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PubMedDate not supplied

Comparison of extraction techniques for extraction of bioactive molecules from Hypericum perforatum L. plant.

Three methods commonly used for the extraction of bioactive molecules from natural plant material are compared. Dried Hypericum perforatum L. plant material is subjected to Soxhlet extraction, extraction by ultrasonication, and accelerated solvent extraction. The percentage of two bioactive compounds, hyperforin and hypericin, in the extracts is used as a parameter for comparison of the extraction procedure.

Chromatography, High Pressure Liquid↗

PubMed2004

Traditional and Modern Biomedical Prospecting: Part I-the History: Sustainable Exploitation of Biodiversity (Sponges and Invertebrates) in the Adriatic Sea in Rovinj (Croatia).

Nature, especially the marine environment, provides the most effective drugs used in human therapy. Among the metazoans, the marine sponges (phylum Porifera), which are sessile filter feeders, produce the most potent and highly selective bioactive secondary metabolites. These animals (or their associated symbiotic microorganisms) synthesize secondary metabolites whose activity and selectivity has developed during their long evolutionary history (evochemistry). The exploitation of these resources has become possible due to the progress in molecular and cell biology. BIOTECmarin, the German Center of Excellence follows this rationale. In the past, these animals have been successfully and extensively utilized to isolate bioactive compounds and biomaterials for human benefit. Pharmaceuticals prepared from marine animals, primarily sponges, have been applied since ancient times (Hippocrates, Aristotle and later Plinius). It has been reported that extracts and/or components from sponges can be used for the treatment of specific diseases. For a systematic and applied-oriented exploitation, the successful development of effective compounds largely depends on quality of the institutional infrastructure of marine stations and more so on the biodiversity. The Center for Marine Research in Rovinj (Croatia) fulfils these prerequisites. Founded in 1891, this institute has to its credit major discoveries related to exploitation of secondary metabolites/biomaterials from sponges for therapeutical application and to obtain biomaterials for general wellbeing. This is the first part of a review focusing on biomedical prospecting. Here, we have mainly described the historic background. The details of techniques, substances, approaches and outlooks will be discussed in the second part.

Journal Article↗

PubMed2005

An Overview of Bee Venom Acupuncture in the Treatment of Arthritis.

Bee venom acupuncture (BVA), as a kind of herbal acupuncture, exerts not only pharmacological actions from the bioactive compounds isolated from bee venom but also a mechanical function from acupuncture stimulation. BVA is growing in popularity, especially in Korea, and is used primarily for pain relief in many kinds of diseases. We aimed to summarize and evaluate the available evidence of BVA for rheumatoid arthritis and osteoarthritis. Computerized literature searches for experimental studies and clinical trials of BVA for arthritis were performed on the databases from PUBMED, EMBASE and the Cochrane Library. In addition, two leading Korean journals (The Journal of Korean Society for Acupuncture and Moxibustion and The Journal of Korean Oriental Medicine) were searched for relevant studies. The search revealed 67 studies, 15 of which met our criteria. The anti-inflammation and analgesic actions of BVA were proved in various kinds of animal arthritic models. Two randomized controlled trials and three uncontrolled clinical trials showed that BVA was effective in the treatment of arthritis. It is highly likely that the effectiveness of BVA for arthritis is a promising area of future research. However, there is limited evidence demonstrating the efficacy of BVA in arthritis. Rigorous trials with large sample size and adequate design are needed to define the role of BVA for these indications. In addition, studies on the optimal dosage and concentration of BVA are recommended for future trials.

Journal Article↗

PubMed1994

Uptake and metabolism of sphingolipids in isolated intestinal loops of mice.

