Consortium for Advancing Research on Botanical and Other Natural Products (CARBON) Program

Consortium for Advancing Research on Botanical and Other Natural Products (CARBON) Program is sponsored by NIH Office of Dietary Supplements (ODS) and National Center for Complementary and Integrative Health (NCCIH). The CARBON Program promotes collaborative, transdisciplinary research on the safety, effectiveness, and mechanisms of action of botanical dietary supplements with high potential to benefit human health.

NIH Consortium for Advancing Research on Botanical and Other Natural Products (CARBON) Program NIH Consortium for Advancing Research on Botanical and Other Natural Products (CARBON) Program The Office of Dietary Supplements (ODS) initiated the Consortium for Advancing Research on Botanical and Other Natural Products (CARBON) Program in partnership with the National Center for Complementary and Integrative Health (NCCIH) in 1999, in response to a Congressional mandate.

Examining Gut Microbiome as a Determinant of Blueberry Polyphenol Bioavailability to Optimize Dose and Phytochemical Standardization for Functional Effects in Humans NIH grant #: RM1 AT013318 Principal Investigators: Tiffany L. Weir, Ph. D.

(contact PI), Sarah A. Johnson, Ph. D.

, Anandh Pon Velayutham, Ph. D. , Jessica E.

Prenni, Ph. D. , Kelly C.

Wrighton, Ph. D. Institution: Colorado State University, Fort Collins, CO Partners: University of Utah, Salt Lake City, UT This new Center will conduct a rigorous exploration in both humans and mouse models of how the gut microbiota modulate the cardiovascular effects of food polyphenols.

The data from this project will be used to expand and validate a database of polyphenol metabolites, the gut microbiota that produce these metabolites, and their effects on flow-mediated dilation, which is a valuable parameter in assessing cardiovascular risk. Botanicals Enhancing Neurological and Functional Resilience in Aging (BENFRA) NIH grant #: U19 AT010829 Principal Investigator: Amala Soumyanath, Ph. D.

Institution: Oregon Health and Science University, Portland, OR Website: https://www. ohsu.

edu/benfra-bdsrc Partners: Oregon State University, Corvallis, OR; Oregon's Wild Harvest, Inc., Redmond, OR; University of Mississippi, Oxford, MS This new Center will establish a pipeline of experimental approaches and techniques required to optimize the design and interpretation of future clinical trials of botanicals traditionally used for resilience to age-related changes in sleep, mood and cognition.

In vivo and in vitro activities and biomarkers of activity will be studied for two such botanicals, Centella asiatica (gotu kola), and Withania somnifera (ashwagandha), in preclinical models including fruit flies, mouse primary neuron cultures, mouse brain slices and intact mice. This work will help to identify the most appropriate clinical outcomes to be assessed in a clinical trial.

Biological testing and chemical profiling will optimize conditions for cultivating the source plants, and guide the composition and doses to be used in future clinical trials. Influence of Dietary Botanical Supplements on Biological and Behavioral Resilience NIH grant #: U19 AT010835 Principal Investigators: Giulio M. Pasinetti, M.

D. , Ph. D.

, and James W. Murrough, M. D.

, Ph. D. Institution: Icahn School of Medicine at Mount Sinai, New York, NY Website: https://icahn.

mssm. edu/research/molecular-neuroresilience/research Partner: Rutgers, The State University of New Jersey, New Brunswick, NJ This new Center will acquire data needed to optimize future clinical trials of a polyphenol-containing dietary supplement derived from grapes for resilience to stress-induced psychological impairment.

Clinical studies of bioavailability and pharmacokinetics of the product will be combined with preliminary assessments of the clinical effects. Preclinical and clinical studies will assess and validate biomarkers of activity. Spirulina Oral Supplement for Enhancing Host Resilience to Virus Infection NIH grant #: U19 AT010838 Principal Investigators: Ikhlas Khan, Ph.

D. and Nirmal Pugh, Ph. D.

Institution: University of Mississippi, University, MS Website: https://umbdsrc. org/ Partner: University of Mississippi Medical Center, Jackson, MS Extracts of Arthrospira platensis , or spirulina, have been reported to enhance resilience to and recovery from respiratory viral infections.

Looking at resilience to influenza viruses in preclinical models and in biomarker-based clinical studies, this new Center will determine the best formulation, timing, and dose of a bioassay-standardized spirulina extract, optimize the methods used to standardize the extract, and identify the optimal immune outcomes to use in a future clinical trial.

