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. 2015 Nov 12;58(21):8360-72.
doi: 10.1021/acs.jmedchem.5b00417. Epub 2015 Jul 21.

Development of Safe and Effective Botanical Dietary Supplements

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Free PMC article

Development of Safe and Effective Botanical Dietary Supplements

Richard B van Breemen. J Med Chem. .
Free PMC article

Abstract

Regulated differently than drugs or foods, the market for botanical dietary supplements continues to grow worldwide. The recently implemented U.S. FDA regulation that all botanical dietary supplements must be produced using good manufacturing practice is an important step toward enhancing the safety of these products, but additional safeguards could be implemented, and unlike drugs, there are currently no efficacy requirements. To ensure a safe and effective product, botanical dietary supplements should be developed in a manner analogous to pharmaceuticals that involves identification of mechanisms of action and active constituents, chemical standardization based on the active compounds, biological standardization based on pharmacological activity, preclinical evaluation of toxicity and potential for drug-botanical interactions, metabolism of active compounds, and finally, clinical studies of safety and efficacy. Completing these steps will enable the translation of botanicals from the field to safe human use as dietary supplements.

Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
Steps for the development, evaluation, and production of safe, reproducible, and effective botanical dietary supplements.
Figure 2
Figure 2
UHPLC–MS/MS chemical characterization of two licorice species. By comparison of the UHPLC–MS/MS profiles of (A) a mixture of 13 standards representing characteristic licorice secondary metabolites with extracts of two licorice species, the botanical species were distinguished and uniquely identified as (B) Glycyrrhiza glabra and (C) G. inflata. Whereas all of the detected compounds indicate the genus as Glycyrrhiza, glabridin (9) and licochalcone A (12) distinguish the species and G. glabra and G. inflata, respectively. Key: 1, liquiritin; 2, isoliquiritin; 3, liquiritin apioside; 4, isoliquiritin apioside; 5, licuraside; 6, liquiritigenin; 7, isoliquiritigenin; 8, glycyrrhizin; 9, glabridin; 10, licochalcone A; 11, 2-(4-hydroxybenzyl)malonic acid.
Figure 3
Figure 3
To identify active compounds in complex mixtures of natural products, the reiterative process of bioassay-guided fractionation is typically used. Alternatively, mass spectrometry-guided approaches such as PUF-MS or magnetic bead MS screening may be used to expedite this process.
Figure 4
Figure 4
Magnetic bead LC–MS screening for the identification of ligands to a receptor (R). Magnetic beads containing (A) immobilized receptor or (B) no receptor (control) are incubated with a botanical extract. Application of a magnetic field to the particles facilitates the rapid separation of unbound compounds in the extract from the ligands bound to the immobilized receptor. Finally, the ligands are released from the receptor using organic solvent and characterized using LC–MS.
Figure 5
Figure 5
LC–MS/MS (reversed phase HPLC interfaced with electrospray and tandem mass spectrometry with selected reaction monitoring, SRM) measurement of prenylated phenols during the chemical standardization of a hop dietary supplement. On the basis of an external standard curve with normalization to an internal standard (8-isopentylnaringenin), levels of isoxanthohumol (IX), 8-prenylnaringenin (8-PN), 6-prenylnaringenin (6-PN), and xanthohumol (XN) were determined. Reproduced with permission from Biomedical Chromatography (Krause E.; Yuan Y.; Hajirahimkhan A.; Dong H.; Dietz B. M.; Nikolic D.; Pauli G. F.; Bolton J. L.; van Breemen R. B.Biological and Chemical Standardization of a Hop (Humulus lupulus) Botanical Dietary Supplement), Vol. 28, pp 729–734.39 Copyright 2014. John Wiley and Sons.
Figure 6
Figure 6
Resveratrol phase II metabolism by human Caco-2 cells or human hepatocytes.
Figure 7
Figure 7
UHPLC–MS/MS detection of glutathione conjugates of oxidized glabridin from licorice (G. glabra) formed during incubation with human liver microsomes, NADPH, and glutathione. Two glutathione conjugates (∗) were formed by nucleophilic addition of glutathione from above or below the plane of the ring system and then detected selectively using UHPLC combined with positive ion electrospray tandem mass spectrometry with constant neutral loss scanning for the characteristic glutathione fragment ion of [MH – 129]+. (From ref (69).)
Figure 8
Figure 8
Serum concentration–time curves of the four major prenylated hop phenols following oral administration of single doses of an extract of spent hops to five women. Reproduced with permission from Molecular Nutrition & Food Research (van Breemen R. B.; Yuan Y.; Banuvar S.; Shulman L. P.; Qiu X.; Ramos Alvarenga R. F.; Chen S.-N.; Dietz B. M.; Bolton J. L.; Pauli G. F.; Krause E.; Viana M.; Nikolic D.Pharmacokinetics of Prenylated Hop Phenols in Women Following Oral Administration of a Standardized Extract of Hops), Vol. 58, pp 1962–1969.47 Copyright 2014. John Wiley and Sons.
Figure 9
Figure 9
Reduction of vasomotor symptoms including hot flashes and night sweats as the primary outcome of a 12-month randomized, placebo-controlled, double-blind phase II clinical trial of two botanical dietary supplements, black cohosh and red clover. The standard of care, opposed estrogen hormone therapy, was used as a positive control. Reproduced with permission from Menopause (Geller S. E.; Shulman L. P.; van Breemen R. B.; Banuvar S.; Zhou Y.; Epstein G.; Hedayat S.; Nikolic D.; Krause E. C.; Piersen C. E.; Bolton J. L.; Pauli G. F.; Farnsworth N. R.Safety and Efficacy of Black Cohosh and Red Clover for the Management of Vasomotor Symptoms: A Randomized Controlled Trial), Vol. 16, pp 1156–1166.41 Copyright 2009. Wolters Kluwer Health, Inc.

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References

    1. Mahady G. B. Global Harmonization of Herbal Health Claims. J. Nutr. 2001, 131, 1120S–1123S. - PubMed
    1. Bannerman R.; Burton J.; Chen W. C.Traditional Medicine and Health Care Coverage; World Health Organization: Geneva, Switzerland, 1983.
    1. Bailey R. L.; Gahche J. J.; Lentino C. V.; Dwyer J. T.; Engel J. S.; Thomas P. R.; Betz J. M.; Sempos C. T.; Picciano M. F. Dietary Supplement Use in the United States, 2003–2006. J. Nutr. 2011, 141, 261–266. 10.3945/jn.110.133025. - DOI - PMC - PubMed
    1. Herbal Supplements and Remedies. http://www.marketresearch.com/Global-Industry-Analysts-v1039/Herbal-Supplements-Remedies-7544379/ Accessed Mar 13, 2015.
    1. Dietary Supplement Health and Education Act of 1994. Public Law 103-417: 103rd Congress. October 25, 1994. http://dshedu.com/DSHEA_Legal/dshea.html. Accessed Mar 13, 2015.

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