Sphingolipids are found in all eukaryotic organisms. However, little is known about the digestion, uptake and subsequent metabolism of these constituents of food. In this study, radiolabeled sphingolipids were placed in isolated intestinal segments of female CF1 mice, and the metabolism and distribution of the radiolabel were followed. Most of the sphingomyelin was degraded to ceramide and other products in all regions of the intestine, and increasing amounts of several [3H]-labeled sphingolipids appeared in the tissues. Small amounts of the radiolabel disappeared from the intestinal loops and appeared in liver within the first 30 to 60 min implying that neither intact sphingomyelin nor its metabolites are transported very efficiently from the intestine to other organs. There were different degrees of uptake and metabolism of sphingomyelin, [4,5-3H-sphinganyl]ceramide, and [3H]sphingosine. The [3H]sphingomyelin was also administered by gavage and the appearance along the intestine measured. After 90 min, 12% was found in the cecum and colon. These results establish that some of the sphingomyelin that enters the gastrointestinal tract is hydrolyzed and taken up by the intestine, with the lipid backbone being degraded or reutilized for complex sphingolipid synthesis; however, at least a portion passes into the large intestine. The appearance of bioactive compounds throughout the gastrointestinal tract may alter the behavior of intestinal cells.

Administration, Oral↗

PubMed1997

Importance of sphingolipids and inhibitors of sphingolipid metabolism as components of animal diets.

Sphingolipids are highly bioactive compounds that participate in the regulation of cell growth, differentiation, diverse cell functions, and apoptosis. They are present in both plant and animal foods in appreciable amounts, but little is known about their nutritional significance. Recent studies have shown that feeding sphingomyelin to female CF1 mice treated with a colon carcinogen (1,2-dimethylhydrazine) reduced the number of aberrant colonic crypt foci; longer-term feeding also affected the appearance of colonic adenocarcinomas. Therefore, dietary sphingolipids should be considered in studies of the relationships between diet and cancer. Sphingolipids have also surfaced as important factors in understanding the mechanism of action of a recently discovered family of mycotoxins, termed fumonisins. Fumonisins are produced by fungi commonly found on maize and a few related foods, and their consumption can result in equine leukoencephalomalacia, porcine pulmonary edema and a number of other diseases of veterinary animals and, perhaps, humans. A cellular target of fumonisins is the enzyme ceramide synthase, and disruption of sphingolipid metabolism by fumonisins has been established by studies with both cells in culture and animals that have consumed these toxic mycotoxins. These findings underscore the ways in which sphingolipids and agents that affect sphingolipid utilization should be given consideration in selecting animal diets for nutritional and toxicological studies.

Animal Feed↗

PubMed2001

A cross-sectional study of human serum sphingolipids, diet and physiologic parameters.

Sphinganine and sphingosine, the two sphingoid base backbones of sphingolipids, are highly bioactive compounds that are of increasing interest to nutritionists because they occur in food and their metabolism can be altered by fungal toxins that contaminate some foods. Nonetheless, no studies of diet and sphinganine or sphingosine concentrations in serum have yet been reported. Here we describe a cross-sectional study of 265 residents of Linxian, People's Republic of China, which examines potential demographic, physiologic and dietary correlates of serum sphinganine and sphingosine in this population. Median concentrations of serum sphinganine and sphingosine were compared among strata for 29 different variables. For sphinganine, no significant differences were found. For sphingosine, significant differences were seen among strata of age, menstruation status, serum cholesterol, carotenoids, retinol, tocopherols, fresh and dried vegetable and fresh fruit consumption. Using multivariate linear regression with stepwise selection, we found that the significant predictors for serum sphingosine included total tocopherols, age, serum selenium and retinol, with a final R(2) = 0.22; for sphinganine, tooth loss was the sole correlate, with R(2) = 0.015. Analyses using ranked sphingolipid data or principal components analysis, to simplify the food variables, did not materially alter these results. This study represents the largest report of human serum sphingolipid concentrations to date and provides insight into potential explanatory variables that can be incorporated into future studies.

Adult↗

PubMed2003

Mechanisms of dairy modulation of adiposity.

