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Improvement of behavioural pattern and alpha-synuclein levels in autism spectrum disorder after consumption of a beta-glucan food supplement in a randomized, parallel-group pilot clinical study

TL;DR: In this article, the authors evaluated the childhood autism rating scale (CARS) and alpha-synuclein levels in this parallel-group, multiple-arm pilot clinical study after supplementation with a biological response modifier beta-glucan food supplement (Nichi Glucan).
Abstract: Background Autism spectrum disorders (ASDs) are a wide range of behavioural disabilities for which there are no definite interventional modalities available. Remedial therapies remain the only option but with varying outcomes. We have evaluated the childhood autism rating scale (CARS) and alpha-synuclein levels in this parallel-group, multiple-arm pilot clinical study after supplementation with a biological response modifier beta-glucan food supplement (Nichi Glucan). Methods Six subjects with ASD (n = 6) Gr. 1 underwent conventional treatment comprising remedial behavioural therapies and L-carnosine 500 mg per day, and 12 subjects (n = 12) Gr. 2 underwent supplementation with the Nichi Glucan 0.5 g twice daily along with the conventional treatment. Results There was a significant decrease in the CARS score in all of the children of the Nichi Glucan Gr.2 compared to the control (p-value = 0.034517). Plasma levels of alpha-synuclein were significantly higher in Gr. 2 (Nichi Glucan) than in the control group Gr. 1 (p-value = 0.091701). Conclusion Improvement of the behavioural pattern CARS score and a correlating alpha-synuclein level, followed by a safe beta-glucan food supplement, warrants further research on other parameters, such as gut-microbiota evaluation, and relevant neuronal biomarkers which is likely to cast light on novel solutions.

Summary (2 min read)

Methods:

  • This study was approved by the institutional ethics committee of the and was registered as a clinical trial in the national clinical trial registry.
  • The caregiver of all the subjects gave their informed consent for inclusion before participation in the study.
  • The study was conducted in accordance with the Declaration of Helsinki.

Study design:

  • The subjects enrolled in the study had received a diagnosis of ASD by a developmental paediatrician and were verified by a psychologist using a clinical interview for a behavioural pattern that incorporated CARS.
  • Eighteen subjects (n =18) with ASD in total were enrolled in this prospective, open-label, pilot clinical trial comprising of two arms.
  • Arm 1 or Gr. 1: Control: Six subjects with ASD (n = 6) underwent conventional treatment comprising remedial behavioural therapies and L-Carnosine 500 mg per day.
  • Arm 2 or Gr. 2: Treatment arm: 12 subjects (n = 12) underwent supplementation with Nichi Glucan food supplement along with conventional treatment.
  • Each subject consumed two sachets (0.5 g each) of Nichi Glucan daily-one sachet with a meal twice daily-for a period of 90 days.

Inclusion criteria:

  • (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
  • The copyright holder for this preprint this version posted June 29, 2021.
  • Parents/caretakers willing to provide consent for their children to actively participate in the study.

Exclusion criteria:

  • I. Subjects aged more than 18 years old ii.
  • Any child with acute general illness or who has been on any antibiotic, antiinflammatory, or antioxidant treatment in the two weeks prior to enrolment in the study iii.
  • Hyperallergic to any of the investigational products iv.

Childhood autism rating scale (CARS):

  • The CARS was monitored at baseline and after 90 days between the Gr.1 and Gr.2 (Nichi Glucan).
  • The CARS score was calculated based on a cumulative score obtained on the CARS scale, wherein a score below 30 indicates absence of sufficient signs and symptoms indicative of autism, a score between 30 and 36 indicates mild-to-moderately severe autism, and a score from 37 to 60 is correlated with severe autism (Ramaekers et al., 2019) .
  • The psychologist who performed the assessment and the parents were blind to the participant's treatment status; hence, this is a double-blind study.

ii. Evaluation of plasma alpha-synuclein:

  • Human alpha-synuclein (α-syn) levels in plasma were measured in peripheral blood at baseline and after the study's completion at 90 days.
  • The measurement was performed All rights reserved.
  • (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
  • The copyright holder for this preprint this version posted June 29, 2021.

