Journal of Literature Pharmacy Sciences

Geçmişten Günümüze Hypericum perforatum (Sarı Kantaron) ve Depresyon Tedavisi-Neler Biliyoruz?
Hypericum perforatum (St John's Wort) for Depression Treatment from Past to Present-What Do We Know?
Ezgi ERSOYa, Esra EROĞLU ÖZKANa
aİstanbul Üniversitesi Eczacılık Fakültesi, Farmakognozi ABD, İstanbul, TÜRKİYE
J Lit Pharm Sci. 2020;9(2):137-48
doi: 10.5336/pharmsci.2019-72764
Article Language: TR
Full Text
ÖZET
Hypericum perforatum L., antik çağlardan beri depresyon dâhil pek çok farklı hastalığın tedavisinde kullanılan çok yıllık bir bitkidir. Antidepresan etkisiyle ilgili bilinen ilk kayıt 1. yüzyıla aittir. Bitkinin antidepresan özelliklerini araştırmak üzere çok sayıda çalışma yapılmış ve bunların sonucunda bitkinin plaseboya göre daha etkili olduğu, standart antidepresanlarla aynı etkinliği gösterdiği ve bunlara kıyasla daha az yan etkiye neden olduğu belirlenmiştir. Bitkinin sahip olduğu antidepresan etki, bileşiminde bulunan farklı bileşiklerden oluşan zengin karışımdan kaynaklanmaktadır. Bu karışımda bulunan ve bir floroglusinol türevi olan hiperforin aktiviteden sorumlu ana bileşiktir. Antidepresan etki mekanizması günümüzde hâlâ tam olarak bilinememekle birlikte, bitkideki flavonoidlerin antidepresan aktivitede rol oynadığını gösteren bazı kanıtlar mevcuttur. Hem dünyada hem de Türkiye'de en çok satılan bitkisel ilaçlardan biri olması dolayısıyla H. perforatum ve sahip olduğu antidepresan etki ile ilgili daha fazla bilgi edinmek oldukça önemli hâle gelmiştir. Olası bazı ilaç etkileşimleri, aynı zamanda ürünlerin kalitesinin oldukça değişken olması, hatta bazı ürünlerin hiç etken madde içermediğinin tespit edilmesi gibi nedenlerden dolayı bitkinin kontrolsüzce kullanımı sorun teşkil etmektedir. Bu çalışmanın amacı, H. perforatum bitkisinin geçmişten günümüze depresyon tedavisinde kullanımı, yapılan çalışmalarla sunulan kanıtlar, kayıt altına alınan muhtemel yan etkiler ve ilaç etkileşimleri ile ilgili bilgi vermektir.

Anahtar Kelimeler: Hypericum perforatum; sarı kantaron; depresyon
ABSTRACT
Hypericum perforatum L., is a perennial herb that has been used since ancient times for the treatment of several diseases including depression. The first record about its antidepressant effect is from the 1st century. There have been numerous studies designed to investigate its antidepressant properties, and accordingly it can be said that the plant is more effective than placebo, and as effective as the standard antidepressants with significantly less side effects. The antidepressant properties of the plant are attributed to its rich mixture of different compounds, among them the floroglucinol derivative hyperforin is mainly responsible for the activity. Although the exact mechanism of action still remains unknown, there is evidence that flavonoids of the plant also play a role in antidepressant activity. Being one of the most selling herbal drugs in the world and also in Turkey, it has become crucial to gain more knowledge about the antidepressant properties of H. perforatum. The uncontrolled use of the plant could be problematic because of the possible drug interactions, besides the quality of the preparations can differ considerably, and it has been showed that some of the products do not even contain any bioactive consituents. This study aims to give information about H. perforatum for the treatment of depression, including evidence provided by the studies, the possible side effects and drug interactions recorded from past to present.

