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Physiologically relevant screening of polyphenol-rich commercial preparations for bioactivity in vascular endothelial cells and application to healthy volunteers: a viable workflow and a cautionary tale

Jones, Huw; Papageorgiou, M.; Gordon, A.; Ehtesham; Javed, Z.; Wells, L. K.; Greetham, S.; Doyle, B.; Hayes, N.; Rigby, A.; Atkin, S. L.; Courts, F. L.; Sathyapalan, T.

Authors

Huw Jones

M. Papageorgiou

A. Gordon

Ehtesham

Z. Javed

L. K. Wells

S. Greetham

B. Doyle

N. Hayes

A. Rigby

S. L. Atkin

F. L. Courts

T. Sathyapalan



Abstract

© 2019 Elsevier Inc. This study describes the screening of 13 commercially-available plant extracts for pharmacological activity modulating vascular function using an endothelial cell model. A French maritime pine bark extract (FMPBE) was found to have the greatest effect upon nitric oxide availability in control (181% ± 36% of untreated cells) and dysfunctional cells (132% ± 8% of untreated control cells). In healthy volunteers, the FMPBE increased plasma nitrite concentrations 8 h post-consumption compared to baseline (baseline corrected median 1.71 ± 0.38 (25% IQR) and 4.76 (75% IQR) µM, p < 0.05). This was followed by a placebo-controlled, healthy volunteer study, which showed no effects on plasma nitrite. It was confirmed that different batches of extract had been used in the healthy volunteer studies, and this second batch lacked bioactivity, assessed using the in vitro model. No difference in plasma catechin levels was seen at 8 h following supplementation between the studies (252 ± 194 nM versus 50 ± 64 nM, p > 0.05), however HPLC-UV fingerprinting showed that the new batch had a 5–15% in major constituents (including procyanidins A2, B1 and B2) compared to the original batch. This research describes a robust mechanism for screening bioactive extracts for vascular effects. It also highlights batch variability as a significant limitation when using complex extracts for pharmacological activity, and suggests the use of in vitro systems as a tool to identify this problem in future studies.

Citation

Jones, H. S., Jones, H., Papageorgiou, M., Gordon, A., Ehtesham, , Javed, Z., …Sathyapalan, T. (2020). Physiologically relevant screening of polyphenol-rich commercial preparations for bioactivity in vascular endothelial cells and application to healthy volunteers: a viable workflow and a cautionary tale. Biochemical Pharmacology, 173, https://doi.org/10.1016/j.bcp.2019.113754

Journal Article Type Article
Acceptance Date Dec 9, 2019
Online Publication Date Dec 16, 2019
Publication Date 2020-03
Deposit Date Feb 24, 2020
Publicly Available Date Dec 17, 2020
Journal Biochemical Pharmacology
Print ISSN 0006-2952
Electronic ISSN 1873-2968
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 173
Article Number 113754
DOI https://doi.org/10.1016/j.bcp.2019.113754
Public URL https://hull-repository.worktribe.com/output/3323379

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