Results:

  • During enrolment, six subjects with ASD (n = 6) could be enrolled in the control group (Gr. 1), whereas in the treatment group (Gr. 2), one of them dropped out before the start of the study.
  • During the study, four subjects were lost follow-up: two in Gr. 1 (one dropped out due to social problems in the family, and the other relocated to another city) and two in Gr. 2 (one dropped out due to social problems in the family, and the other relocated to another city).

Adverse effects:

  • Only one child exhibited possible mild adverse effects related to increased bowel movements in Gr. 2 for one week after supplementation with Nichi Glucan, which settled on its own.
  • No adverse effects were found in any of the other children.

Score on CARS scale:

  • (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
  • The copyright holder for this preprint this version posted June 29, 2021.
  • Thus, there was a significant decrease in the CARS score in all of the children in the Nichi Glucan Gr.2 group compared to the control (pvalue = 0.034517), with an average of 3 points in the improvement of autism's signs and symptoms, whereas the improvement was very mild or nil in Gr.1 .

Discussion:

  • The copyright holder for this preprint this version posted June 29, 2021.
  • In their study, which is the first of its kind, the plasma alpha-synuclein levels showed significant increase after Nichi Glucan supplementation, and the levels were in line with those that were reported for children without ASD (Kadak et al., 2015; Sriwimol et al., 2018) .
  • The gut environment must be conducive for such probiotic supplementation.

Conclusion:

  • Patients with ASD showed improvement in behavioural symptoms and improved levels of plasma alpha-synuclein; thus, this pilot clinical study of nutritional supplementation with an AFO-202 strain of black yeast aureobasidium pullulans produced the biological response modifier beta-glucan (Nichi Glucan).
  • Evaluation as per the CARS score has also shown significant beneficial effects.
  • Further research on the mechanisms of its action in improving alpha-synuclein levels and balancing the immune system in the context of managing chronic inflammation and gut-microbiota regulation as a prebiotic is likely to improve understanding of other diseases caused by neuroinflammation such as PD and AD.

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1
Title: Improvement of behavioural pattern and alpha-synuclein levels in autism spectrum
disorder after consumption of a beta-glucan food supplement in a randomized, parallel-group
pilot clinical study
Running head: β-Glucan improves behaviour of kids with autism
Authors:
Kadalraja Raghavan
1,2
(drkraghavan27@gmail.com)
Vidyasagar Devaprasad Dedeepiya
3
(dedeepiya_76@yahoo.co.in)
Nobunao Ikewaki
4,5
(nikewaki@phoenix.ac.jp)
Tohru Sonoda
5
(sonoda@phoenix.ac.jp)
Masaru Iwasaki
6
(miwasaki@yamanashi.ac.jp)
Senthilkumar Preethy
7
(drspp@nichimail.jp)
Samuel JK Abraham
3,6,8
(drsam@nichimail.jp)
Affiliations:
1. Department of Paediatric Neurology, Kenmax Medical Service Private Limited,
Madurai, India.
2. Department of Paediatric Neurology, Sarvee Integra Private Limited, Chennai, India.
3. The Mary-Yoshio Translational Hexagon (MYTH), Nichi-In Centre for Regenerative
Medicine (NCRM), Chennai, India.
4. Dept. of Medical Life Science, Kyushu University of Health and Welfare, Japan
5. Institute of Immunology, Junsei Educational Institute, Nobeoka, Miyazaki, Japan
6. Centre for Advancing Clinical Research (CACR), University of Yamanashi - School of
Medicine, Chuo, Japan.
All rights reserved. No reuse allowed without permission.
(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
The copyright holder for this preprintthis version posted June 29, 2021. ; https://doi.org/10.1101/2021.06.28.21259619doi: medRxiv preprint
NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice.

