Bifidobacterium bifidum BGN4 Paraprobiotic Supplementation Alleviates Experimental Colitis by Maintaining Gut Barrier and Suppressing Nuclear Factor Kappa B Activation Signaling Molecules.

Inflammatory bowel diseases, including Crohn's disease and ulcerative colitis, are characterized by chronic gastrointestinal inflammation with continuous relapse-remission cycles. This study aimed to evaluate the protective effect of Bifidobacterium bifidum BGN4 as a probiotic or paraprobiotic against dextran sulfate sodium (DSS)-induced colitis in mice. Ten-week-old female BALB/c mice were randomly divided into five groups. The control (CON) and DSS groups received oral gavage of PBS, whereas the live B. bifidum (LIVE), heat-killed B. bifidum BGN4 (HEAT), and lysozyme-treated B. bifidum BGN4 (LYSOZYME) groups received live B. bifidum BGN4, heat-killed B. bifidum BGN4, and lysozyme-treated B. bifidum BGN4, respectively, for 10 days, followed by DSS supply to induce colitis. The paraprobiotic (HEAT and LYSOZYME) groups had less body weight loss and colon length shortening than the DSS or LIVE groups. The LYSOZYME group exhibited better preserved intestinal barrier integrity than the LIVE group by upregulating gap junction protein expression possibly through activating NOD-like receptor family pyrin domain containing 6/caspase-1/interleukin (IL)-18 signaling. The LYSOZYME group showed downregulated proinflammatory molecules, including p-inhibitor of kappa B proteins alpha (IκBα), cycloxygenase 2 (COX2), IL-1ß, and T-bet, whereas the expression of the regulatory T cell transcription factor, forkhead box P3 expression, was increased. The paraprobiotic groups showed distinct separation of microbiota distribution and improved inflammation-associated dysbiosis. These results suggest that B. bifidum BGN4 paraprobiotics, especially lysozyme-treated BGN4, have a preventive effect against DSS-induced colitis, impacting intestinal barrier integrity, inflammation, and dysbiosis.

In vitro and in vivo inhibition of Helicobacter pylori by Lactobacillus plantarum pH3A, monolaurin, and grapefruit seed extract.

Helicobacter pylori infection is the most common cause of gastritis and gastric ulcers. Considering the severe side effects of current antibiotic therapies, it is crucial to find an alternate treatment for H. pylori infection. In this study, we investigated the anti-H. pylori effects of a newly isolated strain of Lactobacillus plantarum (pH3A), monolaurin, grapefruit seed extract (GSE), and their synergies in vitro and in vivo. Monolaurin and GSE suppressed H. pylori growth and urease activity at a minimal inhibitory concentration (MIC) of 62.5 ppm. Live cells and cell-free culture supernatant (CFCS) of L. plantarum pH3A with or without pH adjustment also significantly inhibited H. pylori growth. Although synergy was not observed between monolaurin and GSE, the addition of CFCS significantly enhanced their anti-H. pylori activities. Moreover, L. plantarum pH3A significantly decreased the ability of H. pylori to adhere to AGS cells and interleukin (IL)-8 production in the H. pylori-stimulated AGS cell line. The addition of GSE or monolaurin strengthened these effects. In the in vivo study, H. pylori colonization of the mouse stomach and total serum IgG production were significantly reduced by L. plantarum pH3A treatment, but the addition of monolaurin or GSE did not contribute to these anti-H. pylori activities. Therefore, the L. plantarum pH3A strain can potentially be applied as an alternative anti-H. pylori therapy, but evidence of its synergy with monolaurin or GSE in vivo is still lacking.

Effects of Selenium- and Zinc-Enriched Lactobacillus plantarum SeZi on Antioxidant Capacities and Gut Microbiome in an ICR Mouse Model.

