Skip to content
2000
Volume 25, Issue 21
  • ISSN: 1568-0266
  • E-ISSN: 1873-4294

Abstract

Background

This review is delving into determining the content and significance of hypericin, a pharmacologically important constituent commonly known as St. John's Wort (SJW). The paper explores the rich history of Hypericin's traditional use in alternative medicine and the recent surge in scientific interest surrounding its bioactive properties.

Objective

This review aims to provide a comprehensive analysis the therapeutic potentials of hypericin, focusing on its chemistry, extraction, sources, stability, pharmacokinetics, safety profile, and multifunctional applications in drug and medicinal fields as well as advancements in Bioengineering Approaches for Enhanced Hypericin Delivery.

Methods

We performed a non-systematic search of journals. Literature using computerized methods was conducted, utilizing databases such as Medline (PubMed), ChemSciFinder, China National Knowledge Infrastructure (CNKI) and Scirus Library. To effectively identify the most important and relevant research articles, scientific studies, clinical studies and review articles on hypericin were searched using different keywords: “Hypericum”, “traditional use”, “phytochemistry”, “pharmacology”, “drug delivery” and “bioactivity”. Thus, articles available from 1984 to 2024 were analyzed and collected. The selection process for the review primarily considered the originality of the paper and its clinical applications.

Results

Although hypericin is not a novel compound within the research community, it is gaining renewed recognition and showing great effectiveness as a promising agent in the field of medical diagnostics and has promising applications as a therapeutic.

Conclusion

Here, our current comprehensive review of hypericin, its potential and its activities is intended to contribute to this ongoing process actively. Overall, this review provided theoretical direction for future hypericin research. Future studies should, therefore, focus further on the pharmacological processes, pharmacokinetics, and chemistry of hypericin and hypericin-based drug delivery systems. This comprehensive review of hypericin aims to actively contribute to ongoing research and provide a theoretical direction for future studies.

Loading

Article metrics loading...

/content/journals/ctmc/10.2174/0115680266330142250224101958
2025-02-27
2025-11-09
Loading full text...

Full text loading...