Dietary calcium plays a pivotal role in the regulation of energy metabolism, in that we have found high calcium diets to attenuate adipocyte lipid accretion and weight gain during periods of overconsumption of an energy-dense diet and to increase lipolysis and preserve thermogenesis during caloric restriction, thereby markedly accelerating weight loss. Our studies of the agouti gene in obesity and insulin resistance demonstrate a key role for intracellular Ca(2+) in regulating adipocyte lipid metabolism and triglyceride storage, with increased intracellular Ca(2+), resulting in stimulation of lipogenic gene expression and lipogenesis, and suppression of lipolysis, resulting in adipocyte lipid filling and increased adiposity. Moreover, we have recently demonstrated that the increased calcitriol produced in response to low calcium diets stimulates Ca(2+) influx in human adipocytes and thereby promotes adiposity. Accordingly, suppressing calcitriol levels by increasing dietary calcium is an attractive target for the prevention and management of obesity. In support of this concept, transgenic mice expressing the agouti gene specifically in adipocytes (a humanlike pattern) respond to low calcium diets with accelerated weight gain and fat accretion, whereas high calcium diets markedly inhibit lipogenesis, accelerate lipolysis, increase thermogenesis and suppress fat accretion and weight gain in animals maintained at identical caloric intakes. Further, low calcium diets impede body fat loss, whereas high calcium diets markedly accelerate fat loss in transgenic mice subjected to caloric restriction. Notably, dairy sources of calcium exert markedly greater effects in attenuating weight and fat gain and accelerating fat loss. This augmented effect of dairy vs. supplemental calcium is likely attributable to additional bioactive compounds in dairy that act synergistically with calcium to attenuate adiposity; among these are angiotensin converting enzyme inhibitory peptides, which limit angiotensin II production and thereby limit angiotensin II stimulation of adipocyte lipogenesis. These concepts are confirmed by both epidemiological and clinical data, which similarly demonstrate that dairy products exert a substantially greater effect on both fat loss and fat distribution compared to an equivalent amount of supplemental calcium.

Adipocytes↗

PubMed2003

Berry intake increases the activity of the gamma-glutamylcysteine synthetase promoter in transgenic reporter mice.

A diet rich in fruit and vegetables is associated with decreased risk of disease. One possible mechanism for this is that dietary antioxidants positively regulate protective genes. Toward our goal to identify bioactive compounds with such functions in plants, we developed transgenic mice that express luciferase controlled by the gamma-glutamylcysteine synthetase heavy subunit (GCS(h)) promoter. Mice that consumed a nonpurified diet ad libitum were supplemented with juices or extracts of antioxidant-rich berries for 42 h or 3-4 wk. The treatments generally increased luciferase activity in brain and skeletal muscle and decreased it in liver compared with controls fed water. The same overall pattern was also found in mice fed ellagic acid (EA), a phenolic acid found in many berries. This change in GCS(h) promoter activity after berry treatment occurred in only approximately 50% of the mice, indicating that they were either responders or nonresponders. Our results demonstrate for the first time that berry extracts rich in polyphenols and EA can induce GCS(h) in vivo. The induction of protective enzymes may be important for the chemopreventive effects of fruits and vegetables.

Animals↗

PubMed2003

Cereal alkylresorcinols are absorbed by humans.

Currently there is no biomarker to link consumption of whole grain cereals and their observed health benefits. A candidate for a biomarker of whole grain wheat and rye intake is a class of phenolic lipids, the alkylresorcinols (AR). Studies to determine the uptake of AR in humans were carried out with a low fiber diet based on white wheat bread (AR free) and a high fiber diet based on rye bran-enriched bread (AR rich). For each diet, two meal frequencies were used: nibbling (7 small meals/d) and ordinary (3 large meals/d). Ten human ileostomy-operated subjects started with the AR-free diet for 2 wk, wk 1 on either nibbling or ordinary and wk 2 on the other meal frequency in a crossover design, followed by a 1-wk washout period, before the AR-rich diet performed as the AR-free diet. Food and ileostomy samples were analyzed for AR. Approximately 40% of AR were recovered in effluent from the small intestine, indicating that 60% of AR are taken up from or converted in the small intestine (ileal digestibility) with no difference between nibbling and ordinary meal frequencies. AR absorbed by humans may be of importance as bioactive compounds, or as a biomarker of whole grain wheat and rye intake.

Adult↗

PubMed2004

Potential synergy of phytochemicals in cancer prevention: mechanism of action.

