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Yeni Çalışmalar Işığında Hypericum Türlerinin Farmakolojik Aktiviteleri Pharmacological Acti̇ Vi̇ Ti̇ Es of Hypericum Species in Light of New Studies

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Yeni Çalışmalar Işığında Hypericum Türlerinin Farmakolojik Aktiviteleri Pharmacological Acti̇ Vi̇ Ti̇ Es of Hypericum Species in Light of New Studies Ersoy E, Eroğlu-Özkan E, Mat A İstanbul Üniversitesi Sağlık Bilimleri Enstitüsü Sağlık Bilimlerinde İleri Araştırmalar Dergisi Istanbul University Institute of Health Sciences Journal of Advanced Research in Health Sciences Sağlık Bilimlerinde İleri Araştırmalar Dergisi 2019, Cilt 2, Sayı 2 DOI: 10.26650/JARHS2019-616370 Derleme / Review Yeni Çalışmalar Işığında Hypericum Türlerinin Farmakolojik Aktiviteleri Pharmacological Acti̇ vi̇ ti̇ es of Hypericum Species in Light of New Studies Ezgi Ersoy1 , Esra Eroğlu Özkan2 , Afife Mat3 ÖZ Hypericaceae familyasına ait Hypericum türleri, özellikle en çok bilinen tür olan Hypericum perforatum, tüm dünyada en çok kullanılan tıbbi bitkilerdendir. Son yıllarda H. perforatum içeren ürün sayısı tüm dünyada ciddi oranda artmıştır.1 H. perforatum türünün özellikle yara iyi edici ve antidepresan özellikleri nedeniyle antik çağlardan beri kullanıldığına, hatta Ortaçağ Avrupası’nda kutsal kabul edildiğine ve birçok dini ritüelin parçası olduğuna dair kanıtlar mevcuttur.2 Türkçe’ de en bilinen ismi “Sarı Kantaron” olan bitki, yurt dışında “St. John’s Wort” ismiyle tanınmaktadır. Hypericum türlerinin kimyasal bileşenleri ve biyolojik aktiviteleri üzerinde çok sayıda çalışma yapılmıştır. Buna göre, H. perforatum türünün majör aktif bileşikleri bir floroglusinol türevi olan hiperforin ve bir naftodiantron bileşiği olan hiperisindir. Bitkide bunun yanında flavonoitler, fenolik asitler, tanenler, uçucu yağlar, ksanton bileşikleri gibi başka çeşitli biyolojik aktif maddeler de bulunmaktadır.3 1 Dr. Ecz., İstanbul Üniversitesi, Eczacılık Bugüne dek, Hypericum türlerinin birçok farklı farmakolojik etkisi kayıt altına alınmıştır. Fakültesi, Farmakognozi Anabilim Dalı, Bu çalışma; Hypericum türlerinin antidepresan etkisi, yara iyi edici etkisi, antienflamatuar İstanbul, Türkiye etkisi, antioksidan etkisi, antimikrobiyal etkisi, nörodejeneratif hastalıklar üzerine etkisi, 2 Dr. Öğr. Üyesi, İstanbul Üniversitesi, Eczacılık sitotoksik etkisi, analjezik ve antinosiseptif etkisi gibi önemli bazı etkileri ile ilgili yapılan Fakültesi, Farmakognozi Anabilim Dalı, İstanbul, Türkiye güncel çalışmaları özet olarak sunmaktadır. 3 Prof. Dr., İstanbul Üniversitesi, Eczacılık Anahtar Kelimeler: Hypericum, Sarı Kantaron, Biyolojik Aktivite Fakültesi, Farmakognozi Anabilim Dalı, İstanbul, Türkiye ABSTRACT The Hypericum species that belong to the family Hypericaceae, especially the most common ORCID: E.E. 0000-0002-6913-1952; Hypericum perforatum, are presently one of the most consumed medicinal plants in the world. E.E.