References

  1. RadusieneJ. StaniusZ. CirakC. OdabasM.S. Quantitative effects of temperature and light intensity on accumulation of] bioactive compounds in St. John’s worth.Acta Hortic.201092513514010.17660/ActaHortic.2011.925.18
    [Google Scholar]
  2. ZhangJ. GaoL. HuJ. WangC. HagedoornP.L. LiN. ZhouX. Hypericin: source, determination, separation, and properties.Separ. Purif. Rev.202251111010.1080/15422119.2020.1797792
    [Google Scholar]
  3. Davatgaran TaghipourY. HajialyaniM. NaseriR. HesariM. MohammadiP. StefanucciA. MollicaA. FarzaeiM.H. AbdollahiM. Nanoformulations of natural products for management of metabolic syndrome.Int. J. Nanomedicine2019145303532110.2147/IJN.S213831 31406461
    [Google Scholar]
  4. ÇlrakC. RadušieneJ. JanulisV. IvanauskasL. ArslanB. Chemical constituents of some Hypericum species growing in Turkey.J. Plant Biol.200750663263510.1007/BF03030606
    [Google Scholar]
  5. OnoueS. SetoY. OchiM. InoueR. ItoH. HatanoT. YamadaS. In vitro photochemical and phototoxicological characterization of major constituents in St. John’s Wort (Hypericum perforatum) extracts.Phytochemistry20117214-151814182010.1016/j.phytochem.2011.06.011 21782201
    [Google Scholar]
  6. TawahaK. GharaibehM. El-ElimatT. AlaliF.Q. Determination of hypericin and hyperforin content in selected Jordanian Hypericum species.Ind. Crops Prod.201032324124510.1016/j.indcrop.2010.04.017
    [Google Scholar]
  7. PenjweiniR. LoewH.G. EisenbauerM. KratkyK.W. Modifying excitation light dose of novel photosensitizer PVP-Hypericin for photodynamic diagnosis and therapy.J. Photochem. Photobiol. B201312012012910.1016/j.jphotobiol.2012.12.013 23375215
    [Google Scholar]
  8. SkalkosD. GiotiE. StalikasC.D. MeyerH. PapazoglouT.G. FilippidisG. Photophysical properties of Hypericum perforatum L. extracts – Novel photosensitizers for PDT.J. Photochem. Photobiol. B200682214615110.1016/j.jphotobiol.2005.11.001 16388961
    [Google Scholar]
  9. WynnJ.L. CottonT.M. Spectroscopic properties of hypericin in solution and at surfaces.J. Phys. Chem.199599124317432310.1021/j100012a063
    [Google Scholar]
  10. GaleottiN. Hypericum perforatum (St John’s wort) beyond depression: A therapeutic perspective for pain conditions.J. Ethnopharmacol.201720013614610.1016/j.jep.2017.02.016 28216196
    [Google Scholar]
  11. ZhangR. JiY. ZhangX. KennellyE.J. LongC. Ethnopharmacology of Hypericum species in China: A comprehensive review on ethnobotany, phytochemistry and pharmacology.J. Ethnopharmacol.202025411268610.1016/j.jep.2020.112686 32101776
    [Google Scholar]
  12. YadavN. DeshmukhR. MajumderR. A Comprehensive Review on the Use of Traditional Chinese Medicine for Cancer Treatment. Pharmacological Research -.Zhongguo Xiandai Zhongyao2024100423
    [Google Scholar]
  13. BarnesJ. AndersonL.A. PhillipsonJ.D. St John’s wort ( Hypericum perforatum L.): a review of its chemistry, pharmacology and clinical properties.J. Pharm. Pharmacol.200153558360010.1211/0022357011775910 11370698
    [Google Scholar]
  14. RuJ. LiP. WangJ. ZhouW. LiB. HuangC. LiP. GuoZ. TaoW. YangY. XuX. LiY. WangY. YangL. TCMSP: a database of systems pharmacology for drug discovery from herbal medicines.J. Cheminform.2014611310.1186/1758‑2946‑6‑13 24735618
    [Google Scholar]
  15. ČernýC. Über das Hypericin (Hypericumrot). Mit zwei Abbildungen im Text.Hoppe Seylers Z. Physiol. Chem.191173537138210.1515/bchm2.1911.73.5.371
    [Google Scholar]
