CC BY
14
Abstracts. PHYTOPHARM 2017
The extract of Vitex agnus-castus berries BNO 1095 (VAC extract of chaste tree, or chaste berries) is clinically effective in treating the symptoms of PMS, yet the mechanisms of how the chemically complex mixture acts are largely unknown.
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 lU/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 to assess the spasmolytic and anti-inflammatory effects of the BNO 1095 extract.
Here, we show that the VAC dry extract BNO 1095 (commercially available as Agnucaston®) targets the uterine myometrial tissue and inflammatory signaling molecules of associated 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.
In conclusion these results provide evidence that BNO 1095, as contained in Agnucaston®, effectively treats menstruation-related complaints including primary dysmenorrhea.
HERG CHANNEL RELATED RISK ASSESSMENT OF BOTANICALS
© Ulrike Grienke, Christina E. Mair, Jadel M. Kratz, Judith M. Rollinger
Department of Pharmacognosy, University of Vienna, Vienna, Austria
A blockage of the human Ether-a-go-go Related Gene (hERG) channel is associated with a drug-induced QT prolongation and increased risk of fatal arrhythmias [1]. Therefore, screening this antitarget is an important part of preclinical safety assessment for drug substances. While all new chemical entities must be investigated for possible hERG channel blockage, the risk portfolio of herbal medicines is still unsatisfying.
To address this issue, the EU project "hERG related risk assessment of botanicals" (PI RSES-GA-2011-295174) was launched in 2012 with the main goal to establish a network between European, South American, North American, and South African educational and research entities for the identification of hERG channel blockers in commonly consumed botanicals and supplements. Three different strategies have been applied for the targeted identification and isolation of hERG channel blocking constituents from natural sources: (i) in vitro screening of relevant plant extracts followed by micro-fractionation and isolation, (ii) investigation of plant materials based on reports of cardiotoxicity without a clear understanding of the molecular mechanism, and (iii) computational approaches for the virtual prediction of hERG channel blockers.
Out of more than 1,200 extracts probed in this recently accomplished project, only 2.5% reduced the hERG channel peak tail current by >30% at 100 ^g/mL
in a voltage-clamp assay on Xenopus oocytes. Here, examples and strategies for the identification of hERG blockers from medicinal plants will be presented [2-5]. This includes also a critical view on the relevance of these findings and a concluding discussion of the outcome of the project.
Acknowledgement: This work was supported by a Marie Curie IRSES Fellowship within the Seventh European Community Framework Programme (hERGscreen, P295174)
Reference:
1. Sanguinetti MC, Tristani-Firouzi M. 2006. Nature. 440:463-469.
2. Kratz JM, Schuster D, Edtbauer M, Saxena P, Mair CE, Kirchebner J, Matuszczak B, Baburin I, Hering S, Rollinger JM. 2014. J Chem Inf Model. 54:2887-2901.
3. Grienke U, Mair CE, Saxena P, Baburin I, Scheel O, Ganzera M, Schuster D, Hering S, Rollinger JM. 2015. J Agric Food Chem. 63:5634-5639.
4. Mair CE, de Miranda Silva C, Grienke U, Kratz JM, Carreno F, Zimmermann ES, de Araüjo BV, Dalla Costa T, Rollinger JM. 2016. Planta Med. 82:10301038.
5. Kratz JM, Mair, CE, Oettl SK, Saxena P, Scheel O, Schuster D, Hering S, Rollinger JM. 2016. Planta Med. 82: 1009-1015.
Obzory po kliniceskoj farmacologii i lekarstvennoj terapii [Reviews of clinical pharmacology and drug therapy] vol. 15/2017/suppLement 1
1 59