Ö. 0000-0002-1569-2535; In recent years, the use of products containing H. perforatum has increased dramatically all A.M. 0000-0002-9225-8572 over the world.1 There is evidence that H. perforatum has been used for its wound healing Sorumlu yazar/Corresponding author: and antidepressant effects since ancient times and was even believed to be “sacred” and was Ezgi Ersoy, a part of religious rituals in medieval Europe.2 H. perforatum is known as “sarı kantaron” in İstanbul Üniversitesi, Eczacılık Fakültesi, Turkish, whereas the most common name in other countries is “St. John’s Wort”. Numerous Farmakognozi Anabilim Dalı, İstanbul, Türkiye Tel: +90 535 395 32 64 studies have been conducted on the chemical constituents and biological activities of the E-posta: [email protected] Hypericum species. The major active constituents are considered to be hyperforin which is a phloroglucinol derivative, and hypericin, a naphthodianthrone compound. Furthermore, Başvuru/Submitted: 13.02.2019 other biologically active constituents, such as flavonoids, phenolic acids, tannins, volatile Revizyon Talebi/Revision Requested: 13.03.2019 3 Son Revizyon/Last Revision Received: 15.04.2019 compounds and xanthones are also present in the plant extracts. Several pharmacological Kabul/Accepted: 16.04.2019 activities of the Hypericum species have been documented so far. The present study gives a summary of the most recent studies related to some important properties, including its Atıf/Citation: Ersoy E., Eroglu-Ozkan E., Mat A. antidepressant effect, wound-healing effect, anti-inflammatory effect, antioxidant effect, (2019): Pharmacological activities of hypericum antimicrobial effect, effects on neurodegenerative disorders, cytotoxic effect, analgesic, and species in light of new studies, Sağlık Bilimlerinde İleri Araştırmalar Dergisi, 2(2): 71-79. antinociceptive effect. https://doi.org/10.26650/JARHS2019-616370 Keywords: Hypericum, St. John’s Wort, Biological Activity Journal of Advanced Research in Health Sciences, June 2019; Volume 2, Issue 2 71 Yeni Çalışmalar Işığında Hypericum Türlerinin Farmakolojik Aktiviteleri GİRİŞ evresindeki taze bitki veya kurutulmuş gövde kısım- Hypericum L. türleri; Hypericaceae familyasına ları (Hyperici herba) kullanılır. Kullanılan bitkinin ait, çok yıllık otsu veya çalımsı bitkilerdir. Dünyada nerede yetiştiği, bu bölgenin iklimi, toplanma za- şu an bilinen 500’den fazla Hypericum türü vardır, manı, kurutma işlemi gibi etmenler drog kalitesine ülkemizde ise 20 seksiyon altında 106 tür tespit edil- doğrudan etki eder. Taze bitkiden homeopatide kul- miştir.4 Tüm dünyada en çok bilinen tür Hypericum lanılan tentürler, bitkinin preslenmesiyle elde edilen 9 perforatum türüdür. H. perforatum, Türkiye’de sarı bitki suları veya yağları hazırlanır. Bitkinin gele- kantaron, binbirdelik otu, kan otu, koyunkıran gibi neksel kullanım alanları ise çok daha geniştir. Yağ isimlerle bilinmektedir. Dünyada ise en yaygın kul- bazlı preparatlar dispepsi şikâyetlerinde tercih edil- lanılan isim ise “Saint John’s Wort”tur. mektedir. Haricen ise yaraları iyi etmede, miyaljide H. perforatum; Hippocrates, Theophrastus, Di- ve yanıklarda kullanılmaktadır. Taze haldeki bitki oscorides, Galenos gibi devirlerinin en önemli bilim ufalandıktan sonra zeytinyağı veya bir başka yağ ile insanlarının eserlerinde çeşitli farmakolojik etkileri güneş ışığında bekletildiğinde oluşan kırmızı renkli nedeniyle yer almaktadır. Bitkinin psikiyatrik ra- yağ haricen direkt olarak kullanılabildiği gibi, mer- hatsızlıklarda kullanılabileceğini kayıt altına alan hemlere karıştırılarak veya kapsül halinde de kulla- ilk kişi, modern tıbbın kurucularından kabul edi- nılabilir. Taze haldeki bitkinin