  16. BrockmannH. KlugeF. MuxfeldtH. Totalsynthese des Hypericins.Chem. Ber.195790102302231810.1002/cber.19570901027
    [Google Scholar]
  17. IonV. IelciuI. CârjeA.G. MunteanD.L. CrişanG. PăltineanR. Hypericum spp.—An Overview of the Extraction Methods and Analysis of Compounds.Separations2022911710.3390/separations9010017
    [Google Scholar]
  18. DravesA.H. WalkerS.E. Determination of hypericin and pseudohypericin in pharmaceutical preparations by liquid chromatography with fluorescence detection.J. Chromatogr., Biomed. Appl.20007491576610.1016/S0378‑4347(00)00383‑2 11129079
    [Google Scholar]
  19. LiuF. PanC. DrummP. AngC.Y.W. Liquid chromatography–mass spectrometry studies of St. John’s wort methanol extraction: active constituents and their transformation.J. Pharm. Biomed. Anal.200537230331210.1016/j.jpba.2004.10.034 15708671
    [Google Scholar]
  20. WilliamsF.B. SanderL.C. WiseS.A. GirardJ. Development and evaluation of methods for determination of naphthodianthrones and flavonoids in St. John’s wort.J. Chromatogr. A200611151-29310210.1016/j.chroma.2006.02.078 16554056
    [Google Scholar]
  21. SmelcerovicA. SpitellerM. ZuehlkeS. Comparison of methods for the exhaustive extraction of hypericins, flavonoids, and hyperforin from Hypericum perforatum L.J. Agric. Food Chem.20065472750275310.1021/jf0527246 16569071
    [Google Scholar]
  22. BenthinB. DanzH. HamburgerM. Pressurized liquid extraction of medicinal plants.J. Chromatogr. A19998371-221121910.1016/S0021‑9673(99)00071‑0 10227181
    [Google Scholar]
  23. CatchpoleO.J. PerryN.B. da SilvaB.M.T. GreyJ.B. SmallfieldB.M. Supercritical extraction of herbs I: Saw Palmetto, St John’s Wort, Kava Root, and Echinacea.J. Supercrit. Fluids200222212913810.1016/S0896‑8446(01)00110‑3
    [Google Scholar]
  24. RamezaniZ. ZamaniM. A simple method for extraction and purification of hypericins from St John’s wort.Jundishapur J. Nat. Pharm. Prod.201712110.5812/jjnpp.13864
    [Google Scholar]
  25. WirzA. Analytical and phytochemical investigations on hypericin and related compounds of Hypericum perforatum.SwitzerlandETH Zurich2000
    [Google Scholar]
  26. KariotiA. VincieriF.F. BiliaA.R. Rapid and efficient purification of naphthodianthrones from St. John’s wort extract by using liquid–liquid extraction and SEC.J. Sep. Sci.20093291374138210.1002/jssc.200800700 19360729
    [Google Scholar]
  27. VandenbogaerdeA.L. KamuhabwaA. DelaeyE. HimpensB.E. MerlevedeW.J. de WitteP.A. Photocytotoxic effect of pseudohypericin versus hypericin.J. Photochem. Photobiol. B1998452-3879410.1016/S1011‑1344(98)00163‑8 9868799
    [Google Scholar]
  28. SantarémE.R. AstaritaL.V. Multiple shoot formation in Hypericum perforatum L.and hypericin production.Braz. J. Plant Physiol.2003151434710.1590/S1677‑04202003000100006
    [Google Scholar]
  29. KariotiA. BiliaA.R. Hypericins as potential leads for new therapeutics.Int. J. Mol. Sci.201011256259410.3390/ijms11020562 20386655
    [Google Scholar]
  30. ZubekS. MielcarekS. TurnauK. Hypericin and pseudohypericin concentrations of a valuable medicinal plant Hypericum perforatum L. are enhanced by arbuscular mycorrhizal fungi.Mycorrhiza201222214915610.1007/s00572‑011‑0391‑1 21626142
    [Google Scholar]
  31. CrockettS.L. SchanebergB. KhanI.A. Phytochemical profiling of new and old world Hypericum (St. John’s Wort) species.Phytochem. Anal.200516647948510.1002/pca.875 16315494
    [Google Scholar]
