- 1. Oestradiol modulation of serotonin reuptake transporter and serotonin metabolism in the brain of monkeys.
Serotonin (5-HT) is an important brain neurotransmitter implicated in mental and neurodegenerative diseases that is modulated by ovarian hormones. Nevertheless, the effect of oestrogens on 5-HT neurotransmission in the primate caudate nucleus, putamen and nucleus accumbens, major components of the basal ganglia, and the anterior cerebral cortex, mainly the frontal and cingulate gyrus is not well documented. We therefore evaluated the response of the 5-HT reuptake transporter (SERT) and 5-HT metabolism in these brain regions to a one-month treatment with 17β-oestradiol in short-term (one month) ovariectomised (OVX) monkeys (macaca fascicularis). SERT specific binding was measured by autoradiography using the radioligand [(3) H]citalopram and biogenic amines concentrations were quantified by HPLC. 17β-oestradiol increased SERT in the superior frontal cortex and in the anterior cingulate cortex, the nucleus accumbens and in subregions of caudate nucleus of OVX monkeys. 17β-oestradiol left unchanged [(3) H]citalopram specific binding in the putamen, the dorsal and medial raphe nucleus. 17β-oestradiol treatment decreased striatal concentrations of the precursor of 5-HT, 5-hydroxytryptophan (5-HTP) and increased 5-HT, dopamine and 3-methoxytyramine concentrations in the nucleus accumbens, caudate nucleus and putamen while the metabolites 5-hydroxyindoleacetic acid, 3,4-dihydroxyphenylacetic acid and homovanillic acid concentrations remained unchanged. No effect of 17β-oestradiol treatment was observed for biogenic amine concentrations in the cortical regions. A significant positive correlation was observed between [(3) H]citalopram specific binding and 5-HT concentrations in the caudate nucleus, putamen, and nucleus accumbens suggesting their link. These results have translational value for women with low oestrogen such as in surgical menopause or in the peri-menopause. © 2013 British Society for Neuroendocrinology....(more)
Sánchez MG, et al. J Neuroendocrinol 2013 Feb 18.
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- 2. Feeding 5-hydroxy-l-tryptophan during the transition from pregnancy to lactation increases calcium mobilization from bone in rats.
An increasing demand for calcium during pregnancy and lactation can result in both clinical and subclinical hypocalcemia during the early lactation period in several mammalian species, in particular the dairy cow. Serotonin (5-HT) was recently identified as a regulator of lactation and bone turnover. The purpose of this study was to determine whether supplementation of the maternal diet with a 5-HT precursor would increase maternal bone turnover and calcium mobilization to maintain appropriate circulating maternal concentrations of ionized calcium during lactation. Female Sprague-Dawley rats (n = 30) were fed either a control diet (n = 15) or a diet supplemented with the 5-HT precursor 5-hydroxytryptophan (5-HTP, 0.2%; n = 15) from day 13 of pregnancy through day 9 of lactation. Maternal serum and plasma (day 1 and day 9 of lactation), milk and pup weight (daily), mammary gland and bone tissue (day 9 of lactation) were collected for analysis. The 5-HTP diet elevated circulating maternal concentrations of 5-HT on day 1 and day 9 of lactation and parathyroid hormone related-protein (PTHrP) on day 9 of lactation (P < 0.033). In addition, 5-HTP supplementation increased total serum calcium concentrations on day 1 of lactation and total milk calcium concentration on day 9 of lactation (P < 0.032). Supplemental 5-HTP did not alter milk yield, maternal body weight, mammary gland structure, or pup litter weights (P > 0.05). Supplemental 5-HTP also resulted in increased concentrations of mammary 5-HT and PTHrP, as well as increased mRNA expression of rate-limiting enzyme in 5-HT synthesis, tryptophan hydroxylase 1, and Pthrp mRNA on day 9 of lactation (P < 0.028). In addition, supplementation of 5-HTP resulted in increased mRNA expression of maternal mammary calcium transporters and resorption of bone in the femur, indicated by increase osteoclast number and diameter as well as mRNA expression of classical markers of bone resorption on day 9 of lactation (P < 0.048). These results show that increasing 5-HT biosynthesis during the transition from pregnancy to lactation could be a potential therapeutic target to explore for prevention of subclinical and clinical hypocalcemia....(more)
Laporta J, et al. Domest Anim Endocrinol 2013 May;44(4):176-84.
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- 3. Synthesis of 2,4-dihydroxychalcone derivatives as potential antidepressant effect.
In this study, twelve 2,4-dihydroxychalcone derivatives were synthesized and evaluated for antidepressant activities using the forced swimming test (FST). The pharmacological test showed that 6 compounds significantly reduced the immobility times in the FST at a dose of 10 mg/kg, indicative of antidepressant activity. Among the derivatives, compounds designated 3d and 3 h exhibited the best antidepressant activity, with reduced immobility time by 32.05% and 34.33%, respectively. In the 5-hydroxytryptophan-induced head-twitch test and yohimbine-induced mortality test, compounds 3d and 3 h increased head-twitch and increased the mortality rate. The mechanisms of the antidepressant effects of compounds 3d and 3 h may be related with the 5-HTP and NE nervous system....(more)
Guan LP, et al. Drug Res (Stuttg) 2013 Jan;63(1):46-51.
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- 4. Serotonin precursor (5-hydroxytryptophan) causes substantial changes in the fighting behavior of male crickets, Gryllus bimaculatus.
This study demonstrates that injection of the serotonin precursor 5-HTP causes substantial changes in the behavioral state, fighting behavior and ability to establish winner-loser relationships in male crickets (Gryllus bimaculatus). The characteristic features of 5-HTP-treated crickets include an elevated posture, enhanced general activity, longer duration of fighting, enhanced rival singing and a decreased ability to produce a clear fight loser. In addition, 5-HTP-treated males showed a slightly delayed latency to spread their mandibles, a decreased number of attacks and an equal potential to win in comparison to controls (physiological solution-treated males). The obtained results imply a significant role for serotonin in the regulation of social status-related behaviors in G. bimaculatus. Specifically, these data indicate that a decrease in serotonergic activity may be functionally important for the control of loser behavior and that some behavioral features of dominant male crickets are likely to be connected with the activation of the serotonergic system....(more)
Dyakonova VE, et al. J Comp Physiol A Neuroethol Sens Neural Behav Physiol 2013 Mar 6.
