Sarı Kantaron'a Dair (Hypericum Perforatum L.): Morfoloji, Etki Mekanizmaları, Aktivite, Yan Etkileri ve İlaç Etkileşimlerinin İncelenmesi

Year 2021, Volume: 3 Issue: 1, 1 - 37, 31.07.2021

Fatma Şengül , Melikşah Çakır , Beyza Öztürk , Ayşenur Çakmak Hüsamettin Vatansev

Abstract

Amaç: Bu derleme St. John’s wort olarak bilinen Hypericum perforatum L. bitkisi hakkında bilgiler sunmaktadır. H.perforatum hakkında pek çok çalışma yapılmış, belirli aktiviteler üzerine derlemeler yazılmış olmasına rağmen literatürde sarı kantaron bitkisini kapsamlı olarak ele alan derlemeye rastlanmamıştır. Bu çalışmada bitkinin morfolojik özellikleri, kimyasal bileşimi, bu bileşiklerin terapötik etkileri, etki mekanizmaları, ilaç etkileşimleri ve yan etkileri hakkında detaylı bir derleme oluşturulmuştur. Derlememiz bitkiye ait kapsamlı içeriğiyle farklılık ortaya koymayı amaçlamaktadır.
Metot: Derleme hazırlanırken sağlık alanında uluslararası çalışmaların yayınlandığı PubMed ve Google Scholar veri tabanları kullanılarak 1992-2021 arasında sarı kantaron hakkında yapılan çalışmalardan faydalanılmıştır.
Bulgular: Geçmişten günümüze insanlar bitkilerin tedavi edici özelliklerinden yararlanmıştır. Bitkilerin çeşitli hastalıkları tedavi edici özelliklerinin görülmesi, bilim insanlarını bitkilerin kimyasını araştırmaya yöneltmiştir. Bitkilerdeki biyolojik aktif bileşiklerin ortaya konmasıyla birlikte etken maddeler preklinik ve klinik çalışmalara konu edilmiştir. Bununla birlikte bitkilerin etken maddelerinden ayrışmadan kullanılması da çalışmalarda yer almıştır. Sarı kantaron bitkisi halkımız tarafından terapötik amaçla sıklıkla kullanılan, aynı zamanda pek çok bilimsel araştırmaya konu olmuş, önemli bir bitkidir. Hypericaceae familyasına ait olan bitki parlak sarı, sıklıkla üçlü kümeler şeklinde beş petale sahiptir ve yaprakları, minik saydam yağ bezlerine benzeyen delikler içerir. Aktif major bileşenleri hiperisin ve hiperforindir. Sıklıkla, yara ve yanıkların tedavisinde topikal olarak; depresyon, akut ve kronik ağrı tedavisinde ise oral olarak kullanılmaktadır.
Sonuç: Sarı kantaron bitkisinin vücuttaki çeşitli metabolik yolakları kullanarak pek çok hastalık için terapötik etki potansiyeli sunduğu, bununla birlikte kullanımının ilaç etkileşimleri ve yan etki profili göz önüne alınarak doktor kontrolünde yapılmasının fayda sağlayacağı ortaya konulmuştur.

Keywords

Hypericum perforatum, St. John’s wort, Bitki-ilaç etkileşimi, Depresyon

Supporting Institution

Destekleyen kurum bulunmamaktadır.

Project Number

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Thanks

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About St. John's Wort (Hypericum Perforatum L.): Investigation of Morphology, Mechanisms of Action, Activity, Side Effects and Drug Interactions

