| [1] |
Crockett SL, Robson NK. 2011. Taxonomy and chemotaxonomy of the genus Hypericum. Medicinal and Aromatic Plant Science and Biotechnology 5:1−13 |
| [2] |
Robson NKB. 2003. Hypericum botany. In Hypericum: the genus Hypericum, ed. Ernst E. London: Taylor & Francis. pp. 1–22. (Medicinal and aromatic plants - industrial profiles). www.crcpress.com/product/isbn/9780415369541 |
| [3] |
Menković N, Šavikin K, Tasić S, Zdunić G, Stešević D, et al. 2011. Ethnobotanical study on traditional uses of wild medicinal plants in Prokletije Mountains (Montenegro). Journal of Ethnopharmacology 133(1):97−107 doi: 10.1016/j.jep.2010.09.008 |
| [4] |
Mustafa B, Hajdari A, Krasniqi F, Hoxha E, Ademi H, et al. 2012. Medical ethnobotany of the Albanian Alps in Kosovo. Journal of Ethnobiology Ethnomedicine 8:6 doi: 10.1186/1746-4269-8-6 |
| [5] |
Agostinis P, Vantieghem A, Merlevede W, De Witte PAM. 2002. Hypericin in cancer treatment: more light on the way. The International Journal of Biochemistry & Cell Biology 34(3):221−41 doi: 10.1016/s1357-2725(01)00126-1 |
| [6] |
Dong X, Zeng Y, Zhang Z, Fu J, You L, et al. 2021. Hypericin-mediated photodynamic therapy for the treatment of cancer: a review. Journal of Pharmacy and Pharmacology 73(4):425−36 doi: 10.1093/jpp/rgaa018 |
| [7] |
Karioti A, Bilia AR. 2010. Hypericins as Potential Leads for New Therapeutics. International Journal of Molecular Sciences 11(2):562−94 doi: 10.3390/ijms11020562 |
| [8] |
Kasper S, Caraci F, Forti B, Drago F, Aguglia E. 2010. Efficacy and tolerability of Hypericum extract for the treatment of mild to moderate depression. European Neuropsychopharmacology 20(11):747−65 doi: 10.1016/j.euroneuro.2010.07.005 |
| [9] |
Whiskey E, Werneke U, Taylor D. 2001. A systematic review and meta-analysis of Hypericum perforatum in depression: a comprehensive clinical review. International Clinical Psychopharmacology 16(5):239−52 doi: 10.1097/00004850-200109000-00001 |
| [10] |
Hanlidou E, Karousou R, Kleftoyanni V, Kokkini S. 2004. The herbal market of Thessaloniki (N Greece) and its relation to the ethnobotanical tradition. Journal of Ethnopharmacology 91(2):281−99 doi: 10.1016/j.jep.2004.01.007 |
| [11] |
Jarić S, Popović Z, Mačukanović-Jocić M, Djurdjević L, Mijatović M, et al. 2007. An ethnobotanical study on the usage of wild medicinal herbs from Kopaonik Mountain (Central Serbia). Journal of Ethnopharmacology 111(1):160−75 doi: 10.1016/j.jep.2006.11.007 |
| [12] |
Pieroni A, Quave CL, Santoro RF. 2004. Folk pharmaceutical knowledge in the territory of the Dolomiti Lucane, inland southern Italy. Journal of Ethnopharmacology 95(2):373−84 doi: 10.1016/j.jep.2004.08.012 |
| [13] |
Smith T, Resetar H, Morton C. 2022. US Sales of Herbal Supplements Increase by 9.7% in 2021. HerbalGram 136 |
| [14] |
Hölzl J, Petersen M. 2003. Chemical constituents of Hypericum ssp. In Hypericum: the genus Hypericum. Ed. Ernst E. London: Taylor & Francis. pp. 77–90. (Medicinal and aromatic plants - industrial profiles). www.crcpress.com/product/isbn/9780415369541 |
| [15] |
Kitanov GM. 2001. Hypericin and pseudohypericin in some Hypericum species. Biochemical Systematics and Ecology 29(2):171−78 doi: 10.1016/S0305-1978(00)00032-6 |
| [16] |
Kimáková K, Kimáková A, Idkowiak J, Stobiecki M, Rodziewicz P, et al. 2018. Phenotyping the genus Hypericum by secondary metabolite profiling: emodin vs. skyrin, two possible key intermediates in hypericin biosynthesis. Analytical and Bioanalytical Chemistry 410(29):7689−99 doi: 10.1007/s00216-018-1384-0 |
