Anti-Obesity Properties of Blackberries Fermented with L. plantarum JBMI F5 via Suppression of Adipogenesis Signaling Mechanisms.

Blackberries (Rubus fruticosus), which are known to include a variety of bioactive substances, have been extensively studied for their antioxidant properties. Blackberries possess multiple health beneficial effects, including anti-inflammation, anti-atherosclerosis, anti-tumor and immunomodulatory activity. However, the potential biological effects and precise molecular mechanisms of the fermented extracts remain largely unexplored. In this research, we demonstrate the effect of blackberries fermented with Lactobacillus for addressing obesity. We investigated the effect of blackberries fermented by Lactobacillus on mice fed a high-fat (60% kcal) diet for 12 weeks. Fermented blackberry administration reduced the body weight and epididymal fat caused by a high-fat diet compared to the obese group. The triglyceride and total cholesterol, which are blood lipid indicators, and the levels of leptin, which is an insulin resistance indicator, were significantly increased in the obese group but were significantly decreased in the fermented blackberries-treated group. Additionally, the expression of adipogenesis marker proteins, such as CEBPα, PPAR-γ and SREBP-1, was significantly increased in the obese group, whereas it was decreased in the fermented blackberries-treated group. These results suggest that fermented blackberries have a protective effect against high-fat-diet-induced obesity by inhibiting adipogenesis and are a potential candidate for the treatment of obesity.

Therapeutic Effect of Enzymatically Hydrolyzed Cervi Cornu Collagen NP-2007 and Potential for Application in Osteoarthritis Treatment.

Cervi cornu extracts have been used in traditional medicine for the treatment of various disorders, including osteoporosis. However, since it is not easy to separate the active ingredients, limited research has been conducted on their functional properties. In this study, we extracted the low-molecular-weight (843 Da) collagen NP-2007 from cervi cornu by enzyme hydrolyzation to enhance absorption and evaluated the therapeutic effect in monosodium iodoacetate-induced rat osteoarthritis (OA) model. NP-2007 was orally administered at 50, 100, and 200 mg/kg for 21 days. We showed that the production of matrix metalloproteinase-2, -3, and -9, decreased after NP-2007 treatment. The levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, and prostaglandin E2 were also reduced after treatment of NP-2007. Furthermore, the administration of NP-2007 resulted in effective preservation of both the synovial membrane and knee cartilage and significantly decreased the transformation of fibrous tissue. We verified that the treatment of NP-2007 significantly reduced the production of nitric oxide and pro-inflammatory cytokines including TNF-α, IL-1ß, and IL-6 in lipopolysaccharides-stimulated RAW 264.7 cells by regulation of the NF-kB and MAPK signaling pathways. This study indicates that NP-2007 can alleviate symptoms of osteoarthritis and can be applied as a novel treatment for OA treatment.

Discovery of novel cage-like heterocyclic hybrids as anti-inflammatory agents through the inhibition of nitrite, PGE2 and TNF-α.

Novel cage-like indolizine-acenaphthene-pyridinone heterocyclic hybrids were synthesized in good yields through [bmim]Br mediated tandem 1,3-dipolar cycloaddition-annulation sequence. The anti-inflammatory activity of these hybrids was performed using carrageenan-induced hind paw oedema, croton oil-induced ear oedema and cotton pellet-induced granuloma models. Four of these cage-like heterocyclic hybrids viz. 4b, 4d, 4e and 4j showed substantial anti-inflammatory activities against acute and chronic inflammatory models and also showed significant inhibition of PGE2, TNF-α, and nitrite levels in carrageenan-induced hind paw oedema.

Hominis Placenta facilitates hair re-growth by upregulating cellular proliferation and expression of fibroblast growth factor-7.

