treatment improved bone microarchitecture and mitigated histomorphological damage relative to the Model group. The osteoblast number (Ob.N/BS) and area (Ob.S/BS) were increased, whereas adipocyte number (adipocyte/tissue area) and area (adipocyte area/tissue area) were decreased in the JGSQP group. JGSQP treatment reduced the mRNA expression of Akt and adipogenesis-related genes (Fndc5, PPARγ, and Fabp4) while promoting osteogenesis-related genes (Wnt10b and Osx) mRNA expression. Additionally, the expression of p-AKT, BMP2, and COL1A1 proteins was increased and FNDC5 protein expression was decreased after JGSQP treatment. Conclusions. JGSQP treatment reversed murine ovariectomy-induced osteoporosis with KYD by controlling bone-fat balance via AKT pathway.

Antioxidant and Cytotoxic Activities of Distillates Purified by Means of Molecular Distillation from Ginger Extract Obtained with Supercritical CO2 Fluid.

The ginger extract obtained with supercritical CO2 fluid was purified by molecular distillation (MD), and the chemical compositions, antioxidant and cytotoxic activities of ginger extract and its distillates were investigated. Analysis revealed that the ginger extract was rich in terpene hydrocarbons, along with oxygenated terpenes and other non-volatile compounds. The MD distillates were prepared in a series of stages and the active compounds like terpenes and gingerols could be separated by MD. The major compounds of the distillates purified by MD at 40 °C, 80 Pa and 60 °C, 80 Pa were terpene hydrocarbons. Additional distillates obtained by MD at 80 °C, 80 Pa and 100 °C, 60 Pa were predominated by terpene hydrocarbons and oxygenated terpenes. Until the operating conditions of MD reached 150 °C and 2 Pa, some non-volatile compounds were concentrated in the final distillate. Moreover, antioxidant activities and the cytotoxic effects on three human cancer cells in final MD distillate were superior to other extracts, and this phenomenon could be mainly supported by the phenols. The MD could be used to prepare ginger distillates with better antioxidant and cytotoxic activities.

Preparative isolation and purification of steroidal glycoalkaloid from the ripe berries of Solanum nigrum L. by preparative HPLC-MS and UHPLC-TOF-MS/MS and its anti-non-small cell lung tumors effects in vitro and in vivo.

Overcoming epidermal growth factor receptor resistance is a critical problem that needs to be solved in clinical practice. Drugs that downregulate the fatty acid synthase-epidermal growth factor receptor will become novel treatments for non-small cell lung cancer. Solanum nigrum, extracted with water at 4°C, shows strong cytotoxic activity and inhibits tumor growth in Lewis tumor bearing-mice in a dose-dependent manner. A novel active compound in S. nigrum, solaoiacid, was successfully separated and purified from S. nigrum by preparative high-performance liquid chromatography with mass spectrometry and ultra high performance liquid chromatography with time-of-flight tandem mass spectrometry. The IC50 of solaoiacid on lung cancer cells was 2.3 µmol/L, which was significantly lower than that of the known steroidal glycoalkaloid. Label-free proteomics and STRING Network analysis were used to identify significantly deregulated proteins in lung cancer cells that were treated with the fresh ripe fruit extracts of S. nigrum. S. nigrum regulates multiple signal pathways, including the epidermal growth factor receptor pathway. S. nigrum downregulated 24 main proteins with direct roles in fatty acid biosynthesis. Both S. nigrum and solaoiacid showed strong downregulation of the fatty acid synthase-epidermal growth factor receptor and anti-non-small cell lung cancer effects, and thus will become a novel drug for the treatment of non-small cell lung cancer.

Effect of Plastrum Testudinis Extracts on the Proliferation and Osteogenic Differentiation of rBMSCs by Regulating p38 MAPK-Related Genes.