Abstract

Objective: This review provides information about Hypericum perforatum L., known as St. John's Wort. Although many studies have been conducted on H. perforatum and reviews have been written on certain activities, no comprehensive review of St. John's wort plant has been found in the literature. Our review reveals a difference in the comprehensive content of the plant. In this study, many studies about St. John's Wort have been scanned and a detailed review has been made on the plant's morphological properties, chemical composition, therapeutic effects, mechanisms of action, drug interactions and side effects of these compounds.
Methods: The studies about St. John's Wort plant between 1992 and 2021 were utilized by using PubMed and Google Scholar databases where international studies in the field of health are published.
Results: Humans have benefited from the therapeutic properties of plants from past to present. Observing the therapeutic properties of plants for various diseases has directed scientists to search chemistry of plants. Active pharmaceutical ingredients were achieved with the discovery of biologically active compounds from plants. Hypericum perforatum L. is one of the plants that has been the subject of many studies. However, the use of herbs without separating the active ingredients has also been included in the studies. John's wort plant is an important plant that is frequently used by our people for therapeutic purposes and has also been the subject of many scientific researches. It is perennial herbaceous plant a belonging to the Hypericaceae family. The bright yellow, star-shaped flowers, often clustered in a trio, have five petals and the leafs contain tiny transparent oil glands resembling perforations. The active components of the plant are hypericin and hyperforin. It is generally used internally in the treatment of acute and chronic pain and externally in the treatment of scars and burns.
Conclusions: It has been demonstrating that St. John's Wort plant offers therapeutic effect potential for many diseases by using various metabolic pathways in the body, however, it has been shown that its use will be beneficial under the supervision of a doctor by taking into considering the drug interactions and side effect profile.

Keywords

Herb-drug interactions, Depression, Hypericum perforatum, St. John’s wort.

