Études intéressantes pour naturopathes

Épigénétique et renversement de l'immunosénescence: nouveau paradigme pour la longévité sur la base de preuves 

  • Karriem H. Ali, M.D. scientifique en chef, Pharmacognosia and iPraxic.org 

RÉSUMÉ: L'humanité a souvent pensé que le vieillissement était une dégradation progressive et conditionnée dans le temps de la santé et de la qualité de vie se manifestant par une apparition de plus en plus fréquente de maladies chroniques épuisantes et au déroulement de plus en plus difficile. L'optique de la médecine actuelle offre une vue nouvelle et plus optimiste du vieillissement. La médecine clinique se concentre toujours davantage sur la manière de modérer les effets du vieillissement plutôt que de renverser le processus proprement dit. Cependant le progrès actuel en épigénétique et immunologie nous fait avancer jusqu'à être prêt à relever un nouveau défit - celui de stopper voire de renverser le processus de vieillissement. Il existe une quantité énorme de textes scientifiques qui mettent en évidence le fait que le déséquilibre du système immunitaire - notamment de l'immunité innée - peut être un facteur déterminant de la déficience inévitable de son fonctionnement en âge avancé. Ce qui est typique pour ce déséquilibre, c'est un état exagérément réactif, non intensif et constant des processus du système immunitaire qui supporte, que ce soit seul ou en coopération avec d'autres facteurs, les manifestations pathognomoniques de plusieurs maladies chroniques que nous mettons en rapport avec le vieillissement (comme, par exemple, les maladies cardio-vasculaires, la maladie d'Alzheimer, le cancer, l'ostéoarthrite, la résistance à l'insuline ou le diabète). 

Nouveau rapport de cas - Neuer Fallbericht - New case report


Enhancing effect of streptozotocin-induced insulin deficit on antitumor innate immune defense in rats.

  • Hajto Tibor, Péczely László, Kuzma Monika, Hormay Edina, Ollmann Tamás, Jaksó Pál, Baranyai Lilla and Karádi Zoltán

Abstract: 

Background: There are conflicting data about the relationship between diabetes mellitus and cancer risk in that growing evidence suggest a possible role of endogenous elevated insulin level which is often found in Non-Insulin-Dependent-Diabetes-Mellitus or an exogenous hyperinsulinemia observed often in Insulin-Dependent-Diabetes-Mellitus. In the last years higher attention focused on the role of immunoregulation both in the insulin production by β-cell of Langerhans-islets and in the insulin sensitivity (resistance) of insulin receptors. Interestingly, cytokines from type-2 innate immune cells, such as M2 macrophages or D2 dendritic cells exhibit a protective effect on both types of diabetes. However, the effect of insulin on the balance between type-1 and type-2 natural immune mechanisms, which is important for the tumour defence, was poorly investigated. 

Material and methods: Streptozotocin (STX)-treated Wister rats was treated per oral with a non-optimal single dose of an evidence based and standardized plant immunomodulator, namely Rice Bran Arabinoxylan Concentrate (RBAC) which has been shown to activate type-1 innate immune cells (such as M1, D1 and NK cells). 24h after a single dose of RBAC (45mg/kg) four parameters of NK cells were determined with flow cytometry using stained CD161-APC and CD314-PE monoclonal antibodies and by haematological examinations. The results were compared with negative controls (without STX or RBAC treatment).

Results: Since STX caused a significantly reduced lymphocyte production in bone marrow, only the RBAC-induced relative increases in number of NKR-P1+ and LGL cells among the all lymphocyte population parallel with the frequency and intensity of the most important Killing Activator Receptor, namely NKG2D among the total NK cell population were determined. In the STX-untreated group RBAC induced only not significant increases compared with negative control values. However, in STX-treated groups all four NK parameters revealed RBAC-induced significant increases (p<0.05) compared to the negative controls.

Conclusion: These results suggest the hypothesis that insulin deficit can increase the immunomodulator-induced activation of type-1 innate immune cells indicating that insulin takes part on regulation of the natural immune balance inhibiting the type-1 innate antitumor defence.