BACKGROUND: Hominis Placenta (HP) known as a restorative medicine in Traditional Chinese Medicine (TCM), has been widely applied in the clinics of Korea and China as an anti-aging agent to enhance the regeneration of tissue. This study was conducted to investigate whether topical treatment of HP promotes hair regrowth in the animal model. METHODS: The dorsal hairs of 8-week-old C57BL/6 mice were depilated to synchronize hair follicles to the anagen phase. HP was applied topically once a day for 15 days. Hair growth was evaluated visually and microscopically. The incorporation of bromodeoxyuridine (BrdU) and expression of proliferating cell nuclear antigen (PCNA), fibroblast growth factor-7 (FGF-7) in dorsal skin tissue was examined by immunohistochemical analysis. Reverse transcription polymerase chain reaction (RT-PCR) was used to measure the mRNA expression of FGF-7. RESULTS: HP exhibited potent hair growth-promoting activity in C57BL/6 mice. Gross examination indicated that HP markedly increased hair regrowth as well as hair density and diameter. Histologic analysis showed that HP treatment enhanced the anagen induction of hair follicles. Immunohistochemical analysis revealed that BrdU incorporation and the expressions of PCNA were increased by treatment of HP. HP treatment significantly increased the expression of FGF-7, which plays pivotal roles to maintain anagen phase both protein and mRNA levels. CONCLUSIONS: Taken together, our results indicate that HP has a potent hair growth-promoting activity; therefore, it may be a good candidate for the treatment of alopecia.

Inactivation of the phosphoglucomutase gene pgm in Paenibacillus polymyxa leads to overproduction of fusaricidin.

Fusaricidin, a lipodepsipeptide isolated from Paenibacillus polymyxa, has high antimicrobial activity against fungi and Gram-positive bacteria. Through mutagenesis, we obtained two mutant strains, N1U7 and N17U7, which produce 6.2- to 7.9-fold more fusaricidin than their parent strain. Causal mutations were identified by whole-genome sequencing, and the two strains each contained at least eleven point mutations, including four common mutations. A mutation in the PPE04441 gene (pgm), encoding an α-phosphoglucomutase, was found to be an important factor in fusaricidin overproduction by complementation experiments. Null mutation of pgm in the parental strain increased fusaricidin production by 5.2-fold. Increased growth and cell viability in stationary phase, reduced exopolysaccharide production, and increased fusA expression were observed in the pgm mutant strains, which might be related to fusaricidin overproduction. This is the first report revealing that PGM deficiency leads to an overproduction of fusaricidin.

Saussurea lappa extract suppresses TPA-induced cell invasion via inhibition of NF-κB-dependent MMP-9 expression in MCF-7 breast cancer cells.

BACKGROUND: Saussurea lappa (SL) has been used as a traditional herbal medicine to treat abdominal pain and tenesmus, and has been suggested to possess various biological activities, including anti-tumor, anti-ulcer, anti-inflammatory, anti-viral, and cardiotonic activities. The effect of SL on breast cancer metastasis, however, is unknown. Cell migration and invasion are crucial in neoplastic metastasis. Matrix metalloproteinase-9 (MMP-9), which degrades the extracellular matrix, is a major component in cancer cell invasion. METHODS: Cell viability was examined by MTT assay, whereas cell motility was measured by invasion assay. Western blot, Real-time PCR, and Zymography assays were used to investigate the inhibitory effects of ESL on matrix metalloproteinase-9 (MMP-9) expression level in MCF-7 cells. EMSA confirmed the inhibitory effects of ESL on DNA binding of NF- κB in MCF-7 cells. RESULTS: Cells threated with various concentrations of Saussurea lappa (ESL) for 24 h. Concentrations of 2 or 4 µM did not lead to a significant change in cell viability or morphology. Therefore, subsequent experiments utilized the optimal non-toxic concentration (2 or 4 µM) of ESL. In this study, we investigated the inhibitory effect of ethanol extract of ESL on MMP-9 expression and cell invasion in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced MCF-7 cells. ESL inhibited the TPA-induced transcriptional activation of nuclear factor-kappa B (NF-κB). However, this result obtained that ESL did not block the TPA-induced phosphorylation of the kinases: p38, ERK, and JNK. Therefore, ELS-mediated inhibition of TPA-induced MMP-9 expression and cell invasion involves the suppression of NF-kB pathway in MCF-7 cells. CONCLUSIONS: These results indicate that ELS-mediated inhibition of TPA-induced MMP-9 expression and cell invasion involves the suppression of NF-kB pathway in MCF-7 cells. Thus, ESL has potential for controlling breast cancer invasiveness in vitro.

Metabolic Profiling Changes Induced by Fermented Blackberries in High-Fat-Diet-Fed Mice Utilizing Gas Chromatography-Mass Spectrometry Analysis.