Selenium and zinc are essential trace minerals for humans with various biological functions. In this study, selenium- and zinc-tolerant lactic acid bacteria (LAB) isolates were screened out from human fecal samples. Amongst three hundred LAB isolates, the Lactobacillus plantarum SeZi strain displayed the tolerance against selenium and zinc with the greatest biomass production and bioaccumulation of selenium and zinc. To further assess the characteristics of this strain, the lyophilized L. plantarum SeZi were prepared and administered to Institute of Cancer Research (ICR) mice. The mice were divided into four groups, provided with normal chow (Con), or normal chow supplemented with Na2SeO3 and ZnSO4∙7H2O (SZ), L. plantarum SeZi (Lp), or selenium- and zinc-enriched L. plantarum SeZi (SZ + Lp), respectively. After 4 weeks of oral administration, the concentrations of selenium and zinc in blood were significantly increased in the SZ + Lp group when compared to the control or SZ group (p < 0.05). The increased selenium level led to an enhanced glutathione peroxidase activity and decreased blood malondialdehyde level in the SZ + Lp group (p < 0.05). Meanwhile, the results of bacterial community and microbial metabolic pathway analysis via 16S rRNA gene amplicon sequencing showed that L. plantarum SeZi significantly promoted the utilization of selenocysteine, seleno-cystathionine and seleno-methionine in the selenocompounds metabolism. Here, the in vivo antioxidant capacities of the selenium- and zinc-enriched lactobacillus strain showed us the utilization of a unique probiotic as a Se/Zn supplement with high availability, low toxicity, and additional probiotic advantages.

Microbial biocatalysis of quercetin-3-glucoside and isorhamnetin-3-glucoside in Salicornia herbacea and their contribution to improved anti-inflammatory activity.

Salicornia herbacea (glasswort) is a traditional Asian medicinal plant which exhibits multiple nutraceutical and pharmaceutical properties. Quercetin-3-glucoside and isorhamnetin-3-glucoside are the major flavonoid glycosides found in S. herbacea. Multiple researchers have shown that flavonoid glycosides can be structurally transformed into minor aglycone molecules, which play a significant role in exerting physiological responses in vivo. However, minor aglycone molecule levels in S. herbacea are very low. In this study, Bifidobacterium animalis subsp. lactis AD011, isolated from infant feces, catalyzed >85% of quercetin-3-glucoside and isorhamnetin-3-glucoside into quercetin and isorhamnetin, respectively, in 2 h, without breaking down flavonoid backbones. Functionality analysis demonstrated that the quercetin and isorhamnetin produced showed improved anti-inflammatory activity vs. the original source molecules against lipopolysaccharide induced RAW 264.7 macrophages. Our report highlights a novel protocol for rapid quercetin and isorhamnetin production from S. herbacea flavonoids and the applicability of quercetin and isorhamnetin as nutraceutical molecules with enhanced anti-inflammatory properties.

Production of Selenomethionine-Enriched Bifidobacterium bifidum BGN4 via Sodium Selenite Biocatalysis.

Selenium is a trace element essential for human health that has received considerable attention due to its nutritional value. Selenium's bioactivity and toxicity are closely related to its chemical form, and several studies have suggested that the organic form of selenium (i.e., selenomethionine) is more bioavailable and less toxic than its inorganic form (i.e., sodium selenite). Probiotics, especially Bifidobacteriium and Lactobacillus spp., have received increasing attention in recent years, due to their intestinal microbial balancing effects and nutraceutical benefits. Recently, the bioconversion (a.k.a biotransformation) of various bioactive molecules (e.g., minerals, primary and secondary metabolites) using probiotics has been investigated to improve substrate biofunctional properties. However, there have been few reports of inorganic selenium conversion into its organic form using Bifidobacterium and Lactobacillus spp. Here we report that the biosynthesis of organic selenium was accomplished using the whole cell bioconversion of sodium selenite under controlled Bifidobacterium bifidum BGN4 culture conditions. The total amount of organic and inorganic selenium was quantified using an inductively coupled plasma-atomic emission spectrometer (ICP-AES). The selenium species were separated via anion-exchange chromatography and analyzed with inductively coupled plasma-mass spectrometry (ICP-MS). Our findings indicated that the maximum level of organic selenium was 207.5 µg/g in selenium-enriched B. bifidum BGN4. Selenomethionine was the main organic selenium in selenium-enriched B. bifidum BGN4 (169.6 µg/g). Considering that B. bifidum BGN4 is a commercial probiotic strain used in the functional food industry with clinically proven beneficial effects, selenium-enriched B. bifidum BGN4 has the potential to provide dual healthy functions as a daily supplement of selenium and regulator of intestinal bacteria. This is the first report on the production of organic selenium using B. bifidum spp.