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- 5. Serotonin (5-HT) affects expression of liver metabolic enzymes and mammary gland glucose transporters during the transition from pregnancy to lactation.
The aim of this experiment was to demonstrate the ability of feeding serotonin (5-HT; 5-hydroxytryptamine) precursors to increase 5-HT production during the transition from pregnancy to lactation and the effects this has on maternal energy metabolism in the liver and mammary gland. Pregnant rats (n=45) were fed one of three diets: I) control (CON), II) CON supplemented with 0.2% 5-hydroxytryptophan (5-HTP) or III) CON supplemented with 1.35% L-tryptophan (L-TRP), beginning on d13 of pregnancy through d9 of lactation (d9). Serum (pre and post-partum), milk (daily), liver and mammary gland tissue (d9) were collected. Serum 5-HT was increased in the 5-HTP fed dams beginning on d20 of gestation and remained elevated through d9, while it was only increased on d9 in the L-TRP fed dams. 5-HT levels were increased in mammary gland and liver of both groups. Additionally, 5-HTP fed dams had serum and milk glucose levels similar to the CON, while L-TRP had decreased serum (d9) and milk glucose (all dates evaluated). Feeding 5-HTP resulted in increased mRNA expression of key gluconeogenic and glycolytic enzymes in liver and glucose transporters 1 and 8 (GLUT-1, -8) in the mammary gland. We demonstrated the location of GLUT-8 in the mammary gland both in the epithelial and vascular endothelial cells. Finally, phosphorylated 5' AMP-activated protein kinase (pAMPK), a known regulator of intracellular energy status, was elevated in mammary glands of 5-HTP fed dams. Our results suggest that increasing 5-HT production during the transition from pregnancy to lactation increases mRNA expression of enzymes involved in energy metabolism in the liver, and mRNA abundance and distribution of glucose transporters within the mammary gland. This suggests the possibility that 5-HT may be involved in regulating energy metabolism during the transition from pregnancy to lactation....(more)
Laporta J, et al. PLoS One 2013;8(2):e57847.
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- 6. Protein profiling of paraquat-exposed rat lungs following treatment with Acai (Euterpe oleracea Mart.) berry extract.
Paraquat (1,1'-dimethyl-4,4'-bipyridinium chloride, PQ) is a non-selective herbicide, and PQ poisoning by accidental or intentional ingestion is a cause of numerous fatalities around the world every year. Although a great deal of research has been conducted into the development of an acceptable treatment for PQ poisoning, no effective guidelines for patients have been developed thus far. Acai berry extract and juice have been highlighted in this regard, due to their observed antioxidant effects in various diseases. Furthermore, the acai berry has been used in dietary supplements, as it contains a variety of nutrients, including proteins, lipids, vitamins A, C and E and polyphenols. In this study, we conducted proteomic analysis of PQ-poisoned rat lungs to evaluate the changes in protein expression induced by PQ and to identify any protective effects of acai berry on the PQ poisoning. Our data revealed that the expression of the calcium signaling-related proteins calcium binding protein 1 (CaBP1), FK506 binding protein 4 (FKBP4), S100A6 and secreted protein acidic and rich in cysteine (Sparc, also known as osteonectin) were induced by PQ treatment and downregulated by acai berry treatment. However, the levels of protein kinase C substrate 80K-H were shown to be downregulated as the result of PQ treatment. Our results indicated that these proteins may function as biomarkers for acute poisoning by PQ exposure. Further studies may be necessary to understand their clinical relevance with regard to PQ poisoning....(more)
Kim YS, et al. Mol Med Rep 2013 Mar;7(3):881-6.
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- 7. Nasal Acai polysaccharides potentiate innate immunity to protect against pulmonary Francisella tularensis and Burkholderia pseudomallei Infections.
Pulmonary Francisella tularensis and Burkholderia pseudomallei infections are highly lethal in untreated patients, and current antibiotic regimens are not always effective. Activating the innate immune system provides an alternative means of treating infection and can also complement antibiotic therapies. Several natural agonists were screened for their ability to enhance host resistance to infection, and polysaccharides derived from the Acai berry (Acai PS) were found to have potent abilities as an immunotherapeutic to treat F. tularensis and B. pseudomallei infections. In vitro, Acai PS impaired replication of Francisella in primary human macrophages co-cultured with autologous NK cells via augmentation of NK cell IFN-γ. Furthermore, Acai PS administered nasally before or after infection protected mice against type A F. tularensis aerosol challenge with survival rates up to 80%, and protection was still observed, albeit reduced, when mice were treated two days post-infection. Nasal Acai PS administration augmented intracellular expression of IFN-γ by NK cells in the lungs of F. tularensis-infected mice, and neutralization of IFN-γ ablated the protective effect of Acai PS. Likewise, nasal Acai PS treatment conferred protection against pulmonary infection with B. pseudomallei strain 1026b. Acai PS dramatically reduced the replication of B. pseudomallei in the lung and blocked bacterial dissemination to the spleen and liver. Nasal administration of Acai PS enhanced IFN-γ responses by NK and γδ T cells in the lungs, while neutralization of IFN-γ totally abrogated the protective effect of Acai PS against pulmonary B. pseudomallei infection. Collectively, these results demonstrate Acai PS is a potent innate immune agonist that can resolve F. tularensis and B. pseudomallei infections, suggesting this innate immune agonist has broad-spectrum activity against virulent intracellular pathogens....(more)
Skyberg JA, et al. PLoS Pathog 2012;8(3):e1002587.
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- 8. The antimicrobial effects of cranberry against Staphylococcus aureus.
