What do you know about Plants and Neutraceuticals?
Author and Curator: Larry H. Bernstein, MD, FCAP
This is a series of articles that is within a multipart series on related and standalone topics of discussion that raise some issues and controversies, but perhaps open our eyes to our relationship to the environment and its effects on living organisms, our uniqueness among eukeriotes, and or interdependence with the living plant and animal world. In our self-centerness, there is a cross-cultural, perhaps innate tendancy to disregard this interdependence and to disrupt our surroundings in the same manner that families within diverse and mixed-societies become corrupted. The amazing use of herbal medicines precedes the development of a formal scientific method, and has existed in Asia and Africa for centuries, and probably prior to biblical record. Of course, there is substantial knowledge in the last century that has led to a better understanding of previously unknown medicinal benefits from the emergence of organic, inorganic and medicinal chemistry, aligned with discoveries in microbiology, and of fungi and algae, and the only recent development of synthetic biology and application of chemical engineering to biology. These topics do not stand alone.
The series will be segmented as follows:
- An introduction to plants and the microbiome.
- What do you know about plants and neutraceuticals?
- Antimicrobial and drug resistance.
- What do you know about plants and neutraceuticals?
Other articles published in this Open Access Online Scientific Journal include the following:
The Omega-3 Lie
The Discovery and Properties of Avemar – Fermented Wheat Germ Extract: Carcinogenesis Suppressor
Plant flavonoid found to reduce inflammatory response in the brain: luteolin
2,000-year-old herb regulates autoimmunity and inflammation / Chang Shan, from a type of hydrangea that grows in Tibet and Nepal
Plant flavonoid luteolin blocks cell signaling pathways in colon cancer cells
Study Finds Shu Gan Liang Xue Herbal Formula Has Breast Cancer Anti Tumor Effect
Omega-3 fatty acids, depleting the source, and protein insufficiency in renal disease
Scientists develop new cancer-killing compound from salad plant / 1,200 times more specific in killing certain kinds of cancer cells than currently available drugs
Protein heals wounds, boosts immunity and protects from cancer – Lactoferrin
Malnutrition in India, high newborn death rate and stunting of children age under five years
Inula helenium ( elecampane ) 100% Effective against MRSA in vitro, 200 Strains
Thymoquinone, an extract of nigella sativa seed oil, blocked pancreatic cancer cell growth and killed the cells by enhancing the process of programmed cell death.
Garlic compound fights source of food-borne illness better than antibiotics (100 times more effective than two popular antibiotics)
Study suggests consuming whey protein before meals could help improve blood glucose control in people with diabetes
There are several other contents to consider.
Synthetic derivatives of THC may weaken HIV-1 infection to enhance antiviral therapies
Federation of American Societies for Experimental Biology April 30, 2013
A new research report shows that compounds that stimulate the cannabinoid type 2 receptor in white blood cells, specifically macrophages, appear to weaken HIV-1 infection.
A new use for compounds related in composition to the active ingredient in marijuana may be on the horizon: a new research report published in the Journal of Leukocyte Biology shows that compounds that stimulate the cannabinoid type 2 (CB2) receptor in white blood cells, specifically macrophages, appear to weaken HIV-1 infection. The CB2 receptor is the molecular link through which the pharmaceutical properties of cannabis are manifested. Diminishing HIV-1 infection in this manner might make current anti-viral therapies more effective and provide some protection against certain HIV-1 complications.
“The synthetic compounds we used in our study may show promise in helping the body fight HIV-1 infection,'” said Yuri Persidsky, M.D., Ph.D., a researcher involved in the work from the Department of Pathology and Laboratory Medicine at Temple University School of Medicine in Philadelphia, PA. “As compounds like these are improved further and made widely available, we will continue to explore their potential to fight other viral diseases that are notoriously difficult to treat.”
To make this discovery, scientists used a cell culture model to infect human macrophages with HIV-1 and added synthetic compounds similar to the active ingredient in marijuana to activate the CB2 receptor. At different times during the infection, samples from the culture were taken to see if the replication of the HIV virus was decreased. The researchers observed diminished HIV growth and a possible protective effect from some HIV-1 complications.
“HIV/AIDS has posed one of the most significant health challenges in modern medicine,” said John Wherry, Ph.D., Deputy Editor of the Journal of Leukocyte Biology. “Recent high profile vaccine failures mean that all options need to be on the table to prevent or treat this devastating infection. Research on the role of cannabinoid type 2 receptors and viral infection may one day allow targeting these receptors to be part of combination therapies that use exploit multiple weaknesses of the virus simultaneously.”
The above story is based on materials provided by Federation of American Societies for Experimental Biology. Note: Materials may be edited for content and length.
S. H. Ramirez, N. L. Reichenbach, S. Fan, S. Rom, S. F. Merkel, X. Wang, W.-z. Ho, Y. Persidsky. Attenuation of HIV-1 replication in macrophages by cannabinoid receptor 2 agonists. Journal of Leukocyte Biology, 2013; 93 (5): 801 http://dx.doi.org:/10.1189/jlb.1012523
Federation of American Societies for Experimental Biology. “Synthetic derivatives of THC may weaken HIV-1 infection to enhance antiviral therapies.” ScienceDaily. ScienceDaily, 30 April 2013. <www.sciencedaily.com/releases/2013/04/130430131530.htm>.
Marijuana-like chemicals inhibit human immunodeficiency virus (HIV) in late-state AIDS
Mount Sinai Medical Center March 20, 2012
Marijuana-like chemicals trigger receptors on human immune cells that can directly inhibit a type of human immunodeficiency virus (HIV) found in late-stage AIDS, research suggests.
Mount Sinai School of Medicine researchers have discovered that marijuana-like chemicals trigger receptors on human immune cells that can directly inhibit a type of human immunodeficiency virus (HIV) found in late-stage AIDS, according to new findings published online in the journal PLoS ONE.
Medical marijuana is prescribed to treat pain, debilitating weight loss and appetite suppression, side effects that are common in advanced AIDS. This is the first study to reveal how the marijuana receptors found on immune cells — called cannabinoid receptors CB1 and CB2 — can influence the spread of the virus. Understanding the effect of these receptors on the virus could help scientists develop new drugs to slow the progression of AIDS.
