Effects of Achillea millefolium extract on spontaneous and oxytocin-induced isolated rat uterine contractions

Abstract

Objective: Achillea millefolium (AM) is widely used in traditional medicine in a wide geography due to its effects on the female reproductive system. However, its effect on uterine smooth muscle contractions is unknown. Our study aims to investigate the effects of AM on spontaneous and oxytocin-induced isolated rat uterine contractions. Method: Myometrial strips were obtained from 32 adult Wistar Albino rats. Contraction amplitudes and frequencies were recorded by isolated tissue bath system after either of the following: administration of only Krebs-Hanseleit (KBH) solution, administration of Achillea millefolium extract (AME); administration of KBH or AME after inducing contractions with oxytocin. The differences at the level of p<0.05 was considered significant. Results: When AM extract was administered at a dose of 2mg/ml, it significantly reduced the spontaneous (non-induced) contraction frequency compared to the control group with only KBH addition to the medium (AME: 2.37±0.49, KBH: 9.25±1.69, p=0.002). AME significantly reduced the amplitude of spontaneous uterine contractions in the administrations of 0.5, 1, and 2mg/ml (p <0.05). On the other hand, AME significantly reduced the amplitude of oxytocin-induced contractions in each increasing dose (p <0.05). Conclusion: It was revealed that AME significantly reduced the frequency and amplitude of both spontaneous and oxytocin-induced uterine contractions depending on the dose. AME should be used with caution in cases of preterm birth or miscarriage risk.

Keywords

• Achillea millefolium
• oxytocin
• oxytocin-induced contraction
• uterine contraction
• yarrow

Achillea millefolium ekstraktının spontan ve oksitosin ile indüklenen izole sıçan uterus kasılmaları üzerine etkileri

Abstract

Amaç: Achillea millefolium (AM), kadın üreme sistemi üzerindeki etkileri nedeniyle geniş bir coğrafyada geleneksel tıpta yaygın olarak kullanılmaktadır. Ancak uterus düz kas kasılmaları üzerindeki etkisi bilinmemektedir. Çalışmamız AM’nin spontan ve oksitosin kaynaklı izole sıçan uterus kasılmaları üzerindeki etkilerini araştırmayı amaçlamaktadır. Yöntem: Myometrial şeritler 32 yetişkin Wistar Albino sıçanından elde edildi. Kasılma genlikleri ve frekansları, belirtilen uygulamaların ardından izole organ banyosu sisteminde kaydedildi: Yalnızca Krebs-Hanseleit (KBH) çözeltisinin uygulanması, Achillea millefolium ekstraktının (AME) uygulanması; oksitosin ile kasılmaları indükledikten sonra KBH veya AME uygulaması. p<0.05 değeri anlamlı olarak kabul edildi. Bulgular: AM ekstraktı 2mg/ml dozunda uygulandığında, ortama sadece KBH ilavesi ile spontan (uyarılmamış) kasılma sıklığını kontrol grubuna kıyasla önemli ölçüde azalttı (AME: 2.37±0.49, KBH: 9.25±1.69, p=0.002). AME, 0.5, 1 ve 2 mg/ml’lik uygulamalarda spontan uterus kasılmalarının amplitüdünü önemli ölçüde azalttı (p <0.05). Öte yandan AME, artan her dozda oksitosin kaynaklı kasılmaların amplitüdünü önemli ölçüde azalttı (p <0.05). Sonuç: AME’nin doza bağlı olarak hem spontan hem de oksitosin kaynaklı uterus kasılmalarının sıklığını ve amplitüdünü önemli ölçüde azalttığı ortaya çıktı. AME, erken doğum veya düşük riski durumlarında dikkatli kullanılmalıdır.

Keywords

• Achillea millefolium
• oksitosin
• oksitosinle indüklenmiş kasılma
• uterin kasılma
• civanperçemi