  32. ZobayedS.M.A. AfreenF. GotoE. KozaiT. Plant-environment interactions: Accumulation of hypericin in dark glands of Hypericum perforatum.Ann. Bot. (Lond.)200698479380410.1093/aob/mcl169 16891333
    [Google Scholar]
  33. SotákM. CzerankováO. KleinD. JurčackováZ. LiL. ČellárováE. Comparative transcriptome reconstruction of four hypericum species focused on Hypericin biosynthesis.Front. Plant Sci.20167103910.3389/fpls.2016.01039 27468294
    [Google Scholar]
  34. KirakosyanA. SirventT.M. GibsonD.M. KaufmanP.B. The production of hypericins and hyperforin by in vitro cultures of St. John’s wort (Hypericum perforatum).Biotechnol. Appl. Biochem.2004391718110.1042/BA20030144 14521510
    [Google Scholar]
  35. ZdunicG. GodjevacD. SavikinK. Comparative analysis of phenolic compounds in seven hypericum species and their antioxidant properties.Nat. Prod. Commun.2017121118051811
    [Google Scholar]
  36. CirakC. RadusieneJ. JakstasV. IvanauskasL. SeyisF. YaylaF. Secondary metabolites of seven Hypericum species growing in Turkey.Pharm. Biol.201654102244225310.3109/13880209.2016.1152277 26958815
    [Google Scholar]
  37. DoukaniK. SellesAS. BouhenniH. Hypericin and pseudohypericin.Naturally Occurring Chemicals Against Alzheimer’s Disease.Academic Press202115516510.1016/B978‑0‑12‑819212‑2.00013‑X
    [Google Scholar]
  38. HosniK. MsaâdaK. TaâritM.B. HammamiM. MarzoukB. Bioactive components of three Hypericum species from Tunisia: A comparative study.Ind. Crops Prod.201031115816310.1016/j.indcrop.2009.09.018
    [Google Scholar]
  39. ÇιrakC. RadušienėJ. JanulisV. IvanauskasL. Secondary metabolites in Hypericum perfoliatum: variation among plant parts and phenological stages.Bot. Helv.20071171293610.1007/s00035‑007‑0777‑z
    [Google Scholar]
  40. KakouriE. TrigasP. DafereraD. SkottiE. TarantilisP.A. KanakisC. Chemical Characterization and Antioxidant Activity of Nine Hypericum Species from Greece.Antioxidants202312489910.3390/antiox12040899 37107274
    [Google Scholar]
  41. AlahmadA. AlghoraibiI. ZeinR. KraftS. DrägerG. WalterJ.G. ScheperT. Identification of major constituents of Hypericum perforatum L. extracts in Syria by development of a rapid, simple, and reproducible HPLC-ESI-Q-TOF MS analysis and their antioxidant activities.ACS Omega2022716134751349310.1021/acsomega.1c06335 35559140
    [Google Scholar]
  42. FicoG VitaliniS ColomboN Phytochemical and morphological studies.Nat Prod Commun2006
    [Google Scholar]
  43. CirakC. RadusieneJ. JakstasV. IvanauskasL. YaylaF. SeyisF. CamasN. Secondary metabolites of Hypericum species from the Drosanthe and Olympia sections.S. Afr. J. Bot.2016104829010.1016/j.sajb.2015.09.022
    [Google Scholar]
  44. KwiecieńI. MiceliN. KędziaE. CavòE. TavianoM.F. BeerhuesL. EkiertH. Different Types of Hypericum perforatum cvs. (Elixir, Helos, Topas) In vitro Cultures: A Rich Source of Bioactive Metabolites and Biological Activities of Biomass Extracts.Molecules2023285237610.3390/molecules28052376 36903619
    [Google Scholar]
  45. AyanA.K. CirakC. Variation of hypericins in Hypericum triquetrifolium Turra growing in different locations of Turkey during plant growth.Nat. Prod. Res.200822181597160410.1080/14786410701838213 19085414
    [Google Scholar]
  46. SeyrekogluF. TemizH. EserF. YildirimC. Comparison of the antioxidant activities and major constituents of three Hypericum species (H. perforatum, H. scabrum and H. origanifolium) from Turkey.S. Afr. J. Bot.202214672372710.1016/j.sajb.2021.12.012
    [Google Scholar]