| [17] |
Rizzo P, Altschmied L, Stark P, Rutten T, Gündel A, et al. 2019. Discovery of key regulators of dark gland development and hypericin biosynthesis in St. John's Wort (Hypericum perforatum). Plant Biotechnology Journal 17(12):2299−312 doi: 10.1111/pbi.13141 |
| [18] |
Crockett SL, Poller B, Tabanca N, Pferschy-Wenzig EM, Kunert O, et al. 2011. Bioactive xanthones from the roots of Hypericum perforatum (common St John's wort). Journal of the Science of Food and Agriculture 91(3):428−34 doi: 10.1002/jsfa.4202 |
| [19] |
Butterweck V. 2003. Mechanism of action of St John's wort in depression: what is known? CNS Drugs 17:539−62 doi: 10.2165/00023210-200317080-00001 |
| [20] |
Müller WE, Singer A, Wonnemann M. 2001. Hyperforin - antidepressant activity by a novel mechanism of action. Pharmacopsychiatry 34:S98−S102 doi: 10.1055/s-2001-15512 |
| [21] |
Li Y N, Zeng Y R, Yang J, He W, Chen J, et al. 2022. Chemical constituents from the flowers of Hypericum monogynum L. with COX-2 inhibitory activity. Phytochemistry 193:112970 doi: 10.1016/j.phytochem.2021.112970 |
| [22] |
Mohamed FF, Anhlan D, Schöfbänker M, Schreiber A, Classen N, et al. 2022. Hypericum perforatum and its ingredients hypericin and pseudohypericin demonstrate an antiviral activity against SARS-CoV-2. Pharmaceuticals 15(5):530 doi: 10.3390/ph15050530 |
| [23] |
Cao K, Zhang Y, Yao Q, Peng Y, Pan Q, et al. 2022. Hypericin blocks the function of HSV-1 alkaline nuclease and suppresses viral replication. Journal of Ethnopharmacology 296:115524 doi: 10.1016/j.jep.2022.115524 |
| [24] |
Schempp CM, Pelz K, Wittmer A, Schöpf E, Simon JC, et al. 1999. Antibacterial activity of hyperforin from St John's wort, against multiresistant Staphylococcus aureus and gram-positive bacteria. The Lancet 353(9170):2129 doi: 10.1016/S0140-6736(99)00214-7 |
| [25] |
Oliveira AI, Pinho C, Sarmento B, Dias ACP. 2016. Neuroprotective activity of Hypericum perforatum and its major components. Frontiers in Plant Science 7:1004 doi: 10.3389/fpls.2016.01004 |
| [26] |
Süntar IP, Akkol EK, Yilmazer D, Baykal T, Kirmizibekmez H, et al. 2010. Investigations on the in vivo wound healing potential of Hypericum perforatum L. Journal of ethnopharmacology 127(2):468−77 doi: 10.1016/j.jep.2009.10.011 |
| [27] |
Russo E, Scicchitano F, Whalley B J, Mazzitello C, Ciriaco M et al. 2014. Hypericum perforatum: pharmacokinetic, mechanism of action, tolerability, and clinical drug–drug interactions. Phytotherapy research 28(5):643−55 doi: 10.1002/ptr.5050 |
| [28] |
Curtis JD, Lersten NR. 1990. Internal secretory structures in Hypericum (Clusiaceae): H. perforatum L. and H. balearicum L. New Phytologist 114(4):571−80 doi: 10.1111/j.1469-8137.1990.tb00427.x |
| [29] |
Zobayed SMA, Afreen F, Goto E, Kozai T. 2006. Plant–environment interactions: accumulation of hypericin in dark glands of Hypericum perforatum. Annals of Botany 98(4):793−804 doi: 10.1093/aob/mcl169 |
| [30] |
Peng Z, Lu J, Liu K, Xie L, Wang Y, et al. 2023. Hypericin as a promising natural bioactive naphthodianthrone: A review of its pharmacology, pharmacokinetics, toxicity, and safety. Phytotherapy Research 37(12):5639−56 doi: 10.1002/ptr.8011 |
| [31] |