Keywords: Hypericum perforatum; St. John's wort; depression
REFERENCES:
  1. Özbek MU, Koç M, Hamzaoğlu E. Contributions to the hypericum l. section oligostema (boiss.) stef. (hypericaceae), and hypericum turcicum sp. nov. as a new species from Turkey. Turk J Bot. 2019;43(5):694-702. [Crossref] 
  2. Baytop T. Türkiye'de Bitkiler ile Tedavi.
  3. Baskı. İstanbul: Nobel Tıp Kitabevi; 1999. p.94-8.
  4. Ersoy E, Eroglu-Ozkan E, Mat A. Yeni Çalışmalar Işığında Hypericum Türlerinin Farmakolojik Aktiviteleri. Sağlık Bilimlerinde İleri Araştırmalar Dergisi, 2019;2(2):71-9. [Crossref] 
  5. Demirezer O, Ersoz T, Saracoglu I, Sener B. FFD Monografları, 1. Baskı. Ankara: Mn Medikal & Nobel Kitabevi; 2007. p.129-38.
  6. Ernst E. Herbal remedies for depression and anxiety. Adv Psychiatric Treat. 2007;13(4):312-316. [Crossref] 
  7. World Health Organization, The Global Burden of Disease 2004 update, 2008. http://www.who.int/healthinfo/global_burden_disease/GBD_report_2004update_full.pdf Accessed 16.6.2012
  8. Linde K, Berner M, Egger M, Mulrow C. St John's wort for depression: meta-analysis of randomised controlled trials. Br J Psychiatry. 2005;186:99-107. [Crossref]  [PubMed] 
  9. Linde K, Berner MM, Kriston L. St John's wort for major depression. Cochrane Database Syst Rev. 2008;(4):CD000448. [Crossref]  [PubMed]  [PMC] 
  10. Carlo GD, Borrelli F, Ernst E, Izzo AA. St John's wort: Prozac from the plant kingdom. Trends Pharmacol Sci. 2001;22(6):292-7. [Crossref]  [PubMed] 
  11. Capasso F, Gaginella TS, Grandolini G, Izzo AA. Phytotherapy: A Quick Reference to Herbal Medicine. 1st ed. Berlin: Springer & Business Media; 2003. p.424. [Crossref] 
  12. ESCOP, European Scientific Cooperative on Phytotherapy. ESCOP Monographs: The Scientific Foundation for Herbal Medicinal Products. 2nd ed. New York: Thieme; 2003. p.556.
  13. Linde K. St. John's wort - an overview. Forsch Komplementmed.2009;16(3):146-155. [Crossref]  [PubMed] 
  14. Bäcker W, Bart H, Bischoff F, Grabley S, Goedecke R, Johannisbauer W, Jordan V, Stockfleth R, Strube J, Wiesmet V. Phytoextrakte - Produkte und Prozesse 2005; Available online: http://www.dechema.de/dechema_media/Downloads/Extraktion/Phytoextrakte.pdf
  15. Crockett SL, Robson NK. Taxonomy and chemotaxonomy of the genus hypericum. Med Aromat Plant Sci Biotechnol. 2011;5(1):1-13. [PubMed] 
  16. American Botanical Council. Herbal supplement sales experience slight increase in 2008. HerbalGram. 2009;82:58-61.
  17. Guiley R. Harper's encyclopedia of mystical & paranormal experience. 1st ed. San Francisco: HarperSanFrancisco: 1991. p.456-9.
  18. Jurk C. Depression als Ununterscheidbarkeit: Willkommen in der entleerten Diagnosewelt. In Handbuch Therapeutisierung und Soziale Arbeit. Anhorn R, Balzereit M, Springer VS, ed. Wiesbaden; 2016. p.325-39. [Crossref] 
  19. Baytop A. Bitkilerin Bilimsel Adlarındaki Niteleyiciler ve Anlamları. İstanbul: İstanbul Üniversitesi Eczacılık Fakültesi Yayınları; 1995. p.294.
  20. Robson NKB. Hypericum botany. In: Ernst E. ed. Hypericum - The Genus Hypericum. 1st ed. London, New York: Taylor and Francis; 2003. p.1-22.
  21. Rosenthal N. St John's Wort. Your Natural Prozac. 1st ed. London: Thorsons; 1998. p.256.
  22. Galeotti N. Hypericum perforatum (St John's wort) beyond depression: a therapeutic perspective for pain conditions. J Ethnopharmacol. 2017;200:136-46. [Crossref]  [PubMed] 