The antimicrobial effects of the American cranberry (Vaccinium macrocarpon) on a major food-borne pathogen, Staphylococcus aureus, were investigated using commercially obtained Lakewood® organic cranberry juice and Ocean Spray® cranberry juice cocktail and four other berry fruit extracts (acai berry, strawberry, raspberry, and blueberry). The results showed that cranberry is a potent antimicrobial against S. aureus and the most potent among the berries studied. The order of percentage inhibition of bacterial growth at the same concentration of phenolic materials as gallic acid equivalents was Lakewood cranberry juice > Ocean Spray cranberry juice blueberry > acai berry raspberry strawberry. The antimicrobial effect was not due to the acidity of the berries as NaOH-neutralized samples were almost as effective in terms of percentage inhibition of viable cell growth. Solid-phase extraction of cranberry juice using C18 solid phase showed that the antimicrobial effects reside exclusively with the C18-bound materials....(more)
Lian PY, et al. Food Sci Technol Int 2012 Apr;18(2):179-86.
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- 9. Rhabdomyolysis associated with the use of a mislabeled "acai berry" dietary supplement.
INTRODUCTION: This case report describes a patient who developed rhabdomyolysis temporally associated with the use of a mislabeled acai berry dietary supplement. METHODS AND RESULTS.: The authors describe a 22-year-old man presenting with rhabdomyolysis approximately 2 weeks after starting a weight-loss dietary supplement. His medical history was significant only for hypertension treated with amlodipine. The diagnosis of rhabdomyolysis was confirmed (creatine kinase, 84,000 IU/L, positive urine myoglobin) with other potential causes ruled out. The signs and symptoms of the patient gradually resolved and he was discharged on hospital day 5. Assessment using the Naranjo Adverse Drug Reaction Probability Scale yielded a score of 3, indicating a possible relationship between the supplement and rhabdomyolysis. Although the product was labeled and promoted as containing acai berry and additional ingredients, there was no acai berry found on analysis. CONCLUSION: Clinicians should be aware that all dietary supplements may vary in uniformity and contain unknown contaminants....(more)
Elsayed RK, et al. Am J Med Sci 2011 Dec;342(6):535-8.
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- 10. Long-term stability of dentin matrix following treatment with various natural collagen cross-linkers.
OBJECTIVES:
Collagen disorganization is one of the main degradation patterns found in unsuccessful adhesive restorations. The hypothesis of this study was that pretreatment using natural collagen cross-linking agents rich in proanthocyanidin (PA) would improve mechanical properties and stability over time of the dentin collagen and, thus, confer a more resistant and lasting substrate for adhesive restorations.
METHODS:
PA-based extracts, from grape seed (GSE), cocoa seed (CSE), cranberry (CRE), cinnamon (CNE) and açaí berry (ACE) were applied over the demineralized dentin. The apparent elastic modulus (E) of the treated dentin collagen was analyzed over a 12 month period. Specimens were immersed in the respective solution and E values were obtained by a micro-flexural test at baseline, 10, 30, 60, 120 and 240 min. Samples were stored in artificial saliva and re-tested after 3, 6 and 12 months. Data was analyzed using ANOVA and Tukey test.
RESULTS:
GSE and CSE extracts showed a time-dependent effect and were able to improve [240 min (MPa): GSE = 108.96 ± 56.08;CSE = 59.21 ± 24.87] and stabilize the E of the organic matrix [12 months (MPa): GSE = 40.91 ± 19.69;CSE = 42.11 ± 13.46]. CRE and CNE extracts were able to maintain the E of collagen matrices constant over 12 months [CRE = 11.17 ± 7.22;CNE = 9,96 ± 6.11;MPa]. ACE (2.64 ± 1.22 MPa) and control groups immersed in neat distilled water (1.37 ± 0.69 MPa) and ethanol-water (0.95 ± 0.33 MPa) showed no effect over dentin organic matrix and enable their degradation and reduction of mechanical properties.
SIGNIFICANCE:
Some PA-based extracts were capable of improving and stabilizing collagen matrices through exogenous cross-links induction.
Copyright © 2011 Elsevier Ltd. All rights reserved....(more)
Castellan CS, et al. J Mech Behav Biomed Mater 2011 Oct;4(7):1343-50.
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- 11. Addition of açaí (Euterpe oleracea) to cigarettes has a protective effect against emphysema in mice.
Chronic inhalation of cigarette smoke (CS) induces emphysema by the damage contributed by oxidative stress during inhalation of CS. Ingestion of açai fruits (Euterpe oleracea) in animals has both antioxidant and anti-inflammatory effects. This study compared lung damage in mice induced by chronic (60-day) inhalation of regular CS and smoke from cigarettes containing 100mg of hydroalcoholic extract of açai berry stone (CS + A). Sham smoke-exposed mice served as the control group. Mice were sacrificed on day 60, bronchoalveolar lavage was performed, and the lungs were removed for histological and biochemical analyses. Histopathological investigation showed enlargement of alveolar space in CS mice compared to CS + A and control mice. The increase in leukocytes in the CS group was higher than the increase observed in the CS + A group. Oxidative stress, as evaluated by antioxidant enzyme activities, mieloperoxidase, glutathione, and 4-hydroxynonenal, was reduced in mice exposed to CS+A versus CS. Macrophage and neutrophil elastase levels were reduced in mice exposed to CS + A versus CS. Thus, the presence of açai extract in cigarettes had a protective effect against emphysema in mice, probably by reducing oxidative and inflammatory reactions. These results raise the possibility that addition of açaí extract to normal cigarettes could reduce their harmful effects.
Copyright © 2010 Elsevier Ltd. All rights reserved....(more)
de Moura RS, et al. Food Chem Toxicol 2011 Apr;49(4):855-63.
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- 12. Innovations in natural ingredients and their use in skin care.
Natural ingredients have been used traditionally for millennia and their application in topical creams, lotions and preparations within the traditional medicines and healing traditions of many cultures has been observed. Over the last 20 years, clinical and laboratory studies have identified the benefits of an array of natural ingredients for skin care. Consequently, a number of these ingredients and compounds are today being developed, used or considered not only for anti-aging effects, but also for use in dermatologic disorders. Certain ingredients, such as colloidal oatmeal and aloe vera, have been identified as beneficial in the treatment of psoriasis and atopic dermatitis, respectively, due to their anti-inflammatory properties. For combating acne and rosacea, green tea, niacinamide and feverfew are considered efficacious. As to hyperpigmentation and antioxidative capabilities, licorice, green tea, arbutin, soy, acai berry, turmeric and pomegranate are among those plants and compounds found to be most beneficial. Additional research is needed to determine to confirm and elucidate the benefits of these ingredients in the prevention and management of skin disease....(more)
Fowler JF Jr, et al. J Drugs Dermatol 2010 Jun;9(6 Suppl):S72-81; quiz s82-3.