The aim of this study was to investigate the metabolic changes associated with the anti-obesity effects of fermented blackberry extracts in the liver tissues of high-fat-diet-fed mice using mass spectrometry-based metabolomics analysis. C57BL/6J mice were divided into eight groups: normal-diet-fed mice, high-fat-diet-fed mice, high-fat diet treated with blackberry extract, high-fat-diet mice treated with blackberry fermented by L. plantarum, and high-fat diet with blackberry fermented by L. brevis. After 12 weeks, the high-fat-diet group exhibited a greater increase in liver weight compared to the control group, and among the groups, the group administered with blackberry fermented with L. plantarum showed the most pronounced reduction in liver weight. As the primary organ responsible for amino acid metabolism, the liver is crucial for maintaining amino acid homeostasis. In our study, we observed that the levels of several essential amino acids, including isoleucine and valine, were decreased by the high-fat diet, and were recovered by administration of blackberry extract fermented with L. plantarum. Our results demonstrated the potential of blackberry extract fermented with L. plantarum as a functional material for metabolic disorders by restoring some of the amino acid metabolism disturbances induced by a high-fat diet.

Anti-Obesity Effect and Signaling Mechanism of Potassium Poly-γ-Glutamate Produced by Bacillus subtilis Chungkookjang in High-Fat Diet-Induced Obese Mice.

The purpose of this work was to examine the effects of potassium poly-γ-glutamate (PGA-K) on mice fed a high-fat diet consisting of 60% of total calories for 12 weeks. PGA-K administration reduced the increase in body weight, epididymal fat, and liver weight caused by a high-fat diet compared to the obese group. The triglyceride, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol levels, which are blood lipid indicators, were significantly increased in the obese group but were significantly decreased in the PGA-K-treated group. The administration of PGA-K resulted in a significant inhibition of pro-inflammatory cytokines, including tumor necrosis factor α and interleukin 6. Moreover, the levels of leptin and insulin, which are insulin resistance indicators, significantly increased in the obese group but were significantly decreased in the PGA-K-treated group. These results suggest that PGA-K exhibits a protective effect against obesity induced by a high-fat diet, underscoring its potential as a candidate for obesity treatment.

Anti-inflammatory effect and signaling mechanism of 8-shogaol and 10-shogaol in a dextran sodium sulfate-induced colitis mouse model.

Ethnopharmacological relevance: Ginger (Zingiber officinale Roscoe) has been used for food and applied in Ayurvedic medicine in India for thousands of years. With a reputation for strong anti-inflammatory properties, it has been used for to treat colds, migraines, nausea, arthritis, and high blood pressure in China and Southeast Asia. The physiological activity of ginger is attributed to its functional components, including gingerol and shogaol, and their derivatives. Aim of the study: We aimed to investigate the effects of 8- and 10-shogaol and their bioactive signaling mechanisms in a dextran sodium sulfate (DSS)-induced colitis mouse model. The anti-colitis efficacy of 6-, 8-, and 10-derivatives of gingerol and shogaol was comparatively analyzed. Materials and methods: Colitis was induced by providing mice with drinking water containing 5% DSS (w/v) for 8 days. The 6-, 8-, and 10-derivatives of gingerol and shogaol were orally administered for two weeks at a dose of 30 mg/kg. Changes in body weight and disease activity index were measured. The levels of pro-inflammatory cytokines, iNOS and COX-2, as well as the phosphorylation of NF-κB were analyzed using ELISA, PCR, or western blotting. Mucin expression and mRNA levels were measured using alcian blue staining and PCR, respectively. The tight-junction-associated proteins occludin and ZO-1 were assessed using immunohistological staining. Results: The 6-, 8-, and 10-derivatives of gingerol and shogaol exhibited anti-inflammatory effects by regulating NF-κB signaling. Among the compounds administered, 10-shogaol was the most effective against DSS-induced inflammation. Comparative analysis of the chemical structure showed that shogaol, a dehydrated analog of gingerol, was more effective. 6- and 10-shogaol showed similar effects on DSS-induced morphological changes in the colonic mucus layer, mucin expression, and tight junction proteins. Conclusions: 6-, 8-, and 10-Gingerol and 6-, 8-, and 10-shogaol significantly improved the clinical symptoms and intestinal epithelial barrier damage in DSS-induced colitis in mice. The derivatives effectively inhibited DSS-induced inflammation through the regulation of NF-κB signaling. Moreover, 10-shogaol showed the most potent anti-inflammatory effect among the six compounds used in this study. The results indicate that 8- and 10-shogaol, both main ingredients in ginger, may serve as therapeutic candidates for the treatment of colitis.