Epidemiological studies have consistently shown that regular consumption of fruits and vegetables is strongly associated with reduced risk of developing chronic diseases, such as cancer and cardiovascular disease. It is now widely believed that the actions of the antioxidant nutrients alone do not explain the observed health benefits of diets rich in fruits and vegetables, because taken alone, the individual antioxidants studied in clinical trials do not appear to have consistent preventive effects. Work performed by our group and others has shown that fruits and vegetable phytochemical extracts exhibit strong antioxidant and antiproliferative activities and that the major part of total antioxidant activity is from the combination of phytochemicals. We proposed that the additive and synergistic effects of phytochemicals in fruits and vegetables are responsible for these potent antioxidant and anticancer activities and that the benefit of a diet rich in fruits and vegetables is attributed to the complex mixture of phytochemicals present in whole foods. This explains why no single antioxidant can replace the combination of natural phytochemicals in fruits and vegetables to achieve the health benefits. The evidence suggests that antioxidants or bioactive compounds are best acquired through whole-food consumption, not from expensive dietary supplements. We believe that a recommendation that consumers eat 5 to 10 servings of a wide variety of fruits and vegetables daily is an appropriate strategy for significantly reducing the risk of chronic diseases and to meet their nutrient requirements for optimum health.

Antioxidants↗

PubMed2005

Citrus limonoids induce apoptosis in human neuroblastoma cells and have radical scavenging activity.

Citrus limonoid glucosides, a family of fruit bioactive compounds, were postulated to have free radical-scavenging and apoptosis-inducing properties against certain types of cancers. Four highly purified limonoid glucosides, limoin 17beta D-glucopypranoside (LG), obacunone 17beta D-glucopyranoside (OG), nomilinic acid 17beta D-glucopyranoside (NAG), and deacetylnomilinic acid 17beta D-glucopyranoside (DNAG) were tested for superoxide radical (O(2)(-))-quenching activity and cytotoxic action against undifferentiated human SH-SY5Y neuroblastoma cells in culture. All 4 scavenged O(2)(-) as measured by inhibition of pyrogallol decomposition in a spectrophotometric assay. Quenching by NAG in particular emulated an equivalent concentration of vitamin C. When added to the medium of SH-SY5Y cells in culture, micromolar amounts of LG and OG, compared with untreated controls, caused a cessation of cell growth and rapid cell death (P < 0.001); NAG and DNAG were better tolerated, but nonetheless toxic as well. Cytotoxicity was related to a concentration- and time-dependent increase in caspase 3/7 activity, suggesting that limonoid glucosides were capable of inducing apoptosis. Arrested cell growth and the induction of apoptosis were confirmed by flow cytometry and DNA fragmentation analysis. Importantly, caspase induction at 12 h correlated with cell survival at 24 h (P = 0.046), suggesting that apoptosis was the primary cause of cell death. We conclude that citrus limonoid glucosides are toxic to SH-SY5Y cancer cells. Cytotoxicity is exerted through apoptosis by an as yet unknown mechanism of induction. Individual limonoid glucosides differ in efficacy as anticancer agents, and this difference may reside in structural variations in the A ring of the limonoid molecule.

Apoptosis↗

PubMed2003

The use of zebrafish mutants to identify secondary target effects of acetylcholine esterase inhibitors.

We are confronted with a large and steadily growing number of bioactive compounds, including drugs, pesticides, and industrial by-products. The assessment of target specificity and potential toxic effect on human health and the environment generates a strong demand for robust and cost-effective models with high predictive power. We investigated the potential of the zebrafish embryo as a whole organism, vertebrate model to assess the specificity of compounds that are known to inhibit acetylcholinesterase (AChE). Inhibitors of AChE are widely used as drugs and pesticides. By application of simple assays and comparison with the phenotype of embryos with genetic lesions in the ache gene, we demonstrate that only one of the AChE inhibitors (galanthamine) reproduces the phenotype of ache mutant embryos. The other compounds produced additional effects indicating secondary targets. Our work demonstrates the power of a genetic system for toxicological evaluations. The combination of genetics and transgenesis with the other experimental virtues of the zebrafish embryo, such as small size and low cost, offers a whole organism platform for medium to high throughput compound testing.

Acetylcholinesterase↗

PubMed2026

Biocontrol Potential of a Novel Bacillus velezensis Strain Against Major Soft Rot Bacteria Pectobacterium and Dickeya.