  23. Van Arsdall A, Graham T. Saint John's Wort (Hypericum perforatum L.) in the age of paracelsus and the great herbals: assessing the historical claims for a traditional remedy. Herbs and Healers from the Ancient Mediterranean through the Medieval West. 1st ed. London, New York: Routledge; 2016. p.281-322. [Crossref] 
  24. Saddiqe Z, Naeem I, Maimoona A. A review of the antibacterial activity of Hypericum perforatum L. J Ethnopharmacol. 2010;131(3):511-21. [Crossref]  [PubMed] 
  25. Brenner R, Azbel V, Madhusoodanan S, Pawlowska M. Comparison of an extract of Hypericum (LI 160) and sertraline in the treatment of depression: a double-blind, randomized pilot study. Clin Ther. 2000;22(4):411-9. [Crossref]  [PubMed] 
  26. Daniel K. Johanniskraut (Hypericum perforatum) bei psychischen Störungen. Hippokrates. 1935;14:929-32.
  27. Kommission E. Monographie Hyperici herba (Johanniskraut). Bundesanzeiger 228 und Berichtigungin 1989; 43.
  28. Jenike MA. Hypericum: A novel antidepressant. J Geriatr Psychiatry Neurol. 1994;7:1-68. [Crossref] 
  29. Butterweck V, Schmidt M. St. John's wort: role of active compounds for its mechanism of action and efficacy. Wien Med Wochenschr. 2007;157(13-14):356-61. [Crossref]  [PubMed] 
  30. Demisch L, Hölzl J, Gollnik, B. Identification of selective MAO-Typ a inhibition of Hypericum perforatum L [abstract]. Pharmacopsychiatry. 1989;22:194.
  31. Thiede HM, Walper A. Inhibition of MAO and COMT by Hypericum extracts and hypericin. J Geriatr Psychiatry Neurol. 1994;7(Suppl 1):S54-6. [Crossref]  [PubMed] 
  32. Calapai G, Crupi A, Firenzuoli F, Inferrera G, Squadrito F, Parisi A, et al. Serotonin, norepinephrine and dopamine involvement in the antidepressant action of Hypericum perforatum. Pharmacopsychiatry. 2001;34(2):45-9. [Crossref]  [PubMed] 
  33. Gambarana C, Tolu P, Masi F, Rinaldi M, Giachetti D, Morazzoni P, et al. A study of the antidepressant activity of Hypericum perforatum on animal models. Pharmacopsychiatry. 2001;34(1):42-4. [Crossref]  [PubMed] 
  34. Butterweck V, Christoffel V, Nahrstedt A, Petereit F, Spengler B, Winterhoff H. Step by step removal of hyperforin and hypericin: activity profile of different Hypericum preparations in behavioral models. Life Sci. 2003;73(5):627-39. [Crossref]  [PubMed] 
  35. Nürk NM, Madri-án S, Carine MA, Chase MW, Blattner FR. Molecular phylogenetics and morphological evolution of St. John's wort (Hypericum; Hypericaceae). Molecular Phylogenetics and Evolution. 2013;66(1):1-16. [Crossref]  [PubMed] 
  36. Markoglou N, Hsuesh R, Wainer IW. Immobilized enzyme reactors based upon the flavoenzymes monoamine oxidase A and B. J Chromatogr B Analyt Technol Biomed Life Sci. 2004;804(2):295-302. [Crossref]  [PubMed] 
  37. Shih JC, Chen K, Ridd MJ. Monoamine oxidase: from genes to behavior. Annu Rev Neurosci. 1999;22(1):197-217. [Crossref]  [PubMed]  [PMC] 
  38. Yamada M, Yasuhara, H. Clinical pharmacology of MAO inhibitors: safety and future. Neurotoxicology. 2004;25(1-2):215-21. [Crossref]  [PubMed] 
  39. Bladt S, Wagner H. Inhibition of MAO by fractions and constituents of hypericum extract. J Geriatric Psychiatry Neurol. 1994;7(Suppl 1):S57-9. [Crossref]  [PubMed] 
  40. Mann JJ. The medical management of depression. N Engl J Med. 2005;353(17):1819-34. [Crossref]  [PubMed] 
  41. Müller WE, Singer A, Wonnemann M, Hafner U, Rolli M, Schäfer C. Hyperforin represents the neurotransmitter reuptake inhibiting constituent of hypericum extract. Pharmacopsychiatry. 1998;31(Suppl 1):16-21. [Crossref]  [PubMed] 
  42. Müller WE. St. John's Wort and its active principles in depression and anxiety. 1st ed. Springer Science & Business Media, Basel-Switzerland; 2005. p.188. [Crossref] 