Choudhary N, Collignon TE, Tewari D, Bishayee A. 2022. Hypericin and its anticancer effects: From mechanism of action to potential therapeutic application. Phytomedicine 105:154356 doi: 10.1016/j.phymed.2022.154356 |
| [32] |
Zhang M, Wang Y, Qian F, Li P, Xu X. 2016. Hypericin inhibits oligomeric amyloid β42-induced inflammation response in microglia and ameliorates cognitive deficits in an amyloid β injection mouse model of Alzheimer's disease by suppressing MKL1. Biochemical and Biophysical Research Communications 481(1−2):71−76 doi: 10.1016/j.bbrc.2016.11.016 |
| [33] |
Mazur Y, Bock H. 1992. U.S. Preparation of Hypericin. Patent No. 5, 120, 412 |
| [34] |
Karppinen K, Hokkanen J, Mattila S, Neubauer P, Hohtola A. 2008. Octaketide-producing type III polyketide synthase from Hypericum perforatum is expressed in dark glands accumulating hypericins. The FEBS Journal 275(17):4329−42 doi: 10.1111/j.1742-4658.2008.06576.x |
| [35] |
Soták M, Czeranková O, Klein D, Jurčacková Z, Li L et al. 2016. Comparative transcriptome reconstruction of four Hypericum species focused on hypericin biosynthesis. Frontiers in Plant Science 7:1039 doi: 10.3389/fpls.2016.01039 |
| [36] |
Bais HP, Vepachedu R, Lawrence CB, Stermitz FR, Vivanco JM. 2003. Molecular and biochemical characterization of an enzyme responsible for the formation of hypericin in St. John's Wort (Hypericum perforatum L.). Journal of Biological Chemistry 278(34):32413−22 doi: 10.1074/jbc.M301681200 |
| [37] |
Wu S, Malaco Morotti AL, Wang S, Wang Y, Xu X, et al. 2022. Convergent gene clusters underpin hyperforin biosynthesis in St John's wort. New Phytologist 235(2):646−61 doi: 10.1111/nph.18138 |
| [38] |
Wu S, Morotti ALM, Yang J, Wang E, Tatsis EC. 2024. Single-cell RNA sequencing facilitates the elucidation of the complete biosynthesis of the antidepressant hyperforin in St. John's wort. Molecular Plant 17(9):1439−57 doi: 10.1016/j.molp.2024.08.003 |
| [39] |
Karppinen K, Hohtola A. 2008. Molecular cloning and tissue-specific expression of two cDNAs encoding polyketide synthases from Hypericum perforatum. Journal of Plant Physiology 165(10):1079−86 doi: 10.1016/j.jplph.2007.04.008 |
| [40] |
Košuth J, Katkovčinová Z, Olexová P, Čellárová E. 2007. Expression of the hyp-1 gene in early stages of development of Hypericum perforatum L. Plant Cell Reports 26(2):211−17 doi: 10.1007/s00299-006-0240-4 |
| [41] |
Košuth J, Smelcerovic A, Borsch T, Zuehlke S, Karppinen K, et al. 2010. The hyp-1 gene is not a limiting factor for hypericin biosynthesis in the genus Hypericum. Functional Plant Biology 38(1):35 doi: 10.1071/FP10144 |
| [42] |
Košuth J., Hrehorová D., Jaskolski M., & Čellárová E. 2013. Stress-induced expression and structure of the putative gene hyp-1 for hypericin biosynthesis. Plant Cell, Tissue and Organ Culture 114:207−16 doi: 10.1007/s11240-013-0316-0 |
| [43] |
Zhou W, Wang Y, Li B, Petijová L, Hu S, et al. 2021. Whole-genome sequence data of Hypericum perforatum and functional characterization of melatonin biosynthesis by N-acetylserotonin O-methyltransferase. Journal of Pineal Research 70(2):e12709 doi: 10.1111/jpi.12709 |
| [44] |
Yao Y, Kang T, Jin L, Liu Z, Zhang Z, et al. 2019. Temperature-dependent growth and hypericin biosynthesis in Hypericum perforatum. Plant Physiology and Biochemistry 139:613−19 doi: 10.1016/j.plaphy.2019.04.012 |
| [45] |
Su H, Jin L, Li M, Paré PW. 2022. Low temperature modifies seedling leaf anatomy and gene expression in Hypericum perforatum. Frontiers in Plant Science 13:1020857 doi: 10.3389/fpls.2022.1020857 |