Dietary Supplementation with Biobran/MGN-3 Increases Innate Resistance and Reduces the Incidence of Influenza-like Illnesses in Elderly Subjects: A Randomized, Double-Blind, Placebo-Controlled Pilot Clinical Trial

  • Ahmed F. Elsaid, Sudhanshu Agrawal, Anshu Agrawal and Mamdooh Ghoneum 

Abstract: Influenza-like illness (ILI) remains a major cause of severe mortality and morbidity in the elderly. Aging is associated with a decreased ability to sense pathogens and mount effective innate and adaptive immune responses, thus mandating the development of protective nutraceuticals. Biobran/MGN-3, an arabinoxylan from rice bran, has potent anti-aging and immunomodulatory effects, suggesting that it may be effective against ILI. The objective of the current study was to investigate the effect of Biobran/MGN-3 on ILI incidence, natural killer (NK) cell activity, and the expressions of RIG-1 (retinoic acid-inducible gene 1), MDA5 (melanoma differentiation-associated protein 5), and their downstream signaling genes ISG-15 (interferon-stimulated genes 15) and MX1 (myxovirus (influenza) resistance 1, interferon-inducible). A double-blind, placebo-controlled clinical trial included eighty healthy older adults over 55 years old, 40 males and 40 females, who received either a placebo or Biobran/MGN-3 (500 mg/day) for 3 months during known ILI seasonality (peak incidence) in Egypt. The incidence of ILI was confirmed clinically according to the WHO case definition criteria. Hematological, hepatic, and renal parameters were assessed in all subjects, while the activity of NK and NKT (natural killer T) cells was assessed in six randomly chosen subjects in each group by the degranulation assay. The effect of Biobran/MGN-3 on RIG-1 and MDA5, as well as downstream ISG15 and MX1, was assessed in BEAS-2B pulmonary epithelial cells using flow cytometry. The incidence rate and incidence density of ILI in the Biobran/MGN-3 group were 5.0% and 0.57 cases per 1000 person-days, respectively, compared to 22.5% and 2.95 cases per 1000 person-days in the placebo group. Furthermore, Biobran/MGN-3 ingestion significantly enhanced NK activity compared to the basal levels and to the placebo group. In addition, Biobran/MGN-3 significantly upregulated the expression levels of RIG-1, MDA5, ISG15, and MX1 in the human pulmonary epithelial BEAS-2B cell lines. No side effects were observed. Taken together, Biobran/MGN-3 supplementation enhanced the innate immune response of elderly subjects by upregulating the NK activity associated with reduction of ILI incidence. It also upregulated the intracellular RIG-1, MDA5, ISG15, and MX1 expression in pulmonary epithelial tissue cultures. Biobran/MGN-3 could be a novel agent with prophylactic effects against a wide spectrum of respiratory viral infections that warrants further investigation.

L'arabinoxylane de son de riz (ImunoBran) réduit le taux de virémie chez les patients souffrant d'infection chronique HCV : essai randomisé*  

  • Hosny Salama, Eman Medhat, Magda Shaheen, Abdel-Rahman N Zekri, Tarneem Darwish et Mamdooh Ghoneum

Résumé: Le traitement actuel de l'hépatite virale de type C (VHC) est accompagné de lourds effets secondaires et revient très cher. Il est donc bon d'étudier l'efficacité des procédés naturels du traitement de cette maladie ayant des effets moins toxiques et un comut moins onéreux. Dans cette étude, 37 personnes souffrant d'hépatite virale C chronique ont été répartis de façon aléatoire en deux groupes et étaient soignés à l'interféron pégylé (PEG‐IFN) combiné avec de la ribavirine (21 patients), ou avec du ImunoBran contenant de l'arabinoxylane de son de riz (1 g/par jour) (16 patients). On a examiné les taux sériques de virémie, des enzymes du foie, de l'interféron‐γ (IFN‐γ) et de la toxicité avant le traitement et trois mois plus tard. Les résultats relevés trois mois plus tard ont indiqué une réduction importante de la charge virale par rapport aux données d'origine (P <0,05), et ce de semblable envergure auprès des deux groupes. Le traitement au produit ImunoBran a eu par ailleurs pour conséquence une augmentation importante du niveau d'IFN‐γ (P <0,001). Le déroulement du traitement des patients du "groupe PEG‐IFN plus ribavirine" a été marqué par l'apparition de fièvre, d'anémie, de thrombocytopénie et de fatigue légère. Les patients du "groupe ImunoBran" n'ont au contraire ressenti aucun effet secondaire et déclaraient aller bien. En conclusion, nous constatons que le ImunoBran représente un nouveau procédé efficace de traitement de l'hépatite virale C chronique avec un effet semblable à celui du traitement au PEG‐IFN combiné avec la ribavirine sans toutefois les effets secondaires et les coûts onéreux. Cette constatation selon laquelle le ImunoBran agit contre l'infection du VHC requiert des examens plus approfondis basés sur plusieurs essais cliniques (Enregistrement d'essai clinique. NCT02690103). 