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- 13. What is the açaí berry and are there health benefits?
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- 14. "Natural" ingredients in cosmetic dermatology.
Recently, both clinical and bench research has begun to provide scientific validation for the use of certain botanical ingredients. Related findings regarding proposed biological mechanisms of action have translated into clinical practice. Botanical compounds for which dermatologic and cosmetic applications have emerged include: olive oil, chamomile, colloidal oatmeal, oat kernal extract, feverfew, acai berry, coffee berry, curcumin, green tea, pomegranate, licorice, paper mulberry, arbutin, and soy. Many of these botanical sources offer biologically active components that require further in vitro and in vivo investigation in order for us to properly educate ourselves, and our patients, regarding over-the-counter products based on these ingredients....(more)
Baumann L, et al. J Drugs Dermatol 2009 Jun;8(6 Suppl):s5-9.
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- 15. Pharmacokinetics of anthocyanins and antioxidant effects after the consumption of anthocyanin-rich acai juice and pulp (Euterpe oleracea Mart.) in human healthy volunteers.
The acai berry is the fruit of the acai palm and is traditionally consumed in Brazil but has gained popularity abroad as a food and functional ingredient, yet little information exists on its health effect in humans. This study was performed as an acute four-way crossover clinical trial with acai pulp and clarified acai juice compared to applesauce and a non-antioxidant beverage as controls. Healthy volunteers (12) were dosed at 7 mL/kg of body weight after a washout phase and overnight fast, and plasma was repeatedly sampled over 12 h and urine over 24 h after consumption. Noncompartmental pharmacokinetic analysis of total anthocyanins quantified as cyanidin-3-O-glucoside showed Cmax values of 2321 and 1138 ng/L at t max times of 2.2 and 2.0 h, and AUC last values of 8568 and 3314 ng h L(-1) for pulp and juice, respectively. Nonlinear mixed effect modeling identified dose volume as a significant predictor of relative oral bioavailability in a negative nonlinear relationship for acai pulp and juice. Plasma antioxidant capacity was significantly increased by the acai pulp and applesauce. Individual increases in plasma antioxidant capacity of up to 2.3- and 3-fold for acai juice and pulp, respectively were observed. The antioxidant capacity in urine, generation of reactive oxygen species, and uric acid concentrations in plasma were not significantly altered by the treatments. Results demonstrate the absorption and antioxidant effects of anthocyanins in acai in plasma in an acute human consumption trial....(more)
Mertens-Talcott SU, et al. J Agric Food Chem 2008 Sep 10;56(17):7796-802.
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- 16. Resveratrol inhibits LXRα-dependent hepatic lipogenesis through novel antioxidant Sestrin2 gene induction.
Liver X receptor-α (LXRα), a member of the nuclear receptor superfamily of ligand-activated transcription factors, regulates de novo fatty acid synthesis that leads to stimulate hepatic steatosis. Although, resveratrol has beneficial effects on metabolic disease, it is not known whether resveratrol affects LXRα-dependent lipogenic gene expression. This study investigated the effect of resveratrol in LXRα-mediated lipogenesis and the underlying molecular mechanism. Resveratrol inhibited the ability of LXRα to activate sterol regulatory element binding protein-1c (SREBP-1c) and thereby inhibited target gene expression in hepatocytes. Moreover, resveratrol decreased LXRα-RXRα DNA binding activity and LXRE-luciferase transactivation. Resveratrol is known to activate Sirtuin 1 (Sirt1) and AMP-activated protein kinase (AMPK), although its precise mechanism of action remains controversial. We found that the ability of resveratrol to repress T0901317-induced SREBP-1c expression was not dependent on AMPK and Sirt1. It is well established that hepatic steatosis is associated with antioxidant and redox signaling. Our data showing that expression of Sestrin2 (Sesn2), which is novel antioxidant gene, was significantly down-regulated in the livers of high fat diet-fed mice. Moreover, resveratrol up-regulated Sesn2 expression, but not Sesn1 and Sesn3. Sesn2 overexpression repressed LXRα-activated SREBP-1c expression and LXRE-luciferase activity. Finally, Sesn2 knockdown using siRNA abolished the effect of resveratrol in LXRα-induced FAS luciferase gene transactivation. We conclude that resveratrol affects Sesn2 gene induction and contributes to the inhibition of LXRα-mediated hepatic lipogenesis.
Copyright © 2013. Published by Elsevier Inc....(more)
Jin SH, et al. Toxicol Appl Pharmacol 2013 May 4.
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- 17. Resveratrol promotes proteasome-dependent degradation of Nanog via p53 activation and induces differentiation of glioma stem cells.
Glioblastoma is the most common and aggressive primary brain tumor. Glioma stem cells (GSCs) are relatively resistant to chemo-radiotherapy and are responsible for tumor progression and the recurrence of glioblastomas after conventional therapy. Thus, the control of the GSC population is considered key to realizing long-term survival of glioblastoma patients. Here, we identified that resveratrol significantly reduced the self-renewal and tumor-initiating capacity of patient-derived GSCs. Furthermore, resveratrol promoted Nanog suppression via proteasomal degradation, which was inhibited by MG132, a proteasome inhibitor. p53 activation is an important factor in Nanog suppression and treatment with resveratrol was also found to activate the p53/p21 pathway. Importantly, inhibition of Nanog by siRNA provoked inhibitory effects on both the self-renewal and tumor-forming capacity of GSCs. Our findings indicate that Nanog is an essential factor for the retention of stemness and may contribute to the resveratrol-induced differentiation of GSCs. Our results also suggest that targeting GSCs via the p53-Nanog axis, with resveratrol for instance, could be a therapeutic strategy against glioblastoma.
Copyright © 2013 Elsevier B.V. All rights reserved....(more)
Sato A, et al. Stem Cell Res 2013 Apr 11;11(1):601-610.