Fermented Aloe arborescens Miller Leaf Extract Suppresses Acute Alcoholic Liver Injury via Antioxidant and Anti-Inflammatory Effects in C57BL/6J Mice.

This study confirmed the change in functional composition and alcohol-induced acute liver injury in Aloe arborescens after fermentation. An acute liver injury was induced by administration of ethanol (3 g/kg/day) to C57BL/6J mice for 5 days. A fermented A. arborescens Miller leaf (FAAL) extract was orally administered 30 minutes before ethanol treatment. After fermentation, the emodin content was approximately 13 times higher than that of the raw material. FAAL extract significantly attenuated ethanol-induced aspartate aminotransferase, alanine aminotransferase, and triglyceride increases in serum and liver tissue. Histological analysis revealed that FAAL extract inhibits inflammatory cell infiltration and fat accumulation in liver tissues. The cytochrome P450 2E1, superoxide dismutase, and glutathione (GSH), which involved in alcohol-induced oxidative stress, were effectively regulated by FAAL extract in serum and liver tissues, except for GSH. FAAL also maintained the antioxidant defense system by upregulating heme oxygenase 1 and nuclear factor erythroid 2-related factor 2 protein expression. In addition, FAAL extract inhibited the decrease in alcohol dehydrogenase and aldehyde dehydrogenase activity, which promoted alcohol metabolism and prevented the activation of inflammatory response. Our results suggest that FAAL could be used as a potential therapeutic agent for ethanol-induced acute liver injury.

Anti-Inflammatory Effect and Signaling Mechanism of Glycine max Hydrolyzed with Enzymes from Bacillus velezensis KMU01 in a Dextran-Sulfate-Sodium-Induced Colitis Mouse Model.

The purpose of this study was to investigate the effect that Glycine max hydrolyzed with enzymes from Bacillus velezensis KMU01 has on dextran-sulfate-sodium (DSS)-induced colitis in mice. Hydrolysis improves functional health through the bioconversion of raw materials and increase in intestinal absorption rate and antioxidants. Therefore, G. max was hydrolyzed in this study using a food-derived microorganism, and its anti-inflammatory effect was observed. Enzymatically hydrolyzed G. max (EHG) was orally administered once daily for four weeks before DSS treatment. Colitis was induced in mice through the consumption of 5% (w/v) DSS in drinking water for eight days. The results showed that EHG treatment significantly alleviated DSS-induced body weight loss and decreased the disease activity index and colon length. In addition, EHG markedly reduced tumor necrosis factor-α, interleukin (IL)-1ß, and IL-6 production, and increased that of IL-10. EHG improved DSS-induced histological changes and intestinal epithelial barrier integrity in mice. Moreover, we found that the abundance of 15 microorganisms changed significantly; that of Proteobacteria and Escherichia coli, which are upregulated in patients with Crohn's disease and ulcerative colitis, decreased after EHG treatment. These results suggest that EHG has a protective effect against DSS-induced colitis and is a potential candidate for colitis treatment.

Cell Factory Engineering of Undomesticated Bacillus Strains Using a Modified Integrative and Conjugative Element for Efficient Plasmid Delivery.

A large number of Bacillus strains have been isolated from various environments and many of them have great potential as cell factories. However, they have been rarely developed as cell factories due to their poor transformation efficiency. In this study, we developed a highly efficient plasmid delivery system for undomesticated Bacillus strains using a modified integrative and conjugative element (MICE), which was designed to be activated by an inducer, prevent self-transfer, and deliver desired plasmids to the recipient cells. The MICE system was demonstrated to successfully introduce a gfp-containing plasmid into all 41 undomesticated Bacillus subtilis strains tested and eight other Bacillus species. The MICE was used to deliver a cytosine base editor (CBE)-based multiplex genome-editing tool for the cell factory engineering of the Bacillus species. The introduced CBE enabled one-step inactivation of the major extracellular protease genes of the tested strains. The engineered strains were used as hosts for heterologous expression of nattokinase, which resulted in various enzyme expression levels. The results suggested that the MICE and CBE systems can be powerful tools for genetic engineering of undomesticated Bacillus strains, and greatly contribute to the expansion of the Bacillus cell factory.

Comparison of laxative effects of fermented soybeans (Cheonggukjang) containing toxins and biogenic amines against loperamide-induced constipation mouse model.