Du laboratoire à la table de nuit: l'arabinoxylane de son de riz (MGN-3/ImunoBran) utilisé de plus en plus dans le traitement immunologique de cancer

  • Ghoneum, M 

Résumé: Le MGN-3/ImunoBran est de l'hémicellulose dénaturée obtenue à partir de la réaction de l'hémicellulose de son de riz avec de nombreuses enzymes capables d'hydrolyser les hydrocarbones, issues du champignon Shiitaké (lentin du chêne). Au cours des 24 dernières années, notre recherche fondamentale s'est orientée sur l'effet biothérapeutique du MGN-3, étant donné sa faculté d'activer le système immunitaire, sur le cancer. La recherche a été réalisée in vitro et dans le cadre d'études sur les animaux et sur les humains. Cet article présente les effets immuno-modulaires du MGN-3 ainsi que le potentiel du produit en tant que médicament contre le cancer. Les études in vitro ont démontré que la culture de diverses lignées murines et humaines de cellules cancéreuses avec le MGN-3 avait pour résultat une réduction de leur taux de survie. Les études in vivo ont montré par ailleurs que le produit induisait une régression de plusieurs types de tumeurs animales y compris de l'estomac, du neuroblastome et du carcinome d'Ehrlich. En outre, l'action anticancéreuse du MGN-3 a été avérée dans des études cliniques humaines et plusieurs études de cas de patients souffrant de carcinome hépatocellulaire et de cancer en phase de progression et partiellement métastatique. Les patients chez lesquels le traitement conventionnel a été complété par un traitement au MGN-3 ont montré, par rapport à ceux qui n'ont bénéficié que d'un traitement conventionnel : 1) un taux inférieur de récidive du cancer, 2) un taux supérieur de survie, et 3) une meilleure qualité de vie, caractérisée par une meilleure activité physique, un meilleur appétit, un meilleur sommeil, une meilleure digestion et une réduction des douleurs et de l'anxiété. Le présent article fait le résumé des recherches pré-cliniques et cliniques réalisées sur le produit MGN-3/ImunoBran depuis qu'il a été breveté en 1992. Diverses études cliniques effectuées sur des animaux et des humains cincluant différents types de malignités démontrent qu'il s'agit d'un modificateur potentiel de la réponse biologique (MRB) qui améliore la réactivité cytotxique des cellules immunitaires luttant contre le cancer telles que les cellules neturelles tueuses (NK) et les cellules-T CD8+ (par accroissement de leur granulosité), qui stimule la production des interférons IL-2 et IL-12 et qui agit comme un adjuvant naturel des cellules dendritiques (CD). On peut donc l'utiliser dans le cadre des stratégies de vaccination contreles infections et le cancer orientées que l'action des cellules dendritiques. On peut donc qualifier le MGN-3 de MRB exceptionnel étant donné qu'il s'agit d'un produit sûr et non toxique et ne faisant preuve d'aucune hyperréactivité. Le MGN-3 peut devenir un complément immunomodulaire nouveau et prometteur aux moyens immunothérapeutiques existants our les patients souffrant de cancers. 