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- 18. Resveratrol 3-O-d-glucuronide and resveratrol 4'-O-d-glucuronide inhibit colon cancer cell growth: Evidence for a role of A3 adenosine receptors, cyclin D1 depletion, and G1 cell cycle arrest.
SCOPE:
Resveratrol is a plant-derived polyphenol with chemotherapeutic properties in animal cancer models and many biochemical effects in vitro. Its bioavailability is low and raises the possibility that the metabolites of resveratrol have biological effects. Here we investigate the actions of resveratrol 3-O-d-glucuronide, resveratrol 4'-O-d-glucuronide, and resveratrol 3-O-d-sulfate on the growth of colon cancer cells in vitro.
METHODS AND RESULTS:
The growth of Caco-2, HCT-116, and CCL-228 cells was measured using the neutral red and MTT assays. Resveratrol and each metabolite inhibited cell growth with IC50 values of 9.8-31 μM. Resveratrol caused S phase arrest in all three cell lines. Resveratrol 3-O-d-glucuronide and resveratrol 4'-O-d-glucuronide caused G1 arrest in CCL-228 and Caco-2 cells. Resveratrol 3-O-d-sulfate had no effect on cell cycle. Growth inhibition was reversed by an inhibitor of AMP-activated protein kinase (compound C) or an adenosine A3 receptor antagonist (MRS1191). The A3 receptor agonist 2Cl-IB-MECA inhibited growth and A3 receptors were detected in all cell lines. The resveratrol glucuronides also reduced cyclin D1 levels but at higher concentrations than in growth experiments and generally did not increase phosphorylated AMP-activated protein kinase.
CONCLUSION:
Resveratrol glucuronides inhibit cell growth by G1 arrest and cyclin D1 depletion, and our results strongly suggest a role for A3 adenosine receptors in this inhibition.
© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim....(more)
Polycarpou E, et al. Mol Nutr Food Res 2013 May 7.
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- 19. [Advance of resveratrol in treating diabetes mellitus].
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- 20. Resveratrol Inhibits GABAC ρ Receptor-Mediated Ion Currents Expressed in Xenopus Oocytes.
Resveratrol is a phytoalexin found in grapes, red wine, and berries. Resveratrol has been known to have many beneficial health effects, such as anti-cancer, neuroprotective, anti-inflammatory, and life-prolonging effects. However, relatively little is known about the effects of resveratrol on the regulation of ligand-gated ion channels. We have previously reported that resveratrol regulates subsets of homomeric ligand-gated ion channels such as those of 5-HT3A receptors. The γ-aminobutyric acidC (GABAC) receptor is mainly expressed in retinal bipolar cells and plays an important role in visual processing. In the present study, we examined the effects of resveratrol on the channel activity of homomeric GABAC receptor expressed in Xenopus oocytes injected with cRNA encoding human GABAC ρ subunits. Our data show that the application of GABA elicits an inward peak current (IGABA ) in oocytes that express the GABAC receptor. Resveratrol treatment had no effect on oocytes injected with H2O or with GABAC receptor cRNA. Co-treatment with resveratrol and GABA inhibited IGABA in oocytes with GABAC receptors. The inhibition of IGABA by resveratrol was in a reversible and concentration-dependent manner. The IC50 of resveratrol was 28.9±2.8 µM in oocytes expressing GABAC receptor. The inhibition of IGABA by resveratrol was in voltage-independent and non-competitive manner. These results indicate that resveratrol might regulate GABAC receptor expression and that this regulation might be one of the pharmacological actions of resveratrol on the nervous system....(more)
Lee BH, et al. Korean J Physiol Pharmacol 2013 Apr;17(2):175-80.
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- 21. Resveratrol reduces acute lung injury in a LPS?induced sepsis mouse model via activation of Sirt1.
The development of acute lung injury (ALI) during sepsis almost doubles the mortality rate of patients. The efficacy of current treatment strategies is low as treatment is usually initiated following the onset of symptoms. Inflammation is one of the main mechanisms of autoimmune disorders and is a common feature of sepsis. The suppression of inflammation is therefore an important mechanism for the treatment of sepsis. Sirtuin 1 (Sirt1) has been demonstrated to play a role in the regulation of inflammation. Resveratrol, a potent Sirt1 activator, exhibits antiinflammatory properties. However, the role of resveratrol for the treatment of ALI during sepsis is not fully understood. In the present study, the antiinflammatory role of Sirt1 in the lipopolysaccharide (LPS)induced TC1 cell line and its therapeutic role in ALI was investigated in a mouse model of sepsis. The upregulation of matrix metalloproteinase-9, interleukin (IL)1β, IL6 and inducible nitric oxide synthase was induced by LPS in the mouse model of sepsis and the TC1 cell line, and resveratrol suppressed the overexpression of these proinflammatory molecules in a dosedependent manner. Resveratrol decreased pulmonary edema in the mouse model of sepsis induced by LPS. In addition, resveratrol improved lung function and reduced pathological alterations in the mouse model of sepsis. Knockdown of Sirt1 by RNA interference resulted in an increased susceptibility of TC1 cells to LPS stimulation and diminished the antiinflammatory effect of resveratrol. These results demonstrated that resveratrol inhibits LPSinduced ALI and inflammation via Sirt1, and indicated that Sirt1 is an efficient target for the regulation of LPSinduced ALI and inflammation. The present study provides insights into the treatment of ALI during sepsis....(more)
Li T, et al. Mol Med Rep 2013 Jun;7(6):1889-95.
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- 22. Resveratrol vs. calorie restriction: Data from rodents to humans.
Calorie restriction extends lifespan and confers metabolic benefits similar to the effect of lifestyle interventions. Poor compliance to long-term dietary restriction, however, hinders the success of this approach. Evidence is now persuasive for a role of resveratrol supplementation (a polyphenol in red grapes) as potential alternative to calorie restriction. This review summarizes the latest literature on the effects and the molecular mechanisms by which calorie restriction and resveratrol confer health benefits. The activation of SIRT1 and the associated improvement in energy utilization and insulin sensitivity closely resemble the benefits of calorie restriction. Current data largely support resveratrol as a potential calorie restriction mimetic to improve metabolic and probably functional health. Future studies which characterize the bioavailability and efficacy of resveratrol supplementation are critical to provide evidence for its long-term health benefits.