Center for High Content Functional Annotation of Natural Products NIH grant #: U41 AT008718 Principal Investigators: John B. MacMillan, Ph. D.

, Nadja B. Cech, Ph. D.

, Roger G. Linington, Ph. D.

Institution: University of California, Santa Cruz, CA Website: https://hifan2. sites. ucsc.

edu/ Partners: University of North Carolina, Greensboro, NC; Simon Fraser University, Burnaby, British Columbia, Canada While it is hypothesized that additive or synergistic activities of individual chemical constituents contribute to the biological effects of botanical extracts and other chemically complex natural products, this has been clearly demonstrated in only a few cases.

Bottlenecks that contribute to slowing this research include the challenges of accurately defining the chemical composition of complex mixtures, and of elucidating the contributions of individual constituents and sets of constituents to the biological activity.

This Center proposes to address these challenges through the integration of orthogonal assay systems using sophisticated informatics approaches, an approach that has been demonstrated to work with complex mixtures as well as with pure compounds.

Project 1 will employ innovative, cell-based, high content phenotypic screening in primary macrophages, epithelial cells, and primary neurons, providing agnostic and extensive coverage of critical biological pathways that are believed to be relevant to the health effects of botanicals.

Project 2 will take advantage of developments in untargeted metabolomics,and feature reduction to develop a robust pipeline to accurately, replicably, and efficiently define the chemical composition of complex mixtures.

The third project specifically addresses the question of synergy and additivity through the development of informatics approaches that use the comprehensive biological and chemical signatures generated in the other projects. This project will develop universal tools that will allow the community to probe their own biological and chemical assay results to generate compound-activity maps.

The Center as a synergistic whole will deliver critical technology platforms for the in-depth study of botanicals and other natural products, and tools based on these platforms that can be used by the research community. Natural Products Magnetic Resonance Database (NP-MRD) NIH grant #: U24 AT010811 Principal Investigator: John R. Cort, Ph.

D. Institution: Pacific Northwest National Laboratory, Richland, WA Website: https://www. np-mrd.

org/ Partners: Simon Fraser University, Burnaby, British Columbia, Canada; University of Alberta, Edmonton, Alberta, Canada; University of Missouri, Columbia, MO. This Center will develop the Natural Products Magnetic Resonance Database (NP-MRD), a central, user-friendly repository for NMR data generated by the natural products community, with powerful associated tools.

The core of the NP-MRD will be an open-access, web-enabled, community-focused, FAIR (findable, accessible, interoperable, reusable)-compliant database containing NMR data and structures for an estimated 350,000 natural products.

The database will contain (1) legacy NMR data derived from the literature, existing public databases, and "private" data archives, (2) new NMR data submitted by depositors for novel NPs, and (3) calculated NMR data for all NPs. Data deposition will be both rapid (less than five minutes) and simple. The NP-MRD will be closely integrated with "sister" databases containing mass spectrometry, biosynthetic gene cluster, and bioactivity data.

It will provide rigorous validation and data checking, and powerful database search, filtering, and querying tools. In addition to data storage, retrieval, and curation, the NP-MRD will host an extensive suite of software tools for natural products research.

2023–2025 Pilot Project Award Effects of Digestion on Composition and Bioavailability of Compounds from Ashwagandha: An in vitro Study NIH grant #: R03 AT012460 Principal Investigator: Wendy Strangman, Ph. D.

Institution: University of North Carolina, Wilmington, NC 2022–2024 Pilot Project Awards Centella asiatica Effects on Neuroinflammatory Responses in Drosophila Models of Acute Inflammation and Aging NIH grant #: R03 AT011871 Co-Principal Investigators: Lukasz M. Ciesla, Ph. D.

, Urmila Maitra, Ph. D. Institution: University of Alabama in Tuscaloosa, Tuscaloosa, AL Development of an In-house Proton Spin Network Database to Characterize the Pharmacophores of Centella asiatica for Standardization and Quality Control NIH grant #: R03 AT011872 Principal Investigator: Liva Harinantenaina Rakotondraibe, Ph.

D. Institution: Ohio State University, Columbus, OH 2021–2023 Pilot Project Award Evaluation of the Potential of Ashwagandha Extracts to Produce CYP-mediated Drug Interactions NIH grant #: R03 AT011501 Principal Investigator: Robert D. Arnold, Ph.

D. Institution: Auburn University, Auburn, AL