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Planta Med 2021; 87(08): 611-619
DOI: 10.1055/a-1351-1038
Biological and Pharmacological Activity
Original Papers

BNO 1095, a Standardized Dry Extract from the Fruits of Vitex agnus-castus, Impairs Angiogenesis-related Endothelial Cell Functions In Vitro

Iris Bischoff-Kont
1   Institute of Pharmaceutical Biology, Goethe University Frankfurt/Main, Germany
,
Laura Brabenec
1   Institute of Pharmaceutical Biology, Goethe University Frankfurt/Main, Germany
,
Rebecca Ingelfinger
1   Institute of Pharmaceutical Biology, Goethe University Frankfurt/Main, Germany
2   LOEWE Center Translational Biodiversity Genomics (TBG), Frankfurt/Main, Germany
,
Bernhard Nausch
3   Bionorica SE, Neumarkt, Germany
,
Robert Fürst
1   Institute of Pharmaceutical Biology, Goethe University Frankfurt/Main, Germany
2   LOEWE Center Translational Biodiversity Genomics (TBG), Frankfurt/Main, Germany
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Abstract

BNO 1095, a standardized dry extract from the fruits of Vitex agnus-castus, represents an approved herbal medicinal product for the treatment of premenstrual syndrome. Angiogenesis, the formation of new blood vessels from pre-existing capillaries, plays a major role in physiological situations, such as wound healing or tissue growth in female reproductive organs, but it is also of great importance in pathophysiological conditions such as chronic inflammatory diseases or cancer. Angiogenesis is a highly regulated multi-step process consisting of distinct key events that can be influenced pharmacologically. Few studies suggested anti-angiogenic actions of V. agnus-castus fruit extracts in in vivo and ex vivo models. Here, we provide for the first time profound in vitro data on BNO 1095-derived anti-angiogenic effects focusing on distinct angiogenesis-related endothelial cell functions that are inevitable for the process of new blood vessel formation. We found that V. agnus-castus extract significantly attenuated undirected and chemotactic migration of primary human endothelial cells. Moreover, the extract efficiently inhibited endothelial cell proliferation and reduced the formation of tube-like structures on Matrigel. Of note, the treatment of endothelial cell spheroids almost blocked endothelial sprouting in a 3D collagen gel. Our data present new and detailed insights into the anti-angiogenic actions of BNO 1095 and, therefore, suggest a novel scope of potential therapeutic applications of the extract for which these anti-angiogenic properties are required.

Key words

Vitex agnus-castus - Lamiaceae - endothelial cells - angiogenesis-related cell functions

Supporting Information

    A HPLC fingerprint of UV absorbance measurement at 205 nm of BNO 1095 (lot number 770 134) was performed.

  • Supporting Information


Publication History

Received: 12 October 2020

Accepted after revision: 04 January 2021

Article published online:
02 February 2021

© 2021. Thieme. All rights reserved.