“We knew that cannabinoid drugs like marijuana can have a therapeutic effect in AIDS patients, but did not understand how they influence the spread of the virus itself,” said study author Cristina Costantino, PhD, Postdoctoral Fellow in the Department of Pharmacology and Systems Therapeutics at Mount Sinai School of Medicine. “We wanted to explore cannabinoid receptors as a target for pharmaceutical interventions that treat the symptoms of late-stage AIDS and prevent further progression of the disease without the undesirable side effects of medical marijuana.”
HIV infects active immune cells that carry the viral receptor CD4, which makes these cells unable to fight off the infection. In order to spread, the virus requires that “resting” immune cells be activated. In advanced AIDS, HIV mutates so it can infect these resting cells, gaining entry into the cell by using a signaling receptor called CXCR4. By treating the cells with a cannabinoid agonist that triggers CB2, Dr. Costantino and the Mount Sinai team found that CB2 blocked the signaling process, and suppressed infection in resting immune cells.
Triggering CB1 causes the drug high associated with marijuana, making it undesirable for physicians to prescribe. The researchers wanted to explore therapies that would target CB2 only. The Mount Sinai team infected healthy immune cells with HIV, then treated them with a chemical that triggers CB2 called an agonist. They found that the drug reduced the infection of the remaining cells.
“Developing a drug that triggers only CB2 as an adjunctive treatment to standard antiviral medication may help alleviate the symptoms of late-stage AIDS and prevent the virus from spreading,” said Dr. Costantino. Because HIV does not use CXCR4 to enhance immune cell infection in the early stages of infection, CB2 agonists appear to be an effective antiviral drug only in late-stage disease.
As a result of this discovery, the research team led by Benjamin Chen, MD, PhD, Associate Professor of Infectious Diseases, and Lakshmi Devi, PhD, Professor of Pharmacology and Systems Therapeutics at Mount Sinai School of Medicine, plans to develop a mouse model of late-stage AIDS in order to test the efficacy of a drug that triggers CB2 in vivo. In 2009 Dr. Chen was part of a team that captured on video for the first time the transfer of HIV from infected T-cells to uninfected T-cells.
Funding for this study was provided to Drs. Chen and Devi by the National Institutes of Health in Bethesda, Maryland. Dr. Costantino is supported by a National Institutes of Health Clinical and Translational Science Award grant awarded to Mount Sinai School of Medicine.
Cristina Maria Costantino, Achla Gupta, Alice W. Yewdall, Benjamin M. Dale, Lakshmi A. Devi, Benjamin K. Chen Cristina Maria Costantino. Cannabinoid Receptor 2-Mediated Attenuation of CXCR4-Tropic HIV Infection in Primary CD4 T Cells. PLoS ONE, 20 Mar 2012 http://dx.doi.org:/10.1371/journal.pone.0033961
Mount Sinai Medical Center. “Marijuana-like chemicals inhibit human immunodeficiency virus (HIV) in late-state AIDS.” ScienceDaily. ScienceDaily, 20 March 2012. <www.sciencedaily.com/releases/2012/03/120320195252.htm>.
Identification of Endocannabinoid System-Modulating N‑Alkylamides from Heliopsis helianthoides var. scabra and Lepidium meyenii
Z Hajdu, S Nicolussi, M Rau, L Lorantfy, P Forgo, J Hohmann, D Csupor, J Gertsch
†Department of Pharmacognosy, University of Szeged, H-6720 Szeged, Hungary
‡Institute of Biochemistry and Molecular Medicine, NCCR TransCure, University of Bern, CH-3012 Bern, Switzerland
J. Nat. Prod. Apr 2, 2014 http://dx.doi.org:/10.1021/np500292g
ABSTRACT: The discovery of the interaction of plant-derived N-alkylamides (NAAs) and the mammalian endocannabinoid system (ECS) and the existence of a plant endogenous Nacylethanolamine signaling system have led to the re-evaluation of this group of compounds. Herein, the isolation of seven NAAs and the assessment of their effects on major protein targets in the ECS network are reported. Four NAAs, octadeca-2E,4E,8E,10Z,14Z-pentaene-12-ynoic acid isobutylamide (1), octadeca-2E,4E,8E,10Z,14Z-pentaene-12-ynoic acid 2′-methylbutylamide (2), hexadeca-2E,4E,9Z-triene-12,14-diynoic acid isobutylamide (3), and hexadeca-2E,4E,9,12-tetraenoic acid 2′-methylbutylamide (4), were identified from Heliopsis helianthoides var. scabra. Compounds 2−4 are new natural products, while 1 was isolated for the first time from this species. The previously described macamides, N-(3-methoxybenzyl)-(9Z,12Z,15Z)-octadecatrienamide (5), N-benzyl-(9Z,12Z,15Z)-octadecatrienamide (6), and N-benzyl-(9Z,12Z)-octadecadienamide (7), were isolated from Lepidium meyenii (Maca). NMethylbutylamide 4 and N-benzylamide 7 showed submicromolar and selective binding affinities for the cannabinoid CB1 receptor (Ki values of 0.31 and 0.48 μM, respectively). Notably, compound 7 also exhibited weak fatty acid amide hydrolase (FAAH) inhibition (IC50 = 4 μM) and a potent inhibition of anandamide cellular uptake (IC50 = 0.67 μM) that was stronger than the inhibition obtained with the controls OMDM-2 and UCM707. The pronounced ECS polypharmacology of compound 7 highlights the potential involvement of the arachidonoyl-mimicking 9Z,12Z double-bond system in the linoleoyl group for the overall cannabimimetic action of NAAs. This study provides additional strong evidence of the endocannabinoid substrate mimicking of plant-derived NAAs and uncovers a direct and indirect cannabimimetic action of the Peruvian Maca root.