Extracts from plastrum testudinis (PTE) are active compounds that have been used to treat bone diseases in traditional Chinese medicine for thousands of years. In previous studies, we demonstrated their effects on glucocorticoid-induced osteoporosis both in vivo and in vitro. However, the mechanisms by which PTE regulates the osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells (rBMSCs) in vitro remain poorly understood. In this study, rBMSCs were treated with medium (CON), PTE, osteogenic induction (OI), and a combination of PTE and OI (PTE+OI) over a 21-day period. We found that PTE significantly promoted rBMSCs osteogenic differentiation and mineralisation after 21 days of culturing. Moreover, PTE+OI further enhanced the differentiation and mineralisation process. PTE upregulated STE20, IGF1R, and p38 MAPK mRNA expression and downregulated TRAF6 mRNA expression. The extracts inhibited TRAF6 protein expression and promoted STE20, IGF1R, and phosphorylated p38 MAPK protein expression. Our results imply that PTE promotes the proliferation and osteogenic differentiation of rBMSCs by upregulating p38 MAPK, STE20, and IGF1R and downregulating TRAF6 expression, which may provide experimental evidence of the potential of PTE in the treatment of osteoporosis.

The associations between plasma phytoestrogens concentration and metabolic syndrome risks in Chinese population.

Metabolic syndrome (MetS) has become an important issue in the healthcare systems of both developed and developing countries. Phytoestrogens have shown estrogenic effects, which may involve in the etiology of MetS. The current study consisted of 293 MetS cases and 264 healthy controls. The concentrations of seven plasma phytoestrogens (daidzein, genistein, glycitein, equol, enterolactone, enterodiol and coumestrol) were detected by UPLC-MS/MS. Adjusted unconditional logistic regression was used to assess the associations between plasma phytoestrogens concentration and risks of MetS, as well as the associations between plasma phytoestrogens concentration and MetS components. Linear regression was used to evaluate the associations between equol concentration in equol-producers and MetS components. Higher concentrations of total isoflavone and equol were associated with decreased risk of MetS. The equol concentration was negatively associated with waist circumference and positively associated with HDL-C level. Increased daidzein was associated with both lower waist circumference and lower fasting blood glucose levels. Our results suggested that higher plasma total isoflavone, equol and daidzein might decrease MetS risk.

[Determination of 1, 2, 3, 4, 6-penta-O-galloyl-D-glucose in forty four kinds of Chinese traditional medicines by HPLC].

OBJECTIVE: To determine 1, 2, 3, 4, 6-penta-O-galloyl-D-glucose (PGG) in forty four kinds of Chinese traditional medicines by HPLC. METHOD: The PGG was extracted with a solvent consisting of ethanol and water (50:50) in ultrasonic bath at 50-60 degrees C for 1 hour. A Diamonsil C18 column (4.6 mm x 250 mm, 5 microm) was used for the separation and analysis of PGG with a mobile phase consisting of acetonitrile and 2. 5 % acetic acid solution (18:82). The wavelength of detection was at 280 nm, and flow rate was set at 1.0 mL min(-1). RESULT: The calibration curve for PGG is linear over the range of 1-150 microg mL(-1) (r =0.9994), and PGG was found in seventeen kinds of Chinese traditional medicines, such as gall tree peony bark, red peony root, white peony root, and so on. CONCLUSION: The contents of PGG were determined in forty four kinds of Chinese traditional medicines by a rapid and precision HPLC method.

The novel inhibitory effect of Pangdahai on fatty acid synthase.

Recently, animal fatty acid synthase (FASN) is reported as a potential therapeutic target for obesity and cancer. Considerable interest has been developed in searching for novel inhibitors of this enzyme. An extract from Pangdahai has been found to inhibit FASN in both reversible and irreversible manners, with an IC(50) of 3.5 microg/ml and an apparent inactivation rate constant of k(obs) of 2.2 x 10(-3)/min. The kinetic study showed that the Pangdahai extract inhibited the overall FASN reaction uncompetitively with acetyl-CoA, but it presented in a mixed manner both with NADPH and with malonyl-CoA. Its major reacting site on this enzyme, as compared between two IC(50) values, is not in the beta-ketoacyl reduction domain. A weight reducing experiment in rats showed that the extract significantly reduced the adipose and food intake, but in view of statistics (P < 0.05), a correlation between the reductions in the adipose and in the food consumption and the inhibition of hepatic FASN could not be established. Three known flavonoid compounds were isolated from the extract and the structure-activity relationship was discussed.

