Selection and characterization of botanical natural products for research studies: a NaPDI center recommended approach

Kellogg, Joshua J.; Paine, Mary F.; Oberlies, Nicholas H.; Cech, Nadja B.

doi:10.1039/c8np00065d

“…122,123 Characterization sufficient for the detection of such minor components, known or unknown, is therefore critical for quality control and for monitoring batch-to-batch variation and stability. 17,22,114,125 3.2 | Chemical and metabolic factors ADME is a multistep, dynamic biological process that may be modified by product characteristics as well as by host characteristics 115,[126][127][128][129] including physiology and behavior. 14,124 Descriptions of approaches to NP selection and characterization have been published recently.…”

Section: Np Specifications and Integritymentioning

confidence: 99%

“…Replicability of outcomes depends on correct and clearly reported identification and archiving of source materials [12][13][14]17 and consistent preparation and activity of the NP. 17,22,26,114 Some attendees felt that since the effects of complex NP preparations may not be due to only the identifiable components, transparent reporting of methods, including consistent product preparation and quality control via an in vitro assay relevant to bioactivity, is sufficient for replicable NP research. Others argued that in many research context it is also critical to understand which NP components are responsible for the bioactivities of interest, as this information can inform NP quality control, as well as being utilized in assessments of bioavailability, pharmacokinetics and to inform comparisons of different studies 115 (Table 4).…”

Section: Np Specifications and Integritymentioning

confidence: 99%

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Improving natural product research translation: From source to clinical trial

Sorkin

¹

,

Kuszak

²

,

Bloss

³

et al. 2019

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While great interest in health effects of natural product (NP) including dietary supplements and foods persists, promising preclinical NP research is not consistently translating into actionable clinical trial (CT) outcomes. Generally considered the gold standard for assessing safety and efficacy, CTs, especially phase III CTs, are costly and require rigorous planning to optimize the value of the information obtained. More effective bridging from NP research to CT was the goal of a Septe mber, 2018 trans disci plina ry workshop. Participants emphasized that replicability and likelihood of successful translation depend on rigor in experimental design, interpretation, and reporting across the continuum of NP research. Discussions spanned good practices for NP characterization and quality control; use and interpretation of models (computational through in vivo) with strong clinical predictive validity; controls for experimental artefacts, especially for in vitro interrogation of bioactivity and mechanisms of action; rigorous assessment and interpretation of prior research; transparency in all reporting; and prioritization of research questions. Natural product clinical trials prioritized based on rigorous, convergent supporting data and current public health needs are most likely to be informative and ultimately affect public health. Thoughtful, coordinated implementation of these practices should enhance the knowledge gained from future NP research. K E Y W O R D S clinical predictive validity, dietary supplements, model systems, rigor and replicability, value of information | 43 SORKIN et al.still provide invaluable guidance, the results of such trials are often met with concerns that different design choiceswhether of product, dose, timing, participant eligibility criteria, outcomes, etc.-might have yielded a substantially different result. Each interventional trial represents a substantial investment, with well-powered Phase III CTs typically consuming more than $10 million and many person-years. 9,10 Additionally, as time and funds are limited, and participant pools may also be constrained, a decision to invest in a CT often precludes pursuing other research questions, 11 which may provide more useful public health-relevant knowledge than an RCT with an insufficient evidence base.

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“…Replicability of outcomes depends on correct and clearly reported identification and archiving of source materials (11-13, 15) and consistent preparation and activity of the NP (21, 25,113,114).…”

Section: Np Characteristics Critical For Replicability Np Specificatimentioning

confidence: 99%

“…information on mechanisms of action, appropriate uses, and expected health effects poses challenges for formulating hypotheses and designing CT. The ready availability of a variety of preparations of similar NPs and their occurrence in complex matrices such as foods or dietary supplements further increases the challenges for the design, conduct, and interpretation of NPCTs (14)(15)(16). The variety of NPs in the marketplace poses challenges for product selection; in addition, participants must be monitored for inadvertent or otherwise unreported exposure to the intervention or components thereof (drop-ins).…”