BACKGROUND/OBJECTIVES: Cheonggukjang is a traditional fermented soybean paste with significant health-promoting effects. On the other hand, there have been insufficient studies on the safety and efficacy of Cheonggukjang, which is produced using traditional methods containing toxins and biogenic amines (BAs). This study compared the laxative effect of Cheonggukjang, containing high or low levels of toxins and BAs (HTBC or LTBC) in a loperamide (Lop)-induced constipation mouse model. MATERIALS/METHODS: To induce constipation, Lop (5 mg/kg) was administered orally to ICR mice twice a day for 4 days, and the dose was increased to 8 mg/kg after a 3-day rest period. Cheonggukjang (500 mg/kg, HTBC, or LTBC respectively) was administered for four weeks before the Lop treatment. RESULTS: The number of stools, fecal weight, water contents, gastrointestinal transit, and histological alterations were recovered significantly in the HTBC or LTBC groups. HTBC and LTBC administration did not induce significant changes in body weight, dietary intake, and behavior. The opioid-receptor downstream signaling pathway in colon tissues was also evaluated. The c-Kit, stem cell kinase, and mitogen-activated protein kinases subfamilies, including extracellular signal-regulated kinase 1/2, c-Jun N-terminal kinases, and p38, were all downregulated in the HTBC or LTBC-administered mice colon compared to the Lop group. CONCLUSION: These results show that Cheonggukjang, containing high levels of toxins and BAs, have a similar laxative effect in a mouse model of Lop-induced constipation.

Protective Effects of Fermented Soybeans (Cheonggukjang) on Dextran Sodium Sulfate (DSS)-Induced Colitis in a Mouse Model.

Inflammatory bowel disease (IBD) is a chronic inflammatory disease, and the incidence of IBD is increasing every year owing to changes in dietary structure. Although the exact pathogenesis of IBD is still unclear, recent evidence suggests that gut dysbiosis is closely associated with IBD pathogenesis. Cheonggukjang is a traditional Korean fermented soybean paste produced using traditional and industrial methods, and contains probiotics, which affect the gut microbiota composition. However, the protective effect of Cheonggukjang against IBD is unknown. In this study, we investigated the bacterial community structure of traditional and commercial Cheonggukjang samples, as well as the protective effect of Cheonggukjang on a dextran sulfate sodium (DSS)-induced colitis mouse model. Traditional and commercial Cheonggukjang were found to contain various type of useful probiotics in their bacterial community structure. Cheonggukjang reduced the progression of DSS-induced symptoms, such as body weight loss, colonic shortening, disease activity index, and histological changes. Further, Cheonggukjang improved the intestinal epithelial barrier integrity on DSS-induced colitis mice. In addition, Cheonggukjang suppressed the expression of proinflammatory cytokines and inflammatory mediators through the inactivation of NF-κB and MAPK signaling pathways. These results indicate that Cheonggukjang exerts protective effects against DSS-induced colitis, suggesting its possible application as a functional food for improving inflammatory diseases.

Effects of Roasted Schisandra Chinensis (Turcz.) Baill and Lycium Chinense Mill. and Their Combinational Extracts on Antioxidant and Anti-Inflammatory Activities in RAW 264.7 Cells and in Alcohol-Induced Liver Damage Mice Model.

Schisandra chinensis (Turcz.) Baill (SC) and Lycium chinense Mill. (LC) are widely distributed in Asia, where the fruit has traditionally been used for medicinal herbs. We previously reported that the roasting process improved the antioxidant and their hangover relieving effects. In this study, we assessed the antioxidant and anti-inflammatory effects of water extract of SC, LC, and a mass ratio 1 : 1 mixture (SL), after roasting in RAW264.7 macrophage cells stimulated with lipopolysaccharide (LPS). Roasted SL (RSL) extracts showed greater enhancement potential than the others, based on the inhibition of NO (nitric oxide) and intracellular reactive oxygen species (ROS) production in RAW264.7 cells. RSL also significantly decreased the proinflammatory markers (e.g., iNOS, COX-2, TNF-α, and IL-1ß) and NAD(P)H oxidase (NOX) signaling proteins (i.e., NOX (-1, -2, and -4), p22phox, p47phox, and p67phox). The inflammatory cytokine, tumor necrosis factor-alpha, interferon-1 beta levels, NF-kB, and mitogen-activated kinase activations were also significantly inhibited by RSL treatment. Based on the results of cellular levels, we compared the promotion effects of RSL extract on liver injury mediated by alcohol-induced inflammation and oxidative stress in mice. Mice were fed a Lieber-DeCarli regular liquid alcohol diet with or without SL and RSL extracts for six weeks. Alcohol intake caused liver injury, evidenced by an increase in serum alanine aminotransferase and aspartate aminotransferase activities. Consistent with the results in cell levels, RSL treatment remarkably downregulated ROS and inflammatory factors, as well as their signaling molecules, in serum and tissues. These results suggest that the roasting of SC and LC could potentially elevate the inhibition effect on alcohol-induced inflammation and oxidative stress and consequently prevent alcoholic liver damage. Also, the combination of SC and LC may provide a more synergistic effect than either alone.