Management of soft rot Pectobacteriaceae (SRP) remains a major challenge because effective control options such as bactericides, chemical treatments, or resistant commercial varieties are currently lacking. In a quest for an effective control measure against SRP, we isolated bacteria from soil and potato samples from potato fields across Montana. The bacterial isolates were screened for their effective suppression of major soft rot and blackleg pathogens Pectobacterium brasiliense strain Pb1692 and Dickeya dianthicola strain ME23. We screened more than 3,000 bacterial isolates using inhibition-zone assays on nutrient agar plates. From this collection, we identified a strong antagonist effective against Pb1692 and ME23. This isolate successfully suppressed potato soft rot and blackleg disease in both laboratory and greenhouse evaluations. Genome sequencing identified the bacterial antagonist as Bacillus velezensis strain DN539, which can survive well at 8°C, a potato postharvest storage temperature. We enriched the B. velezensis DN539 supernatant in bioactive fractions, and mass spectrometry analysis identified the bioactive compound as isomers of surfactin. Scanning electron microscopy identified that surfactin-enriched fraction resulted in the leakage of the cellular content of phytobacteria tested in our study in as little as 10 min, followed by complete degradation of bacterial cells within 1 h. The surfactin-enriched fraction also had antimicrobial effects against other economically important phytobacteria such as Erwinia amylovora, Xanthomonas campestris, and Pseudomonas syringae. These indicate that surfactin synthesized by Bacillus velezensis DN539 has potential to be developed as a biocontrol agent against broad range of phytobacteria.

Pectobacterium↗

PubMed2001

Dietary catechins in relation to coronary heart disease death among postmenopausal women.

Catechins, one of the major groups of flavonoids, are bioactive compounds present in a variety of plant foods and beverages. Experimental data suggest that they might prevent chronic diseases in humans. We studied whether the intake of catechins was inversely associated with the risk of coronary heart disease death in a prospective study of postmenopausal women from Iowa. Between 1986 and 1998, 767 of 34,492 participants initially free of cardiovascular diseases died from coronary heart disease. There was a strong inverse association between the intake of (+)-catechin and (-)-epicatechin and coronary heart disease death, which was somewhat attenuated after multivariate adjustment (risk ratios from lowest to highest quintile: 1.00, 0.95, 0.97, 0.77, 0.76). This inverse association was most pronounced in women at low risk of coronary heart disease (non-smokers, free of diabetes mellitus and cardiovascular diseases). A high intake of "gallates," catechins typical of tea, was not associated with coronary heart disease death. Of the major catechin sources, apples and wine were inversely associated with coronary heart disease death. Our data suggest that preventive effects might be limited to certain types of catechins, or that these are indicators of other dietary components or a healthy lifestyle in general.

Aged↗

PubMed1996

Endothelial cell activity varies in patients at risk for the adult respiratory distress syndrome.

OBJECTIVE: The endothelial cell produces many bioactive compounds that are presumed to play important roles in the pathogenesis of the adult respiratory distress syndrome (ARDS). We postulated that individuals with sepsis and trauma-two at-risk diagnoses for the development of ARDS--might demonstrate differences in the degree of endothelial cell activity. DESIGN: Prospective cohort study. SETTING: Intensive care unit patients in a tertiary, university-affiliated, city hospital. PATIENTS: Fifty-five intensive care unit patients (19 with sepsis and 36 trauma patients). INTERVENTIONS: Plasma measurements of three endothelial cell products--von Willebrand factor antigen, soluble intercellular adhesion molecule-1 (ICAM-1), and soluble E-selectin-were performed within 8 hrs of patients meeting our inclusion criteria, and at the clinical onset of ARDS. MEASUREMENTS AND MAIN RESULTS: Twenty-six percent of the septic patients and 25% of the trauma patients developed ARDS. The median (and 25% to 75% quartiles) concentrations of all three mediators measured in the sepsis patients (von Willebrand factor antigen 399% [375% to 452%], ICAM-1 573 ng/mL [470 to 980], and soluble E-selectin 180 ng/mL [81 to 340]) were significantly higher (p < .001 for each individual analysis) than in the trauma patients (von Willebrand factor antigen 256% [217% to 310%], ICAM-1 148 ng/mL [113 to 210], and soluble E-selectin 42 ng/mL [31 to 65 ng/ mL]). In addition, neither the ICAM-1 nor soluble E-selectin concentrations measured in the trauma patients were different (p = .17 and p = .24, respectively) from normal controls. In those patients who developed ARDS, the differences in the concentrations of all three endothelial cell mediators between the sepsis and trauma patients persisted (p = .008 for von Willebrand factor antigen, p = .003 for ICAM-1, and p = .003 for E-selectin). CONCLUSION: These findings suggest that differences in endothelial cell activity exist between sepsis and trauma patients who are at risk for the development of ARDS.