Anti-Obesity Effects of a Mixture of Fermented Ginseng, Bifidobacterium longum BORI, and Lactobacillus paracasei CH88 in High-Fat Diet-Fed Mice.

Ginseng and probiotics have anti-obesity effects in mice fed a high-fat diet (HFD). Absorption of ginsenoside and colonization of probiotics occur in the intestine. In this study, a mixture of fermented ginseng and two probiotics, Bifidobacterium longum BORI and Lactobacillus paracasei CH88, was administered to HFD-fed mice for 9 weeks. The mixture significantly suppressed weight gain (p < 0.05, n = 8) and lipid deposition in the liver and adipose tissues as well as increased the mice's food intake. The adipocyte size of the adipose tissue was significantly decreased in the mixture-fed group, especially when 0.5% fermented ginseng and 5 × 108/ml of the two probiotics were used (p < 0.05, n = 10). The expression of TNF-α in adipose tissue was efficiently downregulated in the mixture-fed group (p < 0.05, n = 4). The supplement also improved the mice's fasting blood glucose levels (p < 0.05, n = 8) and total cholesterol feces excretion (p < 0.05, n = 8). The mixture of fermented ginseng and B. longum BORI and L. paracasei CH88 could have an anti-obesity effect and suppress lipid deposit in the liver and adipose tissues.

Anti-obese effects of two Lactobacilli and two Bifidobacteria on ICR mice fed on a high fat diet.

Previous researchers have documented that probiotic bacteria can have anti-obesity effects on mice fed a high fat diet (HFD) and improve metabolic syndrome. The beneficial effects of the probiotic bacteria are suggested to be strain dependent. In this study, two candidate lactobacteria strains, Lactobacillus casei IBS041, Lactobacillus acidophilus AD031 and two bifidobacteria strains, Bifidobacterium bifidum BGN4 and Bifidobacterium longum BORI, were individually administered to HFD-fed mice for 8 weeks. B. longum BORI significantly suppressed mouse weight gain without affecting food intake. L. acidophilus and B. bifidum BGN4 significantly decreased triglyceride levels in mouse liver while B. longum BORI significantly lowered total cholesterol levels in liver. L. acidophilus and B. bifidum BGN4 significantly inhibited serum activities of aspartate transaminase and alanine transaminase. Diet supplementation with L. acidophilus, B. bifidum BGN4 and B. longum BORI efficiently improved hepatocyte hydropic degeneration and hepatic steatosis. Of the four probiotic candidates, the bifidobacteria B. longum BORI and B. bifidum BGN4, developed in our laboratory, and L. acidophilus AD031showed excellent anti-obesity effects and suppressed lipid deposition in liver.

Korean Ginseng Berry Fermented by Mycotoxin Non-producing Aspergillus niger and Aspergillus oryzae: Ginsenoside Analyses and Anti-proliferative Activities.

To transform ginsenosides, Korean ginseng berry (KGB) was fermented by mycotoxin non-producing Aspergillus niger and Aspergillus oryzae. Changes of ginsenoside profile and anti-proliferative activities were observed. Results showed that A. niger tended to efficiently transform protopanaxadiol (PPD) type ginsenosides such as Rb1, Rb2, Rd to compound K while A. oryzae tended to efficiently transform protopanaxatriol (PPT) type ginsenoside Re to Rh1 via Rg1. Butanol extracts of fermented KGB showed high cytotoxicity on human adenocarcinoma HT-29 cell line and hepatocellular carcinoma HepG2 cell line while that of unfermented KGB showed little. The minimum effective concentration of niger-fermented KGB was less than 2.5 µg/mL while that of oryzae-fermented KGB was about 5 µg/mL. As A. niger is more inclined to transform PPD type ginsenosides, niger-fermented KGB showed stronger anti-proliferative activity than oryzae-fermented KGB.