2
7. The Fujio-Eiji Academic Terrain (FEAT), Nichi-In Centre for Regenerative Medicine
(NCRM), Chennai, India.
8. Antony- Xavier Interdisciplinary Scholastics (AXIS)GN Corporation Co. Ltd., Kofu,
Japan
Corresponding Author Information:
Dr. Samuel JK Abraham,
University of Yamanashi - School of Medicine, Chuo, Japan,
Correspondence Address: 3-8, Wakamatsu, Kofu, Yamanashi 400-0866, Japan.
Email id- drsam@nichimail.jp ; Alternate email id: drspp@nichimail.jp
Phone: +81-55-235-7527
Financial disclosure:
No external funding was received for the study
Non-financial disclosure:
Author Samuel Abraham is a shareholder in GN Corporation, Japan which in turn is a
shareholder in the manufacturing company of the AFO 202 Beta Glucan.
Acknowledgements:
The authors thank
1. Mr. Mohan Ponnusamy & staff of Kenmax for their assistance during the clinical study
and data collection of the manuscript.
2. Mr. Takashi Onaka, Mr. Yasunori Ikeue, Mr. Mitsuru Nagataki (Sophy Inc, Kochi,
Japan), for necessary technical clarifications.
All rights reserved. No reuse allowed without permission.
(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
The copyright holder for this preprintthis version posted June 29, 2021. ; https://doi.org/10.1101/2021.06.28.21259619doi: medRxiv preprint

3
3. Loyola-ICAM College of Engineering and Technology (LICET) for their support to
our research work.
Ethical approval:
The study was registered in India’s clinical trial registry CTRI, Ref no: CTRI/2020/10/028322.
URL:
http://ctri.nic.in/Clinicaltrials/showallp.php?mid1=47623&EncHid=&userName=kenmax.
The study was approved by the Institutional Ethics Committee (IEC) of Saravana
Multispeciality Hospital, Madurai, India on 24th August, 2019.
All rights reserved. No reuse allowed without permission.
(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
The copyright holder for this preprintthis version posted June 29, 2021. ; https://doi.org/10.1101/2021.06.28.21259619doi: medRxiv preprint

4
Abstract:
Background:
Autism spectrum disorders (ASDs) are a wide range of behavioural disabilities for which there
are no definite interventional modalities available. Remedial therapies remain the only option
but with varying outcomes. We have evaluated the childhood autism rating scale (CARS) and
alpha-synuclein levels in this parallel-group, multiple-arm pilot clinical study after
supplementation with a biological response modifier beta-glucan food supplement (Nichi
Glucan).
Methods:
Six subjects with ASD (n = 6) Gr. 1 underwent conventional treatment comprising remedial
behavioural therapies and L-carnosine 500 mg per day, and 12 subjects (n = 12) Gr. 2
underwent supplementation with the Nichi Glucan 0.5 g twice daily along with the
conventional treatment.
Results:
There was a significant decrease in the CARS score in all of the children of the Nichi Glucan
Gr.2 compared to the control (p-value = 0.034517). Plasma levels of alpha-synuclein were
significantly higher in Gr. 2 (Nichi Glucan) than in the control group Gr. 1 (p-value =
0.091701).
Conclusion:
Improvement of the behavioural pattern CARS score and a correlating alpha-synuclein level,
followed by a safe beta-glucan food supplement, warrants further research on other parameters,
All rights reserved. No reuse allowed without permission.
(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
The copyright holder for this preprintthis version posted June 29, 2021. ; https://doi.org/10.1101/2021.06.28.21259619doi: medRxiv preprint

5
such as gut-microbiota evaluation, and relevant neuronal biomarkers which is likely to cast
light on novel solutions.
Keywords: Autism spectrum disorders (ASDs); Alpha-synuclein; Childhood autism rating
scale (CARS); beta-glucan; food supplement; Nichi Glucan
All rights reserved. No reuse allowed without permission.
(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
The copyright holder for this preprintthis version posted June 29, 2021. ; https://doi.org/10.1101/2021.06.28.21259619doi: medRxiv preprint