Adult↗

PubMed2000

Superoxide dismutase and glutathione peroxidase content of human milk from mothers of premature and full-term infants during the first 3 months of lactation.

BACKGROUND: Human milk contains various bioactive compounds including numerous immunologic factors, enzymes, growth factors, and hormones. However, the change during the course of lactation in many of these compounds has not been fully characterized. Therefore, the objective of the present study was to measure the activity of the enzymes superoxide dismutase (SOD; Enzyme Commission number [EC] 1.15.1.1) and glutathione peroxidase (SeGSHPx; EC 1.11.1.9) in human milk, to record changes in enzyme activity over time and to determine whether there are differences in activity between the milk of mothers of full-term (FT) and premature (PT) infants. METHODS: Nine samples were collected from each of 15 mothers (32 +/- 4 years of age; mean +/- standard deviation) of FT infants (gestational age, 40 +/- 1 weeks; birth weight, 3544 +/- 417 g) and 19 mothers (28 +/- 5 years of age) of healthy PT infants (gestational age, 29 +/- 4 weeks; birth weight, 1312 +/- 479 g). Samples were collected within a week of birth (+/- 1 day) and thereafter for 8 weeks, with a final collection at 12 weeks. RESULTS: During the 12-week study period, in both groups, total milliunits of GHSPx and SeGHSPx per milligram protein and SOD per per milligram protein increased, whereas protein content declined. SeGHSPx per milliliter milk was higher in the PT group at week 1 (92 +/- 30 mU/mL vs. 73 +/- 21 mU/mL), week 2 (93 +/- 28 mU/mL vs. 75 +/- 24 mU/mL), and week 7 (85 +/- 24 mU/mL vs. 68 +/- 22 mU/mL). The SOD activity per milliliter milk and milligram protein was higher throughout the entire study in the FT milk. CONCLUSIONS: Because mothers of PT infants may produce less milk than those of FT infants, PT infants may be at a disadvantage for antioxidant protection from these enzymes.

Adult↗

PubMed1994

Egg consumption and cancer of the colon and rectum.

We systematically reviewed 15 previous case-control and cohort studies that examined egg consumption as a risk factor for cancers of the colon and rectum. Nine of the 11 studies of colon cancer reported risk estimates consistent with a positive association; in three of these studies the association was statistically significant. The positive association for egg consumption was generally stronger for females than for males, and for cancer of the proximal, rather than distal colon. Six of eight studies of cancer of the rectum reported risk estimates consistent with a positive association; in two of these studies the association was statistically significant. Notably, in every study that met specific design criteria (defined a priori), risk estimates were consistent with a positive association. Two studies reported seven- to eight-fold increases in risk with high egg consumption. In some studies, positive associations remained after adjustment for intakes of macronutrients or for other food groups. The presence of a variety of bioactive compounds, including cholesterol, lends biological plausibility to a role of egg consumption in the aetiology of colorectal cancer.

Adolescent↗

PubMedDate not supplied

Do Nuts Have a Place in a Healthful Diet?

A wealth of nutrition information has been published during the past decade on the healthful nature of nuts. As nut consumption increases, cardiovascular disease risk decreases. This cardioprotective effect of nut consumption is beyond what would be predicted from the fatty acid profile alone. Nuts are a rich source of many other nutrients and bioactive compounds, similar to other whole-plant foods, such as fruits and vegetables. Additional studies during the next decade will delineate additional healthful nutrients of these foods.

Journal Article↗