Review on Bifidobacterium bifidum BGN4: Functionality and Nutraceutical Applications as a Probiotic Microorganism.

Bifidobacterium bifidum BGN4 is a probiotic strain that has been used as a major ingredient to produce nutraceutical products and as a dairy starter since 2000. The various bio-functional effects and potential for industrial application of B. bifidum BGN4 has been characterized and proven by in vitro (i.e., phytochemical bio-catalysis, cell adhesion and anti-carcinogenic effects on cell lines, and immunomodulatory effects on immune cells), in vivo (i.e., suppressed allergic responses in mouse model and anti-inflammatory bowel disease), and clinical studies (eczema in infants and adults with irritable bowel syndrome). Recently, the investigation of the genome sequencing was finished and this data potentially clarifies the biochemical characteristics of B. bifidum BGN4 that possibly illustrate its nutraceutical functionality. However, further systematic research should be continued to gain insight for academic and industrial applications so that the use of B. bifidum BGN4 could be expanded to result in greater benefit. This review deals with multiple studies on B. bifidum BGN4 to offer a greater understanding as a probiotic microorganism available in functional food ingredients. In particular, this work considers the potential for commercial application, physiological characterization and exploitation of B. bifidum BGN4 as a whole.

Whole-Cell Biocatalysis for Producing Ginsenoside Rd from Rb1 Using Lactobacillus rhamnosus GG.

Ginsenosides are the major active ingredients in ginseng used for human therapeutic plant medicines. One of the most well-known probiotic bacteria among the various strains on the functional food market is Lactobacillus rhamnosus GG. Biocatalytic methods using probiotic enzymes for producing deglycosylated ginsenosides such as Rd have a growing significance in the functional food industry. The addition of 2% cellobiose (w/v) to glucose-free de Man-Rogosa-Sharpe broths notably induced ß-glucosidase production from L. rhamnosus GG. Enzyme production and activity were optimized at a pH, temperature, and cellobiose concentration of 6.0, 40°C, and 2% (w/v), respectively. Under these controlled conditions, ß-glucosidase production in L. rhamnosus GG was enhanced by 25-fold. Additionally, whole-cell homogenates showed the highest ß-glucosidase activity when compared with disrupted cell suspensions; the cell disruption step significantly decreased the ß-glucosidase activity. Based on the optimized enzyme conditions, whole-cell L. rhamnosus GG was successfully used to convert ginsenoside Rb1 into Rd.

The anti-obesity effects of the dietary combination of fermented red ginseng with levan in high fat diet mouse model.

In this study, to evaluate the anti-obesity effects of fermented red ginseng (FG), levan (L), and their combination (FGL), we investigated their effects on the weights of body, liver and white adipose tissue, lipid profiles, and biomarkers for insulin resistance in high fat diet (HFD)-induced obese C57BL/6J male mice. Furthermore, the levels of leptin in the serum were measured. FG (150 mg/kg/d), L (100 mg/kg/d), and FGL (150 mg/kg/d of FG plus 100 mg/kg/d of L) were administered orally to mice daily for 11 weeks. After 11 weeks feeding, FGL showed significantly lower body weight and fat mass with decreasing food efficiency ratio than the HFD control mice. In addition, the FGL group was significantly lower in the levels of total cholesterol and fasting blood glucose and score of the homeostatic model assessment of insulin resistance. Furthermore, FGL decreased serum leptin levels compared to the HFD control group. Taken together, FGL showed a significant anti-obesity effect in HFD-induced obese mice and prevent insulin and leptin resistance. FGL may be potentially useful for the prevention of obesity.

The effect of fermented red ginseng on depression is mediated by lipids.