Citations
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Posted ContentDOI
27 Oct 2021-medRxiv
TL;DR: In this article, a randomized pilot clinical study was undertaken and compared with an aim of gaining a mechanistic insight, which showed that AFO-202 beta 1,3-1,6 glucan was able to balance the gut microbiome, which is considered beneficial in children with ASD.
Abstract: Background/objective: Gut dysbiosis is one of the major pathologies in children with autism spectrum disorder (ASD). In previous studies, Aureobasidium pullulans (i.e., black yeast AFO-202-produced beta glucan found in Nichi Glucan) yielded beneficial clinical outcomes related to sleep and behaviour. Evaluation of gut microbiota of the subjects in the present randomized pilot clinical study was undertaken and compared with an aim of gaining a mechanistic insight. Methods: The study involved 18 subjects with ASD who were randomly allocated: six subjects in the control group (Group 1) underwent conventional treatment comprising remedial behavioural therapies and L-carnosine 500 mg per day, and 12 subjects (Group 2) underwent supplementation with Nichi Glucan 0.5 g twice daily along with the conventional treatment for 90 days. The subjects stool samples were collected at baseline and after the intervention. Whole genome metagenome (WGM) sequencing was performed. Results: WGM sequencing followed by bioinformatic analysis in 13 subjects who completed the study showed that among genera of relevance, the abundance of Enterobacteria was decreased almost to zero in Group 2 after intervention, whereas it increased from 0.36% to 0.85% in Group 1. The abundance of Bacteroides increased from 16.84% to 19.09% in Group 1, whereas it decreased from 11.60% to 11.43% in Group 2. The abundance of Prevotella increased in both Group 1 and Group 2. The decrease in abundance of lactobacillus was significant in Group 2 compared to Group 1. Among species, a decrease was seen in Escherichia coli, Akkermansia muciniphila CAG:154, Blautia spp., Coprobacillus sp., and Clostridium bolteae CAG:59, with an increase of Faecalibacterium prausnitzii and Prevotella copri, which are both beneficial. Conclusion: AFO-202 beta 1,3-1,6 glucan was able to balance the gut microbiome, which is considered beneficial in children with ASD. Effective control of curli-producing enterobacteria that leads to α-synuclein (αSyn) misfolding and accumulation, which apart from being advantageous in alleviating ASD symptoms, may have a prophylactic role in Parkinsons and Alzheimers diseases where the Alpha Syn misfolding and amyloid deposition are central to their pathogenesis. Additionally, stimulation of natural killer cells to help clear accumulated Alpha Syn amyloids, beneficial microbiome reconstitution, and microglial rejuvenation lead us to recommend larger clinical studies in neurodevelopmental and neurodegenerative diseases of this safety-proven food supplement.

8 citations

Journal ArticleDOI
TL;DR: In this article, multiple regression and combined receiver operating characteristic (ROC) curve analyses were used to determine the relationship between the neuroinflammatory marker α-synuclein and lipid mediator markers related to inflammation induction, such as cyclooxygenase-2 and prostaglandin-EP2 receptors, in the etiology of ASD.
Abstract: Background Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social interaction and restricted and repetitive behaviors. Neuroinflammation and abnormal lipid mediators have been identified in multiple investigations as an acknowledged etiological mechanism of ASD that can be targeted for therapeutic intervention. Methods In this study, multiple regression and combined receiver operating characteristic (ROC) curve analyses were used to determine the relationship between the neuroinflammatory marker α-synuclein and lipid mediator markers related to inflammation induction, such as cyclooxygenase-2 and prostaglandin-EP2 receptors, in the etiology of ASD. Additionally, the study aimed to determine the linear combination that maximizes the partial area under ROC curves for a set of markers. Forty children with ASD and 40 age- and sex-matched controls were enrolled in the study. Using ELISA, the levels of α-synuclein, cyclo-oxygenase-2, and prostaglandin-EP2 receptors were measured in the plasma of both groups. Statistical analyses using ROC curves and multiple and logistic regression models were performed. Results A remarkable increase in the area under the curve was observed using combined ROC curve analyses. Moreover, higher specificity and sensitivity of the combined markers were reported. Conclusions The present study indicates that measurement of the predictive value of selected biomarkers related to neuroinflammation and lipid metabolism in children with ASD using a ROC curve analysis should lead to a better understanding of the etiological mechanism of ASD and its link with metabolism. This information may facilitate early diagnosis and intervention.