Cytosine Base Editor-Mediated Multiplex Genome Editing to Accelerate Discovery of Novel Antibiotics in Bacillus subtilis and Paenibacillus polymyxa.

Genome-based identification of new antibiotics is emerging as an alternative to traditional methods. However, uncovering hidden antibiotics under the background of known antibiotics remains a challenge. To over this problem using a quick and effective genetic approach, we developed a multiplex genome editing system using a cytosine base editor (CBE). The CBE system achieved simultaneous double, triple, quadruple, and quintuple gene editing with efficiencies of 100, 100, 83, and 75%, respectively, as well as the 100% editing efficiency of single targets in Bacillus subtilis. Whole-genome sequencing of the edited strains showed that they had an average of 8.5 off-target single-nucleotide variants at gRNA-independent positions. The CBE system was used to simultaneously knockout five known antibiotic biosynthetic gene clusters to leave only an uncharacterized polyketide biosynthetic gene cluster in Paenibacillus polymyxa E681. The polyketide showed antimicrobial activities against gram-positive bacteria, but not gram-negative bacteria and fungi. Therefore, our findings suggested that the CBE system might serve as a powerful tool for multiplex genome editing and greatly accelerating the unraveling of hidden antibiotics in Bacillus and Paenibacillus species.

Citric acid and enzyme-assisted modification of flavonoids from celery (Apium graveolens) extract and their anti-inflammatory activity in HMC-1.2 cells.

Apium graveolens (celery) of the family Apiaceae contains bioactive compounds including luteolin and apigenin. The purpose of this study was to increase the extraction yield of apigenin and luteolin in celery extract using green technology and to evaluate their biological activities. The results showed that CA and ß-glucosidase-assisted celery extraction transformed apiin in the celery to apigenin with an increase in luteolin concentration. The CA and ß-glucosidase-treated celery extract (CAGE) improved the anti-inflammatory properties of celery extract by inhibiting the expression and production of inflammatory cytokines (IL-6, IL-8, IL-31, and TNF-α) in IL-33-stimulated mast cells (HMC-1.2 cells). Their mechanism of action was tied to the inhibition of ERK, JNK, IKKα, IκBα, and NF-κB activation by CAGE in the stimulated cells. In conclusion, CA and enzyme treatment can be considered as a useful biotechnology tool for the improvement of bioactive compounds in celery and hence improve on their bioactivity. PRACTICAL APPLICATIONS: Apium graveolens commonly called celery is an edible agricultural product cultivated throughout the world and known as a "superfood." Celery contains bioactive compounds including apigenin and luteolin that contribute to their described biological activities. However, extracting celery using normal extraction procedures such as hot water and ethanol methods yields only a small amount of apigenin and luteolin. In the present study, we introduced an eco-friendly method using citric and ß-glucosidase to obtain apigenin and luteolin-rich celery extract with improved anti-inflammatory activities. The present work will spark studies on the conversion of less biologically active compounds in functional food materials to more active compounds using CA and ß-glucosidase, and the development of functional food with specifically enriched bioactive substances at the industrial levels.

Protective Effects of Fermented Paprika (Capsicum annuum L.) on Sodium Iodate-Induced Retinal Damage.