  43. Rahimi R, Nikfar S, Abollahi M. Efficacy and tolerability of Hypericum perforatum in major depressive disorder in comparison with selective serotonin reuptake inhibitors: A meta-analysis. Prog Neuropsychopharmacol Biol Psychiatry. 2009;33(1):118-27. [Crossref]  [PubMed] 
  44. Cui YH, Zheng, Y. A meta-analysis on the efficacy and safety of St John's wort extract in depression therapy in comparison with selective serotonin reuptake inhibitors in adults. Neuropsychiatr Dis Treat. 2016;12:1715-23. [Crossref]  [PubMed]  [PMC] 
  45. Xiang Q, Venkatanarayanan N, Ho CYX. Clinical use of Hypericum perforatum (St John's wort) in depression: a meta-analysis. J Affect Disord. 2017;210:211-21. [Crossref]  [PubMed] 
  46. Rodríguez-Landa JF, Contreras CM. A review of clinical and experimental observations about antidepressant actions and side effects produced by Hypericum perforatum extracts. Phytomedicine. 2003;10(8):688-99. [Crossref]  [PubMed] 
  47. Schulz V. Safety of St. John's Wort extract compared to synthetic antidepressants. Phytomedicine. 2006;13(3):199-204. [Crossref]  [PubMed] 
  48. Knüppel L, Linde K. Adverse effects of St. John's Wort: a systematic review. J Clin Psychiatry. 2004;65(11):1470-9. [Crossref]  [PubMed] 
  49. Woelk H, Burkard G, Grünwald J. Benefits and risks of the Hypericum extract LI 160: drug-monitoring study with 3250 patients. J Geriatr Psychiatry Neurol. 1994;7(Suppl 1):S34-8. [Crossref]  [PubMed] 
  50. De Smet PAGM, Nolen WA. St John's Wort as an antidepressant. BMJ. 1996;313(7052):241-2. [Crossref]  [PubMed]  [PMC] 
  51. Durán N, Song PS. Hypericin and its photodynamic action. Photochem Photobiol. 1986;43(6):677-80. [Crossref]  [PubMed] 
  52. Golsch S, Vocks E, Rakoski J, Brockow K, Ring J. [Reversible increase in photosensitivity to UV-B caused by St. John's wort extract]. Hautarzt. 1997;48(4):249-52. [Crossref]  [PubMed] 
  53. Bernd A, Simon S, Bosca AR, Kippenberger S, Alperi JD, Miquel J, et al. Phototoxic effects of Hypericum extract in cultures of human keratinocytes compared with those of psoralen. Photochem Photobiol. 1999;2(2):218-21. [Crossref]  [PubMed] 
  54. Jacobson JM, Feinman L, Liebes L, Ostrow N, Koslowski V, Tobia A, et al. Pharmacokinetics, safety, and antiviral effects of hypericin, a derivative of St. John's wort plant, in patients with chronic hepatitis C virus infection. Antimicrob Agents Chemother. 2001;45(2):517-24. [Crossref]  [PubMed]  [PMC] 
  55. Boiy A, Roelandts R, Roskams T, de Witte PA. Effect of vehicles and esterification on the penetration and distribution of hypericin in the skin of hairless mice. Photodiagnosis Photodyn Ther. 2007;4(2):130-9. [Crossref]  [PubMed] 
  56. Hammerness P, Basch E, Ulbricht C, Barrette EP, Foppa I, Basch S, et al. St. John's wort: a systematic review of adverse effects and drug interactions for the consultation psychiatrist. Psychosomatics. 2003;44(4):271-82. [Crossref]  [PubMed] 
  57. Breidenbach TH, Kliem V, Burg M, Radermacher J, Hoffmann MW, Klempnauer J. Profound drop of cyclosporin a whole blood trough levels caused by St. John′ s Wort (Hypericum perforatum). Transplantation. 2000;69(10):2229-30. [Crossref]  [PubMed] 
  58. Karliova M, Treichel U, Malagò M, Frilling A, Gerken G, Broelsch CE. Interaction of Hypericum perforatum (St John's wort) with cyclosporin a metabolism in a patient after liver transplantation. J Hepatol. 2000;33(5):853-5. [Crossref]  [PubMed] 
  59. Yue QY, Bergquist C, Gerdén B. Safety of St John's wort (Hypericum perforatum). Lancet. 2000;355(9203):576-7. [Crossref]  [PubMed] 
