Synergy quantifications to identify individual contributions of combination partners to the overall activity - The example of STW 5.
Ca(2+)
Combination index
Functional gastrointestinal diseases
IL-8
Multitargeting
Reflux-esophagitis
Synergy
Journal
Phytomedicine : international journal of phytotherapy and phytopharmacology
ISSN: 1618-095X
Titre abrégé: Phytomedicine
Pays: Germany
ID NLM: 9438794
Informations de publication
Date de publication:
Jul 2019
Jul 2019
Historique:
received:
04
04
2019
revised:
20
06
2019
accepted:
02
07
2019
pubmed:
22
7
2019
medline:
18
12
2019
entrez:
22
7
2019
Statut:
ppublish
Résumé
The rationale of combinations of plant extracts is often questioned. The common argument for combinations is a higher efficacy of the combination partners by multitargeting and the elimination of adverse events. STW5, a well-known fixed herbal multicomponent preparation, is recommended in the German treatment guidelines for functional gastrointestinal diseases. The study assessed effects of STW5, its single plant components and combinations thereof on different targets to identify synergistic, additive or antagonistic effects of the combination partners. STW5, its nine components and triple combinations thereof were investigated in two in vitro models - human esophageal epithelial cells (Het1A) and intestinal smooth muscle cells (HISMC) - in comparison to Omeprazole (OM) for the release of interleukin 8 (IL-8) as surrogate for inflammation and of Ca In Het-1A cells, STW5 showed, under non-inflammatory as well as inflammatory conditions, releases of IL-8 (49.3 ± 4.2 pg/ml, 33.7 ± 2 pg/ml) comparable to the untreated control (46.3 ± 4.8 pg/ml). CAP increased IL-8 releases to 85.8 ± 14 pg/ml (p < 0.005). Among the single plant extracts the Iberis amara extract (IBE) induced high IL-8 releases under non-inflammatory (441 ± 177 pg/ml) and inflammatory (625± 121 pg/ml) conditions. The Silybum marianum (L.) extract (SM) reduced releases up to 20.1 ± 8 pg/ml (inflammation). The CI-values of triple combinations with IBE ranged from high synergy (CI<0.03) to antagonism (CI:480). Within the triple combinations SM was the most effective combination partner to reduce IL-8. The combination of Angelica archangelica (L.)/Carum carvi (L.) was also effective. In HISMCs, STW5 induced concentration dependent higher Ca In Het-1A, STW5 inhibited Il-8 releases, although one of its components (IBE) stimulated IL-8 strongly. The combination partners in STW5 assured an overall marked anti-inflammatory action. In the triple combinations SM was identified as most important combination partner for the IL-8 reduction. CI-measurements can support the identification of active combination partners in a multicomponent preparation and can give directions towards the search for multitarget effects.
Sections du résumé
BACKGROUND
BACKGROUND
The rationale of combinations of plant extracts is often questioned. The common argument for combinations is a higher efficacy of the combination partners by multitargeting and the elimination of adverse events.
AIM
OBJECTIVE
STW5, a well-known fixed herbal multicomponent preparation, is recommended in the German treatment guidelines for functional gastrointestinal diseases. The study assessed effects of STW5, its single plant components and combinations thereof on different targets to identify synergistic, additive or antagonistic effects of the combination partners.
STUDY DESIGN/METHODS
METHODS
STW5, its nine components and triple combinations thereof were investigated in two in vitro models - human esophageal epithelial cells (Het1A) and intestinal smooth muscle cells (HISMC) - in comparison to Omeprazole (OM) for the release of interleukin 8 (IL-8) as surrogate for inflammation and of Ca
RESULTS
RESULTS
In Het-1A cells, STW5 showed, under non-inflammatory as well as inflammatory conditions, releases of IL-8 (49.3 ± 4.2 pg/ml, 33.7 ± 2 pg/ml) comparable to the untreated control (46.3 ± 4.8 pg/ml). CAP increased IL-8 releases to 85.8 ± 14 pg/ml (p < 0.005). Among the single plant extracts the Iberis amara extract (IBE) induced high IL-8 releases under non-inflammatory (441 ± 177 pg/ml) and inflammatory (625± 121 pg/ml) conditions. The Silybum marianum (L.) extract (SM) reduced releases up to 20.1 ± 8 pg/ml (inflammation). The CI-values of triple combinations with IBE ranged from high synergy (CI<0.03) to antagonism (CI:480). Within the triple combinations SM was the most effective combination partner to reduce IL-8. The combination of Angelica archangelica (L.)/Carum carvi (L.) was also effective. In HISMCs, STW5 induced concentration dependent higher Ca
CONCLUSION
CONCLUSIONS
In Het-1A, STW5 inhibited Il-8 releases, although one of its components (IBE) stimulated IL-8 strongly. The combination partners in STW5 assured an overall marked anti-inflammatory action. In the triple combinations SM was identified as most important combination partner for the IL-8 reduction. CI-measurements can support the identification of active combination partners in a multicomponent preparation and can give directions towards the search for multitarget effects.
Identifiants
pubmed: 31326154
pii: S0944-7113(19)30179-5
doi: 10.1016/j.phymed.2019.153013
pii:
doi:
Substances chimiques
CXCL8 protein, human
0
Interleukin-8
0
Plant Extracts
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
153013Informations de copyright
Copyright © 2019 The Authors. Published by Elsevier GmbH.. All rights reserved.