Copyright © 2013. Published by Elsevier Inc....(more)
Lam YY, et al. Exp Gerontol 2013 Apr 25.
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- 23. Does resveratrol improve insulin signaling in chronically ischemic myocardium?
BACKGROUND:
Resveratrol is a naturally occurring polyphenol believed to be cardioprotective. We previously demonstrated that resveratrol improves insulin signaling and glucose metabolism in liver and skeletal muscle of swine with metabolic syndrome. Although resveratrol has metabolic benefits in peripheral tissues, its effect on insulin signaling in ischemic myocardium (IM) is unclear. Therefore, we developed a clinically relevant swine model of metabolic syndrome and chronic myocardial ischemia to investigate the effects of resveratrol on insulin signaling in cardiac tissue.
MATERIALS AND METHODS:
Thirteen male Yorkshire swine were fed a high-cholesterol diet for 4 wk then underwent surgical placement of an ameroid constrictor to their circumflex artery to induce chronic myocardial ischemia. The high-cholesterol control group was given no drug (n = 7). The experimental group was provided the same diet and received supplemental resveratrol (100 mg/kg/d) (n = 6). Tissue was harvested 7 wk after ameroid placement for western blot and histological analyses.
RESULTS:
In IM, there was no significant difference between the two groups in the insulin signaling markers studied. In nonischemic myocardium, there was a significant decrease in phosphorylated AMP-activated protein kinase α (P = 0.021) in the group treated with resveratrol; otherwise, there were no significant differences between the groups. Immunostaining for glucose transporter 4 and Periodic acid-Schiff staining for myocardial glycogen stores was similar between the groups.
CONCLUSIONS:
Resveratrol has complex effects on glucose metabolism. Although prior studies demonstrated that resveratrol supplementation improves insulin sensitivity in peripheral tissues, in chronically IM, there are no significant alterations.
Copyright © 2013 Elsevier Inc. All rights reserved....(more)
Sabe AA, et al. J Surg Res 2013 Mar 29.
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- 24. Resveratrol-loaded lipid-core nanocapsules treatment reduces in vitro and in vivo glioma growth.
The development of novel therapeutic strategies to treat gliomas remains critical as a result of the poor prognoses, inef-. ficient therapies and recurrence associated with these tumors. In this context, biodegradable nanoparticles are emerging as efficient drug delivery systems for the treatment of difficult-to-treat diseases such as brain tumors. In the current study, we evaluated the antiglioma effect of trans-resveratrol-loaded lipid-core nanocapsules (RSV-LNC) based on in vitro (C6 glioma cell line) and in vivo (brain-implanted C6 cells) models of the disease. In vitro, RSV-LNC decreased the viability of C6 glioma cells to a higher extent than resveratrol in solution. Interestingly, RSV-LNC treatment was not cytotoxic to hippocampal organotypic cultures, a model of healthy neural cells, suggesting selectivity for cancer cells. RSV-LNC induced losses in glioma cell viability through induction of apoptotic cell death, as assessed by Annexin-FITC/PI assay, which was preceded by an early arrest in the S and G1 phases of the cell cycle. In brain-implanted C6 tumors, treatment with RSV-LNC (5 mg/kg/day, i.p.) for 10 days promoted a marked decrease in tumor size and also reduced the incidence of some malignant tumor-associated characteristics, such as intratumoral hemorrhaging, intratumoral edema and pseudopalisading, compared to resveratrol in solution. Taken together, the results presented herein suggest that nanoencapsulation of resveratrol improves its antiglioma activity, thus providing a provocative foundation for testing the clinical usefulness of nanoformulations of this natural compound as a new chemotherapeutic strategy for the treatment of gliomas....(more)
Figueiró F, et al. J Biomed Nanotechnol 2013 Mar;9(3):516-26.
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- 25. Effect of Resveratrol on Cultured Skin Fibroblasts from Patients with Oxidative Phosphorylation Defects.
Few therapeutic options are available to patients with oxidative phosphorylation disorders. Administering pharmacological agents that are able to stimulate mitochondrial biogenesis have been put forward as a possible treatment, yet the approach remains in need of thorough testing. We investigated the effect of resveratrol in an in vitro setting. Mitochondrial enzymatic activities were tested in cultured skin fibroblasts from patients harboring a nuclear defect in either complex II or complex IV (n = 11), and in fibroblasts from healthy controls (n = 11). In the latter, preincubation with resveratrol resulted in a significant increase of citrate synthase, complex II and complex IV enzyme activity. In patients with complex II or complex IV deficiency, however, activity of the deficient complex could not be substantially augmented, and response was dependent upon the residual activity. We conclude that resveratrol is not capable of normalizing oxidative phosphorylation activities in deficient cell lines. Copyright © 2013 John Wiley & Sons, Ltd.
Copyright © 2013 John Wiley & Sons, Ltd....(more)
De Paepe B, et al. Phytother Res 2013 Apr 26.
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- 26. Achyranthes bidentata Blume extract protects cultured hippocampal neurons against glutamate-induced neurotoxicity.
We have prepared an aqueous extract of Achyranthes bidentata Blume, a Chinese medicinal herb commonly prescribed for arthritis treatment or immnopotentiation, and have found that Achyranthes bidentata extract promotes nerve growth and prevents neuronal apoptosis....(more)
Zhou S, et al. J Ethnopharmacol 2009 Apr 21;122(3):547-54.
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- 27. The repair effects of Achyranthes bidentata extract on the crushed common peroneal nerve of rabbits.
In this study the effect of the Achyranthes bidentata root aqueous extract on regeneration of the crushed common peroneal nerve in rabbits by using a combination of electrophysiological assessment and histological aspect were investigated. The examined functional and morphological parameters suggest that A. bidentata extract could accelerate peripheral nerve regeneration in a dose-dependent manner (10-20 microg/kg, i.v.)....(more)
Ding F, et al. Fitoterapia 2008 Apr;79(3):161-7.
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- 28. Sodium beta-aescin may be an effective therapeutic agent for Bell's palsy.