  60. Schwarz UI, Büschel B, Kirch W. Unwanted pregnancy on self-medication with St John's wort despite hormonal contraception. Br J Clin Pharmacol. 2003;55(1):112-3. [Crossref]  [PubMed] 
  61. Sugimoto K, Ohmori M, Tsuruoka S, Nishiki K, Kawaguchi A, Harada K, et al. Different effects of St John's wort on the pharmacokinetics of simvastatin and pravastatin. Clin Pharmacol Ther. 2001;70(6):518-24. [Crossref]  [PubMed] 
  62. Smith M, Lin K, Zheng Y. PIII-89 an open trial of nifedipine herb interactions: nifedipine with St John's wort, ginseng or ginkgo biloba. Clin Pharmacol Ther. 2001;69(2):86.
  63. Waksman JC, Hard K, Jolliff H, Daly FFS, Bogdan GM, Dart RC. Serotonin syndrome associated associated with the use of St. John's wort (Hypericum perforatum) and paroxetine [abstract]. J Toxicol Clin Toxicol. 2000;38:521.
  64. Fahmi M. Huang C, Schweitzer I. A case of mania induced by hypericum. World J Biol Psychiatry. 2002;3:58-9. [Crossref]  [PubMed] 
  65. Spinella M, Eaton LA. Hypomania induced by herbal and pharmaceutical psychotropic medicines following mild traumatic brain injury. Brain Inj. 2002;16(4):359-67. [Crossref]  [PubMed] 
  66. Vandenbogaerde A, Zanoli P, Puia G, Truzzi C, Kamuhabwa A, De Witte P, et al. Evidence that total extract of Hypericum perforatum affects exploratory behavior and exerts anxiolytic effects in rats. Pharmacol Biochem Behav. 2000;65(4):627-33. [Crossref]  [PubMed] 
  67. Flausino OA, Zangrossi H, Salgado JV, Viana MB. Effects of acute and chronic treatment with Hypericum perforatum L. (LI 160) on different anxiety-related responses in rats. Pharmacol Biochem Behav. 2002;71(1-2):251-7. [Crossref]  [PubMed] 
  68. Schulz H, Jobert M. Effects of hypericum extract on the sleep EEG in older volunteers. J Geriatr Psychiatry Neurol. 1994;7(Suppl 1):S39-43. [Crossref]  [PubMed] 
  69. Taylor LH, Kobak KA. An open-label trial of St. John's Wort (Hypericum perforatum) in obsessive-compulsive disorder. J Clin Psychiatry. 2000;61(8):575-8. [Crossref]  [PubMed] 
  70. Kobak KA, Taylor LVH, Bystritsky A, Kohlenberg CJ, Greist JH, Tucker P, et al. St John's wort versus placebo in obsessive-compulsive disorder: results from a double-blind study. Int Clin Psychopharmacol. 2005;20(6):299-304. [Crossref]  [PubMed] 
  71. Griffith TN, Varela-Nallar L, Dinamarca MC, Inestrosa NC. Neurobiological effects of Hyperforin and its potential in Alzheimer's disease therapy. Curr Med Chem. 2016;17(5):391-406. [Crossref]  [PubMed] 
  72. Talić S, Dragičević I, Ćorajević L, Martinović AB. Acetylcholinesterase and butyrylcholinesterase inhibitory activity of extracts from medicinal plants. Bull Chem Technol Bosnia Herzegovina. 2014;43:11-4.
  73. Hernandez MF, Falé PL, Araújo MEM, Serralheiro MLM. Acetylcholinesterase inhibition and antioxidant activity of the water extracts of several Hypericum species. Food Chemistry. 2010;120(4):1076-82. [Crossref] 
  74. del Rio MAG, Sánchez-Reus MI, Iglesias I, Pozo MA, García-Arencibia M, Fernández-Ruiz J, et al. Neuroprotective properties of standardized extracts of hypericum perforatum on rotenone model of Parkinson's disease. CNS Neurol Disord Drug Targets. 2013;12(5):665-79. [Crossref]  [PubMed] 
  75. Ittner LM, Götz J. Amyloid-β and tau - - a toxic pas de deux in Alzheimer's disease. Nat Rev Neurosci. 2011;12(2):67-72. [Crossref]  [PubMed] 
  76. Nussbaum JM, Seward ME, Bloom GS. Alzheimer disease: a tale of two prions. Prion. 2013;7(1):14-9. [Crossref]  [PubMed]  [PMC] 