  47. KucharíkováA. KimákováK. JanfeltC. ČellárováE. Interspecific variation in localization of hypericins and phloroglucinols in the genus Hypericum as revealed by desorption electrospray ionization mass spectrometry imaging.Physiol. Plant.2016157121210.1111/ppl.12422 26822391
    [Google Scholar]
  48. AyanA.K. ÇirakC. Hypericin and Pseudohypericin Contents in Some Hypericum. Species Growing in Turkey.Pharm. Biol.200846428829110.1080/13880200701741211
    [Google Scholar]
  49. YasudaT. YamakiM. IimuraA. ShimotaiY. ShimizuK. NoshitaT. FunayamaS. Anti-influenza virus principles from Muehlenbeckia hastulata.J. Nat. Med.201064220621110.1007/s11418‑009‑0386‑9 20082146
    [Google Scholar]
  50. KusariS. LamshöftM. ZühlkeS. SpitellerM. An endophytic fungus from Hypericum perforatum that produces hypericin.J. Nat. Prod.200871215916210.1021/np070669k 18220354
    [Google Scholar]
  51. MurthyH.N. KimY.S. ParkS.Y. PaekK.Y. Hypericins: biotechnological production from cell and organ cultures.Appl. Microbiol. Biotechnol.201498229187919810.1007/s00253‑014‑6119‑3 25301586
    [Google Scholar]
  52. ScharfenbergS FrankeK HelmutB Discovery of key regulators of dark gland development and hypericin biosynthesis in St. John’s Wort (Hypericum perforatum).Plant Biotechnol. J.2019171222992312
    [Google Scholar]
  53. TavakoliF. RafieiolhossainiM. RavashR. EbrahimiM. Subject: UV-B radiation and low temperature promoted hypericin biosynthesis in adventitious root culture of Hypericum perforatum.Plant Signal. Behav.2020157176418410.1080/15592324.2020.1764184 32419579
    [Google Scholar]
  54. ArbeitsvorschrftA. BestmannH.J. Synthese von Protohypericin aus Emodin.2000895556
    [Google Scholar]
  55. KošuthJ. SmelcerovicA. BorschT. ZuehlkeS. KarppinenK. SpitellerM. HohtolaA. ČellárováE. The hyp-1 gene is not a limiting factor for hypericin biosynthesis in the genus Hypericum.Funct. Plant Biol.2011381354310.1071/FP10144 32480860
    [Google Scholar]
  56. GonçalvesR.S. RabelloB.R. CésarG.B. PereiraP.C.S. RibeiroM.A.S. MeurerE.C. HiokaN. NakamuraC.V. BruschiM.L. CaetanoW. An efficient multigram synthesis of hypericin improved by a low power LED based photoreactor.Org. Process Res. Dev.201721122025203110.1021/acs.oprd.7b00317
    [Google Scholar]
  57. BaisH.P. VepacheduR. LawrenceC.B. StermitzF.R. VivancoJ.M. Molecular and biochemical characterization of an enzyme responsible for the formation of hypericin in St. John’s wort (Hypericum perforatum L.).J. Biol. Chem.200327834324133242210.1074/jbc.M301681200 12799379
    [Google Scholar]
  58. SouthwellI.A. BourkeC.A. Seasonal variation in hypericin content of Hypericum perforatum L. (St. John’s Wort).Phytochemistry200156543744110.1016/S0031‑9422(00)00411‑8 11261576
    [Google Scholar]
  59. MichalskaK. FernandesH. SikorskiM. JaskolskiM. Crystal structure of Hyp-1, a St. John’s wort protein implicated in the biosynthesis of hypericin.J. Struct. Biol.2010169216117110.1016/j.jsb.2009.10.008 19853038
    [Google Scholar]
  60. SliwiakJ. DauterZ. JaskolskiM. Crystal structure of Hyp-1, a Hypericum perforatum PR-10 protein, in complex with melatonin.Front. Plant Sci.2016766810.3389/fpls.2016.00668 27242869
    [Google Scholar]
  61. KarppinenK. HokkanenJ. MattilaS. NeubauerP. HohtolaA. Octaketide‐producing type III polyketide synthase from Hypericum perforatum is expressed in dark glands accumulating hypericins.FEBS J.2008275174329434210.1111/j.1742‑4658.2008.06576.x 18647343
    [Google Scholar]