Resveratrol modulates the inflammatory response via an estrogen receptor-signal integration network
JC Nwachukwu, S Srinivasan, NE Bruno, AA Parent, TS Hughes, et al.
eLife Apr 2014;10.7554/eLife.02057 http://dx.doi.org/10.7554/eLife.02057
Resveratrol has beneficial effects on aging, inflammation and metabolism, which are thought to result from activation of the lysine deacetylase, sirtuin 1 (SIRT1), the cAMP pathway, or AMP-activated protein kinase. Here we report that resveratrol acts as a pathway-selective estrogen receptor-α (ERα) ligand to modulate the inflammatory response but not cell proliferation. A crystal structure of the ERα ligand-binding domain (LBD) as a complex with resveratrol revealed a unique perturbation of the coactivator-binding surface, consistent with an altered coregulator recruitment profile. Gene expression analyses revealed significant overlap of TNFα genes modulated by resveratrol and estradiol. Furthermore, the ability of resveratrol to suppress interleukin-6 transcription was shown to require ERα and several ERα coregulators, suggesting that ERα functions as a primary conduit for resveratrol activity.
Diets rich in antioxidant resveratrol fail to reduce deaths, heart disease or cancer
Johns Hopkins Medicine May 12, 2014
Summary: A study of Italians who consume a diet rich in resveratrol — the compound found in red wine, dark chocolate and berries — finds they live no longer than and are just as likely to develop cardiovascular disease or cancer as those who eat or drink smaller amounts of the antioxidant.
A study of Italians who consume a diet rich in resveratrol — the compound found in red wine, dark chocolate and berries — finds they live no longer than and are just as likely to develop cardiovascular disease or cancer as those who eat or drink smaller amounts of the antioxidant.
“The story of resveratrol turns out to be another case where you get a lot of hype about health benefits that doesn’t stand the test of time,” says Richard D. Semba, M.D., M.P.H., a professor of ophthalmology at the Johns Hopkins University School of Medicine and leader of the study described May 12 in JAMA Internal Medicine. “The thinking was that certain foods are good for you because they contain resveratrol. We didn’t find that at all.”
Despite the negative results, Semba says, studies have shown that consumption of red wine, dark chocolate and berries does reduce inflammation in some people and still appears to protect the heart. “It’s just that the benefits, if they are there, must come from other polyphenols or substances found in those foodstuffs,” he says. “These are complex foods, and all we really know from our study is that the benefits are probably not due to resveratrol.”
The new study did not include people taking resveratrol supplements, though few studies thus far have found benefits associated with them.
Semba is part of an international team of researchers that for 15 years has studied the effects of aging in a group of people who live in the Chianti region of Italy. For the current study, the researchers analyzed 24 hours of urine samples from 783 people over the age of 65 for metabolites of resveratrol. After accounting for such factors as age and gender, the people with the highest concentration of resveratrol metabolites were no less likely to have died of any cause than those with no resveratrol found in their urine. The concentration of resveratrol was not associated with inflammatory markers, cardiovascular disease or cancer rates.
Semba and his colleagues used advanced mass spectrometry to analyze the urine samples.
The study participants make up a random group of people living in Tuscany where supplement use is uncommon and consumption of red wine — a specialty of the region — is the norm. The study participants were not on any prescribed diet.
Resveratrol is also found in relatively large amounts in grapes, peanuts and certain Asiatic plant roots. Excitement over its health benefits followed studies documenting anti-inflammatory effects in lower organisms and increased lifespan in mice fed a high-calorie diet rich in the compound.
The so-called “French paradox,” in which a low incidence of coronary heart disease occurs in the presence of a high dietary intake of cholesterol and saturated fat in France, has been attributed to the regular consumption of resveratrol and other polyphenols found in red wine.
Johns Hopkins Medicine. “Diets rich in antioxidant resveratrol fail to reduce deaths, heart disease or cancer.” ScienceDaily. ScienceDaily, 12 May 2014. <www.sciencedaily.com/releases/2014/05/140512214128.htm>.
Richard D. Semba, Luigi Ferrucci, Benedetta Bartali, Mireia Urpí-Sarda, Raul Zamora-Ros, Kai Sun, Antonio Cherubini, Stefania Bandinelli, Cristina Andres-Lacueva. Resveratrol Levels and All-Cause Mortality in Older Community-Dwelling Adults. JAMA Internal Medicine, 2014;
Curcumin regulates gene expression of insulin like growth factor, B-cell CLL/lymphoma 2 and antioxidant enzymes in streptozotocin induced diabetic rats
Sabryl M El-Bahr
BMC Complementary and Alternative Medicine 2013, 13:368
The effects of curcumin on the activities and gene expression of antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), glutathione-S-transferase (G-ST), B-cell CLL/lymphoma 2 (Bcl-2) and insulin like growth factor-1 (IGF-1) in diabetic rats were studied.
The effects of curcumin on the activities and gene expression of antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), glutathione-S-transferase (G-ST), B-cell CLL/lymphoma 2 (Bcl-2) and insulin like growth factor-1 (IGF-1) in diabetic rats were studied.
Methods: Twenty four rats were assigned to three groups (8 rats for each). Rats of first group were non diabetic and rats of the second group were rendered diabetic by streptozotocin (STZ).
Both groups received vehicle, corn oil only (5 ml/kg body weight) and served as negative and positive controls, respectively. Rats of the third group were rendered diabetic and received oral curcumin dissolved in corn oil at a dose of 15 mg/5 ml/kg body weight for 6 weeks.
Results: Diabetic rats showed significant increase of blood glucose, thiobarbituric acid reactive substances (TBARS) and activities of all antioxidant enzymes with significant reduction of reduced glutathione (GSH) compare to the control non diabetic group.
Gene expression of Bcl2, SOD, CAT, GPX and GST was increased significantly in diabetic untreated rats compare to the control non diabetic group. The administration of curcumin to diabetic rats normalized significantly their blood sugar level and TBARS values and increased the activities of all antioxidant enzymes and reduced glutathione concentration.
In addition, curcumin treated rats showed significant increase in gene expression of IGF-1, Bcl2, SOD and GST compare to non diabetic and diabetic untreated rats.
Conclusion: Curcumin was antidiabetic therapy, induced hypoglycemia by up-regulation of IGF-1 gene and ameliorate the diabetes induced oxidative stress via increasing the availability of GSH, increasing the activities and gene expression of antioxidant enzymes and Bcl2. Further studies are required to investigate the actual mechanism of action of curcumin regarding the up regulation of gene expression of examined parameters.