L'arabinoxylane de son de riz (MGN-3/Biobran) améliore la cytoxicité par les cellules tueuses naturelles en présence de neuroblastome in vitro et in vivo

  • Antonio Pérez-Martínez, Jaime Valentín , Lucía Fernández , Enrique Hernández-Jimé Nez , Eduardo López-Collazo , Petra Zerbes , Ellen Schwörer , Fernando Nuñéz, Inmaculada Génesis Martín, Hannah Sallis, Miguel Ángel Díaz, Rupert Handgretinger et Matthias Manuel Pfeiffer

Résumé Objectifs de l'étude : l'activité cytotoxique des cellules tueuses naturelles (cellules NK) joue un rôle important dans la défense immunologique naturelle dans les cas de tumeurs malignes. Les cellules NK apparaissent comme un nouvel outil de traitement oncologique adoptif. L'arabinoxylane du son de riz (MGN-3/Biobran) est décrit comme un modificateur de la réponse biologique capable d'améliorer l'activité cytotoxique des cellules NK. Cette étude s'est donnée pour but d'évaluer l'effet du produit MGN3/Biobran sur l'activation, l'expansion et la cytotoxicité des cellules NK en présence de cellules de neuroblastome. Méthodes : nous avons stimulé au moyen du produit MGN-3/Biobran les cellules NK enrichies de billes magnétiques. Nous avons procédé à l'évaluation de l'activation des cellules NK en faisant l'analyse de leurs phénotypes et nous avons suivi leur capacité d'expansion. La capacité cytotoxique des cellules NK a été testée in vitro sur des lignées cellulaires K562, Jurkat, A673, NB1691, A-204, RD et RH-30, et in vivo sur des cellules de lignée NB1691. Résultats : la stimulation des cellules NK au moyen du MGN-3/Biobran a induit une augmentation de l'expression des récepteurs CD25 et CD69 associés à l'activation comparativement aux cellules dormeuses (P < 0.05). L'expression des récepteurs NKG2D, DNAM, NCR et TLR est restée inchangée. La stimulation réalisée au moyen du MGN-3/Biobran pendant la nuit a augmenté l'activité cytotoxique des cellules NK par rapport à toutes les lignées cellulaires testées in vitro et a ralenti la croissance du neuroblastome in vivo. Pour ce qui est du produit MGN-3/Biobran, ce mécanisme n'est pas dû à la contamination par les lipopolysaccharides. Par ailleurs, l'application du MGN-3/Biobran a renforcé l'expansion des cellules NK et la réduction des cellules T in vitro. Conclusion : nos données indiquent que le MGN-3/Biobran régule à la hausse les marqueurs d'activation des cellules NK, stimule l'activité cytotoxique des cellules NK en présence de neuroblastome in vitro et in vivo, et provoque de manière sélective l'expansion des cellules tueuses. Ces résultats peuvent être utiles à l'avenir pour le traitement du neuroblastome lors du développement des stratégies thérapeutiques basées sur l'activité des cellules NK.

Les inhibiteurs des récepteurs de l'EGF peuvent-ils accroître les effets immunomodulateurs des extraits de plantes standardisés (de lectine de gui et d'arabinoxylane) avec un résultat clinique avéré? Rapport de cas d'un patient souffrant d'adénocarcinome pulmonaire