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  • References

  • 1 Rafieian-Kopaei M, Movahedi M. Systematic review of premenstrual, postmenstrual and infertility disorders of Vitex agnus castus . Electron Physician 2017; 9: 3685-3689
    CrossrefPubMedGoogle Scholar
  • 2 Daniele C, Coon JT, Pittler MH, Ersnt E. Vitex agnus castus: a systematic review of adverse events. Drug Saf 2005; 28: 319-332
    CrossrefPubMedGoogle Scholar
  • 3 Wuttke W, Jarry H, Christoffel V, Spengler B, Seidlová-Wuttke D. Chaste tree (Vitex agnus-castus)–pharmacology and clinical indications. Phytomedicine 2003; 10: 348-357
    CrossrefPubMedGoogle Scholar
  • 4 Hobbs C. The chaste tree: Vitex agnus castus . Pharm Hist 1991; 33: 19-24
    PubMedGoogle Scholar
  • 5 Souto EB, Durazzo A, Nazhand A, Lucarini M, Zaccardelli M, Souto SB, Silva AM, Severino P, Novellino E, Santini A. Vitex agnus-castus L.: main features and nutraceutical perspectives. Forests 2020; 11: 761
    CrossrefPubMedGoogle Scholar
  • 6 Chen SN, Friesen JB, Webster D, Nikolic D, van Breemen RB, Wang J, Fong HHS, Farnsworth NR, Pauli GF. Phytoconstituents from Vitex agnus-castus fruits. Fitoterapia 2011; 82: 528-533
    CrossrefPubMedGoogle Scholar
  • 7 Sliutz G, Speiser P, Schultz AM, Spona J, Zeillinger R. Agnus castus extracts inhibit prolactin secretion of rat pituitary cells. Horm Metab Res 1993; 25: 253-255
    Article in Thieme ConnectPubMedGoogle Scholar
  • 8 Jarry H, Leonhardt S, Gorkow C, Wuttke W. In vitro prolactin but not LH and FSH release is inhibited by compounds in extracts of Agnus castus: direct evidence for a dopaminergic principle by the dopamine receptor assay. Exp Clin Endocrinol 1994; 102: 448-454
    Article in Thieme ConnectPubMedGoogle Scholar
  • 9 Certo G, Costa R, DʼAngelo V, Russo M, Albergamo A, Dugo G, Germanò MP. Anti-angiogenic activity and phytochemical screening of fruit fractions from Vitex agnus castus . Nat Prod Res 2017; 31: 2850-2856
    CrossrefPubMedGoogle Scholar
  • 10 Sahib HB, Al-Zubaidy AA, Jasim GA. Anti angiogenic activity of Vitex agnus castus methanol extract in vivo study. Iranian Journal of Pharmaceutical Sciences 2016; 12: 59-68
    PubMedGoogle Scholar
  • 11 Nishida N, Yano H, Nishida T, Kamura T, Kojiro M. Angiogenesis in cancer. Vasc Health Risk Manag 2006; 2: 213-219
    CrossrefPubMedGoogle Scholar
  • 12 Sahib HB, Al-Zubaidy AA, Hussain SM, Jassim GA. The anti angiogenic activity of Vitex agnus-castus leaves extracts. Int J Pharm Pharm Sci 2014; 6: 863-869
    PubMedGoogle Scholar
  • 13 Qutub AA, Popel AS. Elongation, proliferation & migration differentiate endothelial cell phenotypes and determine capillary sprouting. BMC Syst Biol 2009; 3: 13
    CrossrefPubMedGoogle Scholar
  • 14 Alimohamadi R, Fatemi I, Naderi S, Hakimizadeh E, Rahmani MR, Allahtavakoli M. Protective effects of Vitex agnus-castus in ovariectomy mice following permanent middle cerebral artery occlusion. Iran J Basic Med Sci 2019; 22: 1097-1101
    PubMedGoogle Scholar
  • 15 Kim YW, Byzova TV. Oxidative stress in angiogenesis and vascular disease. Blood 2014; 123: 625-631
    CrossrefPubMedGoogle Scholar
  • 16 Kikuchi H, Yuan B, Yuhara E, Imai M, Furutani R, Fukushima S, Hazama S, Hirobe C, Ohyama K, Takagi N, Toyoda H. Involvement of histone H3 phosphorylation via the activation of p38 MAPK pathway and intracellular redox status in cytotoxicity of HL-60 cells induced by Vitex agnus-castus fruit extract. Int J Oncol 2014; 45: 843-852
    CrossrefPubMedGoogle Scholar
  • 17 Ahangarpour A, Najimi SA, Farbood Y. Effects of Vitex agnus-castus fruit on sex hormones and antioxidant indices in a d-galactose-induced aging female mouse model. J Chin Med Assoc 2016; 79: 589-596
    CrossrefPubMedGoogle Scholar
  • 18 Smith SK. Regulation of angiogenesis in the endometrium. Trends Endocrinol Metab 2001; 12: 147-151
    CrossrefPubMedGoogle Scholar
  • 19 Kressin P, Wolber EM, Wodrich H, Meyhöfer-Malik A, Buchweitz O, Diedrich K, Malik E. Vascular endothelial growth factor mRNA in eutopic and ectopic endometrium. Fertil Steril 2001; 76: 1220-1224
    CrossrefPubMedGoogle Scholar
  • 20 Laschke MW, Menger MD. Anti-angiogenic treatment strategies for the therapy of endometriosis. Hum Reprod Update 2012; 18: 682-702
    CrossrefPubMedGoogle Scholar
  • 21 Zheng W, Cao L, Xu Z, Ma Y, Liang X. Anti-Angiogenic alternative and complementary medicines for the treatment of endometriosis: a review of potential molecular mechanisms. Evid Based Complement Alternat Med 2018; 2018: 4128984
    CrossrefPubMedGoogle Scholar
  • 22 Laschke MW, Schwender C, Scheuer C, Vollmar B, Menger MD. Epigallocatechin-3-gallate inhibits estrogen-induced activation of endometrial cells in vitro and causes regression of endometriotic lesions in vivo . Hum Reprod 2008; 23: 2308-2318
    CrossrefPubMedGoogle Scholar
  • 23 Rudzitis-Auth J, Körbel C, Scheuer C, Menger MD, Laschke MW. Xanthohumol inhibits growth and vascularization of developing endometriotic lesions. Hum Reprod 2012; 27: 1735-1744
    CrossrefPubMedGoogle Scholar
  • 24 Becker CM, Sampson DA, Rupnick MA, Rohan RM, Efstathiou JA, Short SM, Taylor GA, Folkman J, DʼAmato RJ. Endostatin inhibits the growth of endometriotic lesions but does not affect fertility. Fertil Steril 2005; 84: 1144-1155
    CrossrefPubMedGoogle Scholar
  • 25 Oktem M, Esinler I, Eroglu D, Haberal N, Bayraktar N, Zeyneloglu HB. High-dose atorvastatin causes regression of endometriotic implants: a rat model. Hum Reprod 2007; 22: 1474-1480
    CrossrefPubMedGoogle Scholar
  • 26 Delgado-Rosas F, Gómez R, Ferrero H, Gaytan F, Garcia-Velasco J, Simón C, Pellicer A. The effects of ergot and non-ergot-derived dopamine agonists in an experimental mouse model of endometriosis. Reproduction 2011; 142: 745-775
    CrossrefPubMedGoogle Scholar
  • 27 Nausch B, Pace S, Pein H, Koeberle A, Rossi A, Künstle G, Werz O. The standardized herbal combination BNO 2103 contained in Canephron((R)) N alleviates inflammatory pain in experimental cystitis and prostatitis. Phytomedicine 2019; 60: 152987
    CrossrefPubMedGoogle Scholar
  • 28 Jaffe EA, Nachman RL, Becker CG, Minick CR. Culture of human endothelial cells derived from umbilical veins. Identification by morphologic and immunologic criteria. J Clin Invest 1973; 52: 2745-2756
    CrossrefPubMedGoogle Scholar
  • 29 Riccardi C, Nicoletti I. Analysis of apoptosis by propidium iodide staining and flow cytometry. Nat Protoc 2006; 1: 1458-1461
    CrossrefPubMedGoogle Scholar