Project Number

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References

• Agostinis, P., Vantieghem, A., Merlevede, W., & de Witte, P. A. M. (2002). Hypericin in cancer treatment: more light on the way. The International Journal of Biochemistry & Cell Biology, 34(3), 221-241. doi:https://doi.org/10.1016/S1357-2725(01)00126-1
• ANDERSEN, F. A. (2001). Final report on the safety assessment of Hypericum perforatum extract and Hypericum perforatum oil. International journal of toxicology, 20, 31-39.
• Barnes, J., Anderson, L. A., & Phillipson, J. D. (2001). St John's wort (Hypericum perforatum L.): a review of its chemistry, pharmacology and clinical properties. Journal of Pharmacy and Pharmacology, 53(5), 583-600.
• Barone, G. W., Gurley, B. J., Ketel, B. L., Lightfoot, M. L., & Abul-Ezz, S. R. (2000). Drug interaction between St. John's wort and cyclosporine. Annals of Pharmacotherapy, 34(9), 1013-1016.
• Bell, E. C., Ravis, W. R., Chan, H. M., & Lin, Y.-J. (2007). Complementary and Alternative Medicine: Lack of Pharmacokinetic Interaction Between St. John's Wort and Prednisone. Annals of Pharmacotherapy, 41(11), 1819-1824.
• Bell, E. C., Ravis, W. R., Lloyd, K. B., & Stokes, T. J. (2007). Effects of St. John's wort supplementation on ibuprofen pharmacokinetics. Annals of Pharmacotherapy, 41(2), 229-234.
• Benedı́, J., Arroyo, R., Romero, C., Martı́n-Aragón, S., & Villar, A. M. (2004). Antioxidant properties and protective effects of a standardized extract of Hypericum perforatum on hydrogen peroxide-induced oxidative damage in PC12 cells. Life Sciences, 75(10), 1263-1276.
• Bolley, R., Zülke, C., Kammerl, M., Fischereder, M., & Krämer, B. K. (2002). Tacrolimus-induced nephrotoxicity unmasked by induction of the CYP3A4 system with St John’s wort. Transplantation, 73(6), 1009.
• Bork, P. M., Bacher, S., Schmitz, M. L., Kaspers, U., & Heinrich, M. (1999). Hypericin as a non-antioxidant inhibitor of NF-κB. Planta medica, 65(04), 297-300.
• Borrelli, F., & Izzo, A. A. (2009). Herb–drug interactions with St John’s wort (Hypericum perforatum): an update on clinical observations. The AAPS journal, 11(4), 710-727.
• Butterweck, V., & Schmidt, M. (2007). St. John's wort: role of active compounds for its mechanism of action and efficacy. Wiener Medizinische Wochenschrift, 157(13-14), 356-361.
• Canning, S., Waterman, M., Orsi, N., Ayres, J., Simpson, N., & Dye, L. (2010). The efficacy of Hypericum perforatum (St John’s Wort) for the treatment of premenstrual syndrome. CNS Drugs, 24(3), 207-225.
• Chang, Y., & Wang, S.-J. (2010). Hypericin, the active component of St. John's wort, inhibits glutamate release in the rat cerebrocortical synaptosomes via a mitogen-activated protein kinase-dependent pathway. European journal of pharmacology, 634(1-3), 53-61.
• Chen, X.-W., B Sneed, K., Pan, S.-Y., Cao, C., R Kanwar, J., Chew, H., & Zhou, S.-F. (2012). Herb-drug interactions and mechanistic and clinical considerations. Current drug metabolism, 13(5), 640-651.
• Chrubasik-Hausmann, S., Vlachojannis, J., & McLachlan, A. J. (2019). Understanding drug interactions with St John's wort (Hypericum perforatum L.): impact of hyperforin content. J Pharm Pharmacol, 71(1), 129-138. doi:10.1111/jphp.12858
• Clewell, A., Barnes, M., Endres, J. R., Ahmed, M., & Ghambeer, D. (2012). Efficacy and tolerability assessment of a topical formulation containing copper sulfate and hypericum perforatum on patients with herpes skin lesions: a comparative, randomized controlled trial. Journal of drugs in dermatology: JDD, 11(2), 209.
• Crupi, R., Abusamra, Y. A., Spina, E., & Calapai, G. (2013). Preclinical data supporting/refuting the use of Hypericum perforatum in the treatment of depression. CNS & Neurological Disorders-Drug Targets (Formerly Current Drug Targets-CNS & Neurological Disorders), 12(4), 474-486.
• Eatemadnia, A., Ansari, S., Abedi, P., & Najar, S. (2019). The effect of Hypericum perforatum on postmenopausal symptoms and depression: A randomized controlled trial. Complementary therapies in medicine, 45, 109-113.