| [46] |
Tavakoli F, Rafieiolhossaini M, Ravash R, Ebrahimi M. 2020. UV-B radiation and low temperature promoted hypericin biosynthesis in adventitious root culture of Hypericum perforatum. Plant Signaling & Behavior 15(7):1764184 doi: 10.1080/15592324.2020.1764184 |
| [47] |
Liu XN, Zhang XQ, Sun JS. 2007. Effects of cytokinins and elicitors on the production of hypericins and hyperforin metabolites in Hypericum sampsonii and Hypericum perforatum. Plant Growth Regulation 53:207−14 doi: 10.1007/s10725-007-9220-0 |
| [48] |
Walker T S, Bais H P, Vivanco J M. 2002. Jasmonic acid-induced hypericin production in cell suspension cultures of Hypericum perforatum L. (St. John's wort). Phytochemistry 60(3):289−93 doi: 10.1016/S0031-9422(02)00074-2 |
| [49] |
Noormohammadi N, Ismaili A, Sobhani Najafabadi A, Nazarian-Firouzabadi F. 2023. Transcriptional responses of hypericin and hyperforin to methyl jasmonate elicitation in Hypericum perforatum. Plant Biotechnology Reports 17(2):229−41 doi: 10.1007/s11816-022-00794-6 |
| [50] |
Ohmori S, Kimizu M, Sugita M, Miyao A, Hirochika H, et al. 2009. MOSAIC FLORAL ORGANS1, an AGL6-like MADS box gene, regulates floral organ identity and meristem fate in rice. The Plant Cell 21(10):3008−25 doi: 10.1105/tpc.109.068742 |
| [51] |
Stracke R, Werber M, Weisshaar B. 2001. The R2R3-MYB gene family in Arabidopsis thaliana. Current Opinion in Plant Biology 4(5):447−56 doi: 10.1016/S1369-5266(00)00199-0 |
| [52] |
Beerhues L. 2006. Hyperforin. Phytochemistry 67(20):2201−7 doi: 10.1016/j.phytochem.2006.08.017 |
| [53] |
Smelcerovic A, Verma V, Spiteller M, Ahmad SM, Puri SC, et al. 2006. Phytochemical analysis and genetic characterization of six Hypericum species from Serbia. Phytochemistry 67(2):171−77 doi: 10.1016/j.phytochem.2005.10.021 |
| [54] |
Gronquist M, Bezzerides A, Attygalle A, Meinwald J, Eisner M, et al. 2001. Attractive and defensive functions of the ultraviolet pigments of a flower (Hypericum calycinum). Proceedings of the National Academy of Sciences of the United States of America 98(24):13745−50 doi: 10.1073/pnas.231471698 |
| [55] |
Adam P, Arigoni D, Bacher A, Eisenreich W. 2002. Biosynthesis of Hyperforin in Hypericum perforatum. Journal of Medicinal Chemistry 45(21):4786−93 doi: 10.1021/jm0209782 |
| [56] |
Ciccarelli D, Andreucci AC, Pagni AM. 2001. Translucent glands and secretory canals in Hypericum perforatum L. (Hypericaceae): morphological, anatomical and histochemical studies during the course of ontogenesis. Annals of Botany 88(4):637−44 doi: 10.1006/anbo.2001.1514 |
| [57] |
Singer A, Wonnemann M, Müller WE. 1999. Hyperforin, a Major Antidepressant Constituent of St. John's Wort, Inhibits Serotonin Uptake by Elevating Free Intracellular Na+1 1. Journal of Pharmacology and Experimental Therapeutics 290(3):1363−68 |
| [58] |
Treiber K, Singer A, Henke B, Müller WE. 2005. Hyperforin activates nonselective cation channels (NSCCs). British Journal of Pharmacology 145(1):75−83 doi: 10.1038/sj.bjp.0706155 |
| [59] |
Schempp CM, Kirkin V, Simon-Haarhaus B, Kersten A, Kiss J, et al. 2002. Inhibition of tumour cell growth by hyperforin, a novel anticancer drug from St. John's wort that acts by induction of apoptosis. Oncogene 21(8):1242−50 doi: 10.1038/sj.onc.1205190 |
| [60] |