5 citations

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TL;DR: This paper suggests that ASD is associated with an unbalanced gut microbiota (dysbiosis), and the consumption of specific probiotics may represent a side-effect free tool to re-establish gut homeostasis and promote gut health.
Abstract: New research points to a possible link between autism spectrum disorder (ASD) and the gut microbiota as many autistic children have co-occurring gastrointestinal problems. This review focuses on specific alterations of gut microbiota mostly observed in autistic patients. Particularly, the mechanisms through which such alterations may trigger the production of the bacterial metabolites, or leaky gut in autistic people are described. Various altered metabolite levels were observed in the blood and urine of autistic children, many of which were of bacterial origin such as short chain fatty acids (SCFAs), indoles and lipopolysaccharides (LPS). A less integrative gut-blood-barrier is abundant in autistic individuals. This explains the leakage of bacterial metabolites into the patients, triggering new body responses or an altered metabolism. Some other co-occurring symptoms such as mitochondrial dysfunction, oxidative stress in cells, altered tight junctions in the blood-brain barrier and structural changes in the cortex, hippocampus, amygdala and cerebellum were also detected. Moreover, this paper suggests that ASD is associated with an unbalanced gut microbiota (dysbiosis). Although the cause-effect relationship between ASD and gut microbiota is not yet well established, the consumption of specific probiotics may represent a side-effect free tool to re-establish gut homeostasis and promote gut health. The diagnostic and therapeutic value of bacterial-derived compounds as new possible biomarkers, associated with perturbation in the phenylalanine metabolism, as well as potential therapeutic strategies will be discussed.

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TL;DR: The data suggest that elevating consumption of β-glucan-rich foods is an easily implementable nutritional strategy to alleviate detrimental features of gut-brain dysregulation and prevent neurodegenerative diseases associated with Westernized dietary patterns.
Abstract: “Western” style dietary patterns are characterized by a high proportion of highly processed foods rich in fat and low in fiber. This diet pattern is associated with a myriad of metabolic dysfunctions, including neuroinflammation and cognitive impairment. β-glucan, the major soluble fiber in oat and barley grains, is fermented in the lower gastrointestinal tract, potentially impacting the microbial ecosystem and thus may improve elements of cognition and brain function via the gut-brain axis. The present study aimed to evaluate the effect of β-glucan on the microbiota gut-brain axis and cognitive function in an obese mouse model induced by a high-fat and fiber-deficient diet (HFFD). After long-term supplementation for 15 weeks, β-glucan prevented HFFD-induced cognitive impairment assessed behaviorally by object location, novel object recognition, and nesting building tests. In the hippocampus, β-glucan countered the HFFD-induced microglia activation and its engulfment of synaptic puncta, and upregulation of proinflammatory cytokine (TNF-α, IL-1β, and IL-6) mRNA expression. Also, in the hippocampus, β-glucan significantly promoted PTP1B-IRS-pAKT-pGSK3β-pTau signaling for synaptogenesis, improved the synaptic ultrastructure examined by transmission electron microscopy, and increased both pre- and postsynaptic protein levels compared to the HFFD-treated group. In the colon, β-glucan reversed HFFD-induced gut barrier dysfunction increased the thickness of colonic mucus (Alcian blue and mucin-2 glycoprotein immunofluorescence staining), increased the levels of tight junction proteins occludin and zonula occludens-1, and attenuated bacterial endotoxin translocation. The HFFD resulted in microbiota alteration, effects abrogated by long-term β-glucan supplementation, with the β-glucan effects on Bacteroidetes and its lower taxa particularly striking. Importantly, the study of short-term β-glucan supplementation for 7 days demonstrated pronounced, rapid differentiating microbiota changes before the cognitive improvement, suggesting the possible causality of gut microbiota profile on cognition. In support, broad-spectrum antibiotic intervention abrogated β-glucan’s effects on improving cognition, highlighting the role of gut microbiota to mediate cognitive behavior. This study provides the first evidence that β-glucan improves indices of cognition and brain function with major beneficial effects all along the gut microbiota-brain axis. Our data suggest that elevating consumption of β-glucan-rich foods is an easily implementable nutritional strategy to alleviate detrimental features of gut-brain dysregulation and prevent neurodegenerative diseases associated with Westernized dietary patterns.