  • Tibor Hajto*, Anna Horváth, Lilla Baranyai, Monika Kuzma et Pál Perjési 

Résumé: Contexte : on a suffisamment documenté le fait que les cellules cancéreuses se caractérisent par une perte ou régulation à la baisse des molécules HLA de classe I irréversible et irréparable, ceci conduisant à une échappée définitive des cellules tumorales de la lyse des cellules T. En conséquence, on prête une attention de plus en plus grande aux cellules effectrices du système immunitaire inné capables de tuer les cellules cancéreuses d'une manière non restreinte au complexe majeur d'histocompatibilité. Toutefois, parallèlement à la progression de la tumeur, les cellules d'immunité innée de type 1 empêchant la croissance de la tumeur sont régulées à la baisse et, parmi d'autres facteurs, une dérégulation de la signalisation de l'EGF associée à une tumeur peut jouer également un rôle important. Matériel et méthodes : on a affaire à une patiente âgée de 74 ans atteinte d'un adénocarcinome pulmonaire inopérable avec progression de la maladie après quatre cycles de Carboplatin et de Paclitaxel. Une seconde série de traitement comprenant 75 mg/jour d'Erlotinib (Terceva) a donc été mise en place et prescrite pendant sept mois. Cette thérapie à l'inhibiteur de tyrosine kinase du récepteur de l'EGF a été combinée avec des immunomoduleurs de plantes standardisés - dont les structures se sont avérées semblables à des motifs moléculaires associés à des pathogènes (MAMP) pouvant stimuler les cellules immunitaires innées de type1- et ce à raison de 0,75 ng/kg de lectine de gui et de 0,45 mg/kg d'arabinoxylane deux fois par semaine. Résultats : entre la fin de la chimiothérapie et le début de la seconde série de traitement, la patiente se trouvait en phase terminale de la maladie nécessitant des soins intensifs. Elle possédait des métastases multiples dans le foie, dans les nodules lymphatiques ainsi que dans la plèvre. Après sept mois de traitement à l'Erlotinib et aux immunomoduleurs, une rémission presque totale a pu être constatée par IMG et sa qualité de vie est devenue excellente. Conclusion : ce rapport de cas vient en soutien de l'hypothèse selon laquelle les inihibiteurs de récepteurs d'EGF ainsi que les cellules immunitaires de type-1 qui activent les immunomoduleurs sont en mesure d'inhiber la poussée tumorale de manière synergique. Toutefois, des recherches cliniques plus approfondie visant à clarifier cette question sont nécessaires.

MGN-3 arabinoxylan rice bran modulates innate immunity in multiple myeloma patients

  • Dana Cholujova, Jana Jakubikova, Brarnislav Czako, Michaela Marisova, Luba Hunakova, Jozef Duraj, Martin Mistrik, Jan Sedlak.

Abstract Dendritic cells (DCs) and natural killer (NK) cells are central components of innate immunity for controlling tumor growth. The therapeutic effects of certain anti-myeloma drugs are partially mediated by targeting the innate immune response. In addition, novel types of natural compounds have been developed that efficiently modulate the activity of both the cellular and humoral compartments of immunity. MGN-3 is known as an activator of natural killer cells, inducer of apoptosis and cytokine production, and modulator of dendritic cell maturation and differentiation in vitro. We have performed a randomized, placebo controlled study to examine the effects of MGN-3 on innate immune system parameters in 48 multiple myeloma patients. We performed immunophenotypic analysis of peripheral blood samples, determined NK cell activity, and assessed the cytokine profiles of plasma before and during 3 months of treatment. The results demonstrate a clear increase in NK activity in MGN-3-treated patients compared to the placebo group, an increased level of myeloid DCs in peripheral blood, and augmented concentrations of T helper cell type 1-related cytokines. The present study suggests that MGN-3 may represent an immunologically relevant product for activating innate immunity in multiple myeloma patients and warrants further testing to demonstrate clinical efficacy.

The enhancing efects of Biobran/MGN‑3, an arabinoxylan rice bran, on healthy old adults' health‑related quality of life: a randomized, double‑blind, placebo‑controlled clinical trial 

  • Karriem H. Ali , Angelica B. Melillo , Susanna M. Leonard , Deshratn Asthana, Judi M. Woolger , Aaron H. Wolfson , H. Reginald McDaniel and John E. Lewis 

Abstract Purpose The world's older population is growing rapidly and the need to fnd measures to combat age-associated decline of physical, mental, and cognitive functions and improve their health-related quality of life (HRQOL) is escalating. Biobran/ MGN-3, an arabinoxylan rice bran, has been previously reported to improve the quality of life in cancer patients. The objective of the current study was to examine the efect of a low dose of Biobran/MGN-3 supplementation on the HRQOL in a healthy older adult population. Methods Sixty apparently healthy subjects, 40 males and 20 females, over 56 years old were recruited and blindly randomized into two group receiving either placebo or Biobran/MGN-3 (250 mg/day for 3 months). Participants did not take any vitamins or medications during the study and their health was closely monitored. HRQOL was assessed at the initiation and termination of the study using the previously validated Arabic version of SF-12v2 questionnaire. Results For all measured HRQOL domains, there was no statistically signifcant diference in baseline scores between the two groups. Compared to baseline values and placebo-treated subjects, Biobran/MGN-3 supplementation signifcantly enhanced the levels of physical and mental component summary scores as well as role-physical, bodily pain, vitality, and social functioning subdomain scores. Conclusion These results show that Biobran/MGN-3 is a promising psychoneuroimmune modulatory agent that could improve the HRQOL in healthy old adults.