Although Bell's palsy is the most common acute facial paralysis, the cause of it is still unknown. This made the treatment for it remain very limited. Many methods are simply symptomatic treatment. Up to now we have known that Bell's palsy is related to viral infection and the pathomechanism of Bell's palsy involves inflammatory oedema and entrapment neuropathy in the narrow bony facial canal. So treatment plans for Bell's palsy mainly focus on antiviral therapy, relieving inflammatory oedema and accelerating facial nerve recovery. Sodium beta-aescin is derived from horse chestnut and its major constituent is aescigenin which has been approved by China national drug standard. The pharmacologic action of sodium beta-aescin is to relieve tissue oedema, recover vasopermeability and eliminate pressure caused by oedema. Nowadays sodium beta-aescin has been widely used clinically for encephaledema or tumefaction caused by trauma or operation. It also can be used for treating disease of digestive system and increasing intravenous tension and improving microcirculation. Although many papers had been published on the anti-edema effects of sodium beta-aescin, little was known about the effects in treating oedema complicated by Bell's palsy....(more)
Liu J, et al. Med Hypotheses 2008 Nov;71(5):762-4.
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- 29. Optimization of the cultivation conditions for mushroom production with European wild strains of A. subrufescens and Brazilian cultivars.
BACKGROUND:
The almond mushroom is cultivated at a commercial level in Brazil and some Asian countries on local substrates and casing mixtures. Despite its tropical origin, Agaricus subrufescens (formerly A. blazei, A. brasiliensis) might be a seasonal option for the mushroom growers in western countries where some wild strains had been isolated. For this purpose, cultivation conditions were developed starting from substrate and casing mixture commonly used for Agaricus bisporus commercial production in France.
RESULTS:
The commercial compost, based on wheat straw and horse manure, used for the button mushroom and the casing mixture (peat and limestone) supplemented with fine sand proved efficient to grow A. subrufescens. Increasing the depth of the casing layer improved significantly the yield and time to fruiting. Daily variations in temperature did not markedly modify the yield. Significantly higher mushroom biomass was obtained with three wild European strains compared to three Brazilian cultivars. The very productive wild strain CA438-A gave mushrooms of size and dry matter content comparable to those of a cultivar.
CONCLUSION:
a commercial production of A. subrufescens can be developed in western countries on the wheat straw based substrate commonly used for A. bisporus in these regions, with a simple modification of the casing mixture, and maintaining the incubation temperature throughout the crop, which is expected to save energy during summer. Good yields were obtained cultivating European strains under optimised parameters.
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Llarena Hernández CR, et al. J Sci Food Agric 2013 Apr 30.
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- 30. Genome-wide survey of repetitive DNA elements in the button mushroom Agaricus bisporus.
Repetitive DNA elements are ubiquitous constituents of eukaryotic genomes. The biological roles of these repetitive elements, supposed to impact genome organization and evolution, are not completely elucidated yet. The availability of whole genome sequence offers the opportunity to draw a picture of the genome-wide distribution of these elements and provide insights into potential mechanisms of genome plasticity. The present study uses in silico approaches to describe tandem repeats and transposable elements distribution in the genome of the button mushroom, Agaricus bisporus. Transposable elements comprised 12.43% of the assembled genome, and 66% of them were found clustered in the centromeric or telomeric regions. Methylation of retrotransposon has been demonstrated. A total of 1996 mini-, 4062 micro-, and 37 satellites motifs were identified. The microsatellites appeared widely and evenly spread over the whole genome sequence, whereas the minisatellites were not randomly distributed. Indeed, minisatellites were found to be associated with transposable elements clusters. Telomeres exhibited a specific sequence with a TnAGn signature. A comparison between the two available genome sequences of A. bisporus was also performed and sheds light on the genetic divergence between the two varieties. Beyond their role in genome structure, repeats provide a virtually endless source of molecular markers useful for genetic studies in this cultivated species.
Copyright © 2013 Elsevier Inc. All rights reserved....(more)
Foulongne-Oriol M, et al. Fungal Genet Biol 2013 Apr 20.
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- 31. A comparative genomic analysis of the oxidative enzymes potentially involved in lignin degradation by Agaricus bisporus.
The oxidative enzymatic machinery for degradation of organic substrates in Agaricus bisporus (Ab) is at the core of the carbon recycling mechanisms in this fungus. To date, 156 genes have been tentatively identified as part of this oxidative enzymatic machinery, which includes 26 peroxidase encoding genes, nine copper radical oxidase [including three putative glyoxal oxidase-encoding genes (GLXs)], 12 laccases sensu stricto and 109 cytochrome P450 monooxygenases. Comparative analyses of these enzymes in Ab with those of the white-rot fungus, Phanerochaete chrysosporium, the brown-rot fungus, Postia placenta, the coprophilic litter fungus, Coprinopsis cinerea and the ectomychorizal fungus, Laccaria bicolor, revealed enzyme diversity consistent with adaptation to substrates rich in humic substances and partially degraded plant material. For instance, relative to wood decay fungi, Ab cytochrome P450 genes were less numerous (109 gene models), distributed among distinctive families, and lacked extensive duplication and clustering. Viewed together with P450 transcript accumulation patterns in three tested growth conditions, these observations were consistent with the unique Ab lifestyle. Based on tandem gene arrangements, a certain degree of gene duplication seems to have occurred in this fungus in the copper radical oxidase (CRO) and the laccase gene families. In Ab, high transcript levels and regulation of the heme-thiolate peroxidases, two manganese peroxidases and the three GLX-like genes are likely in response to complex natural substrates, including lignocellulose and its derivatives, thereby suggesting an important role in lignin degradation. On the other hand, the expression patterns of the related CROs suggest a developmental role in this fungus. Based on these observations, a brief comparative genomic overview of the Ab oxidative enzyme machinery is presented.
Copyright © 2013 Elsevier Inc. All rights reserved....(more)
Doddapaneni H, et al. Fungal Genet Biol 2013 Apr 10.
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- 32. Characterization of the Key Odorants in Pan-Fried White Mushrooms ( Agaricus bisporus L.) by Means of Molecular Sensory Science: Comparison with the Raw Mushroom Tissue.
