Vitex agnus-castus dry extract BNO 1095 (Cyclodynon®) inhibits uterine hyper-contractions and inflammation in experimental models for primary dysmenorrhea

Background. For many women, the monthly suffering induced by menstrual “cramps” is severe enough to profoundly disrupt their quality of life. In the case of primary dysmenorrhea, a condition related to premenstrual syndrome (PMS), intense uterine contractions are thought to trigger moderate to inten...

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Main Authors: J. Röhrl, O. Werz, A. Ammendola, G. Künstle
Format: Article
Language:English
Published: Publishing House TRILIST 2017-10-01
Series:Репродуктивная эндокринология
Subjects:
Online Access:http://reproduct-endo.com/article/view/117649
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author J. Röhrl
O. Werz
A. Ammendola
G. Künstle
author_facet J. Röhrl
O. Werz
A. Ammendola
G. Künstle
author_sort J. Röhrl
collection DOAJ
description Background. For many women, the monthly suffering induced by menstrual “cramps” is severe enough to profoundly disrupt their quality of life. In the case of primary dysmenorrhea, a condition related to premenstrual syndrome (PMS), intense uterine contractions are thought to trigger moderate to intense pain despite the absence of an underlying infection or other medically-identifiable disease states. The associated uterine hyper-contractility is reminiscent of labor, and associated pain is likely to be mediated by the release of prostaglandins, leukotrienes and the infiltration of leukocytes that normally accompany the breakdown of the endometrial lining. Standardized extracts of Vitex agnus-castus berries (VAC extracts of chaste tree, or chaste berries) are clinically effective in treating the symptoms of PMS, yet the mechanisms of how the chemically complex mixture acts are largely unknown. Methods. Using an in vivo dysmenorrhea model rats were treated with 10 mg/kg estradiol-benzoate i.p. once daily for 12 days and with 2.1, 10.3 or 20.7 mg/kg VAC dry extract p.o. once daily for 7 days prior to induction of convulsions. Uterine contractions where induced with 2 IU/kg oxytocin i.p., followed by monitoring of abdominal convulsions and signs of pain on the last day of the experiment. Moreover, in vitro methods were applied that are described in the methods section. Results. Here, we show that the VAC herbal dry extract BNO 1095 (commercially available as Cyclodynon®) targets the uterine myometrial tissue and inflammatory signaling molecules of associated migratory/inflammatory cells. Specifically, BNO 1095 dose-dependently inhibited oxytocin-induced uterine contractions in a rat dysmenorrhea model in vivo and drug-induced contractions in isolated human and rat uterine tissue in vitro. Furthermore, BNO 1095 showed a promising anti-inflammatory capacity by potently inhibiting 5-lipoxygenase activity and leukotriene production and by reducing the production of reactive oxygen species and inflammatory cytokines in vitro. Conclusion. These results provide evidence that BNO 1095 effectively treats menstruation-related complaints including primary dysmenorrhea.
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spelling doaj.art-8705d5a3b9014bb396cb877c82d753202022-12-22T02:38:20ZengPublishing House TRILISTРепродуктивная эндокринология2309-41172411-12952017-10-0137788810.18370/2309-4117.2017.37.78-88109030Vitex agnus-castus dry extract BNO 1095 (Cyclodynon®) inhibits uterine hyper-contractions and inflammation in experimental models for primary dysmenorrheaJ. Röhrl0O. Werz1A. Ammendola2G. Künstle3Department of Preclinical Research and Development, Bionorica SE, Neumarkt, GermanyDepartment of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich-Schiller-University, Jena, GermanyDepartment of Preclinical Research and Development, Bionorica SE, Neumarkt, GermanyDepartment of Preclinical Research and Development, Bionorica SE, Neumarkt, GermanyBackground. For many women, the monthly suffering induced by menstrual “cramps” is severe enough to profoundly disrupt their quality of life. In the case of primary dysmenorrhea, a condition related to premenstrual syndrome (PMS), intense uterine contractions are thought to trigger moderate to intense pain despite the absence of an underlying infection or other medically-identifiable disease states. The associated uterine hyper-contractility is reminiscent of labor, and associated pain is likely to be mediated by the release of prostaglandins, leukotrienes and the infiltration of leukocytes that normally accompany the breakdown of the endometrial lining. Standardized extracts of Vitex agnus-castus berries (VAC extracts of chaste tree, or chaste berries) are clinically effective in treating the symptoms of PMS, yet the mechanisms of how the chemically complex mixture acts are largely unknown. Methods. Using an in vivo dysmenorrhea model rats were treated with 10 mg/kg estradiol-benzoate i.p. once daily for 12 days and with 2.1, 10.3 or 20.7 mg/kg VAC dry extract p.o. once daily for 7 days prior to induction of convulsions. Uterine contractions where induced with 2 IU/kg oxytocin i.p., followed by monitoring of abdominal convulsions and signs of pain on the last day of the experiment. Moreover, in vitro methods were applied that are described in the methods section. Results. Here, we show that the VAC herbal dry extract BNO 1095 (commercially available as Cyclodynon®) targets the uterine myometrial tissue and inflammatory signaling molecules of associated migratory/inflammatory cells. Specifically, BNO 1095 dose-dependently inhibited oxytocin-induced uterine contractions in a rat dysmenorrhea model in vivo and drug-induced contractions in isolated human and rat uterine tissue in vitro. Furthermore, BNO 1095 showed a promising anti-inflammatory capacity by potently inhibiting 5-lipoxygenase activity and leukotriene production and by reducing the production of reactive oxygen species and inflammatory cytokines in vitro. Conclusion. These results provide evidence that BNO 1095 effectively treats menstruation-related complaints including primary dysmenorrhea.http://reproduct-endo.com/article/view/117649cytokinesdysmenorrhealeukotrienelipoxygenasemenstrual complaintspremenstrual syndromespasmolyticvitex agnus-castuscyclodynon
spellingShingle J. Röhrl
O. Werz
A. Ammendola
G. Künstle
Vitex agnus-castus dry extract BNO 1095 (Cyclodynon®) inhibits uterine hyper-contractions and inflammation in experimental models for primary dysmenorrhea
Репродуктивная эндокринология
cytokines
dysmenorrhea
leukotriene
lipoxygenase
menstrual complaints
premenstrual syndrome
spasmolytic
vitex agnus-castus
cyclodynon
title Vitex agnus-castus dry extract BNO 1095 (Cyclodynon®) inhibits uterine hyper-contractions and inflammation in experimental models for primary dysmenorrhea
title_full Vitex agnus-castus dry extract BNO 1095 (Cyclodynon®) inhibits uterine hyper-contractions and inflammation in experimental models for primary dysmenorrhea
title_fullStr Vitex agnus-castus dry extract BNO 1095 (Cyclodynon®) inhibits uterine hyper-contractions and inflammation in experimental models for primary dysmenorrhea
title_full_unstemmed Vitex agnus-castus dry extract BNO 1095 (Cyclodynon®) inhibits uterine hyper-contractions and inflammation in experimental models for primary dysmenorrhea
title_short Vitex agnus-castus dry extract BNO 1095 (Cyclodynon®) inhibits uterine hyper-contractions and inflammation in experimental models for primary dysmenorrhea
title_sort vitex agnus castus dry extract bno 1095 cyclodynon r inhibits uterine hyper contractions and inflammation in experimental models for primary dysmenorrhea
topic cytokines
dysmenorrhea
leukotriene
lipoxygenase
menstrual complaints
premenstrual syndrome
spasmolytic
vitex agnus-castus
cyclodynon
url http://reproduct-endo.com/article/view/117649
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