OBJECTIVES: The cortico-limbic hypothalamic-pituitary-adrenal axis has emerged as an important area for the cause and treatment of depression. The primary aim of this study was to test the hypothesis that hormones, energy sources, and minerals have a causal relationship with depression. The secondary aim was to test whether consumption of fermented red ginseng (FRG) would influence that causal relationship. METHODS: For this study, 93 postmenopausal women were randomly divided into two groups. One group (49 women) was supplied with FRG capsules, and the other group (44 women) with placebo capsules, for 2 weeks. Both before and after the study, the participants filled out the Beck depression inventory questionnaire, and then blood samples were collected. The structural regression model was established. The causative latent variables were hormone (adrenocorticotropic hormone and cortisol), energy (low-density lipoprotein (LDL) cholesterol, total cholesterol, and blood glucose), mineral 1 (potassium, sodium, chloride, and iron), and mineral 2 (magnesium, calcium), and the resultant latent variables were cognitive depression (CD) and somatic depression. The goodness-of-fit statistics of the final model were good (root mean square error of approximation =0.033, comparative fit index =0.877, and Tucker-Lewis index =0.870). RESULTS: The structural regression path of the energy factor on CD showed a significant difference between the FRG group (0.259) and the placebo group (-0.201). The factor loadings of total cholesterol (1.236) and LDL cholesterol (1.000) on the energy factor were much higher than that of glucose (0.166). CONCLUSION: Based on the analysis used in this model, the effect of FRG consumption on CD occurred via the energy factor, which is mainly attributable to cholesterol.

Bioconversion of flavones during fermentation in milk containing Scutellaria baicalensis extract by Lactobacillus brevis.

Scutellaria baicalensis (SB), a traditional herb with high pharmacological value, contains more than 10% flavone by weight. To improve the biological activity of flavones in SB, we aimed to enhance the bioconversion of baicalin (BG) to baicalein (B) and wogonoside (WG) to wogonin (W) in SB during fermentation using beta-glucuronidase produced from Lactobacillus brevis RO1. After activation, L. brevis RO1 was cultured in milk containing SB root extract with various carbon or nitrogen sources at 37°C for 72 h. During fermentation, the growth patterns of L. brevis RO1 and changes in the flavone content were assessed using thin-layer chromatography and high-performance liquid chromatography. After 72 h of fermentation, the concentrations of B and W in the control group increased by only 0.15 and 0.12 mM, respectively, whereas they increased by 0.57 and 0.24 mM in the fish peptone group. The production of B and W was enhanced by the addition of 0.4% fish peptone, which not only improved the growth of L. brevis RO1 (p < 0.001) but also enhanced the bioconversion of flavones. In conclusion, the bioconversion of flavones in SB may provide a potential application for the enhancement of the functional components in SB.

Diabetes-ameliorating effects of fermented red ginseng and causal effects on hormonal interactions: testing the hypothesis by multiple group path analysis.

Although diagnostic criteria for metabolic syndrome (MtS) vary among various health professionals and organizations, blood glucose dysregulation and insulin resistance are common to all definitions. Red ginseng is beneficial for glucose regulation and insulin sensitivity but the mechanism is not yet elucidated. Ginsenosides Rh1 and Rg3 act as ligands of the estrogen receptor, and Rh2 and compound K act as ligands of the glucocorticoid receptors, which may influence the diabetes markers. The objective of this study was to test the hypothesis that there are significant causal relationships among diabetes-related markers and several hormones, and assess whether or not the consumption of fermented red ginseng (FRG) influences these causal relationships by multiple group path analysis and conventional statistical analyses. The 93 postmenopausal women were randomly divided into two groups for a double-blind trial. FRG powder and placebo were provided for 2 weeks. The data were analyzed by multiple group path analysis and the mean between groups were compared. The model's goodness of fit was excellent, with a root mean square error of approximation of 0.00, and comparative fit index of 1.00. The FRG group exhibited significantly increased levels of dehydroepiandrosterone sulfate (DHEAS), growth hormone (GH), and estradiol (E2), and they exhibited decreased levels of glycosylated hemoglobin (HbA1c), insulin, and homeostatic model assessment of insulin resistance. With regard to the hypothesis, the blood glucose lowering effects of FRG were due to the negative effects of aldosterone and increased GH, which was associated with DHEAS and E2. Even though the differences of variables between both groups were small, the total effects of these variables may indicate beneficial changes for the prevention of diabetes in healthy postmenopausal women.