Diseases of the outer retina, including age-related macular degeneration (AMD), are major cause of permanent visual damage. The pathogenesis of AMD involves oxidative stress and damage of the retinal pigment epithelium. Capsicum annuum L. (paprika) fruits have been known as a source of vitamins, carotenoids, phenolic compounds, and metabolites with a well-known antioxidant activity, which have positive effects on human health and protection against AMD and cataracts. In this study, we investigated whether paprika (fermented (FP), yellow, and orange colored) fermented with Lactobacillus (L.) plantarum could increase the protective effect of retinal degeneration using in vitro and in vivo models. FP significantly increased cell survival and reduced levels of lactate dehydrogenase as well as intracellular reactive oxygen species (ROS) increase in SI (sodium iodate, NaIO3)-treated human retinal pigment epithelial (ARPE-19) cells. We developed a model of retinal damage in C57BL/6 mice using SI (30 mg/kg) via intraperitoneal injection. Seven days after SI administration, deformation and a decrease in thickness were observed in the outer nuclear layer, but improved by FP treatment. FP administration protected the SI-mediated reduction of superoxide dismutase and glutathione levels in the serum and ocular tissues of mice. The overproduction of cleaved poly(ADP-Ribose) Polymerase (PARP)1, caspase-3 and -8 proteins were significantly protected by FP in SI-treated cells and ocular tissues. In addition, we evaluated the potentiating effects of FP on antioxidants and their underlying mechanisms in RAW 264.7 cells. Lipopolysaccharide (LPS)-induced nitrite increase was markedly blocked by FP treatment in RAW 264.7 cells. Furthermore, FP reduced LPS-induced inducible nitric oxide synthase and cyclooxygenase-2 activation. The FP also enhanced the inhibitory effects on mitogen activated kinase signaling protein activation in ARPE-19 and RAW 264.7 cells and ocular tissues. There was no significant difference in total phenol and flavonoid content in paprika by fermentation, but the vitamin C content was increased in orange colored paprika, and protective effect against oxidative stress-mediated retinal damage was enhanced after fermentation. These results suggest that FP may be a potential candidate to protect against retinal degenerative diseases through the regulation of oxidative stress.

Acute effects of Amomum villosum Lour. fruit extract on postprandial glycemia and insulin secretion: A single-blind, placebo-controlled, crossover study in healthy subjects.

BACKGROUND: Amomum villosum Lour., (Zingiberaceae) an herbaceous plant in the ginger family, has been used to treat various diseases. In a single-blind, randomized, crossover study, we assessed the postprandial blood insulin and blood glucose responses in healthy subjects (n = 40) after the Amomum villosum water extract (AVE) (5 g/person) or a placebo (5 g/person) consumption. METHODS: During each treatment course, the healthy subject consumed a regular late afternoon meal, followed by fasting for 12 h, and arrived at the clinical study center the next morning. Blood insulin and blood glucose levels were assessed at 0, 30, 60, 90, and 120 min after AVE consumption. Between each treatment, the subjects accomplished one week of a washout period. RESULTS: The AVE intake demonstrated a significant (67.26%) decline in postprandial blood glucose AUC0-120 min (incremental area under the curve from 0 to 120 min) versus the placebo (P = 0.011). Furthermore, AVE reduced postprandial blood insulin AUC0-120 min by 59.95% compared to the placebo group (P < 0.003), supporting the blood glucose results. CONCLUSION: This study revealed that AVE consumption significantly reduced postprandial insulin and glucose levels in healthy individuals, due in part to inhibition of α-glucosidase, and glucose transport.

Perilla frutescens Sprout Extract Protect Renal Mesangial Cell Dysfunction against High Glucose by Modulating AMPK and NADPH Oxidase Signaling.

Perilla frutescens (L.) Britt. var. japonica (Hassk.) Hara (PF), is a medical herb of the Lamiaceae family. We have previously reported that the PF sprout extract (PFSE) is effective in treating hyperglycemia. However, the role of PFSE on glomerular mesangial cells (MCs) proliferation and the extracellular matrix (ECM) accumulation in a diabetic condition are still unclear. Therefore, in this study, we have investigated the role of PFSE on cell proliferation and ECM accumulation in murine glomerular MCs (MMCs), cultured under a high glucose (HG) condition. PFSE treatment attenuated HG-induced MMCs proliferation and hypertrophy. Moreover, the HG-induced ECM protein, collagen IV and fibronectin, overexpression was abolished by the PFFSE treatment. In addition, PFSE inhibited reactive oxygen species (ROS) overproduction and NOX2 and NOX4 expression in MMCs under a HG condition. Our data further revealed the involvement of mesangial cell damage in AMP-activated kinase (AMPK) activation. PFSE strongly activated AMPK in MMCs under hyperglycemic conditions. These results suggest that PFSE inhibits HG-medicated MC fibrosis through suppressing the activation of NOX2/4 and the AMPK activation mechanism. PFSE may be useful for the prevention or treatment of diabetic nephropathy.