• Ekor, M. (2014). The growing use of herbal medicines: issues relating to adverse reactions and challenges in monitoring safety. Frontiers in pharmacology, 4, 177.
• Ernst, E., Rand, J. I., Barnes, J., & Stevinson, C. (1998). Adverse effects profile of the herbal antidepressant St. John's wort (Hypericum perforatum L.). Eur J Clin Pharmacol, 54(8), 589-594. doi:10.1007/s002280050519
• Fahami, F., Asali, Z., Aslani, A., & Fathizadeh, N. (2010). A comparative study on the effects of Hypericum Perforatum and passion flower on the menopausal symptoms of women referring to Isfahan city health care centers. Iranian journal of nursing and midwifery research, 15(4), 202.
• Final report on the safety assessment of Hypericum perforatum extract and Hypericum perforatum oil. (2001). Int J Toxicol, 20 Suppl 2, 31-39. doi:10.1080/10915810160233749
• Fugh-Berman, A. (2000). Herb-drug interactions. Lancet, 355(9198), 134-138. doi:10.1016/S0140-6736(99)06457-0
• Galeotti, N. (2017). Hypericum perforatum (St John's wort) beyond depression: A therapeutic perspective for pain conditions. Journal of ethnopharmacology, 200, 136-146.
• Galeotti, N., Farzad, M., Bianchi, E., & Ghelardini, C. (2014). PKC-Mediated Potentiation of Morphine Analgesia by St. John’s Wort in Rodents and Humans. Journal of Pharmacological Sciences, 124(4), 409-417. doi:https://doi.org/10.1254/jphs.13226FP
• Galeotti, N., Vivoli, E., Bilia, A. R., Bergonzi, M. C., Bartolini, A., & Ghelardini, C. (2010). A prolonged protein kinase C-mediated, opioid-related antinociceptive effect of St John's Wort in mice. The Journal of Pain, 11(2), 149-159.
• Galeotti, N., Vivoli, E., Bilia, A. R., Vincieri, F. F., & Ghelardini, C. (2010). St. John's Wort reduces neuropathic pain through a hypericin-mediated inhibition of the protein kinase C γ and ɛ activity. Biochemical Pharmacology, 79(9), 1327-1336. doi:https://doi.org/10.1016/j.bcp.2009.12.016
• Gaster, B., & Holroyd, J. (2000). St John's wort for depression: a systematic review. Archives of internal medicine, 160(2), 152-156.
• Greeson, J. M., Sanford, B., & Monti, D. A. (2001). St. John's wort (Hypericum perforatum): a review of the current pharmacological, toxicological, and clinical literature. Psychopharmacology, 153(4), 402-414.
• Hammerness, P., Basch, E., Ulbricht, C., Barrette, E.-P., Foppa, I., Basch, S., . . . Collaboration, N. S. R. (2003). St. John’s wort: a systematic review of adverse effects and drug interactions for the consultation psychiatrist. Psychosomatics, 44(4), 271-282.
• Harrer, G., & Schulz, V. (1994). Clinical investigation of the antidepressant effectiveness of hypericum. J Geriatr Psychiatry Neurol, 7 Suppl 1, S6-8. doi:10.1177/089198879400700103.
• Isacchi, B., Bergonzi, M. C., Carnevali, F., Van der Esch, S., Vincieri, F., & Bilia, A. (2007). Analysis and stability of the constituents of St. John's wort oils prepared with different methods. Journal of pharmaceutical and biomedical analysis, 45(5), 756-761.
• Izzo, A. A., & Ernst, E. (2001). Interactions between herbal medicines and prescribed drugs. Drugs, 61(15), 2163-2175.
• Izzo, A. A., Hoon-Kim, S., Radhakrishnan, R., & Williamson, E. M. (2016). A Critical Approach to Evaluating Clinical Efficacy, Adverse Events and Drug Interactions of Herbal Remedies. Phytother Res, 30(5), 691-700. doi:10.1002/ptr.5591
• Jiang, X., Williams, K. M., Liauw, W. S., Ammit, A. J., Roufogalis, B. D., Duke, C. C., . . . McLachlan, A. J. (2004). Effect of St John's wort and ginseng on the pharmacokinetics and pharmacodynamics of warfarin in healthy subjects. British journal of clinical pharmacology, 57(5), 592-599.
• Kleinert, H., Art, J., & Pautz, A. (2010). Regulation of the expression of inducible nitric oxide synthase. In Nitric Oxide (pp. 211-267): Elsevier.
• Kraus, B., Wolff, H., Elstner, E. F., & Heilmann, J. (2010). Hyperforin is a modulator of inducible nitric oxide synthase and phagocytosis in microglia and macrophages. Naunyn-Schmiedeberg's archives of pharmacology, 381(6), 541-553.