Anti-hyperglycemic effect of fermented ginseng in type 2 diabetes mellitus mouse model.

Ginseng has shown an efficacy in preventing and managing various health conditions. This study aimed to evaluate the effect of the fermented ginseng extract (FGE) in type 2 diabetes mellitus murine model. FGE was provided to male C57BL/ksJ-db/db mice for 8 weeks at 0.1% (w/w) dose in contrast to water for the control group. Potential anti-diabetic mechanisms were investigated with blood glucose, serum insulin, serum adiponectin, hemoglobin A1c (HbA1c), glucose tolerance, insulin secretion assay, quantitative real-time polymerase chain reaction, and hematoxylin-eosin staining. Compared with the control group, the FGE group had lower levels of blood glucose after 6 and 9 h fasting, HbA1c, and the area under the curve in an oral glucose tolerance test and higher levels of adiponectin and serum insulin (p < 0.05). The FGE group had higher levels of peroxisome proliferator-activated receptor gamma 2 and glucose transporter protein 2 mRNAs, a lower level of tumor necrosis factor-α (TNF-α) (p < 0.05), and less lymphocytes in pancreas than the control group had. The FGE exerted anti-diabetic effects in type 2 diabetic mice.

Enhancement of the tyrosinase inhibitory activity of Mori Cortex Radicis extract by biotransformation using Leuconostoc paramesenteroides PR.

Mori Cortex Radicis (MCR), the root bark of Morus alba L., consists of various phytochemicals and exhibits a strong inhibitory effect on tyrosinase. To enhance the tyrosinase inhibitory activity of MCR extract without further purification of bioactive compounds, whole MCR extract was biotransformed with crude enzyme extract from a selected lactic acid bacterium, Leuconostoc paramesenteroides PR (LP). Mulberroside A (MA), a major stilbene glucoside of MCR, contains two ß-glucosyl residues at the C3 and C4' positions of oxyresveratrol (OXY). The crude enzyme of LP hydrolyzed the two glycosidic bonds of MA effectively, and 97.1% of MA was biotransformed into OXY within 2 h. Commercial almond ß-glucosidase hydrolyzed only one site of the two glycosidic bonds of MA, and 68.7% of MA was biotransformed to OXY-glucoside. The tyrosinase inhibitory activity of the crude extract of MCR was increased approximately 6.5-fold by biotransformation using LP, and the IC(50) value of the transformed MCR was 3.7 µg/mL.

Oral administration of fermented red ginseng suppressed ovalbumin-induced allergic responses in female BALB/c mice.

Anti-allergic efficacy of red ginseng (RG) and fermented red ginseng (FRG) was evaluated. RG or FRG were administered to ovalbumin (OVA)-sensitized mice for 8 weeks. Immunoglobulins (Igs), Th1/Th2 type cytokines, and ß-lactoglobulin (BLG) in serum, and intestinal barrier-related molecules in jejunum were measured using enzyme-linked immunosorbent assay or reverse transcription-polymerase chain reaction. Mice sensitized with OVA increased serum IgG1, IgE, OVA-IgG1, and OVA-IgE. Both RG and FRG decreased serum IgE, OVA-IgE, and pro-inflammatory cytokines. Serum BLG, a marker of gut permeability, was significantly higher in sensitized animals and was decreased in mice fed RG or FRG. In addition, intestinal barrier-related markers such as MMCP-1, IL-4, TNF-α, COX-2, and iNOS mRNA expressions were decreased by RG or FRG. Our results suggest in vivo anti-allergic activities of RG or FRG, which are associated with the regulation of Th1/Th2 balance, intestinal inflammation and subsequent the suppression of IgE.

Therapeutic effects of fermented red ginseng in allergic rhinitis: a randomized, double-blind, placebo-controlled study.