Klingauf P, Beuerle T, Mellenthin A, El-Moghazy SAM, Boubakir Z, et al. 2005. Biosynthesis of the hyperforin skeleton in Hypericum calycinum cell cultures. Phytochemistry 66(2):139−45 doi: 10.1016/j.phytochem.2004.11.003 |
| [61] |
Jepson C, Karppinen K, Daku RM, Sterenberg BT, Suh D. 2014. Hypericum perforatum hydroxyalkylpyrone synthase involved in sporopollenin biosynthesis – phylogeny, site-directed mutagenesis, and expression in nonanther tissues. The FEBS Journal 281(17):3855−68 doi: 10.1111/febs.12920 |
| [62] |
Boubakir Z, Beuerle T, Liu B, Beerhues L. 2005. The first prenylation step in hyperforin biosynthesis. Phytochemistry 66(1):51−57 doi: 10.1016/j.phytochem.2004.10.020 |
| [63] |
Sayed HMB, Nassar S, Kaufholdt D, Beerhues L, Liu B, et al. 2023. Biosynthesis of polyprenylated xanthones in Hypericum perforatum roots involves 4-prenyltransferase. Plant Physiology 192(4):2971−88 doi: 10.1093/plphys/kiad219 |
| [64] |
Ruan J, Zheng C, Liu Y, Qu L, Yu H, et al. 2017. Chemical and Biological Research on Herbal Medicines Rich in Xanthones. Molecules 22(10):1698 doi: 10.3390/molecules22101698 |
| [65] |
Liu B, Falkenstein-Paul H, Schmidt W, Beerhues L. 2003. Benzophenone synthase and chalcone synthase from Hypericum androsaemum cell cultures: cDNA cloning, functional expression, and site-directed mutagenesis of two polyketide synthases. The Plant Journal 34(6):847−55 doi: 10.1046/j.1365-313X.2003.01771.x |
| [66] |
El-awaad I, Bocola M, Beuerle T, Liu B, Beerhues L. 2016. Bifunctional CYP81AA proteins catalyse identical hydroxylations but alternative regioselective phenol couplings in plant xanthone biosynthesis. Nature Communications 7:11472 doi: 10.1038/ncomms11472 |
| [67] |
Schmidt W, Peters S, Beerhues L. 2000. Xanthone 6-hydroxylase from cell cultures of Centaurium erythraea RAFN and Hypericum androsaemum L. Phytochemistry 53(4):427−31 doi: 10.1016/S0031-9422(99)00566-X |
| [68] |
Winkel-Shirley B. 2001. Flavonoid biosynthesis. a colorful model for genetics, biochemistry, cell biology, and biotechnology. Plant Physiology 126(2):485−93 doi: 10.1104/pp.126.2.485 |
| [69] |
Butterweck V, Jürgenliemk G, Nahrstedt A, Winterhoff H. 2000. Flavonoids from Hypericum perforatum show antidepressant activity in the forced swimming test. Planta Medica 66(1):3−6 doi: 10.1055/s-2000-11119 |
| [70] |
Butterweck V, Hegger M, Winterhoff H. 2004. Flavonoids of St. John's Wort reduce HPA axis function in the rat. Planta Medica 70:1008−11 doi: 10.1055/s-2004-832631 |
| [71] |
Liu W, Feng Y, Yu S, Fan Z, Li X, et al. 2021. The Flavonoid biosynthesis network in plants. International Journal of Molecular Sciences 22(23):12824 doi: 10.3390/ijms222312824 |
| [72] |
Wang Y, Cui Z, Li Q, Zhang S, Li Y, et al. 2023. The parallel biosynthesis routes of hyperoside from naringenin in Hypericum monogynum. Horticulture Research 10(9):uhad166 doi: 10.1093/hr/uhad166 |
| [73] |
Crockett SL. 2010. Essential oil and volatile components of the genus Hypericum (Hypericaceae). Natural Product Communications 5(9):1493−506 |
| [74] |
Grafakou ME, Barda C, Karikas GA, Skaltsa H. 2022. Hypericum essential oils—composition and bioactivities: an update (2012–2022). Molecules 27(16):5246 doi: 10.3390/molecules27165246 |
| [75] |
Grafakou ME, Diamanti A, Simirioti E, Terezaki A, Barda C, et al. 2021. Wound healing effects from 3 Hypericum spp. essential oils. Planta Medica International Open 8:e69−77 doi: 10.1055/a-1492-3634 |