An open-label, randomized clinical trial to assess the immunomodulatory activity of a novel oligosaccharide compound in healthy adults 

  • K. H. Ali, A. B. Melillo, S. M. Leonard, D. Asthana, Judi M. Woolger, A. H. Wolfson, H. R. McDaniel, J. E. Lewis

ABSTRACT: Background: Rice Bran Arabinoxylan Compound (RBAC) is a nutritional supplement produced by enzymatic hydrolysis of hemicellulose B derived from rice bran. Several in vitro studies and clinical reports have shown RBAC to possess promising immunomodulating effects, specifically with respect to natural killer cell and cytokine activity. The concept of a true immunomodulator is an agent possessing a broad range of activity dependent upon the existing state of health and immunity in the individual host. The present study investigated the immunomodulatory effect of RBAC in a healthy adult human population over 60 days by assessing changes in natural killer cell cytotoxicity (NKCC) and cytokines and growth factors. Subjects participated in a two-group, randomized intervention, where one group (n=10) consumed 1 gram/day and the other (n=10) consumed 3 gram/day. Safety and tolerability of RBAC were assessed with total bilirubin, total protein, creatinine, and liver function tests. 

Results: We found that both groups had similar responses for NKCC, cytokines, and growth factors. The NKCC peaked at 1 week, whereas interferon-γ, tumor necrosis factor-α, interleukins-1α, -1β, -8, and -10, and epidermal growth factor peaked at 30 days. All subjects tolerated the supplement without any adverse reactions. Conclusions: Our results showed transient, bi-directional, immune marker effects consistent with true, multifactorial immunomodulation rather than simply immunostimulation or immunosuppression. Given our findings, the immunomodulatory activity of RBAC merits study in conditions where the immune system is functionally compromised (e.g., otherwise-healthy smokers and HIV/AIDS or cancer patients). RBAC may not only help to destroy tumor cells and viruses directly, but also increase the activity of immune cells, thereby optimizing the immune system, especially NKCC, which can increase the chance and speed of host recovery.

Comparative study of four fluorescent probes for evaluation of natural kill-er cell cytotoxicity assays

  • Dana Cholujova, Jana Jakubıkova, Miroslav Kubes, Barbora Arendacka, Michal Sapake, Ihnatko Robertc, Jan Sedlak 

Abstract Cytotoxicity is one of the major defence mechanisms against both virus-infected and tumor cells. Radioactive 51chromium (51Cr) release assay is a ''gold standard'' for assessment of natural killer (NK) cytolytic activity in vitro. Several disadvantages of this assay led us to design alternative tools based on flow cytometry analysis. Four different fluorescent dyes, calcein acetoxymethyl ester (CAM), carboxyfluorescein succinimidyl ester (CFSE), Vybrant DiO (DiO) and MitoTracker Green (MTG) were tested for labeling of NK target K-562 cells. Target staining stability, spontaneous release of fluorochromes and subsequent accumulation in bystander unstained cells were measured using fluorimetry and flow cytometry. Healthy donor peripheral blood mononuclear cells and affinity column purified NK cells were used as effectors coincubated with target K-562 cells at different E:T ratios for 3 h and 90 min, respectively. Fluorescent probe 7-amino-actinomycin D was used for live and dead cell discrimination. Bland-Altman statistical method was applied to measure true agreement for all CAM-51Cr, CFSE-51Cr, DiO-51Cr and MTG-51Cr pairs analyzed. Based on the data, none of the four proposed methods can be stated equivalent to the standard 51Cr release assay. Considering linear relationships between data obtained with four fluorochromes and 51Cr release assay as well as linear regression analysis with R2 ¼ 0.9393 value for CAM-51Cr pair, we found the CAM assay to be the most closely related to the 51Cr assay. r 2008 Published by Elsevier GmbH.