Antioxidant biomaterial promotes healing
Purple corn anthocyanins inhibit diabetes-associated glomerular monocyte activation and macrophage infiltration
Kang MK, Li J, Kim JL, Gong JH, Kwak SN, Park JH, Lee JY, Lim SS, Kang YH.
1Department of Food and Nutrition, Hallym University, Chuncheon, Korea; and 2Department of Biochemistry, School of Medicine, Hallym University, Chuncheon, Korea
Am J Physiol Renal Physiol 303: F1060–F1069, 2012. http://dx.doi.org:/10.1152/ajprenal.00106.2012
Diabetic nephropathy (DN) is one of the major diabetic complications and the leading cause of end-stage renal disease. In early DN, renal injury and macrophage accumulation take place in the pathological environment of glomerular vessels adjacent to renal mesangial cells expressing proinflammatory mediators. Purple corn utilized as a daily food is rich in anthocyanins exerting disease-preventive activities as a functional food. This study elucidated whether anthocyanin-rich purple corn extract (PCA) could suppress monocyte activation and macrophage infiltration. In the in vitro study, human endothelial cells and THP-1 monocytes were cultured in conditioned media of human mesangial cells exposed to 33 mM glucose (HG-HRMC). PCA decreased the HG-HRMC-conditioned, media-induced expression of endothelial vascular cell adhesion molecule-1, E-selectin, and monocyte integrins-_1 and -_2 through blocking the mesangial Tyk2 pathway. In the in vivo animal study, db/db mice were treated with 10 mg/kg PCA daily for 8 wk. PCA attenuated CXCR2 induction and the activation of Tyk2 and STAT1/3 in db/db mice. Periodic acid-Schiff staining showed that PCA alleviated mesangial expansion-elicited renal injury in diabetic kidneys. In glomeruli, PCA attenuated the induction of intracellular cell adhesion molecule-1 and CD11b. PCA diminished monocyte chemoattractant protein-1 expression and macrophage inflammatory protein 2 transcription in the diabetic kidney, inhibiting the induction of the macrophage markers CD68 and F4/80. These results demonstrate that PCA antagonized the infiltration and accumulation of macrophages in diabetic kidneys through disturbing the mesangial IL-8-Tyk-STAT signaling pathway. Therefore, PCA may be a potential renoprotective agent treating diabetes-associated glomerulosclerosis.
Proximate analysis, phytochemical screening, and total phenolic and flavonoid content of Philippine bamboo Schizostachyum lumampao
Jovale Vincent V. Tongco1*, Remil M. Aguda2 and Ramon A. Razal1
1 Department of Forest Products and Paper Science, College of Forestry and Natural Resources,; 2 Institute of Chemistry, College of Arts and Sciences, University of the Philippines Los Baños, College, Laguna, Philippines
Journal of Chemical and Pharmaceutical Research, 2014, 6(1):709-713
The chemical composition of the leaves of Schizostachyum lumampao, known as “buho” in the Philippines, was determined for its potential use as herbal tea with potential health benefits, such as antioxidant properties. Proximate analysis using standard AOAC methods showed that the air-dried leaves contain 10 % moisture, 30.5 % ash, 22.1 % crude protein, 1.6 % crude fat, 28.7 % crude fiber, and 7.2 % total sugar (by difference). Using a variety of reagents for qualitative phytochemical screening, saponins, diterpenes, triterpenes, phenols, tannins, and flavonoids were detected in both the ethanolic and aqueous leaf extracts, while phytosterols were only detected in the ethanolic extract. Using UV-Vis spectrophotometry, the total phenolic content (in GAE) were 76.7 and 13.5 gallic acid equivalents per 100 g air-dried sample for the ethanolic and aqueous extracts, respectively. The total flavonoid content were 70.2 and 17.86 mg quercetin equivalents per 100 g air-dried sample for the ethanolic and aqueous extracts, respectively. This preliminary study showed the total amount of phenolics and flavonoids present in buho, the phytochemicals present, and its proximate analysis.
Comparison of Nutritional Quality of the Vegan, Vegetarian, Semi-Vegetarian, Pesco-Vegetarian and Omnivorous Diet
(This article belongs to the Special Issue Vegan diets and Human health)
Nutrients 2014, 6(3), 1318-1332; http://dx.doi.org:/10.3390/nu6031318
Abstract: The number of studies comparing nutritional quality of restrictive diets is limited. Data on vegan subjects are especially lacking. It was the aim of the present study to compare the quality and the contributing components of vegan, vegetarian, semi-vegetarian, pesco-vegetarian and omnivorous diets. Dietary intake was estimated using a cross-sectional online survey with a 52-items food frequency questionnaire (FFQ). Healthy Eating Index 2010 (HEI-2010) and the Mediterranean Diet Score (MDS) were calculated as indicators for diet quality. After analysis of the diet questionnaire and the FFQ, 1475 participants were classified as vegans (n = 104), vegetarians (n = 573), semi-vegetarians (n = 498), pesco-vegetarians (n = 145), and omnivores (n = 155). The most restricted diet, i.e., the vegan diet, had the lowest total energy intake, better fat intake profile, lowest protein and highest dietary fiber intake in contrast to the omnivorous diet. Calcium intake was lowest for the vegans and below national dietary recommendations. The vegan diet received the highest index values and the omnivorous the lowest for HEI-2010 and MDS. Typical aspects of a vegan diet (high fruit and vegetable intake, low sodium intake, and low intake of saturated fat) contributed substantially to the total score, independent of the indexing system used. The score for the more prudent diets (vegetarians, semi-vegetarians and pesco-vegetarians) differed as a function of the used indexing system but they were mostly better in terms of nutrient quality than the omnivores.
Comment (Larry H. Bernstein, MD): This article is problematic and makes me curious about the HEI-2010 and the MDS scoring systems. Low intake of saturated fat gives weight to the vegan diet. The vegetarian diet would have higher content of high quality protein, and the omnivorous diet would be just as good if the fat were trimmed, and there was sufficient fruits and vegetables. The problem is that quality of protein is not even weighted. The ration of S/N is 1:20+ in plant sourced AAs, but it is 1:12.5 in animal sourced AAs. This has consequences.
