Red cabbage microgreen modulation of gut microbiota is associated with attenuation of diet-induced obesity risk factors in a mouse model.

Cruciferous vegetable microgreens, such as red cabbage microgreens (RCMG), are of special interest due to their well-documented health-promoting effects compared to their mature counterparts. However, little is known of the biological effects of microgreens. The present study used a rodent diet-induced obesity model to investigate the effect of consuming RCMG on the gut microbiota. We found that the consumption of RCMG exerted profound impacts on the microbial composition in mice. Specifically, the species diversity of mice on both low fat (LF) and high fat (HF) diets was significantly increased by the consumption of RCMG. In comparison with the LF control group, the intake of RCMG increased the gut Firmicutes/Bacteroidetes (F/B) ratio. Furthermore, an unidentified species of the Clostridiales order, increased by RCMG, was found to be negatively correlated with the hepatic cholesterol ester level in mice (r = -0.43, p < 0.05). In addition, RCMG significantly inhibited HF diet-induced elevation of the genus AF12, of which the abundance was positively correlated with the body weight gain (r = 0.52, p < 0.01) and fecal bile acid in mice (r = 0.59, p < 0.01). Overall, our results demonstrated that the consumption of RCMG in the diet can alter the gut microbiota, and attenuation of HF diet-induced body weight gain and altered cholesterol metabolism may be mediated through regulation of the gut microbiota.

Red Cabbage Modulates Composition and Co-Occurrence Networks of Gut Microbiota in a Rodent Diet-Induced Obesity Model.

Red cabbage (RC), a cruciferous vegetable rich in various bioactive substances, can significantly reduce the risk factors of several non-communicable diseases, but the mechanism underlying the biological effects of RC remains unclear. Furthermore, mechanisms that operate through the regulation of gut microbiota also are not known. Given the relationships between diet, gut microbiota, and health, a diet-induced mice obesity model was used to elucidate the influence of RC on gut microbial composition and bacteria-bacteria interactions in mice. After 24 h of dietary intervention, a high-fat (HF) diet with the intake of RC led to increased Firmicutes/Bacteroidetes (F/B) ratios in the feces of mice. RC also reduced the relative abundance of Bifidobacteria, Lactobacillus, and Akkermansia muciniphila in mice fed a low-fat (LF) diet. After 8-weeks of dietary intervention, RC significantly changed the structure and the ecological network of the gut microbial community. Particularly, RC inhibited an HF-diet-induced increase in AF12 in mice, and this genus was positively correlated with body weight, low-density lipoprotein level, and fecal bile acid of mice. Unclassified Clostridiales, specifically increased via RC consumption, were also found to negatively correlate with hepatic free cholesterol levels in mice. Overall, our results demonstrated that RC modulating gut microbial composition and interactions are associated with the attenuation of HF-diet-induced body weight gain and altered cholesterol metabolism in mice.

Construction and evaluation of GPC3-targeted immunotoxins as a novel therapeutic modality for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) accounts for ∼90 % of all liver cancer cases, which was the third most common cause of cancer death worldwide in 2020. Glypican-3 (GPC3) is highly and specifically expressed in HCC, which makes it a promising therapeutic target. We discovered novel antibody sequences against GPC3 from a phage display library and ranked the candidates by their binding affinity and epitope bins. Candidates with single- to double-digit nanomolar affinity were selected and expressed in Fab format and linked to a deimmunized bacterial exotoxin moiety via an intein trans-splicing reaction. The resulting immunotoxins were evaluated for their in vitro binding specificity and affinity, cell surface binding on the HepG2 or Huh7, rate of internalization, and potency of cytotoxicity. The immunotoxin called GT5 exhibited strong antigen binding and cell surface binding, as well as high internalization efficiency. The molecule GT5 was further evaluated for cytotoxicity in HepG2 and Huh7 cell-based assay and assessed for its pharmacokinetics and antitumor activity in a murine tumor xenograft model. GT5 significantly inhibited tumor growth and showed stronger potency than the chemotherapeutic drug sorafenib. In conclusion, GT5, a novel GPC3 targeting immunotoxin, was shown to have a high affinity towards GPC3 and effectively inhibit hepatocellular tumor growth in vitro and in vivo, thus providing the basis for further development of GT5 immunotoxin as a novel therapeutic modality for the treatment of liver cancer.