Therapeutic Effects of Biobran, Modified Arabinoxylan Rice Bran, in Improving Symptoms of Diarrhea Predominant or Mixed Type Irritable Bowel Syndrome: A Pilot, Randomized Controlled Study

  • Takeshi Kamiya, Michiko Shikano, Mamoru Tanaka, Keiji Ozeki, Masahide Ebi, Takahito Katano, Shingo Hamano, Hirotaka Nishiwaki, Hironobu Tsukamoto, Tsutomu Mizoshita, Yoshinori Mori, Eiji Kubota, Satoshi Tanida, Hiromi Kataoka, Noriaki Okuda, and Takashi Joh, (edited by Chris Gutch PhD.)

Background. Recently, it was revealed that low grade mucosal inflammation and/or immune imbalance of the lower digestive tract is one of the mechanisms involved in symptom generation in patients with irritable bowel syndrome (IBS). Biobran, arabinoxylan compound derived from rice bran, has been reported to have several biological actions such as anti-inflammatory and immune modulatory effects. So we investigated the therapeutic effects of Biobran in patients with IBS. Method. Forty patients with diarrhea predominant or mixed type IBS were randomly assigned to either a Biobran group for treatment with Biobran or a placebo group. Therapeutic efficacy and IBS symptoms were assessed subjectively by the patients after 4 weeks of administration. Results. The global assessment was effective in 63.2% of the Biobran group and in 30% of the placebo group (P < 0.05, Biobran group versus placebo group). Biobran group showed a significant decrease in the score of diarrhea and constipation and in CRP value. However, no significant changes were observed in the placebo group. Conclusion. The administration of Biobran improved IBS symptoms. It is likely that anti-inflammatory and/or immune modulatory effects of Biobran might be useful in IBS patients.

Epigenetics and Immunosenescence Reversal: An Evidence-Based Longevity Paradigm  

  • Karriem H. Ali, M.D., (edited by Chris Gutch PhD.)

ABSTRACT:  Humankind has long thought of aging as a gradual, time-dependent, deterioration in one's wellbeing and quality of life, with an increased incidence and severity of debilitating chronic diseases. However, current medical opinion argues for a fresh, and more enlightened perspective on aging. Indeed, until recently, clinical medicine has focused more upon mitigating the effects of aging rather than reversing the process itself. However, current developments in epigenetics and immunology mean that we are now ready to begin the greater challenge of halting or reversing the aging process. There is a vast body of scientific literature indicating that immune dysregulation - specifically of the innate immune system - may be the determinative factor for the seemingly inevitable functional decline of advancing age. This dysregulation is characterized by a continual, low-grade, over-reactive state of systemic immune processes, which promote, in whole or in part, the pathognomonic signs of many of the chronic diseases that we associate with aging (e.g., cardiovascular disease, Alzheimer's disease, cancer, osteoarthritis, insulin-resistance, and diabetes).

The orally administration of the Hydrolysis Rice Bran prevents a common cold syndrome for the elderly people based on immunomodulatory function

  • Kenji Tazawa, Kenichi Ichihashi, Takako Fujii, Kazunobu Omura, Mari Anazawa, Hiroaki Maeda, (edited by Chris Gutch PhD.)

The preventive effect of RIBEX against the common cold syndrome was examined on elderly people. RIBEX, containing arabinoxylan derivatives Hydrolysis Rice Bran (HRB), was prepared from the water soluble dietary fiber fraction from rice bran through partial processing by carbohydrate complex of Lentinus Edodes mycelia (shiitake). Using the non-chemical and non-biological treated water soluble fraction of Rice Bran (RB) as control, the examination was conducted by the cross-over double blind manner through the administration term of 6 weeks for each material. Fifty elderly people who stayed in a care institution under Japan`s Long-term Care Insurance participated in this study. The results of thirty-six participants who showed comparative data in both terms were analyzed stastistically. The most popular reason for withdrawal from the study was "leaving from the institution by a care contact". There was no withdrawal due to the side effects of test foods. We observed symptoms such as "cough", "fatigue", "fever", "sore throat", "sputum", "nasal signs", and "sore breast", and calculated them, based on the juggements of the medical staff. Although thirteen participants (36.1%) experienced at least one symptom in the both terms, the total scores were significantly high value (p<0.05) in the term of R.B. The average duration in which the participants experienced symptoms was 2.6 days in the term of RB whereas 1.2 days in that of HRB, which was not statistically significant. While there are many reports that HRB increases NK cell activity, no significant data was observed in this study because the participants had enough NK cell acitivites from the start.