kurutulmasıyla kuru len İsviçreli hekim ve kimyager Paracelsus (1493- drog elde edilir. Toz haldeki kuru drogun alkol ile 1541)’tur. Paracelsus, H. perforatum bitkisinin kay- ekstraksiyonu sonucu oluşan sıvı ekstre bu şekilde natılarak sterilize edildiği takdirde öfke sorunu ve veya bazı damlaların, merhemlerin veya tentürlerin anksiyete problemi olan kişilerde dahilen kullanıl- bileşimine girmektedir. Alkol ekstresinin yoğun- masını tavsiye etmiştir.5 Bitki, Nicholas Culpeper laştırılması ve sonrasında liyofilizatör ile kuru toz (1616-1654)’in çabalarıyla İngiltere’de de oldukça haline getirilmesi ile oluşan ürün, standardizasyon popüler hale gelmiş ve 1618’de tedavi edici bir bitki aşamasının ardından tablet veya kapsüllerin bileşi- olarak Londra Farmakopesi’nde yer almıştır. Daha mine girerek dâhilen kullanılmaktadır.10 sonra İngiltere, Fransa ve Almanya gibi ülkelerden Yapılan birçok çalışma ile H. perforatum türü- Amerika’ya göç eden kişiler bitkinin bu kıtada da bi- nün kimyasal içeriği aydınlatılmıştır. Buna göre, linmesini sağlamışlar, bu dönemlerde antidepresan naftodiantron yapısındaki bileşikler (hiperisin, psö- etkinliği tüm dünyada bilinir hale gelmiş ve bitki dohiperisin vb), floroglusinoller (hiperforin, adhi- yaygın olarak kullanılmaya başlamıştır.6 1984 yılın- perforin vb), flavonoitler (hiperozit, rutin, kersetin da Almanya Sağlık Bakanlığı tarafından hazırlanan vb), biflavonlar (biapigenin, amentoflavon), fenolik Komisyon E monograflarında H. perforatum ekstre- asitler (ferulik asit, kafeik asit vb), proantosiyani- sinin psiko-vejetatif bozukluklarda, depresif bozuk- dinler, uçucu yağlar ve diğer bazı kimyasal bileşikler luklarda, anksiyete ve/veya ajitasyon durumlarında bulunmaktadır. Bu maddeler bitkinin sahip olduğu ve uyum bozukluklarında kullanıldığı belirtilmekte- önemli farmakolojik etkilerden sorumludur.11 dir.7 Dünya Sağlık Örgütü (WHO) 2002 yılında H. Farmakolojik Aktiviteler perforatum türünü tıbbi bitki olarak ilan etmiş ve Hyperici herba olarak monograflarında geniş bir yer Antidepresan Etki vermiştir. Bu monograflarda bitkinin antidepresan, H. perforatum türünün majör depresif bozukluk, antibakteriyel, antiviral, protein kinaz – C inhibitörü dikkat eksikliği ve hiperaktivite bozukluğu, sosyal ve yara iyi edici etkileri yer almaktadır.8 fobi, obsesif kompulsif bozukluk, distimik bozuk- H. perforatum, çok eski zamanlardan beri teda- luk, somatoform bozukluklar, anksiyöz depresyon ve vide rol oynayan bir bitki olmasının sonucu olarak mevsimsel affektif bozukluk gibi çok farklı psikiyatrik pek çok farklı şekilde hazırlanarak kullanılabilmek- rahatsızlıklarda etkili olduğunu gösteren birçok çalış- tedir. Temel materyal olarak, genellikle çiçeklenme ma mevcuttur.12 ESCOP monografları H. perforatum 72 Sağlık Bilimlerinde İleri Araştırmalar Dergisi, Haziran 2019; Cilt 2, Sayı 2 Ersoy E, Eroğlu-Özkan E, Mat A bitkisinin hidroalkolik ekstre ve tentürlerinin hafif lanılan bitkilerdir. Çiçekli topraküstü kısımlar tentür şiddetteki depresif bozukluklar veya hafif ile orta arası veya yağ halinde yanıklara ve yaralara uygulanmak- şiddetteki depresif bozukluklarda kullanıldığını be- tadır.17 Yara iyi edici etkinin bitkinin fibroblastları lirtmektedir. Tüm dünyada geçerli olan ICD (Interna- uyarması ve kolajen yapımının buna
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