The antibacterial efficacy of an aceraceous plant [Shantung maple (Acer truncatum Bunge)] may be related to inhibition of bacterial beta-oxoacyl-acyl carrier protein reductase (FabG).

Polyphenols, including flavonoids, are the major components of the extracts from aceraceous plants. They possess remarkable antibacterial and antitumour activity. Our study focused on whether the inhibition of the bacterial type II fatty acid synthesis system is the mechanism for the antibacterial effect of the related plant polyphenols. Extracts obtained from the fallen leaves of the Shantung maple (Acer truncatum Bunge) using different solvents, and the related pure compound PGG (1,2,3,4,6-penta-O-galloyl-beta-D-glucose), potently inhibited the FabG (beta-oxoacyl-ACP reductase) steps in the fatty-acid-elongation cycle with the IC(50) values between 0.9 and 7.2 microg/ml. An ethyl acetate extract appeared to inhibit FabG reductase in a mixed manner with NADPH, as did PGG with NADPH, demonstrating that they interfered with the binding of the cofactor to the enzyme. Gram-positive and Gram-negative bacteria and some fungi were used to evaluate the antibacterial abilities of different extract samples. The experiments showed that a higher polyphenol content of the extracts led to a more potent inhibitory capacity against FabG, thus enhancing the antibacterial efficacy.

Evaluation of the inhibitory activities of aceraceous plants on fatty acid synthase.

Fatty acid synthase (FAS) is a very significant lipogenic enzyme participating in energy metabolism in vivo and has been reported as a potential new therapeutic target for cancer treatment. The extracts from sixteen Aceraceae were prepared to assay their inhibitory activities against duck liver FAS and their correlated antitumor bioactivity. Their inhibition of FAS was composed of a reversible fast-binding inhibition, by which 0.41 microg/mL of the A. campestre extract inhibits 50% FAS activity, and an irreversible slow-binding inhibition with inactivation rate constants, k(obs), ranging between 1.5 x 10(-3) and 10.6 x 10(-3) min(-1). Three Aceraceae extracts were selected from their smaller IC50 values to study different type of inhibitions against the three substrates in the FAS overall reaction. As compared with other reported FAS inhibitors including EGCG with regard to inhibition constant and IC50 value, the extracts appeared to be more efficient inhibitors, and exhibited a considerable inhibition against the growth of five types of cancer cells (China patent application number 200610088901.6), which may be related to the inhibition of lipogenesis in these cells.

The extract of leaves of Acer truncatum Bunge: A natural inhibitor of fatty acid synthase with antitumor activity.

Fatty acid synthase (FAS) has been identified as a potential antitumor target. The extract from the leaves of Acer truncatum Bunge (Extr) was prepared to assay its inhibitory activity against FAS, which was isolated from duck liver, and the correlated antitumor bioactivity. Its inhibition of FAS is composed of reversible fast-binding inhibition, IC50 = 0.7 microg/ml, and irreversible slow-binding inhibition following saturation kinetics with a dissociation constant of 0.68 microg/ml and a limiting rate constant of 0.0288 min(-1). The Extr exhibited different type of inhibitions against the three substrates in the FAS overall reaction. Compared with EGCG in inhibition constant and IC50 value, the Extr appeared to be a more efficient inhibitor, and exhibited a considerable inhibition against the growth of four kinds of cancer cells (patent application number 200510068054.2). It was infered that the inhibitory activity is likely attributable to the co-operative effect of the components.