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Principal Investigator: William Joseph Crandall
Organization: EMORY UNIVERSITY
Fiscal Year: 2024
Award: $48,974
Funding agency: National Center for Complementary and Integrative Health
ABSTRACT
Herbal dietary supplements and medicines are used as the primary form of health care for about eighty percent
of the world’s population. In the United States, the use of these botanicals is increasing, accounting for $11.26
billion in sales in the past year alone. Despite widespread and increasing use, herbal dietary supplements and
medicines are severely underregulated compared to western medicine. Exact mechanisms, active compounds
and metabolites, pharmacokinetics, and safety profiles are not fully understood. This study focuses on the top-
selling herbal dietary supplement in the year 2020 in the United States, elderberry (Sambucus nigra L.), which
exhibits antiviral effects. Many natural products can exhibit poor bioavailability and thus despite the promise of
antiviral efficacy in vitro, do not equate to relevant pharmacological effects in vivo. Metabolic degradation
products resulting from host metabolism or gut microbiome metabolism can, however, exhibit increased
bioavailability and pharmacological effects. Few studies have examined the metabolic products, bioavailability,
and pharmacological effects of metabolites of elderberry, and none have done so when regarding its antiviral
activities. Thus, this proposal provides novel research training in pharmacokinetics and pharmacognosy to test
metabolic biotransformation products of elderberry extracts for antiviral efficacy. This proposal will develop the
methods and capabilities for host and gut microbial metabolism of complex botanical mixtures and provide
pharmacological significance regarding the antiviral efficacy of elderberry. Metabolic products of elderberry will
be characterized in vitro models and validated in vivo. Isolation of metabolites generated will be conducted using
preparative high-performance liquid chromatography and their antiviral activity assessed against influenza
models. Antiviral compounds and metabolites will be characterized using high-resolution mass spectrometry
(HRMS), nuclear magnetic resonance (NMR), and X-ray crystallography where applicable. Bioavailability and
contributions of the gut microbiome will be assessed using a gnotobiotic murine model. These studies will identify
metabolites from elderberry exhibiting both antiviral capacities and bioavailability and help establish an
infrastructure for metabolic assessment of other botanicals. This will advance the understanding and
characterization of herbal medicines and promote the development of my career as an independent scientist
capable of conducting relevant research in the fields of pharmacognosy and pharmacology to benefit human
health.
Terms: <Accounting><Address><Adoxaceae><Anthocyanins><Anti-viral Agents><Bioavailability><Biologic Models><Biological><Biological Availability><Biological Models><Biotransformation><Botanical dietary supplements><Botanicals><COVID-19 outbreak><COVID19 outbreak><Cell model><Cellular model><Chemical Structure><Chemicals><Complex><Complex Extracts><Coupled><Crude Extracts><Cyanidin><Cytochrome P-450><Cytochrome P-450 Enzyme System><Cytochrome P450><Cytochrome P450 Family Gene><Development><Dietary supplementation with botanicals><Drug Kinetics><Drug Precursors><Drugs><Elderberry><Environment><Enzyme Gene><Enzymes><Exhibits><Flavanol><Follow-Up Studies><Followup Studies><Foundations><GI microbiome><Germ-Free><Gnotobiotic><Gnotobiotics><Goals><Grippe><HPLC><Health><Healthcare><Hepatic><Herbal Medicine><Herbal dietary supplement><Herbal supplement><High Performance Liquid Chromatography><High Pressure Liquid Chromatography><High Speed Liquid Chromatography><Human><Human Figure><Human Microbiome><Human body><In Vitro><Influenza><Infrastructure><Ingestion><Intermediary Metabolism><Investigation><Knowledge><Liver><Marketing><Mass Photometry/Spectrum Analysis><Mass Spectrometry><Mass Spectroscopy><Mass Spectrum><Mass Spectrum Analyses><Mass Spectrum Analysis><Mediating><Medication><Medicine><Mentors><Metabolic><Metabolic Biotransformation><Metabolic Processes><Metabolism><Methods><Mice><Mice Mammals><Model System><Modeling><Modern Man><Murine><Mus><Natural Products><Nuclear Magnetic Resonance><P450><PK/PD><Pharmaceutical Preparations><Pharmacognosy><Pharmacokinetics><Pharmacology><Physiologic><Physiologic Availability><Physiological><Play><Population><Pro-Drugs><Prodrugs><Public Health><Reaction><Research><Research Training><Resolution><Role><SARS-CoV-2 outbreak><Safety><Sales><Sambucus><Sambucus nigra><Scientist><Severe acute respiratory syndrome coronavirus 2 outbreak><Single Crystal Diffraction><Standardization><Sulfate><Techniques><Testing><Training><Translations><United States><Urine><Viral><Viral Activity><Viral Function><Viral Physiology><X Ray Crystallographies><X-Ray Crystallography><X-Ray Diffraction Crystallography><X-Ray/Neutron Crystallography><Xray Crystallography><absorption><anti-flu><anti-influenza><anti-viral compound><anti-viral drugs><anti-viral efficacy><anti-viral medication><anti-viral therapeutic><anti-virals><antiflu><bacterial microbiome><bacteriome><biologic><botanical supplement><botanical supplementation><career><career development><complex extract><coronavirus disease 2019 outbreak><coronavirus disease-19 outbreak><defined contribution><developmental><diet supplement><dietary supplements><digestive tract microbiome><drug metabolism><drug/agent><enteric microbiome><experiment><experimental research><experimental study><experiments><flu activity><flu infection><flu virus infection><gastrointestinal microbiome><gut microbiome><gut-associated microbiome><health care><hepatic body system><hepatic organ system><human-associated microbiome><improved><in vitro Model><in vivo><infected with flu><infected with flu virus><infected with influenza><infected with influenza virus><influenza activity><influenza infection><influenza virus infection><ingest><intestinal biome><intestinal microbiome><metabolic profile><metabolism measurement><metabolomics><metabonomics><microbial><microbial consortia><microbial flora><microbiome><microbiota><microflora><mouse model><multispecies consortia><murine model><naturally occurring product><novel><nutritional supplement><outbreak of SARS-CoV-2><oxidation><pharmacokinetics and pharmacodynamics><pharmacologic><polyphenol><resolutions><response><social role><tandem mass spectrometry><translation><ultra high pressure><virology>