Multifunctional biosensor constructed by Ag-coating magnetic-assisted unique urchin core porous shell structure for dual SERS enhancement, enrichment, and quantitative detection of multi-components inflammatory markers.

The simultaneous, precise, and quantitative detection of multi-components inflammatory markers (IMs) in sepsis serum by surface-enhanced Raman scattering (SERS) remains a challenging problem. A novel, multifunctional biosensor with dual enrichment and enhancement was designed for the ultrasensitive and quantitative analysis of multi-components IMs. The biosensor contains SERS tags-unique urchin core/porous shell (CPS) structure modified with Raman reporters (RaRs), magnetic assist-Ag coated Fe3O4 magnetic nanoparticles (Ag MNPs) modified with internal standard (IS), and then aptamer (Apt) modification to form the sandwich structure (Ag MNPs/IMs/CPS). This multifunctional sensor used for IMS detection has the following innovations: The intensity ratio IRaRs/IIS with Lg CIMs present a good and wide linear relationship to achieve the simultaneous, precise, and quantitative detection of IMS in serum; The detection results display ultrasensitivity, and the limit of detection (LOD) for CRP, IL-6, and PCT is 100 fg/mL, 0.1 fg/mL, and 1.0 fg/mL, which is lower than other detection techniques; The calculated data of clinical blood samples of sepsis by this SERS method is consistent with the hospital results, and can provide more compositional data of IMs. Thus, this combined approach developed a sensing platform for rapid screening, accurate evaluation, early warning, and diagnosis of sepsis.

Triple-Function Au-Ag-Stuffed Nanopancakes for SERS Detection, Discrimination, and Inactivation of Multiple Bacteria.

New strategies combining sensitive pathogenic bacterial detection and high antimicrobial efficacy are urgently desirable. Here, we report smart triple-functional Au-Ag-stuffed nanopancakes (AAS-NPs) exhibiting (1) controllably oxidative Ag-etching thickness for simultaneously obtaining the best surface-enhanced Raman scattering (SERS) enhancement and high Ag-loading antibacterial drug delivery, (2) expressive Ag+-accelerated releasing capability under neutral phosphate-buffered saline (PBS) (pH ∼ 7.4) stimulus and robust antibacterial effectiveness involving sustainable Ag+ release, and (3) three-in-one features combining specific discrimination, sensitive detection, and inactivation of different pathogenic bacteria. Originally, AAS-NPs were synthesized by particle growth of the selective Ag-etched Au@Ag nanoparticles with K3[Fe(CN)6], followed by the formation of an unstable Prussian blue analogue for specifically binding with bacteria through the cyano group. Using specific bacterial "fingerprints" resulting from the introduction of dual-function 4-mercaptophenylboronic acid (4-MPBA, serving as both the SERS tag and internal standard) and a SERS sandwich nanostructure that was made of bacteria/SERS tags/AAS-NPs, three bacteria (E. coli, S. aureus, and P. aeruginosa) were highly sensitively discriminated and detected, with a limit of detection of 7 CFU mL-1. Meanwhile, AAS-NPs killed 99% of 1 × 105 CFU mL-1 bacteria within 60 min under PBS (pH ∼ 7.4) pretreatment. Antibacterial activities of PBS-stimulated AAS-NPs against S. aureus, E. coli, and P. aeruginosa were extraordinarily increased by 64-fold, 72-fold, and 72-fold versus PBS-untreated AAS-NPs, respectively. The multiple functions of PBS-stimulated AAS-NPs were validated by bacterial sensing, inactivation in human blood samples, and bacterial biofilm disruption. Our work exhibits an effective strategy for simultaneous bacterial sensing and inactivation.