Influences of dietary methionine and cysteine on metabolic responses to immunological stress by Escherichia coli lipopolysaccharide injection, and mitogenic response in broiler chickens
BY K. TAKAHASHI, N. OHTA AND Y. AKIBA
Department of Animal Science, Faculty of Agriculture, Tohoku University, Sendai-shi, 981 Japan
British Journal of Nutrition (1997), 78, 815-821
The present experiments were conducted to investigate influences of dietary methionine and cysteine on metabolic responses to immunological stress induced by Escherichia coli lipopolysaccharide (LPS) injection, and concanavalin A (Con A)-induced mononuclear cell (MNC) proliferation in male broiler chickens. In Expt 1, chicks (12 d of age) were fed on a S amino acid (SAA)-deficient diet (5.6 g SAMg diet) or on three kinds of SAA-sufficient diet (9.3 g SAAkg diet; low-, medium- and high-cysteine diets) which contained 2.8, 4.65 and 6.5 g cysteinekg diet, respectively. Plasma (11-1 acid glycoprotein (AGP) concentration and interleukin (IL)-l-like activity in chicks fed on the SAA deficient diet were lower following a single injection of LPS than those in chicks fed on the SAAsufficient diets. At 16 h after LPS injection, plasma Fe and Zn concentrations and body weight were reduced, but AGP concentration and IL-1-like activity in plasma were significantly increased. These changes in body weight, plasma Zn and Fe concentrations following injection of LPS were not affected by dietary methi0nine:cysteine ratios. Plasma AGP concentration and IL-1-like activity in chicks fed on the high-cysteine diet were, however, greater than those in chicks fed on the other diets following a single injection of LPS. In Expt 2, chicks (7 d of age) were fed on the SAA-sufficient diets as in Expt 1 for 10 d. MNC proliferation in spleen induced by Con A in chicks fed on the high cysteine diet was greater than that in chicks fed on the low- or medium-cysteine diet. The results suggest that dietary cysteine has an impact on the immune and inflammatory responses.
The present experiment showed that plasma IL-1 like activity following LPS injection and T cell activity of the spleen estimated by Con A-induced MNC proliferation were greater in chicks fed on the high-cysteine diet than in chicks fed on the low- or medium cysteine diet, even though the diets contained 9.3 g SAA kg diet which is recommended by the National Research Council (1984) feeding standard. Tsiagbe et al. (19874 showed that cysteine was 70-84 % as efficient as methionine in enhancing IgG production and in delaying hypersensitivity to PHA-P stimulation. Thus dietary cysteine is not only important for T-cell function and antibody production, but also for macrophage response to LPS in broilers. However, our previous study (Takahashi et al. 1995) showed that a low-protein diet enhanced plasma IL-1-like activity compared with a high-protein diet in chicks, even though the supply of SAA from the diet in chicks fed on a low-protein diet was much less than that in chicks fed on a high-protein diet. These observations suggest that supply of SAA may not be the only factor affecting the immune responses. The combined results of the previous (Takahashi et al. 1995) and the present experiments, suggest that, as well as the supply of SAA, the methionine:cysteine ratio in the diet is an important factor affecting some immune responses, e.g. IL- 1-like activity, AGP concentration in plasma and mitogenic response of MNC in spleen. The present results also suggest that dietary cysteine intake has an impact on the immune and inflammatory responses, although replacement of cysteine with methionine in diets would not impair growth and reproduction within certain ratios in the diet (Graber & Baker, 1971; Ohta & Ishibashi, 1994 and the present study).
Methionine: Cysteine: Acute-phase response: Lipopolysaccharide
Antioxidant scaffolds for tissue engineering
When a foreign material like a medical device or surgical implant is put inside the human body, the body always responds. According to Northwestern’s Guillermo Ameer, most of the time, that response can be negative and affect the device’s function.
“You will always get an inflammatory response to some degree,” said Ameer, professor of biomedical engineering in McCormick School of Engineering and Applied Science and professor of surgery in the Feinberg School of Medicine. “A problem with commonly used plastic materials, in particular, is that in addition to that inflammatory response, oxidation occurs.”
We all need oxygen to survive, but a high concentration of oxygen in the body can cause oxidative reactions to fall out of balance, which modifies natural proteins, cells, and lipids and causes them to function abnormally. This oxidative stress is toxic and can contribute to chronic disease, chronic inflammation, and other complications that may cause the failure of implants.
For the first time ever, Ameer and his team have created a biodegradable biomaterial that is inherently antioxidant. The material can be used to create elastomers, liquids that turn into gels, or solids for building devices that are more compatible with cells and tissues. The research is described in the June 26 issue of Biomaterials.
“Plastics can self-oxidize, creating radicals as part of their degradation process,” Ameer said. “By implanting devices made from plastics, the oxidation process can injure nearby cells and create a cascade that leads to chronic inflammation. Our materials could significantly reduce the inflammatory response that we typically see.”
Ameer created the biomaterial, which is a polyester based on citric acid, by incorporating vitamin C as part of the building blocks. In preliminary experiments, his team coated vascular grafts with the antioxidant biomaterial, and the grafts were evaluated in animals by Ameer’s long-time collaborator Melina Kibbe, professor of surgery and the Edward G. Elcock Professor of Surgical Research at Feinberg and a vascular surgeon at Northwestern Memorial Hospital.
As part of the foreign body response, grafts tend to inflame nearby cells and slowly scar over time, which eventually leads to failure. When the antioxidant vascular graft was implanted, however, the scarring was significantly reduced. Ameer’s team, funded by a proof-of-concept grant from the Northwestern University Clinical and Translational Sciences Institute, also found that a water-soluble, thermo-reversible version of the material sped of the healing of diabetic ulcers. Because the material is biodegradable, it harmlessly is absorbed by the body over time.
“In the past, people have added antioxidant vitamins to a polymer and blended it in,” Ameer said. “That can affect the mechanical properties of the material and limit how much antioxidant you can add, so it doesn’t work well. What we’re doing is different. We’re building a material that is already inherently, intrinsically antioxidant.”