HRB shortened the duration of the symptoms, reduced the worse and the necessity of symptomatic therapy, and was useful for the reduction of physical burden of acute respiratory tract infection.

The clinical effectiveness of BioBran/ImunoBran  in immunotherapy for patients with hepatitis B

  • Dr. Tran Thi Minh Phuong, (edited by Chris Gutch PhD.)

Abstract: Hepatitis B virus (HBV) infection is a serious global health problem with devastating consequences of chronic hepatitis, cirrhosis, and hepatocellular carcinoma. More efficacious treatments, mass immunization programs, and safe injection techniques are essential for eliminating HBV infection and reducing global HBV-related morbidity and mortality. Antiviral therapy has been the primary treatments to date. However, conventional treatment has undesirable side-effects and continuous treatment can lead to the development of resistance. In addition, antiviral medicines are costly, thousands of dollars per year, and are not widely available in many countries, especially in the developing world. BioBran is a food supplement that is combined with conventional treatment to improve the outcome of the disease. There were 3 cases of viral B hepatitis patients who have treated by the combination of conventional antiviral therapy and BioBran were described. In these cases, blood samples were taken to measure liver function and immunopotency, and the results were compared with changes in clinical and image condition. Improvements were noted in most of the cases. Finally, some remarks were provided to enhance the effectiveness of treatment progress.

BioBran/ImunoBran-augmented maturation of human monocyte-derived dendritic cells

  • D.Cholujova, J.Jakubikova, J.Sedlak, (edited by Chris Gutch PhD.)

Abstract: BioBran, enzymatically modified arabinoxylan from rice bran was tested for its possible effects on in vitro maturation of human dendritic cells (DC). Immature DC (iDC) derived from plastic-adhered, IL-4 and GM-CSF treated peripheral monocytes (Mo) were further cultured with cytokine maturation mix 1 (CMM1; TNF-α, IL-1β and IL-6) or CMM2 (LPS and IFN-γ) to induce their maturation into mature DC (matDC1 or matDC2, respectively). Different concentrations of BioBran (10, 100, 400 and 1000 μg/ml) were applied in the presence or absence of relevant CMM to assess the effects of BioBran on DC maturation processes. BioBran induced maturation of iDC, as these cells cultured with IL-4/GMCSF/BioBran down-regulated CD14 and CD1a antigens on cell surface and significantly increased expression of maturation marker CD83. The increase of surface density of costimulatory molecules CD80 and CD86 on iDC in the presence of BioBran was also observed. In addition, BioBran induced functional maturation of iDC, confirmed by decreased endocytic activity of iDC. Furtheremore, BioBran enhanced maturation potential of cytokine mixes, as both matDC1 and matDC2 exposed to BioBran completely lost CD14 and upregulated CD83, CD80 and CD86 antigens, in comparison to DC matured with the relevant CMM alone. BioBran also increased CD123 antigen on all DC subsets. Intristingly, matDC2 matured in the presence of BioBran (400µg/ml) expressed higher levels of CD123 and lower levels of CD11c cell surface antigens, the phenotype represented by CD11cdim CD123bright plasmacytoid DC population. These data demonstrate that BioBran is a potent enhancer of DC maturation and suggest that BioBran might be a useful agent to create the environment that favours DC maturation.

Effect of Long-term Administration of Immunomodulatory Food on Cancer Patients Completing Conventional Treatments

  • Hiroshi Tsunekawa, (edited by Chris Gutch PhD.)

A study was conducted to investigate the effects of long-term administration of the immunomodulatory food modified arabinoxylan from rice bran (BioBran/MGN-3), on 16 cancer patients, mainly in stage IV with various conventional lesions, who had just undergone conventional cancer treatments, such as surgery, chemotherapy and radiotherapy. The main clinical observations were the safety and effect of BioBran on the nutritional state of the patiens, who were exhausted due to treatment. During the adminstration period, no decreases in body weight and leukocyte count or significant changes in leukogram were observed. Rather, the leukocyte count increased. In addition, most patients showed an increase in NK cell activity and a remarkable decrease in tumor markers.