Broad ultra-potent neutralization of SARS-CoV-2 variants by monoclonal antibodies specific to the tip of RBD.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) continue to wreak havoc across the globe. Higher transmissibility and immunologic resistance of VOCs bring unprecedented challenges to epidemic extinguishment. Here we describe a monoclonal antibody, 2G1, that neutralizes all current VOCs and has surprising tolerance to mutations adjacent to or within its interaction epitope. Cryo-electron microscopy structure showed that 2G1 bound to the tip of receptor binding domain (RBD) of spike protein with small contact interface but strong hydrophobic effect, which resulted in nanomolar to sub-nanomolar affinities to spike proteins. The epitope of 2G1 on RBD partially overlaps with angiotensin converting enzyme 2 (ACE2) interface, which enables 2G1 to block interaction between RBD and ACE2. The narrow binding epitope but high affinity bestow outstanding therapeutic efficacy upon 2G1 that neutralized VOCs with sub-nanomolar half maximal inhibitory concentration in vitro. In SARS-CoV-2, Beta or Delta variant-challenged transgenic mice and rhesus macaque models, 2G1 protected animals from clinical illness and eliminated viral burden, without serious impact to animal safety. Mutagenesis experiments suggest that 2G1 is potentially capable of dealing with emerging SARS-CoV-2 variants in the future. This report characterized the therapeutic antibodies specific to the tip of spike against SARS-CoV-2 variants and highlights the potential clinical applications as well as for developing vaccine and cocktail therapy.

Transcriptomic Analysis of LNCaP Tumor Xenograft to Elucidate the Components and Mechanisms Contributed by Tumor Environment as Targets for Dietary Prostate Cancer Prevention Studies.

LNCaP athymic xenograft model has been widely used to allow researchers to examine the effects and mechanisms of experimental treatments such as diet and diet-derived cancer preventive and therapeutic compounds on prostate cancer. However, the biological characteristics of human LNCaP cells before/after implanting in athymic mouse and its relevance to clinical human prostate outcomes remain unclear and may dictate interpretation of biological efficacies/mechanisms of diet/diet-derived experimental treatments. In this study, transcriptome profiles and pathways of human prostate LNCaP cells before (in vitro) and after (in vivo) implanting into xenograft mouse were compared using RNA-sequencing technology (RNA-seq) followed by bioinformatic analysis. A shift from androgen-responsive to androgen nonresponsive status was observed when comparing LNCaP xenograft tumor to culture cells. Androgen receptor and aryl-hydrocarbon pathway were found to be inhibited and interleukin-1 (IL-1) mediated pathways contributed to these changes. Coupled with in vitro experiments modeling for androgen exposure, cell-matrix interaction, inflammation, and hypoxia, we identified specific mechanisms that may contribute to the observed changes in genes and pathways. Our results provide critical baseline transcriptomic information for a tumor xenograft model and the tumor environments that might be associated with regulating the progression of the xenograft tumor, which may influence interpretation of diet/diet-derived experimental treatments.

Delineating effect of corn microRNAs and matrix, ingested as whole food, on gut microbiota in a rodent model.

Dietary microRNAs (miRNAs) are thought to regulate a wide range of biological processes, including the gut microbiota. However, it is difficult to separate specific effect(s) of miRNA from that of the food matrix. This study aims to elucidate the specific effect(s) of dietary corn miRNAs, ingested as a whole food, on the gut microbiota. We developed an autoclave procedure to remove 98% of miRNA from corn. A mouse feeding study was conducted comparing autoclaved corn to nonautoclaved corn and purified corn miRNA. Compared to nonspecific nucleotides and corn devoid of miRNAs, feeding purified corn miRNAs or corn to C57BL/6 mice via gavage or diet supplementation for two weeks lead to a decrease in total bacteria in the cecum. The effect appeared to be due to changes in Firmicutes. Additionally, corn matrix minus miRNA and processing also affected gut bacteria. In silico analysis identified corn miRNAs that aligned to Firmicutes genome sequences lending further support to the interaction between corn miRNAs and this bacterium. These data support interactions between plant food miRNA, as well as matrix, and the gut microbiota exist but complex. However, it provides additional support for mechanism by which bioactive dietary components interact with the gut microbiota.

