Department/Unit poster (NCNPR). Corresponding author: Nirmal Pugh (ndpugh@olemiss.edu)https://egrove.olemiss.edu/pharm_annual_posters_2022/1016/thumbnail.jp

Ashfaq, M. Khalid

Chittiboyina, Amar G.

Khan, Iklas A.

Khan, Shabana I.

Marshall, Gailen D.

Pugh, Nirmal D.

Tan, Chalet

English

eGrove (Univ. of Mississippi)

University of Mississippi eGrove Annual Poster Session 2022 Annual Poster Session 10-11-2022 University of Mississippi Botanical Dietary Supplements Research Center Iklas A. Khan University of Mississippi Nirmal D. Pugh University of Mississippi, ndpugh@olemiss.edu Amar G. Chittiboyina University of Mississippi Chalet Tan University of Tennessee Health Sciences Center Gailen D. Marshall University of Mississippi Medical Center See next page for additional authors Follow this and additional works at: https://egrove.olemiss.edu/pharm_annual_posters_2022 Recommended Citation Khan, Iklas A.; Pugh, Nirmal D.; Chittiboyina, Amar G.; Tan, Chalet; Marshall, Gailen D.; Ashfaq, M. Khalid; and Khan, Shabana I., "University of Mississippi Botanical Dietary Supplements Research Center" (2022). Annual Poster Session 2022. 17. https://egrove.olemiss.edu/pharm_annual_posters_2022/17 This Book is brought to you for free and open access by the Annual Poster Session at eGrove. It has been accepted for inclusion in Annual Poster Session 2022 by an authorized administrator of eGrove. For more information, please contact egrove@olemiss.edu. Authors Iklas A. Khan, Nirmal D. Pugh, Amar G. Chittiboyina, Chalet Tan, Gailen D. Marshall, M. Khalid Ashfaq, and Shabana I. Khan This book is available at eGrove: https://egrove.olemiss.edu/pharm_annual_posters_2022/17 University of Mississippi Botanical Dietary Supplements Research Center Khan IA1,2, Pugh ND1, Chittiboyina AG1, Tan C3, Marshall GD4, Ashfaq MK1, Khan SI11National Center for Natural Products Research, 2Department of BioMolecular Sciences, Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi, University, MS 38677. 3Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, TN 38163. 4University of Mississippi Medical Center, Jackson, MS 39216.AcknowledgementsThis research was partially supported by the National Center forComplementary and Integrative Health of the National Institutes of Healthunder Award Number U19AT010838. The content is solely the responsibilityof the authors and does not necessarily represent the official views of theNational Institutes of Health. Additional funding was also provided by a grantfrom the USDA, Agricultural Research Service Specific Cooperative AgreementNo. 58-6060-6-015.Arthrospira/Limnospira oral Supplement for Enhancing Host Resilience to Virus InfectionEstablished in 2020 (www.umbdsrc.org)The University of Mississippi Botanical Dietary Supplements Research Center (UM BDSRC) is a component of the NIH Consortium for Advancing Research on Botanicalsand other Natural Products (CARBON) Program. It was created to foster collaborations between scientists at the University of Mississippi housed at the main campus inOxford and the Medical Center in Jackson.Public health relevance and significanceArthrospira/Limnospira (commonly known as spirulina) is a top selling botanical for improving immune health. This center’s research is directed towards generatingsufficient data to optimally design future human intervention studies to evaluate the utility of Limnospira-derived oral supplements in promoting resilience againstand/or recovery from respiratory viral infections such as influenza. The use of a Limnospira-derived oral supplement may provide an important complementaryapproach to currently available antiviral therapies that is inexpensive, safe and readily available to the public.Influenza virus infection is a continual, worldwide public health problem that has challenged western society for centuries. The CDC estimates that the burden of illnessduring the 2017–2018 flu season included 48.8 million symptomatically infected people in the U.S., 959,000 patient hospitalizations, and 79,400 deaths. Since themodern flu vaccine program has moderated but not eliminated infection risk, enhancement of host antiviral immune response through the use of botanicals mayprovide an important complementary approach.What is the rationale for selecting Limnospira as the botanical product for our research?Limnospira is a cyanobacterium that has been used as a food for centuries and more recently as a health supplement by a large segment of global society. Althoughearly interest in commercial production of Limnospira was focused mainly on its nutrient and protein content, it has emerged as a popular dietary supplement due toscientific evidence supporting various human health benefits such as immune-enhancing and antiviral properties.About 25 years ago the UM National Center for Natural Products Research (NCNPR) established a unit to investigate the immune-enhancing properties of botanicals anddietary supplements. Numerous products that are traditionally used to enhance immune function were evaluated, and extracts from Limnospira were found to behundreds of times more active than all others tested. Based on this discovery, the NCNPR invested substantial research effort to investigate the immune-enhancingproperties and