Pharmacokinetic and pharmacodynamic investigations of select natural products and nutraceuticals for human and veterinary health
Bibliographic record
Abstract
Natural products are teeming with potential therapeutic agents. One group of compounds, polyphenols, from plants, exhibit anti-cancer, anti-inflammatory and anti-oxidant activities. Four polyphenolic compounds and their enantiomers were investigated in this thesis; the stilbene, 3-methoxypterostilbene, a structural analog of resveratrol, and the chiral prenylflavonoids from hops (Humulus lupulus L.); 8-prenylnaringenin, 6-prenylnaringenin and isoxanthohumol. A high performance liquid chromatography method for 3-methoxypterostilbene and enantiospecific liquid chromatography-mass spectrometry assays for the three prenylflavonoids were developed and validated. The methods allowed for quantification of these four polyphenols in biological samples and plant-based materials. Content analysis studies of 3-methoxypterostilbene and the three prenylflavonoids in traditional Chinese medicinal plants and hops-containing nutraceuticals were carried out, respectively. The pharmacokinetics of these four compounds were delineated through intravenous and oral administration in rats. 3-Methoxypterostilbene demonstrated greater bioavailability in rats than reported values for resveratrol. Enantiomeric differences in disposition parameters were observed for the three prenylflavonoids along with differences between compounds despite only small structural differences. The in vitro pharmacodynamics of these four compounds were elucidated including anti-oxidant, anti-inflammatory, anti-diabetic and cytochrome P450 modulation activities. All four compounds demonstrated a range of bioactivities related to chronic diseases and potential drug-botanical interactions. Further studies of polyphenols, especially clinical studies, are needed along with enantiospecific study when applicable to continue delineating the importance of bioactivity, pharmacokinetics and safety. Natural products are further developed into nutraceuticals and sold over-the-counter for both human and veterinary use but are not currently required to demonstrate efficacy prior to marketing. In the final section of this thesis, Phycox®, a multi-component veterinary nutraceutical for joint health was investigated for pharmacological activity in an in vitro model of canine osteoarthritis along with select constituents. A pilot single-dose pharmacokinetic study in dogs was also undertaken. Two liquid chromatography tandem mass spectrometry methods were developed and validated to detect constituents in serum. In vitro study results indicated that Phycox® was able to reduce inflammatory mediators similar to the NSAID, carprofen, and acute pharmacokinetic results revealed that detectable concentrations of glucosamine were evident in serum. It is suggested that further clinical studies of Phycox® are warranted to optimize its usage.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".