Inhibition of Tumor Growth by Dietary Indole-3-Carbinol in a Prostate Cancer Xenograft Model May Be Associated with Disrupted Gut Microbial Interactions.

Accumulated evidence suggests that the cruciferous vegetables-derived compound indole-3-carbinol (I3C) may protect against prostate cancer, but the precise mechanisms underlying its action remain unclear. This study aimed to verify the hypothesis that the beneficial effect of dietary I3C may be due to its modulatory effect on the gut microbiome of mice. Athymic nude mice (5⁻7 weeks old, male, Balb c/c nu/nu) with established tumor xenografts were fed a basal diet (AIN-93) with or without 1 µmoles I3C/g for 9 weeks. The effects of dietary I3C on gut microbial composition and microbial species interactions were then examined by 16s rRNA gene-based sequencing and co-occurrence network analysis. I3C supplementation significantly inhibited tumor growth (p < 0.0001) and altered the structure of gut microbiome. The abundance of the phylum Deferribacteres, more specifically, Mucispirillum schaedleri, was significantly increased by dietary I3C. Additionally, I3C consumption also changed gut microbial co-occurrence patterns. One of the network modules in the control group, consisting of seven bacteria in family S-27, was positively correlated with tumor size (p < 0.009). Moreover, dietary I3C disrupted microbial interactions and altered this association between specific microbial network and tumor development. Our results unraveled complex relationships among I3C ingestion, gut microbiota, and prostate tumor development and may provide a novel insight into the mechanism for the chemopreventive effect of dietary I3C on prostate cancer.

Extensive Degradation and Low Bioavailability of Orally Consumed Corn miRNAs in Mice.

The current study seeks to resolve the discrepancy in the literature regarding the cross-kingdom transfer of plant microRNAs (miRNAs) into mammals using an improved miRNA processing and detection method. Two studies utilizing C57BL/6 mice were performed. In the first study, mice were fed an AIN-93M diet and gavaged with water, random deoxynucleotide triphosphates (dNTP) or isolated corn miRNAs for two weeks (n = 10 per group). In the second study, mice were fed an AIN-93M diet, or the diet supplemented with 3% fresh or autoclaved corn powder for two weeks (n = 10 per group). Corn miRNA levels were analyzed in blood and tissue samples by real-time PCR (RT-PCR) following periodate oxidation and ß elimination treatments to eliminate artifacts. After removing false positive detections, there were no differences in corn miRNA levels between control and treated groups in cecal, fecal, liver and blood samples. Using an in vitro digestion system, corn miRNAs in AIN-93M diet or in the extracts were found to be extensively degraded. Less than 1% was recovered in the gastrointestinal tract after oral and gastric phases. In conclusion, no evidence of increased levels of corn miRNAs in whole blood or tissues after supplementation of corn miRNAs in the diet was observed in a mouse model.

An improved method to quantitate mature plant microRNA in biological matrices using modified periodate treatment and inclusion of internal controls.