Section: Introductionmentioning

confidence: 99%

Improving Natural Product Research Translation: from Source to Clinical Trial

Sorkin¹,

Kuszak²,

Fukagawa³

et al. 2019

Preprint

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While great interest in health effects of natural product (NP) including dietary supplements and foods persists, promising preclinical NP research is not consistently translating into actionable clinical trial (CT) outcomes. Generally considered the gold standard for assessing safety and efficacy, CTs, especially phase III CTs, are costly and require rigorous planning to optimize the value of the information obtained. More effective bridging from NP research to CT was the goal of a https://events-support.com/events/Natural_Product_Clinical_Trials. Participants emphasized that replicability and likelihood of successful translation depend on rigor in experimental design, interpretation, and reporting across the continuum of NP research. Discussions spanned good practices for NP characterization and quality control; use and interpretation of models (computational through in vivo) with strong clinical predictive validity; controls for experimental artefacts, especially for in vitro interrogation of bioactivity and mechanisms of action; rigorous assessment and interpretation of prior research; transparency in all reporting; and prioritization of research questions. Natural product clinical trials prioritized based on rigorous, convergent supporting data and current public health needs are most likely to be informative and ultimately affect public health. Thoughtful, coordinated implementation of these practices should enhance the knowledge gained from future NP research.

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Assessing Transporter‐Mediated Natural Product‐Drug Interactions Via In vitro‐In Vivo Extrapolation: Clinical Evaluation With a Probe Cocktail

Nguyen

¹

,

Tian

²

,

Tanna

³

et al. 2020

Clin Pharma and Therapeutics

Self Cite

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The botanical natural product goldenseal can precipitate clinical drug interactions by inhibiting cytochrome P450 (CYP) 3A and CYP2D6. Besides P‐glycoprotein, effects of goldenseal on other clinically relevant transporters remain unknown. Established transporter‐expressing cell systems were used to determine the inhibitory effects of a goldenseal extract, standardized to the major alkaloid berberine, on transporter activity. Using recommended basic models, the extract was predicted to inhibit the efflux transporter BCRP and uptake transporters OATP1B1/3. Using a cocktail approach, effects of the goldenseal product on BCRP, OATP1B1/3, OATs, OCTs, MATEs, and CYP3A were next evaluated in 16 healthy volunteers. As expected, goldenseal increased the area under the plasma concentration‐time curve (AUC0–inf) of midazolam (CYP3A; positive control), with a geometric mean ratio (GMR) (90% confidence interval (CI)) of 1.43 (1.35–1.53). However, goldenseal had no effects on the pharmacokinetics of rosuvastatin (BCRP and OATP1B1/3) and furosemide (OAT1/3); decreased metformin (OCT1/2, MATE1/2‐K) AUC0–inf (GMR, 0.77 (0.71–0.83)); and had no effect on metformin half‐life and renal clearance. Results indicated that goldenseal altered intestinal permeability, transport, and/or other processes involved in metformin absorption, which may have unfavorable effects on glucose control. Inconsistencies between model predictions and pharmacokinetic outcomes prompt further refinement of current basic models to include differential transporter expression in relevant organs and intestinal degradation/metabolism of the precipitant(s). Such refinement should improve in vitro‐in vivo prediction accuracy, contributing to a standard approach for studying transporter‐mediated natural product‐drug interactions.

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Selection and characterization of botanical natural products for research studies: a NaPDI center recommended approach

Abstract: Dietary supplements, which include botanical (plant-based) natural products, constitute a multi-billion-dollar industry in the US.

Cited by 74 publications

References 178 publications

Improving natural product research translation: From source to clinical trial

Improving natural product research translation: From source to clinical trial

Improving Natural Product Research Translation: from Source to Clinical Trial

Assessing Transporter‐Mediated Natural Product‐Drug Interactions Via In vitro‐In Vivo Extrapolation: Clinical Evaluation With a Probe Cocktail

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