  62. KusariS. ZühlkeS. KošuthJ. ČellárováE. SpitellerM. Light-independent metabolomics of endophytic Thielavia subthermophila provides insight into microbial hypericin biosynthesis.J. Nat. Prod.200972101825183510.1021/np9002977 19746917
    [Google Scholar]
  63. KarppinenK. HohtolaA. Molecular cloning and tissue-specific expression of two cDNAs encoding polyketide synthases from Hypericum perforatum.J. Plant Physiol.2008165101079108610.1016/j.jplph.2007.04.008 17931742
    [Google Scholar]
  64. ZobayedS.M.A. AfreenF. KozaiT. Temperature stress can alter the photosynthetic efficiency and secondary metabolite concentrations in St. John’s wort.Plant Physiol. Biochem.20054310-1197798410.1016/j.plaphy.2005.07.013 16310362
    [Google Scholar]
  65. MosaleeyanonK. ZobayedS.M.A. AfreenF. KozaiT. Relationships between net photosynthetic rate and secondary metabolite contents in St. John’s wort.Plant Sci.2005169352353110.1016/j.plantsci.2005.05.002
    [Google Scholar]
  66. CuiX.H. ChakrabartyD. LeeE.J. PaekK.Y. Production of adventitious roots and secondary metabolites by Hypericum perforatum L. in a bioreactor.Bioresour. Technol.2010101124708471610.1016/j.biortech.2010.01.115 20171884
    [Google Scholar]
  67. OdabaşM.S. RadušienėJ. ÇırakC. ÇamaşN. Models of estimation of the content of secondary metabolites in some Hypericum species.Pharm. Biol.200947121117112210.3109/13880200903008666
    [Google Scholar]
  68. ZobayedS.M.A. AfreenF. KozaiT. Phytochemical and physiological changes in the leaves of St. John’s wort plants under a water stress condition.Environ. Exp. Bot.200759210911610.1016/j.envexpbot.2005.10.002
    [Google Scholar]
  69. WaserM. FalkH. Progress in the chemistry of second generation hypericin based photosensitizers.Curr. Org. Chem.201115233894390710.2174/138527211798072458
    [Google Scholar]
  70. Eggelkraut-GottankaS.G. AbedS.A. MüllerW. SchmidtP.C. Quantitative analysis of the active components and the by‐products of eight dry extracts of Hypericum perforatum L. (St John’s wort).Phytochem. Anal.200213317017610.1002/pca.638
    [Google Scholar]
  71. SmietanskaJ. SliwiakJ. GilskiM. DauterZ. StrzalkaR. WolnyJ. JaskolskiM. A new modulated crystal structure of the ANS complex of the St John’s wort Hyp-1 protein with 36 protein molecules in the asymmetric unit of the supercell.Acta Crystallogr. D Struct. Biol.202076765366710.1107/S2059798320006841 32627738
    [Google Scholar]
  72. HuangL.F. WangZ.H. ChenS.L. Hypericin: chemical synthesis and biosynthesis.Chin. J. Nat. Med.2014122818810.1016/S1875‑5364(14)60014‑5 24636057
    [Google Scholar]
  73. BruniR. SacchettiG. Factors affecting polyphenol biosynthesis in wild and field grown St. John’s Wort (Hypericum perforatum L. Hypericaceae/Guttiferae).Molecules200914268272510.3390/molecules14020682 19214156
    [Google Scholar]
  74. YavariI. AlborziA. MohtatB. Synthesis of highly functionalized 9,10-anthraquinones.Dyes Pigments2006682-3858810.1016/j.dyepig.2005.01.005
    [Google Scholar]
  75. NaeimiH. NamdariR. Rapid, efficient and one pot synthesis of anthraquinone derivatives catalyzed by Lewis acid/methanesulfonic acid under heterogeneous conditions.Dyes Pigments200981325926310.1016/j.dyepig.2008.10.019
    [Google Scholar]
  76. TauchertM.E. KaiserT.R. GöthlichA.P.V. RomingerF. WarthD.C.M. HofmannP. Phosphonite ligand design for nickel-catalyzed 2-methyl-3-butenenitrile isomerization and styrene hydrocyanation.ChemCatChem20102667468210.1002/cctc.201000022
    [Google Scholar]