MicroRNAs (miRNAs) ubiquitously exist in microorganisms, plants, and animals, and appear to modulate a wide range of critical biological processes. However, no definitive conclusion has been reached regarding the uptake of exogenous dietary small RNAs into mammalian circulation and organs and cross-kingdom regulation. One of the critical issues is our ability to assess and distinguish the origin of miRNAs. Although periodate oxidation has been used to differentiate mammalian and plant miRNAs, validation of treatment efficiency and the inclusion of proper controls for this method were lacking in previous studies. This study aimed to address: 1) the efficiency of periodate treatment in a plant or mammalian RNA matrix, and 2) the necessity of inclusion of internal controls. We designed and tested spike-in synthetic miRNAs in various plant and mammalian matrices and showed that they can be used as a control for the completion of periodate oxidation. We found that overloading the reaction system with high concentration of RNA resulted in incomplete oxidation of unmethylated miRNA. The abundant miRNAs from soy and corn were analyzed in the plasma, liver, and fecal samples of C57BL/6 mice fed a corn and soy-based chow diet using our improved methodology. The improvement resulted in the elimination of the false positive detection in the liver, and we did not detect plant miRNAs in the mouse plasma or liver samples. In summary, an improved methodology was developed for plant miRNA detection that appears to work well in different sample matrices.

Reversible Toxic Effects of the Dietary Supplement Indole-3-Carbinol in an Immune Compromised Rodent Model: Intestine as the Main Target.

Dietary supplements are widely used in the United States, but the safety issue remains unresolved. Immuno-deficient or immuno-compromised patients, estimated to exceed 10 million in the United States, are known to use dietary supplements. This population potentially may be susceptible to supplements' adverse effects. The cruciferous vegetable-derived indole-3-carbinol (I3C) is known for its possible protective effects against a number of chronic diseases and is commercially available as a dietary supplement. However, the safety of orally consumed I3C in the general population and particularly in immuno-compromised individuals remains unknown. In this study, rodent model of immune-deficient male BALB/c nu/nu athymic mice were given diets supplemented with 0-100 µmoles I3C/g diet for 4 weeks. We found that BALB/c nu/nu mice were not viable after three days on a 100 µmoles I3C/g supplemented diet. Switching to the control diet (without I3C) after first detection of stress resulted in a 75% recovery of mice. Mice fed with 10-50 µmoles I3C/g supplemented diet survived but showed concentration-dependent adverse effects. More importantly, the intestine appeared to be the target of I3C toxicity. Number and width of intestinal villi were significantly altered by I3C, which associated with a dose-dependent reduction in cell proliferation and increase in apoptosis. Other molecular effects observed for I3C include activation of multiple xenobiotic metabolism pathways. This is the first study to report hazardous effects of I3C supplementation that are specific to the gastrointestinal tract in an immuno-compromised model and should serve as a caution in using I3C as dietary supplements.

Preparation of five 3-MCPD fatty acid esters, and the effects of their chemical structures on acute oral toxicity in Swiss mice.

BACKGROUND: 3-monochloro-1, 2-propanediol fatty acid esters (3-MCPDEs) comprise a group of food toxicants formed during food processing. 3-MCPDEs have received increasing attention concerning their potential negative effects on human health. However, reports on the toxicity of 3-MCPD esters are still limited. To determine the effects of fatty acid substitutions on the toxicity of their esters, 1-stearic, 1-oleic, 1-linoleic, 1-linoleic-2-palmitic and 1-palmitic-2-linoleic acid esters of 3-MCPD were synthesized and evaluated with respect to their acute oral toxicities in Swiss mice. RESULTS: 3-MCPDEs were obtained through the reaction of 3-MCPD and fatty acid chlorides, and their purities and structures were characterized by ultraperformance liquid chromatography-quadrupole-time of flight-mass spectrometry (UPLC-Q-TOF-MS), infrared, 1 H and 13 C spectroscopic analyses. Medial lethal doses of 1-stearic, 1-oleic, 1-linoleic, 1-linoleic-2-palmitic and 1-palmitic-2-linoleic acid esters were 2973.8, 2081.4, 2016.3, 5000 and > 5000 mg kg-1 body weight. For the first time, 3-MCPDEs were observed for their toxic effects in the thymus and lung. In addition, major histopathological changes, as well as blood urea nitrogen and creatinine, were examined for mice fed the five 3-MCPDEs. CONCLUSION: The results from the present study suggest that the degree of unsaturation, chain length, number of substitution and relative substitution locations of fatty acids might alter the toxicity of 3-MCPDEs. © 2016 Society of Chemical Industry.