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4.7. "Turkiye Klinikleri" reserves the right to change the services and the context within the "SITE"  anytime. "Turkiye Klinikleri" may use this right without any notification and timelessly. "USER"s have to make the changes and/or corrections "Turkiye Klinikleri" required immediately. Any changes and/or corrections that are required by "Turkiye Klinikleri", may be made by "Turkiye Klinikleri" when needed. Any harm, criminal and civil liability resulted or will result from changes and/or corrections required by "Turkiye Klinikleri" and were not made on time by the "USER"s belongs completely to the users.

4.8. "Turkiye Klinikleri" may give links through the "SITE" to other websites and/or "CONTEXT"s and/or folders that are outside of their control and owned and run by third parties. These links are provided for ease of reference only and do not hold qualification for support the respective web SITE or the admin or declaration or guarantee for the information inside. "Turkiye Klinikleri" does not hold any responsibility over the web-sites connected through the links on the "SITE", folders and context, the services or products on the websites provided through these links or their context.

4.9. "Turkiye Klinikleri" may use the information provided to them by the "USERS" through the "SITE" in line with the terms of the "PRIVACY POLICY" and "USER CONTRACT". It may process the information or classify and save them on a database. "Turkiye Klinikleri" may also use the USER's or visitor's identity, address, e-mail address, phone number, IP number, which sections of the "SITE" they visited, domain type, browser type, date and time information to provide statistical evaluation and customized services.