Ameer said the new biomaterial could be used to create scaffolds for tissue engineering, coat or build safer medical devices, promote healing in regenerative medicine, and protect cells, genes, and viruses during drug delivery. He added that the new biomaterial is easy to make and inexpensive.
“Citric acid is affordable and in pretty much everything we come in contact with on a daily basis—food and beverages, skin and hair products, drugs, etc.,” Ameer said. “It’s a common, inexpensive raw material to use, and our system can stabilize vitamin C, an antioxidant that we are all familiar with.”
The first author of the study was Robert van Lith, a PhD candidate in Ameer’s research laboratory.
Source: Northwestern Univ.
Pomegranate for Your Cardiovascular Health
Michael Aviram, D.Sc,* and Mira Rosenblat, M.Sc.
The Lipid Research Laboratory, The Rappaport Faculty of Medicine and Research Institute, Technion-Institute of Technology, and Rambam Medical Center, Haifa, Israel
Rambam Medical Center J 2013;4 (2):e0013.
Pomegranate is a source of some very potent antioxidants (tannins, anthocyanins) which are considered to be also potent anti-atherogenic agents. The combination of the above unique various types of pomegranate polyphenols provides a much wider spectrum of action against several types of free radicals. Indeed, pomegranate is superior in comparison to other antioxidants in protecting low-density lipoprotein (LDL, “the bad cholesterol”) and high-density lipoprotein (HDL, “the good cholesterol”) from oxidation, and as a result it attenuates atherosclerosis development and its consequent cardiovascular events. Pomegranate antioxidants are not free, but are attached to the pomegranate sugars, and hence were shown to be beneficial even in diabetic patients. Furthermore, pomegranate antioxidants are unique in their ability to increase the activity of the HDL-associated paraoxonase 1 (PON1), which breaks down harmful oxidized lipids in lipoproteins, in macrophages, and in atherosclerotic plaques. Finally, unique pomegranate antioxidants beneficially decrease blood pressure. All the above beneficial characteristics make the pomegranate a uniquely healthy fruit.
Abbreviations: AAPH, 2,2′-azobis amidinopropane hydrochloride; ACE, angiotensin-converting enzyme; BP, blood pressure; CAS, carotid artery stenosis; CHD, coronary heart disease; CIMT, carotid intima-media thickness; EDV, end-diastolic velocity; GAE, gallic acid equivalents; HDL, high-density lipoprotein; HMDM, human monocyte-derived macrophages; LDL, low-density lipoprotein; LPDS, lipoprotein-deficient serum; MI, myocardial infarction; Ox-LDL, oxidized LDL; PJ, pomegranate juice; POMxl, an extract of the pomegranate outer peel; PON, paraoxonase; PSV, peak systolic velocity; ROS, reactive oxygen species; TAS, total antioxidant status; TBARS, thiobarbituric acid reactive substances; TGs, triglycerides; VLDL, very-low-density lipoprotein.
Citation: Aviram M, Rosenblat M. Pomegranate for Your Cardiovascular Health. RMMJ 2013;4 (2):e0013.
Cocoa Phenolic Extract Protects Pancreatic Beta Cells against Oxidative Stress
MÁ Martín, S Ramos, I Cordero-Herrero, L Bravo and L Goya
1 Department of Metabolism and Nutrition, Instituto de Ciencia y Tecnología de Alimentos y Nutrición (ICTAN–CSIC), Madrid 28040, Spain
2 Centro de Investigación Biomédica en red de Diabetes y Enfermedades Metabólicas Asociadas (ISCIII), Madrid 28039, Spain
Nutrients 2013, 5, 2955-2968; http://dx.doi.org:/10.3390/nu5082955
Abstract: Diabetes mellitus is associated with reductions in glutathione, supporting the critical role of oxidative stress in its pathogenesis. Antioxidant food components such as flavonoids have a protective role against oxidative stress-induced degenerative and age-related diseases. Flavonoids constitute an important part of the human diet; they can be found in most plant foods, including green tea, grapes or cocoa and possess multiple biological activities. This study investigates the chemo-protective effect of a cocoa phenolic extract (CPE) containing mainly flavonoids against oxidative stress induced by tert-butylhydroperoxide (t-BOOH) on Ins-1E pancreatic beta cells. Cell viability and oxidative status were evaluated. Ins-1E cells treatment with 5–20 μg/mL CPE for 20 h evoked no cell damage and did not alter ROS production. Addition of 50 μM t-BOOH for 2 h increased ROS and carbonyl groups content and decreased reduced glutathione level. Pre-treatment of cells with CPE significantly prevented the t-BOOH-induced ROS and carbonyl groups and returned antioxidant defences to adequate levels. Thus, Ins-1E cells treated with CPE showed a remarkable recovery of cell viability damaged by t-BOOH, indicating that integrity of surviving machineries in the CPE-treated cells was notably protected against the oxidative insult.
Keywords: antioxidant defences; cocoa flavanols; dietary polyphenols; Ins-1E cells; oxidative biomarkers; type 2 diabetes mellitus
Flavones as isosteres of 4(1H)-quinolones: discovery of ligand efficient and dual stage antimalarial lead compounds
T Rodrigues, AS Ressurreição, FP da Cruz, IS Albuquerque, J Gut, MP Carrasco, D Gonçalves, RC Guedes, et al.
1Research Institute for Medicines and Pharmaceutical Sciences (iMed.UL), Facultyof Pharmacy, University of Lisbon, Av. Prof. Gama Pinto, 1649-019 Lisbon, Portugal
2Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028 Lisboa, Portugal
3Department of Medicine, San Francisco General Hospital, University of California, San Francisco, Box 0811, San Francisco, California, 94143, U.S.A.