  77. QiuH. LiuR. LongL. Analysis of chemical composition of extractives by acetone and the chromatic aberration of teak (Tectona Grandis LF) from China.Molecules20192410198910.3390/molecules24101989 31126143
    [Google Scholar]
  78. MotoyoshiyaJ. MasueY. NishiY. AoyamaH. Synthesis of hypericin via emodin anthrone derived from a two-fold Diels-Alder reaction of 1, 4-benzoquinone.Nat. Prod. Commun.2007216770
    [Google Scholar]
  79. OumerA. BisratD. MazumderA. AsresK. A new antimicrobial anthrone from the leaf latex of Aloe trichosantha.Nat. Prod. Commun.20149794995210.1177/1934578X1400900717
    [Google Scholar]
  80. MurchS.J. RupasingheH.P. SaxenaP.K. An in vitro and hydroponic growing system for hypericin, pseudohypericin, and hyperforin production of St. John’s wort (Hypericum perforatum CV new stem).Planta Med.200268121108111210.1055/s‑2002‑36352 12494339
    [Google Scholar]
  81. ÇirakC. RadušieneJ. KarpavicieneB. Changes in phenolic content of wild and greenhouse-grown Hypericum triquetrifolium during plant development.Turk. J. Agric. For.201337307314
    [Google Scholar]
  82. PavlíkM. VacekJ. KlejdusB. KubáňV. Hypericin and hyperforin production in St. John’s wort in vitro culture: influence of saccharose, polyethylene glycol, methyl jasmonate, and Agrobacterium tumefaciens.J. Agric. Food Chem.200755156147615310.1021/jf070245w 17608493
    [Google Scholar]
  83. RizzoP. AltschmiedL. RavindranB.M. RuttenT. D’AuriaJ.C. The Biochemical and Genetic Basis for the Biosynthesis of Bioactive Compounds in Hypericum perforatum L., One of the Largest Medicinal Crops in Europe.Genes20201110121010.3390/genes11101210 33081197
    [Google Scholar]
  84. PunegovV.V. KostrominV.I. FominaM.G. ZaynullinV.G. YushkovaE.A. BelyhD.V. ChukichevaI.U. ZaynullinG.G. Microwave-assisted extraction of hypericin and pseudohypericin from Hypericum perforatum.Russ. J. Bioorganic Chem.201541775776110.1134/S1068162015070122
    [Google Scholar]
  85. HölzlJ. PetersenM. Chemical constituents of Hypericum ssp.Hypericum: the genus Hypericum.LondonTaylor & Francis20037790
    [Google Scholar]
  86. HuygensA. KamuhabwaA.R. de WitteP.A.M. Stability of different formulations and ion pairs of hypericin.Eur. J. Pharm. Biopharm.200559346146810.1016/j.ejpb.2004.09.014 15760726
    [Google Scholar]
  87. KerbR. BrockmöllerJ. StaffeldtB. PlochM. RootsI. Single-dose and steady-state pharmacokinetics of hypericin and pseudohypericin.Antimicrob. Agents Chemother.19964092087209310.1128/AAC.40.9.2087 8878586
    [Google Scholar]
  88. JacobsonJ.M. FeinmanL. LiebesL. OstrowN. KoslowskiV. TobiaA. CabanaB.E. LeeD.H. SpritzlerJ. PrinceA.M. 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.200145251752410.1128/AAC.45.2.517‑524.2001 11158749
    [Google Scholar]
  89. SchulzH.U. SchürerM. BässlerD. WeiserD. Investigation of pharmacokinetic data of hypericin, pseudohypericin, hyperforin and the flavonoids quercetin and isorhamnetin revealed from single and multiple oral dose studies with a hypericum extract containing tablet in healthy male volunteers.Arzneimittelforschung20055510561568 16294501
    [Google Scholar]
  90. BrockmöllerJ ReumT BauerS KerbR HübnerWD. RootsI Hypericin and pseudohypericin: Pharmacokinetics and effects on photosensitivity in humans.Pharmacopsychiatry199730Suppl. 29410110.1055/s‑2007‑979527
    [Google Scholar]