References

1. Pieroni A, Quave CL. Traditional pharmacopoeias and medicines among Albanians and Italians in southern Italy: A comparison. J Ethnopharmacol. 2005 Oct 3;101(1-3):258-70. https://doi.org/10.1016/j.jep.2005.04.028
2. Radušiene J, Gudaityte O. Distribution of proazulenes in Achillea millefolium s.l. wild populations in relation to phytosociological dependence and morphological characters. Plant Genet Resour. 2005 Aug;3(2):136-43. https://doi.org/10.1079/PGR200568
3. Passalacqua NG, Guarrera PM, De Fine G. Contribution to the knowledge of the folk plant medicine in Calabria region (Southern Italy). Fitoterapia. 2007 Jan;78(1):52-68. https://doi.org/10.1016/j.fitote.2006.07.005
4. Nemeth E, Bernath J. Biological Activities of Yarrow Species (Achillea spp.). Curr Pharm Des. 2008 Nov 12;14(29):3151-67.https://doi.org/10.2174/138161208786404281
5. Stojanović G, Radulović N, Hashimoto T, Palić R. In vitro antimicrobial activity of extracts of four Achillea species: The composition of Achillea clavennae L. (Asteraceae) extract. J Ethnopharmacol. 2005 Oct 3;101(1-3):185-90. https://doi.org/10.1016/j.jep.2005.04.026
6. Lakshmi T, Geetha R, Roy A, Aravind Kumar S. Yarrow (Achillea millefolium linn). A herbal medicinal plant with broad therapeutic use-A review. Int J Pharm Sci Rev Res. 2011;9(2):136-41.
7. Zakeri S, Gorji N, Moeini R, Memariani Z. Therapeutic Application of Achillea millefolium L. in Female Reproductive Diseases from the Viewpoint of Persian Medicine and Current Medicine. J Med Plants [Internet]. 2019;4(72):107-21.
8. Borrelli F, Romano B, Fasolino I, Tagliatatela-Scafati O,Aprea G,Capasso R et al. Prokinetic effect of a standardized yarrow (Achillea millefolium) extract and its constituent choline: Studies in the mouse and human stomach. Neurogastroenterol Motil. 2012 Feb 1;24(2). https://doi.org/10.1111/j.1365-2982.2011.01827.x

9. Lemmens-Gruber R, Marchart E, Rawnduzi P, Engel N, Benedek B, Kopp B. Investigation of the spasmolytic activity of the flavonoid fraction of Achillea millefolium s.l. on isolated guinea-pig ilea. Arzneimittel-Forschung/Drug Res. 2006;56(8):582-6. https://doi.org/10.1055/s-0031-1296755
10. Ali M, Al-Imari J. Effects of Achillea Millifolium extract consumption by pregnant mice on pregnancy outcome and reproductive system of their female off spring. Kufa Journal For Veterinary Medical Sciences. 2012.
11. Radfar S, Shahoie R, Noori B, Jalilian F, Hashemi Nasab L. Comparative Study on the Effect of Matricaria chamomile and Achillea millefolium Capsules on Primary Dysmenorrhea Intensity of Dormitory Students of Kurdistan University of Medical Sciences, 2018. J Pharm Res Int. 2018;1-7. https://doi.org/10.9734/jpri/2018/v25i330101
12. Yaeesh S, Jamal Q, Khan AU, Gilani AH. Studies on hepatoprotective, antispasmodic and calcium antagonist activities of the aqueous-methanol extract of Achillea millefolium. Phyther Res. 2006 Jul;20(7):546-51. https://doi.org/10.1002/ptr.1897
13. Babaei M, Abarghoei ME, Akhavan MM, Ansari R, Vafaei AA, Taherian AA et al. Antimotility effect of hydroalcoholic extract of yarrow (Achillea millefolium) on the guinea-pig ileum. Pakistan J Biol Sci. 2007 Oct 15;10(20):3673-7. https://doi.org/10.3923/pjbs.2007.3673.3677
14. Moradi M-T, Rafieian-Koupaei M, Imani-Rastabi R, Nasiri J, Shahrani M, Rabiei Z et al. Antispasmodic effects of yarrow (Achillea millefolium L.) extract in the isolated ileum of rat. Afr J Tradit Complement Altern Med [Internet]. 2013 [cited 2020 Apr 8];10(6):499-503. https://doi.org/10.4314/ajtcam.v10i6.19
15. Yadegari M, Khamesipour F, Talebiyan R, Katsande S. Echocardiography Findings After Intravenous Injection of Achillea millefolium (Yarrow) Extract in The Dog. Malays Appl Biol. 2015;44(2):85-91.
16. Grossini E, Marotta P, Farruggio S, Siguado L, Qoqaiche F, Raina G et al. Effects of Artemetin on Nitric Oxide Release and Protection against Peroxidative Injuries in Porcine Coronary Artery Endothelial Cells. Phyther Res. 2015 Sep 1;29(9):1339-48. https://doi.org/10.1002/ptr.5386
17. Petrocelli T, Lye SJ. Regulation of transcripts encoding the myometrial gap junction protein, connexin-43, by estrogen andprogesterone. Endocrinology. 1993;133(1):284-90. https://doi.org/10.1210/endo.133.1.8391423