therapeutic applications of Limnospira.A growing body of evidence generated from the NCNPR and the literature indicate that oral consumption of Limnospira products are particularly useful natural productsfor providing resilience against influenza viral infection. Research demonstrates that a major mechanism by which Limnospira products provide anti-viral resilience isthrough its impact on immune function. Through this research effort Braun-type lipoproteins were identified as the predominant macrophage-activating principal withinLimnospira, and a patented extract (ImmulinaTM) was developed that preferentially enriches for the level of these active macromolecules from the raw material. TheImmulina extract has been commercially available for the last 15 years and is the product research focus for our UM BDSRC.Administrative Supplement (10/1/22 – 6/30/23)The objective is to advance research on the identification of chemicalmarker(s) to monitor subject adherence (the extent to which they consumethe Immulina product). To identify adherence/surrogate marker candidates,the Botanical Core team will implement hyphenated chromatographicmethods (viz., GC- or LC coupled withQToF-MS) to evaluate biological fluidsfrom human volunteers (collected before and after Immulina consumption)for differential levels of compounds using both targeted and non-targetedapproaches.Administrative CoreDr. Ikhlas KhanDirectorDr. Nirmal PughAssociate DirectorGray DaleProgram ManagerThe overall purpose of the Botanical Core is to ensure product integrity and advance the chemistry research on the Limnospira-based product,Immulina, by using a combination of bioassay- and chemical-based approaches.Aim 1.Ensure the unambiguous identification and perform additional safety testing on Limnospira fusiformis raw material that will be used in theproduction of sufficient quantities of Immulina for the proposed research projects.Aim 2.Validate a selective in vitro bioassay for quantitation of the toll-like receptor 2-dependent activity exhibited by the Braun-type lipoproteins inImmulina extracts.Aim 3.Advance the chemistry research on Immulina by establishing chemical-based authentication and standardization approaches, characterization of immune-inhibitory substances, and detailed structural analysis of the active immune-enhancing Braun-type lipoproteins.Aim 4.Perform additional stability studies, provide sufficient quantities of well-characterized and safe Immulina for use in the proposed UM BDSRCresearch projects, and explore collaborative opportunities with other CARBON units.Unraveling Immune Enhancement by ImmulinaAim 1.Develop an optimized liquid formulation for Immulina.Aim 2.Evaluate the pharmacodynamics of Immulina and identify in vivo biomarker(s).Aim 3.Investigate the molecular mechanism on immune enhancement by Immulina.Statement of Potential ImpactThe successful completion of this project will result in the development of an improved formulation of Immulina and the identification of invivo biomarkers for Immulina treatment.Examining the Effects of Immulina to Increase Immune Resilience against Influenza Virus InfectionsMouse model (Years 1-2)Aim 1. Evaluate oral administration of Immulina in three non-lethal mouse models of resilience against influenza A virus infection (prophylaxis,prodrome and recovery) to determine the most effective utility of Immulina for enhancing host immunity to improve antiviral resilience.Aim 2. Confirm that activation of the TLR2 signaling pathway by Braun-type lipoproteins is a causal mechanism through which Immulina enhanceshost immunity against antiviral infection.Human model (Years 3-5)Aim 3. Determine the optimal form and dosage of the Immulina-based supplement that will maximize effects on increasing lymphocyte cellnumbers and/or activity, increased supporting cytokines, ADCC against influenza-infected target cell lines and influenza-specific antibody titers.Aim 4. Establish the timeline for optimal lymphocyte, cytokine and antibody responses in terms of both initial changes and maximal changes andduration of the change once the Immulina is discontinued in normal and immune compromised (elderly) human research participants.Aim 5. Examine the effects of routine influenzas vaccine given before, during, or after Immulina use to investigate influenza antigen-specificantibody responses in individuals receiving Immulina supplement vs placebo.BotanicalCoreProject 1Project 2Dr. Jungmoo HuhPostdocDr. Amar ChittiboyinaCore LeaderDr. Nirmal PughSenior InvestigatorDr. Jin ZhangInvestigatorDr. Iffat ParveenInvestigatorDr. Bharathi AvulaInvestigatorDr. Mona HaronInvestigatorDr. Chalet TanPrincipal InvestigatorDr. Tahir MirInvestigatorDr. Gailen Marshall, Principal InvestigatorDr. Jin ZhangInvestigatorDr. Khalid AshfaqSenior InvestigatorDr. Shabana KhanSenior InvestigatorJohn TrottResearch StaffNan JiPhD StudentMingja WangPhD StudentYusheng LiPhD StudentPranav PankshePhD StudentDr. Kashif ShamimPostdocDr. Siddharth TripathiInvestigator

University of Mississippi Botanical Dietary Supplements Research Center

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University of Mississippi Botanical Dietary Supplements Research Center

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