5. PROPRIETARY RIGHTS

5.1. The information accessed through this "SITE" or provided by the users legally and all the elements (including but not limited to design, text, image, html code and other codes) of the "SITE" (all of them will be called as studies tied to "Turkiye Klinikleri"s copyrights) belongs to "Turkiye Klinikleri". Users do not have the right to resell, process, share, distribute, display or give someone permission to access or to use the "Turkiye Klinikleri" services, "Turkiye Klinikleri" information and the products under copyright protection by "Turkiye Klinikleri". Within hereby "Terms of Use" unless explicitly permitted by "Turkiye Klinikleri" nobody can reproduce, process, distribute or produce or prepare any study from those under "Turkiye Klinikleri" copyright protection.

5.2. Within hereby "Terms of Use", "Turkiye Klinikleri" reserves the rights for "Turkiye Klinikleri" services, "Turkiye Klinikleri" information, the products associated with "Turkiye Klinikleri" copyrights, "Turkiye Klinikleri" trademarks, "Turkiye Klinikleri" trade looks or its all rights for other entity and information it has through this website unless it is explicitly authorized by "Turkiye Klinikleri".

6. CHANGES IN THE TERMS OF USE

"Turkiye Klinikleri" in its sole discretion may change the hereby "Terms of Use" anytime announcing within the "SITE". The changed terms of the hereby "Terms of Use" will become valid when they are announced. Hereby "Terms of Use" cannot be changed by unilateral declarations of users.

7. FORCE MAJEURE

"Turkiye Klinikleri" is not responsible for executing late or never of this hereby "Terms of Use", privacy policy and "USER Contract" in any situation legally taken into account as force majeure. Being late or failure of performance or non-defaulting of this and similar cases like this will not be the case from the viewpoint of "Turkiye Klinikleri", and "Turkiye Klinikleri" will not have any damage liability for these situations. "Force majeure" term will be regarded as outside of the concerned party's reasonable control and any situation that "Turkiye Klinikleri" cannot prevent even though it shows due diligence. Also, force majeure situations include but not limited to natural disasters, rebellion, war, strike, communication problems, infrastructure and internet failure, power cut and bad weather conditions.

8. LAW AND AUTHORISATION TO FOLLOW

Turkish Law will be applied in practicing, interpreting the hereby "Terms of Use" and managing the emerging legal relationships within this "Terms of Use" in case of finding element of foreignness, except for the rules of Turkish conflict of laws. Ankara Courts and Enforcement Offices are entitled in any controversy happened or may happen due to hereby contract.

9. CLOSING AND AGREEMENT

Hereby "Terms of Use" come into force when announced in the "SITE" by "Turkiye Klinikleri". The users are regarded to agree to hereby contract terms by using the "SITE". "Turkiye Klinikleri" may change the contract terms and the changes will be come into force by specifying the version number and the date of change on time it is published in the "SITE".

 

30.03.2014

Privacy Policy

We recommend you to read the terms of use below before you visit our website. In case you agree these terms, following our rules will be to your favor. Please read our Terms of Use thoroughly.

www.turkiyeklinikleri.com website belongs to Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. and is designed in order to inform physicians in the field of health

www.turkiyeklinikleri.com cannot reach to user’s identity, address, service providers or other information. The users may send this information to the website through forms if they would like to. However, www.turkiyeklinikleri.com may collect your hardware and software information. The information consists of your IP address, browser type, operating system, domain name, access time, and related websites. www.turkiyeklinikleri.com cannot sell the provided user information (your name, e-mail address, home and work address, phone number) to the third parties, publish it publicly, or keep it in the website. Gathered information has a directing feature to be a source for the website’s visitor profile, reporting and promotion of the services.

www.turkiyeklinikleri.com uses the taken information:

-To enhance, improve and maintain the quality of the website

-To generate visitor’s profile and statistical data

-To determine the tendency of the visitors on using our website

-To send print publications/correspondences

-To send press releases or notifications through e-mail

-To generate a list for an event or competition

By using www.turkiyeklinikleri.com you are considered to agree that;

-Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. cannot be hold responsible for any user’s illegal and immoral behavior,

-Terms of use may change from time to time,

-It is not responsible for other websites’ contents it cannot control or the harms they may cause although it uses the connection they provided.

Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. may block the website to users in the following events:

-Information with wrong, incomplete, deceiving or immoral expressions is recorded to the website,

-Proclamation, advertisement, announcement, libelous expressions are used against natural person or legal identity,

-During various attacks to the website,

-Disruption of the website because of a virus.

Written, visual and audible materials of the website, including the code and the software are under protection by legal legislation.

Without the written consent of Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. the information on the website cannot be downloaded, changed, reproduced, copied, republished, posted or distributed.

All rights of the software and the design of the website belong to Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc.

Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. will be pleased to hear your comments about our terms of use. Please share the subjects you think may enrich our website or if there is any problem regarding our website.

info@turkiyeklinikleri.com