Red Cabbage Microgreens Lower Circulating Low-Density Lipoprotein (LDL), Liver Cholesterol, and Inflammatory Cytokines in Mice Fed a High-Fat Diet.

Cardiovascular disease (CVD) is the leading cause of death in the United States, and hypercholesterolemia is a major risk factor. Population studies, as well as animal and intervention studies, support the consumption of a variety of vegetables as a means to reduce CVD risk through modulation of hypercholesterolemia. Microgreens of a variety of vegetables and herbs have been reported to be more nutrient dense compared to their mature counterparts. However, little is known about the effectiveness of microgreens in affecting lipid and cholesterol levels. The present study used a rodent diet-induced obesity (DIO) model to address this question. C57BL/6NCr mice (n = 60, male, 5 weeks old) were randomly assigned to six feeding groups: (1) low-fat diet; (2) high-fat diet; (3) low-fat diet + 1.09% red cabbage microgreens; (4) low-fat diet + 1.66% mature red cabbage; (5) high-fat diet + 1.09% red cabbage microgreens; (6) high-fat diet + 1.66% mature red cabbage. The animals were on their respective diets for 8 weeks. We found microgreen supplementation attenuated high-fat diet induced weight gain. Moreover, supplementation with microgreens significantly lowered circulating LDL levels in animals fed the high-fat diet and reduced hepatic cholesterol ester, triacylglycerol levels, and expression of inflammatory cytokines in the liver. These data suggest that microgreens can modulate weight gain and cholesterol metabolism and may protect against CVD by preventing hypercholesterolemia.

Soy and Gut Microbiota: Interaction and Implication for Human Health.

Soy (Glycine max) is a major commodity in the United States, and soy foods are gaining popularity due to their reported health-promoting effects. In the past two decades, soy and soy bioactive components have been studied for their health-promoting/disease-preventing activities and potential mechanisms of action. Recent studies have identified gut microbiota as an important component in the human body ecosystem and possibly a critical modulator of human health. Soy foods' interaction with the gut microbiota may critically influence many aspects of human development, physiology, immunity, and nutrition at different stages of life. This review summarizes current knowledge on the effects of soy foods and soy components on gut microbiota population and composition. It was found, although results vary in different studies, in general, both animal and human studies have shown that consumption of soy foods can increase the levels of bifidobacteria and lactobacilli and alter the ratio between Firmicutes and Bacteroidetes. These changes in microbiota are consistent with reported reductions in pathogenic bacteria populations in the gut, thereby lowering the risk of diseases and leading to beneficial effects on human health.

Identification of liver CYP51 as a gene responsive to circulating cholesterol in a hamster model.

Hypercholesterolaemia is a risk factor for CVD, which is a leading cause of death in industrialised societies. The biosynthetic pathways for cholesterol metabolism are well understood; however, the regulation of circulating cholesterol by diet is still not fully elucidated. The present study aimed to gain more comprehensive understanding of the relationship between circulating cholesterol levels and molecular effects in target tissues using the hamster model. Male golden Syrian hamsters were fed with chow or diets containing 36 % energy from fat with or without 1 % cholesteyramine (CA) as a modulator of circulating cholesterol levels for 35 d. It was revealed that the expression of lanosterol 14α-demethylase (CYP51) instead of 3-hydroxy-3-methyl-glutaryl (HMG)-CoA reductase mRNA expression was responsive to circulating cholesterol in hamsters fed hypercholesterolaemic diets. The high-fat diet increased circulating cholesterol and down-regulated CYP51, but not HMG-CoA reductase. The CA diet decreased cholesterol and increased CYP51 expression, but HMG-CoA reductase expression was not affected. The high-fat diet and CA diet altered the expression level of cholesterol, bile acids and lipid metabolism-associated genes (LDL receptor, cholesterol 7α-hydroxylase (CYP7A1), liver X receptor (LXR) α, and ATP-binding cassette subfamily G member 5/8 (ABCG5/8)) in the liver, which were significantly correlated with circulating cholesterol levels. Correlation analysis also showed that circulating cholesterol levels were regulated by LXR/retinoid X receptor and PPAR pathways in the liver. Using the hamster model, the present study provided additional molecular insights into the influence of circulating cholesterol on hepatic cholesterol metabolism pathways during hypercholesterolaemia.