PURPOSE: Allergic rhinitis is clinically defined as a disorder of the nose induced by IgE mediated inflammation after allergen exposure of the nasal mucosa. Many reports have stated that Panax ginseng and fermented red ginseng have anti-inflammatory effects, especially against Th2-type inflammation. This study was conducted to evaluate the therapeutic effects of fermented red ginseng in allergic rhinitis. METHODS: In this 4-week, double-blind, placebo-controlled study, 59 patients with persistent perennial allergic rhinitis were randomly divided into two groups: those receiving fermented red ginseng tablets (experimental group) and those receiving placebo (control group). The primary efficacy variable was the total nasal symptom score (TNSS; rhinorrhea, sneezing, itchy nose, and nasal congestion). Secondary efficacy variables were the Rhinitis Quality of Life (RQoL) score and skin reactivity to inhalant allergens, as determined by the skin prick test. RESULTS: There was no significant difference in the TNSS score and TNSS duration score between the experimental and placebo groups in weeks 1, 2, 3, or 4. For nasal congestion, fermented red ginseng was significantly effective (P<0.005), while placebo caused no change. The activity and emotion of RQoL improved markedly secondary to treatment with fermented red ginseng (P<0.05), while placebo caused no change. Additionally, fermented red ginseng reduced skin reactivity to sensitized perennial allergens (P<0.05). Fermented red ginseng was well tolerated. CONCLUSIONS: Fermented red ginseng improved nasal congestion symptoms and RQoL in patients with perennial allergic rhinitis.

Blockade of vascular angiogenesis by Aspergillus usamii var. shirousamii-transformed Angelicae Gigantis Radix and Zizyphus jujuba.

The matrix metalloproteinases (MMP) play an important role in tumor invasion, angiogenesis and inflammatory tissue destruction. Increased expression of MMP was observed in benign tissue hyperplasia and in atherosclerotic lesions. Invasive cancer cells utilize MMP to degrade the extracellular matrix and vascular basement membrane during metastasis, where MMP-2 has been implicated in the development and dissemination of malignancies. The present study attempted to examine the antiangiogenic activity of the medicinal herbs of Aspergillus usamii var. shirousamii-transformed Angelicae Gigantis Radix and Zizyphus jujube (tAgR and tZj) with respect to MMP-2 production and endothelial motility in phorbol 12-myristate 13-acetate (PMA)- or VEGF-exposed human umbilical vein endothelial cells (HUVEC). Nontoxic tAgR and tZj substantially suppressed PMA-induced MMP-2 secretion. In addition, 25 microg/mL tAgR and tZj prevented vascular endothelial growth factor-stimulated endothelial cell transmigration and tube formation. The results reveal that tAgR and tZj dampened endothelial MMP-2 production leading to endothelial transmigration and tube formation. tAgR and tZj-mediated inhibition of endothelial MMP may boost a therapeutic efficacy during vascular angiogenesis.

Enzymatic modification of saponins from Platycodon grandiflorum with Aspergillus niger.

Platycodon grandiflorum A. DC (Campanulaceae) is a traditional medicinal plant. Its root, Platycodi Radix, contains an abundant amount of saponin glycosides, platycodins, of which platycodin D is one of the major components. The chemical structures of platycodins can be modified by various types of chemical processing, but a modification mediated with microorganisms has been not reported yet. In this study, platycodin D was modified to several partially degraded platycodin glycosides after treatment with a crude enzyme extract from Aspergillus niger (A. niger). The modified platycodin D possessed a shorter sugar side-chain, and presented a remarkably reduced V79-4 cell (Chinese hamster lung fibroblasts) cytotoxicity and erythrocyte hemolytic toxicity, whereas the nitrite-scavenging activity was increased in the modified platycodin D. Sensory scores for pungency, bitterness and after-taste were improved as well in the modified platycodin D. Results suggest that A. niger mediated modification yielded a novel partially degraded platycodin glycoside which possesses increased bioactivities and improved sensory values, yet with reduced toxic profiles.