• Kubin, A., Wierrani, F., Burner, U., Alth, G., & Grunberger, W. (2005). Hypericin-the facts about a controversial agent. Current pharmaceutical design, 11(2), 233-253.
• Lenoir, S., Degenring, F., & Sailer, R. (1999). A double-blind randomised trial to investigate three different concentrations of a standardised fresh plant extract obtained from the shoot tips of Hypericum perforatum L. Phytomedicine, 6(3), 141-146.
• Leuner, K., Li, W., Amaral, M. D., Rudolph, S., Calfa, G., Schuwald, A. M., . . . Pozzo‐Miller, L. (2013). Hyperforin modulates dendritic spine morphology in hippocampal pyramidal neurons by activating Ca2+‐permeable TRPC6 channels. Hippocampus, 23(1), 40-52.
• Lomagno, P., & Lomagno, R. (1979). Activity of Hypericum perforatum oil in the treatment of the bed sores in old people. Fitoterapia, 50, 201-205.
• Maisenbacher, P., & Kovar, K.-A. (1992). Analysis and stability of Hyperici oleum. Planta medica, 58(04), 351-354.
• Meinke, M. C., Schanzer, S., Haag, S. F., Casetti, F., Müller, M. L., Wölfle, U., . . . Schempp, C. M. (2012). In vivo photoprotective and anti-inflammatory effect of hyperforin is associated with high antioxidant activity in vitro and ex vivo. European Journal of pharmaceutics and Biopharmaceutics, 81(2), 346-350.
• Melzer, V. M., Frhrken, D., & Kolkmann, R. (1998). Hyperforin im Johanniskraut. Deutsche Apotheker Zeitung, 138(49), 56-62. Retrieved from https://www.scopus.com/inward/record.uri?eid=2-s2.0-0032481095&partnerID=40&md5=e3f3c128ceec83f7d12e9660ac40350a
• Miclescu, A., & Gordh, T. (2009). Nitric oxide and pain:‘Something old, something new’. Acta Anaesthesiologica Scandinavica, 53(9), 1107-1120.
• Mohanasundari, M., Srinivasan, M., Sethupathy, S., & Sabesan, M. (2006). Enhanced neuroprotective effect by combination of bromocriptine and Hypericum perforatum extract against MPTP-induced neurotoxicity in mice. Journal of the neurological sciences, 249(2), 140-144.
• Mueller, S. C., Uehleke, B., Woehling, H., Petzsch, M., Majcher-Peszynska, J., Hehl, E. M., . . . Drewelow, B. (2004). Effect of St John's wort dose and preparations on the pharmacokinetics of digoxin. Clin Pharmacol Ther, 75(6), 546-557. doi:10.1016/j.clpt.2004.01.014
• Müller, W. E. (2005). St. John's Wort and its active principles in depression and anxiety: Springer Science & Business Media. Nahrstedt, A., & Butterweck, V. (1997). Biologically active and other chemical constituents of the herb of Hypericum perforatum L. Pharmacopsychiatry, 30(S 2), 129-134.
• Najafizadeh, P., Hashemian, F., Mansouri, P., Farshi, S., Surmaghi, M. S., & Chalangari, R. (2012). The evaluation of the clinical effect of topical St Johns wort (Hypericum perforatum L.) in plaque type psoriasis vulgaris: a pilot study. Australasian journal of dermatology, 53(2), 131-135.
• Nathan, P. J. (2001). Hypericum perforatum (St John's Wort): a non-selective reuptake inhibitor? A review of the recent advances in its pharmacology. Journal of Psychopharmacology, 15(1), 47-54.
• Oliveira, A. I., Pinho, C., Sarmento, B., & Dias, A. C. (2016). Neuroprotective activity of Hypericum perforatum and its major components. Frontiers in plant science, 7, 1004.
• Özbek, M. U., Koc, M., & Hamzaoğlu, E. (2019). Contributions to the Hypericum L. section Oligostema (Boiss.) Stef.(Hypericaceae), and Hypericum turcicum sp. nov. as a new species from Turkey. Turkish Journal of Botany, 43(5), 694-702.
• Philipp, M., Linde, K., Kohnen, R., Hiller, K.-O., & Berner, M. (1999). Hypericum extract versus imipramine or placebo in patients with moderate depression: randomised multicentre study of treatment for eight weeksCommentary: Has hypericum found its place in antidepressant treatment? BMJ, 319(7224), 1534-1539.
• Prenner, L., Sieben, A., Zeller, K., Weiser, D., & Häberlein, H. (2007). Reduction of high-affinity β2-adrenergic receptor binding by hyperforin and hyperoside on rat C6 glioblastoma cells measured by fluorescence correlation spectroscopy. Biochemistry, 46(17), 5106-5113.