Utility of hesperidinase for food function research: enzymatic digestion of botanical extracts alters cellular antioxidant capacities and anti-inflammatory properties.

Food-derived phytochemicals, many known for their health beneficial effects, often exist in conjugated forms containing sugar moieties such as glucose or rhamnose in foods. The uptake of these compounds requires colonic bacterial cleavage of sugar moieties. However, most studies involved in screening extracts for biological activities do not take this process into account. This study seeks to determine the utility of commercially available hesperidinase to mimic colonic digestion and to test the effects of this treatment on the biological properties of extracts. Using hesperidinase resulted in efficient hydrolysis of Engelhardia roxburghiana Wall. extract containing rhamnose conjugates. Enzymatic digestion enhanced the extract's cellular antioxidant ability by 2-fold in HepG2/C3A and the anti-inflammatory effect on lipopolysaccharide-induced interleukin (IL)-1ß and IL-6 expression in mouse macrophage J774A.1 and human monocyte THP-1 cells. Enzymatic digestion also efficiently processed extracts with mixed rhamnose and glucose conjugates and altered their biological activities. Results of the present study supported the importance of considering enzymatic digestion during the biological activity studies of botanicals.

Cholesterol-lowering activity of soy-derived glyceollins in the golden Syrian hamster model.

Hypercholesterolemia is one of the major factors contributing to the risk of cardiovascular disease (CVD), which is the leading cause of death in developed countries. Consumption of soy foods has been recognized to lower the risk of CVD, and phytochemicals in soy are believed to contribute to the health benefits. Glyceollin is one of the candidate phytochemicals synthesized in stressed soy that may account for many unique biological activities. In this study, the in vivo cholesterol-lowering effect of glyceollins was investigated. Male golden Syrian hamsters were fed diets including (1) 36 kcal% fat diet, (2) 36 kcal% fat diet containing 250 mg/kg diet glyceollins, or (3) chow for 28 days. Hepatic cholesterol esters and free cholesterol, hepatic total lipid content, plasma lipoproteins, fecal bile acid, fecal total cholesterol, and cholesterol metabolism related gene expressions were measured. Glyceollin supplementation led to significant reduction of plasma VLDL, hepatic cholesterol esters, and total lipid content. Consistent with changes in circulating cholesterol, glyceollin supplementation also altered expression of the genes related to cholesterol metabolism in the liver. In contrast, no change in plasma LDL and HDL, fecal bile acid, or cholesterol content was observed. The cholesterol-lowering effect of glyceollins appeared not to go through the increase of bile excretion. These results supported glyceollins' role as novel soy-derived cholesterol-lowering phytochemicals that may contribute to soy's health effects.

Prenylated phloroglucinol derivatives from Hypericum sampsonii.

Six new acylphloroglucinol derivatives, sampsonols A-F (1-6), were isolated from the petroleum ether extract of the aerial parts of Hypericum sampsonii. The structures and relative configurations of sampsonols A-F were elucidated by extensive spectroscopic analyses. All these compounds were tested for their in vitro cytotoxic and anti-inflammatory activities. Sampsonols A and B (1 and 2) showed significant cytotoxicity against four human tumor cell lines with IC(50) values in the range of 13-28µM, whereas sampsonols C and F (3 and 6) showed potent inhibitory activities against LPS-induced NO production in RAW 264.7 macrophages with IC(50) values of 27.3 and 29.3µM, respectively.