Application of aroma extract dilution analysis (AEDA) on the volatile fraction isolated from pan-fried white mushrooms ( Agaricus bisporus L.) revealed 40 odor-active compounds in the flavor dilution (FD) factor range of 8-8192, among which the caramel-like smelling 4-hydroxy-2,5-dimethylfuran-3(2H)-one showed the highest FD factor of 8192, followed by 2-propionyl-1-pyrroline (popcorn-like) and 3-hydroxy-4,5-dimethylfuran-2(5H)-one (seasoning-like). A total of 36 compounds are reported for the first time in processed mushrooms, and 25 odorants showing the highest FD factors were then quantitated by stable isotope dilution assays and their odor activity values (OAVs) were calculated as ratio of their concentrations to their odor thresholds. Among them, 3-methylbutanal (malty), 3-(methylthio)propanal (cooked potato), and 2-acetyl-1-pyrroline (popcorn-like) showed the highest OAVs (>100) in the pan-fried mushrooms, followed by 1-octen-3-one, 2-propionyl-1-pyrroline, 4-hydroxy-2,5-dimethylfuran-3(2H)-one, phenylacetaldehyde, 2,3-diethyl-5-methylpyrazine, and 3-hydroxy-4,5-dimethylfuran-2(5H)-one with OAVs >10. An aqueous aroma recombinate containing 13 odorants (OAV > 1) in their actual concentrations in the fried mushrooms showed a good similarity to the original aroma profile. The quantitation of the key odorants in raw mushrooms, identified with high FD factors during the AEDA, revealed that numerous odorants were quantitatively changed by the frying process, but in particular the concentrations of 2-phenylacetaldehyde and 3-methylbutanal were higher by factors of ∼40 and 6, respectively, compared to the amounts in the processed mushrooms. The data suggested an enzymatic formation of both Strecker aldehydes by the cut mushroom tissue. In total, 26 odorants were newly identified in raw mushrooms....(more)
Grosshauser S, et al. J Agric Food Chem 2013 Apr 12.
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- 33. Incidence of Listeria monocytogenes and Listeria spp. in a Small-Scale Mushroom Production Facility.
Listeria monocytogenes is a foodborne pathogen of significant concern to the agricultural and food processing industry because of its ability to grow and persist in cool and moist environments and its association with listeriosis, a disease with a very high mortality rate. Although there have been no listeriosis outbreaks attributed to fresh mushrooms in the United States, retail surveys and recalls are evidence that L. monocytogenes contamination of mushrooms (Agaricus bisporus) can occur. The objective of this study was to determine the prevalence of Listeria spp., including L. monocytogenes, in a small-scale mushroom production facility on the campus of the Pennsylvania State University in the United States. Of 184 samples taken from five production zones within the facility, 29 (15.8%) samples were positive for Listeria spp. Among the Listeria spp. isolates, L. innocua was most prevalent (10.3%) followed by L. welshimeri (3.3%), L. monocytogenes (1.6%), and L. grayi (0.5%). L. monocytogenes was recovered only from the phase I raw material composting area. Isolates of L. monocytogenes were confirmed and serotyped by multiplex PCR. The epidemiological relatedness of the three L. monocytogenes isolates to those serotypes or lineages frequently encountered in listeriosis infections was determined by multi-virulence-locus sequence typing using six virulence genes, namely, prfA, inlB, inlC, dal, clpP, and lisR. The phylogenetic positions of the three isolates in the dendrogram prepared with data from other isolates of L. monocytogenes showed that all isolates were grouped with serotype 4a, lineage IIIA. To date, this serotype has rarely been reported in foodborne disease outbreaks....(more)
Viswanath P, et al. J Food Prot 2013 Apr;76(4):608-15.
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- 34. Agaricus bisporus genome sequence: A commentary.
The genomes of two isolates of Agaricus bisporus have been sequenced recently. This soil-inhabiting fungus has a wide geographical distribution in nature and it is also cultivated in an industrialized indoor process ($4.7bn annual worldwide value) to produce edible mushrooms. Previously this lignocellulosic fungus has resisted precise econutritional classification, i.e. into white- or brown-rot decomposers. The generation of the genome sequence and transcriptomic analyses has revealed a new classification, 'humicolous', for species adapted to grow in humic-rich, partially decomposed leaf material. The Agaricus biporus genomes contain a collection of polysaccharide and lignin-degrading genes and more interestingly an expanded number of genes (relative to other lignocellulosic fungi) that enhance degradation of lignin derivatives, i.e. heme-thiolate peroxidases and β-etherases. A motif that is hypothesized to be a promoter element in the humicolous adaptation suite is present in a large number of genes specifically up-regulated when the mycelium is grown on humic-rich substrate. The genome sequence of A. bisporus offers a platform to explore fungal biology in carbon-rich soil environments and terrestrial cycling of carbon, nitrogen, phosphorus and potassium.
Copyright © 2013 Elsevier Inc. All rights reserved....(more)
Kerrigan RW, et al. Fungal Genet Biol 2013 Apr 2.
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- 35. Agaricus bisporus and Agaricus brasiliensis (1→6)-β-d-glucans show immunostimulatory activity on human THP-1 derived macrophages.
The (1→6)-β-D-glucans from Agaricus bisporus and Agaricus brasiliensis were purified to evaluate their effects on the innate immune system. THP-1 macrophages were used to investigate the induction of the expression of TNF-α, IL1β, and COX-2 by RT-PCR. The purification of the polysaccharides gave rise to fractions containing 96-98% of glucose. The samples were analyzed by GC-MS, HPSEC and (13)C NMR, which confirmed the presence of homogeneous (1→6)-β-D-glucans. The β-glucans were incubated with THP-1 derived macrophages, for 3 h and 6 h to evaluate their effects on the expression of pro-inflammatory genes. Both β-glucans stimulated the expression of such genes as much as the pro-inflammatory control (LPS). When the cells were incubated with LPS+β-glucan, a significant inhibition of the expression of IL-1β and COX-2 was observed for both treatments after 3 h of incubation. By the results, we conclude that the (1→6)-β-D-glucans present an immunostimulatory activity when administered to THP-1 derived macrophages.
Copyright © 2013 Elsevier Ltd. All rights reserved....(more)
Smiderle FR, et al. Carbohydr Polym 2013 Apr 15;94(1):91-9.
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