4 REQUIMTE, Department of Chemistry & Biochemistry, Faculty of Sciences, University of Porto, R. do Campo Alegre, 4169-007 Porto, Portugal
Reference: EJMECH 6410 European Journal of Medicinal Chemistry
PII: S0223-5234(13)00580-1 http://dx.doi.org:/10.1016/j.ejmech.2013.09.008
ABSTRACT: Malaria is responsible for nearly one million deaths annually, and the increasing prevalence of multi-resistant strains of Plasmodium falciparum poses a great challenge to controlling the disease. A diverse set of flavones, isosteric to 4(1H)-quinolones, were prepared and profiled for their antiplasmodial activity against the blood stage of P. falciparum W2 strain, and the liver stage of the rodent parasite l.berghei. Ligand efficient leads were identified as dual stage antimalarials, suggesting that scaffold optimization may afford potent antiplasmodial compounds.
cite as: T. Rodrigues, A.S. Ressurreição, F.P. da Cruz, I.S. Albuquerque, J. Gut, M.P.
Carrasco, D. Gonçalves, R.C. Guedes, D.J.V.A. dos Santos, M.M. Mota, P.J. Rosenthal, R. Moreira, M. Prudêncio, F. Lopes, Flavones as isosteres of 4(1H)-quinolones: discovery of ligand efficient and dual stage antimalarial lead compounds, European Journal of Medicinal Chemistry (2013),
Silencing of the sulfur rich α-gliadin storage protein family in wheat grains (Triticumae stivum L.) causes nounintended side-effects on other metabolites
C Zörb, D Becker, M Hasler, KH Mühling, V Gödde, K Niehaus and CM Geilfus
1 Institute of Biology, University Leipzig, Leipzig, Germany
2 Biocentre Klein Flottbek, EBBT, University of Hamburg, Hamburg, Germany
3 Lehrfach Variations statistik, 4 Institute of Plant Nutrition and Soil Science, Christian Albrechts University Kiel, Kiel, Germany
5 Department of Proteome and Metabolome Research, Faculty of Biology, Bielefeld University, Bielefeld, Germany
Frontiers in Plant Science 17 Sept, 2013; http://dx.doi.org:/10.3389/fpls.2013.00369
Wheat is an important source of proteins and metabolites for human and animal nutrition. To assess the nutritional quality of wheat products, various protein and diverse metabolites have to be evaluated. The grain storage protein family of the α-gliadins are suggested to be the primary initiator of the inflammatory response to gluten in Celiac disease patients .With the technique of RNAi, the α-gliadin storage protein fraction in wheat grains was recently knocked down. From a patient’s perspective, this is a desired approach, however, this study aims to evaluate whether such a down-regulation of these problematic α-gliadins also has unintended side-effects on other plant metabolites. Such uncontrolled and unknown arbitrary effects on any metabolite in plants designated for food production would surely represent an avoidable risk for the consumer. In general,
α-gliadins are rich in sulfur, making their synthesis and content dependent on the sulfur supply. For this reason, the influence of the application of increasing sulfur amounts on the metabolome of α-gliadin-deficient wheat was additionally investigated because it might be possible that e.g., considerable high/low amounts of S might increase or even induce such unintended effects that are not observable under moderate S nutrition. By silencing the α-gliadin genes, a recently developed wheat-line that lacks the set of 75 corresponding α-gliadin proteins has become available. The plants were subsequently tested for RNAi- induced effects on metabolites that were not directly attributable to the specific effects of the RNAi- approach on the α-gliadin proteins. For this,GC-MS-based metabolite profiles were recorded. A comparison of wild type with gliadin-deficient plants cultivated in pot experiments revealed no differences in all 109 analyzed metabolites, regardless of the S-nutritional status.No unintended effects attributable to the RNAi- based specific genetic deletion of a storage protein fraction were observed.
Keywords: sulfur, wheat, gliadin, metabolites, Celiac disease, GC-MS
Olive oil intake and risk of cardiovascular disease and mortality in the PREDIMED Study
Guasch-Ferré et al. BMC Medicine 2014, 12(78):1741-7015 http://www.biomedcentral.com/1741-7015/12/78
Background: It is unknown whether individuals at high cardiovascular risk sustain a benefit in cardiovascular disease from increased olive oil consumption. The aim was to assess the association between total olive oil intake, its varieties (extra virgin and common olive oil) and the risk of cardiovascular disease and mortality in a Mediterranean population at high cardiovascular risk.
Methods: We included 7,216 men and women at high cardiovascular risk, aged 55 to 80 years, from the PREvención con DIeta MEDiterránea (PREDIMED) study, a multicenter, randomized, controlled, clinical trial. Participants were randomized to one of three interventions: Mediterranean Diets supplemented with nuts or extra-virgin olive oil, or a control low-fat diet. The present analysis was conducted as an observational prospective cohort study. The median follow-up was 4.8 years. Cardiovascular disease (stroke, myocardial infarction and cardiovascular death) and mortality were ascertained by medical records and National Death Index. Olive oil consumption was evaluated with validated food frequency questionnaires. Multivariate Cox proportional hazards and generalized estimating equations were used to assess the association between baseline and yearly repeated measurements of olive oil intake, cardiovascular disease and mortality.
Results: During follow-up, 277 cardiovascular events and 323 deaths occurred. Participants in the highest energy-adjusted tertile of baseline total olive oil and extra-virgin olive oil consumption had 35% (HR: 0.65; 95% CI: 0.47 to 0.89) and 39% (HR: 0.61; 95% CI: 0.44 to 0.85) cardiovascular disease risk reduction, respectively, compared to the reference. Higher baseline total olive oil consumption was associated with 48% (HR: 0.52; 95% CI: 0.29 to 0.93) reduced risk of cardiovascular mortality. For each 10 g/d increase in extra-virgin olive oil consumption, cardiovascular disease and mortality risk decreased by 10% and 7%, respectively. No significant associations were found for cancer and all-cause mortality. The associations between cardiovascular events and extra virgin olive oil intake were significant in the Mediterranean diet intervention groups and not in the control group.
Conclusions: Olive oil consumption, specifically the extra-virgin variety, is associated with reduced risks of cardiovascular disease and mortality in individuals at high cardiovascular risk.
Trial registration: This study was registered at controlled-trials.com (http://www.controlled-trials.com/ISRCTN35739639). International Standard Randomized Controlled Trial Number (ISRCTN): 35739639. Registration date: 5 October 2005.