• Saddiqe, Z., Naeem, I., & Maimoona, A. (2010). A review of the antibacterial activity of Hypericum perforatum L. Journal of ethnopharmacology, 131(3), 511-521.
• Saljic, J. (1975). Ointment for the treatment of burns. Ger. Offen, 2, 21.
• Samadi, S., Khadivzadeh, T., Emami, A., Moosavi, N. S., Tafaghodi, M., & Behnam, H. R. (2010). The effect of Hypericum perforatum on the wound healing and scar of cesarean. The Journal of Alternative and Complementary Medicine, 16(1), 113-117.
• Santos, M., Ferreira, F., Faro, C., Pires, E., & Carvalho, A. (1994). The amount of GABA present in aqueous extracts of valerian is sufficient to account for [3H] GABA release in synaptosomes. Planta medica, 60(5), 475-476.
• Sarrell, E. M., Mandelberg, A., & Cohen, H. A. (2001). Efficacy of Naturopathic Extracts in the Management of Ear Pain Associated With Acute Otitis Media. Archives of Pediatrics & Adolescent Medicine, 155(7), 796-799. doi:10.1001/archpedi.155.7.796
• Schmidt, A. H. (2003). Use of an on-line, precolumn photochemical reactor in high-performance liquid chromatography of naphthodianthrones in Hypericum perforatum preparations. Journal of Chromatography A, 987(1-2), 181-187.
• Shakya, P., Marslin, G., Siram, K., Beerhues, L., & Franklin, G. (2019). Elicitation as a tool to improve the profiles of high‐value secondary metabolites and pharmacological properties of Hypericum perforatum. Journal of Pharmacy and Pharmacology, 71(1), 70-82.
• Sindrup, S. H., Madsen, C., Bach, F. W., Gram, L. F., & Jensen, T. S. (2001). St. John's wort has no effect on pain in polyneuropathy. Pain, 91(3), 361-365.
• Sugimoto, K., Ohmori, M., Tsuruoka, S., Nishiki, K., Kawaguchi, A., Harada, K., . . . Fujimura, A. (2001). Different effects of St John's wort on the pharmacokinetics of simvastatin and pravastatin. Clin Pharmacol Ther, 70(6), 518-524. doi:10.1067/mcp.2001.120025
• Suzuki, O., Katsumata, Y., Oya, M., Bladt, S., & Wagner, H. (1984). Inhibition of monoamine oxidase by hypercin. Planta medica, 50(03), 272-274.
• Suzuki, O., Katsumata, Y., Oya, M., Chari, V., Vermes, B., Wagner, H., & Hostettmann, K. (1981). Inhibition of type A and type B monoamine oxidases by naturally occurring xanthones. Planta medica, 42(05), 17-21.
• Tedeschi, E., Menegazzi, M., Margotto, D., Suzuki, H., Förstermann, U., & Kleinert, H. (2003). Anti-inflammatory actions of St. John's wort: inhibition of human inducible nitric-oxide synthase expression by down-regulating signal transducer and activator of transcription-1α (STAT-1α) activation. Journal of pharmacology and experimental therapeutics, 307(1), 254-261.
• Uchida, S., Hirai, K., Hatanaka, J., Hanato, J., Umegaki, K., & Yamada, S. (2008). Antinociceptive Effects of St. John's Wort, <i>Harpagophytum Procumbens</i> Extract and Grape Seed Proanthocyanidins Extract in Mice. Biological and Pharmaceutical Bulletin, 31(2), 240-245. doi:10.1248/bpb.31.240
• Wang, L. S., Zhu, B., El‐Aty, A. A., Zhou, G., Li, Z., Wu, J., . . . An, W. (2004). The influence of St. John's wort on CYP2C19 activity with respect to genotype. The Journal of Clinical Pharmacology, 44(6), 577-581.
• Whitten, D. L., Myers, S. P., Hawrelak, J. A., & Wohlmuth, H. (2006). The effect of St John's wort extracts on CYP3A: a systematic review of prospective clinical trials. Br J Clin Pharmacol, 62(5), 512-526. doi:10.1111/j.1365-2125.2006.02755.x
• Wolfle, U., Seelinger, G., & Schempp, C. M. (2014). Topical application of St. John's wort (Hypericum perforatum). Planta Med, 80(2-3), 109-120. doi:10.1055/s-0033-1351019
• Yue, Q.-Y., Bergquist, C., & Gerdén, B. (2000). Safety of St John's wort (Hypericum perforatum). The Lancet, 355(9203), 576-577.
• Zhou, S., Chan, E., Pan, S. Q., Huang, M., & Lee, E. J. (2004). Pharmacokinetic interactions of drugs with St John's wort. J Psychopharmacol, 18(2), 262-276. doi:10.1177/0269881104042632
• Zhou, S. F., & Lai, X. (2008). An update on clinical drug interactions with the herbal antidepressant St. John's wort. Curr Drug Metab, 9(5), 394-409. doi:10.2174/138920008784746391