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TL;DR: This review aims to emphasize the major contents of probiotics, prebiotics, and prebiotic-like components commonly found in consumable functional foods, and presents an overview of direct and indirect benefits they provide on human health.
Abstract: The bioactive ingredients in commonly consumed foods include, but are not limited to, prebiotics, prebiotic-like components, probiotics, and postbiotics. The bioactive ingredients in functional foods have also been associated with beneficial effects on human health. For example, they aid in shaping of gut microflora and promotion of immunity. These functional components also contribute in preventing serious diseases such as cardiovascular malfunction and tumorigenesis. However, the specific mechanisms of these positive influences on human health are still under investigation. In this review, we aim to emphasize the major contents of probiotics, prebiotics, and prebiotic-like components commonly found in consumable functional foods, and we present an overview of direct and indirect benefits they provide on human health. The major contributors are certain families of metabolites, specifically short-chain fatty acids and polyunsaturated fatty acids produced by probiotics, and prebiotics, or prebiotic-like components such as flavonoids, polyphenols, and vitamins that are found in functional foods. These functional ingredients in foods influence the gut microbiota by stimulating the growth of beneficial microbes and the production of beneficial metabolites that, in turn, have direct benefits to the host, while also providing protection from pathogens and maintaining a balanced gut ecosystem. The complex interactions that arise among functional food ingredients, human physiology, the gut microbiota, and their respective metabolic pathways have been found to minimize several factors that contribute to the incidence of chronic disease, such as inflammation oxidative stress.

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TL;DR: Findings strongly suggest that the Sophy β‐glucan may have unique immune regulatory or enhancing properties that could be exploited by the health food, medical and pharmaceutical industries.
Abstract: We examined the immunological actions of Sophy β-glucan (Ikewaki N., et al. United States Patent 6956120 and Japan Patent 2004-329077), a type of β-1,3–1,6 glucan produced by the black yeast Aureobasidium pullulans (A. pullulans) strain AFO-202, currently available commercially as a health food supplement, using different human in vitro experimental systems. Sophy β-glucan significantly (P<0.01) stimulated the 3H-thymidine incorporation rates (marker of DNA synthesis) in human peripheral blood mononuclear cells (PBMCs) obtained from normal adult donors, in vitro. Enzyme-linked immunoassays (EIAs) revealed that Sophy β-glucan stimulated the production of interleukin-8 (IL-8) or soluble Fas (sFas), but not that of IL-1β, IL-2, IL-6, IL-12 (p70+40), interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α) or soluble Fas ligand (sFasL), in either cultured PBMCs or cells of the human monocyte-like cell line, U937. The induction by Sophy β-glucan of DNA synthesis in PBMCs was completely blocked by the addition of monoclonal antibodies (mAbs) to CD11a, CD54, human leukocyte antigen-class II (HLA-class II), Toll-like receptor-2 (TLR-2), and Toll-like receptor-4 (TLR-4). In these blocking experiments using the mAbs, the main differences in the results between PBMCs and U937 cells were that the mAbs against TLR-2 and TLR-4 did not block the Sophy β-glucan -induced production of IL-8 in the U937 cells. Furthermore, a mAb to the β-glucan receptor, Dectin-1, significantly (P<0.05) blocked the Sophy β-glucan-induced DNA synthesis in the PBMCs, and Sophy β-glucan -induced production of IL-8 in the U937 cells. The Sophy β-glucan-induced production of IL-8 in the U937 cells was significantly (P<0.01) blocked by the conventional protein kinase C (PKC) inhibitor Go6976, the novel PKC inhibitor Rottlerin, the protein kinase A (PKA) inhibitor H-89, and the protein tyrosine kinase (PTK) inhibitor herbimycin A. Among these, the blocking effect of the novel PKC (PKC delta isoenzyme) inhibitor Rottlerin was the most pronounced. Studies employing reverse transcriptase-polymerase chain reaction (RT-PCR) showed that Sophy β-glucan stimulated the expression of IL-8 mRNA in the U937 cells, and that this induction was inhibited by Rottlerin. Sophy β-glucan also blocked the stimulator cell induction of DNA synthesis and IFN-γ production in the responder cells in a one-way mixed lymphocyte reaction (MLR) using allogenic PBMCs. Interestingly, immunoglobulin G (IgG), but not IgM to Sophy β-glucan was detected in the sera derived from normal adult donors and from the umbilical cord blood of neonates. Taken together, these findings strongly suggest that the Sophy β-glucan may have unique immune regulatory or enhancing properties that could be exploited by the health food, medical and pharmaceutical industries.

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