Keywords: Olive oil, Cardiovascular, Mortality, Mediterranean Diet, PREDIMED
Polyphenol intake and mortality risk: a re-analysis of the PREDIMED trial
Tresserra-Rimbau et al. BMC Medicine 2014, 12(77): 1741-7015; http://www.biomedcentral.com/1741-7015/12/77
Background: Polyphenols may lower the risk of cardiovascular disease (CVD) and other chronic diseases due to their antioxidant and anti-inflammatory properties, as well as their beneficial effects on blood pressure, lipids and insulin resistance. However, no previous epidemiological studies have evaluated the relationship between the intake of total polyphenols intake and polyphenol subclasses with overall mortality. Our aim was to evaluate whether polyphenol intake is associated with all-cause mortality in subjects at high cardiovascular risk.
Methods: We used data from the PREDIMED study, a 7,447-participant, parallel-group, randomized, multicenter, controlled five-year feeding trial aimed at assessing the effects of the Mediterranean Diet in primary prevention of cardiovascular disease. Polyphenol intake was calculated by matching food consumption data from repeated food frequency questionnaires (FFQ) with the Phenol-Explorer database on the polyphenol content of each reported food. Hazard ratios (HR) and 95% confidence intervals (CI) between polyphenol intake and mortality were estimated using time-dependent Cox proportional hazard models.
Results: Over an average of 4.8 years of follow-up, we observed 327 deaths. After multivariate adjustment, we found a 37% relative reduction in all-cause mortality comparing the highest versus the lowest quintiles of total polyphenol intake (hazard ratio (HR) = 0.63; 95% CI 0.41 to 0.97; P for trend = 0.12). Among the polyphenol subclasses, stilbenes and lignans were significantly associated with reduced all-cause mortality (HR =0.48; 95% CI 0.25 to 0.91; P for trend = 0.04 and HR = 0.60; 95% CI 0.37 to 0.97; P for trend = 0.03, respectively), with no significant associations apparent in the rest (flavonoids or phenolic acids).
Conclusions: Among high-risk subjects, those who reported a high polyphenol intake, especially of stilbenes and lignans, showed a reduced risk of overall mortality compared to those with lower intakes. These results may be useful to determine optimal polyphenol intake or specific food sources of polyphenols that may reduce the risk of all-cause mortality.
Clinical trial registration: ISRCTN35739639.
Keywords: Polyphenol intake, All-cause mortality, PREDIMED, Mediterranean diet, Stilbenes, Lignans
Effects of Walnuts on Endothelial Function in Overweight Adults with Visceral Obesity: A Randomized, Controlled, Crossover Trial
David L Katz MD, MPHa, Anna Davidhi BSa, Yingying Ma MD, RVTa, Yasemin Kavak BSa,et al.
a Yale University Prevention Research Center, Griffin Hospital, Derby, Connecticut
Journal of the American College of Nutrition, 2013; 31(6) :415-423
Objectives: Metabolic syndrome is a precursor of diabetes and cardiovascular disease (CVD). Walnut ingestion has been shown to reduce CVD risk indices in diabetes. This randomized controlled crossover trial was performed to investigate the effects of daily walnut consumption on endothelial function and other biomarkers of cardiac risk in a population of overweight individuals with visceral adiposity.
Methods: Forty-six overweight adults (average age, 57.4 years; 28 women, 18 men) with elevated waist circumference and 1 or more additional signs of metabolic syndrome were randomly assigned to two 8-week sequences of walnut-enriched ad libitum diet and ad libitum diet without walnuts, which were separated by a 4-week washout period. The primary outcome measure was the change in flow-mediated vasodilation (FMD) of the brachial artery. Secondary measures included serum lipid panel, fasting glucose and insulin, Homeostasis Model Assessment–Insulin Resistance values, blood pressure, and anthropometric measures.
Results: FMD improved significantly from baseline when subjects consumed a walnut-enriched diet as compared with the control diet (1.4% 6 2.4% versus 0.3% 6 1.5%; p¼0.019). Beneficial trends in systolic blood pressure reduction were seen, and maintenance of the baseline anthropometric values was also observed. Other measures were unaltered.
Conclusion: Daily ingestion of 56 g of walnuts improves endothelial function in overweight adults with visceral adiposity. The addition of walnuts to the diet does not lead to weight gain. Further study of the potential role of walnut intake in diabetes and CVD prevention is warranted.
To cite this article: David L Katz MD, MPH, Anna Davidhi BS, Yingying Ma MD, RVT, Yasemin Kavak BS, Lauren Bifulco MPH & Valentine Yanchou Njike MD, MPH (2012) Effects of Walnuts on Endothelial Function in Overweight Adults with Visceral Obesity: A Randomized, Controlled, Crossover Trial, Journal of the American College of Nutrition, 31:6, 415-423, http://dx.doi.org:/10.1080/07315724.2012.10720468
Antioxidant properties of ten high yielding rice varieties of Bangladesh
AK Dutta, PS Gope, S Banik, S Makhnoon, MA Siddiquee, Y Kabir
Asian Pacific Journal of Tropical Biomedicine (2012)S99-S103
Role Of Dietary Fiber In Improving Human Physiology And In Controlling Diseases
Yadav Pn, Srivastava S and Narayan Rp
IJBPAS, January, 2014, 3(1): 98-112
The Importance of Prebiotics in Functional Foods and Clinical Practice
VM Caselato de Sousa, EF dos Santos, VC Sgarbieri
Food and Nutrition Sciences, 2011, 2, 133-144; http://dx.doi.org:/10.4236/fns.2011.22019
Phloem-specific expression of a melon Aux/IAA in tomato plants alters auxin sensitivity and plant development
Guy Golan, Rotem Betzer and Shmuel Wolf*
The Robert H. Smith Facultyof Agriculture, Food and Environment,Otto Warburg Minerva Center for Agricultural Biotechnology,The Robert H. Smith Institute of Plant Sciences and Genetics in Agriculture,The Hebrew University of Jerusalem, Rehovot, Israel
Frontiers in Plant Science Aug 2013; http://dx.doi.org:/10.3389/fpls.2013.00329