  91. RussoE. ScicchitanoF. WhalleyB.J. MazzitelloC. CiriacoM. EspositoS. PatanèM. UptonR. PuglieseM. ChimirriS. MammìM. PalleriaC. De SarroG. Hypericum perforatum: Pharmacokinetic, mechanism of action, tolerability, and clinical drug-drug interactions.Phytother. Res.201428564365510.1002/ptr.5050 23897801
    [Google Scholar]
  92. StaffeldtB. KerbR. BrockmöllerJ. PlochM. RootsI. Pharmacokinetics of hypericin and pseudohypericin after oral intake of the hypericum perforatum extract LI 160 in healthy volunteers.J. Geriatr. Psychiatry Neurol.199471_suppl)(Suppl. 1475310.1177/089198879400701s137857509
    [Google Scholar]
  93. UnterwegerH. SubatzusD. TietzeR. JankoC. PoettlerM. StiegelschmittA. SchusterM. MaakeC. BoccacciniA. AlexiouC. Hypericin-bearing magnetic iron oxide nanoparticles for selective drug delivery in photodynamic therapy.Int. J. Nanomedicine2015106985699610.2147/IJN.S92336 26648714
    [Google Scholar]
  94. FourneronJ.D. HerbetteG. CalopriscoE. Pseudohypericin and hypericin in St. John’s wort extracts. Breakdown of pseudohypericin.C. R. Acad. Sci. Ser. IIc Chim.19992312713110.1016/S1251‑8069(99)80024‑3
    [Google Scholar]
  95. JendželovskýR. JendželovskáZ. KuchárováB. FedoročkoP. Breast cancer resistance protein is the enemy of hypericin accumulation and toxicity of hypericin-mediated photodynamic therapy.Biomed. Pharmacother.20191092173218110.1016/j.biopha.2018.11.084 30551474
    [Google Scholar]
  96. EkorM. The growing use of herbal medicines: Issues relating to adverse reactions and challenges in monitoring safety.Front. Pharmacol.2014417710.3389/fphar.2013.00177 24454289
    [Google Scholar]
  97. SofiS.H. NuraddinS.M. AminZ.A. Al-BustanyH.A. NadirM.Q. Gastroprotective activity of Hypericum perforatum extract in ethanol-induced gastric mucosal injury in Wistar rats: A possible involvement of H+/K+ ATPase α inhibition.Heliyon2020610e0524910.1016/j.heliyon.2020.e05249 33102861
    [Google Scholar]
  98. GregorettiB. StebelM. CandussioL. CrivellatoE. BartoliF. DecortiG. Toxicity of Hypericum perforatum (St. John’s wort) administered during pregnancy and lactation in rats.Toxicol. Appl. Pharmacol.2004200320120510.1016/j.taap.2004.04.020 15504456
    [Google Scholar]
  99. FerraraM. MungaiF. StaraceF. St John’s wort (Hypericum perforatum)-induced psychosis: A case report.J. Med. Case Reports201711113710.1186/s13256‑017‑1302‑7 28502251
    [Google Scholar]
  100. GoeyA.K.L. MooimanK.D. BeijnenJ.H. SchellensJ.H.M. MeijermanI. Relevance of in vitro and clinical data for predicting CYP3A4-mediated herb–drug interactions in cancer patients.Cancer Treat. Rev.201339777378310.1016/j.ctrv.2012.12.008 23394826
    [Google Scholar]
  101. BorrelliF. IzzoA.A. Herb-drug interactions with St John’s wort (Hypericum perforatum): An update on clinical observations.AAPS J.200911471072710.1208/s12248‑009‑9146‑8 19859815
    [Google Scholar]
  102. HendersonL. YueQ.Y. BergquistC. GerdenB. ArlettP. St John’s wort (Hypericum perforatum): Drug interactions and clinical outcomes.Br. J. Clin. Pharmacol.200254434935610.1046/j.1365‑2125.2002.01683.x 12392581
    [Google Scholar]
  103. JohneA. BrockmöllerJ. BauerS. Pharmacokinetics and drug disposition pharmacokinetic interaction of digoxin with an herbal extract from St John’ s wort.Clin. Pharmacol. Ther.199933834510.1053/cp.1999.v66.a101944 10546917
    [Google Scholar]
  104. TannergrenC. EngmanH. KnutsonL. HedelandM. BondessonU. LennernäsH. St John’s wort decreases the bioavailability of R- and S-verapamil through induction of the first-pass metabolism*1.Clin. Pharmacol. Ther.200475429830910.1016/j.clpt.2003.12.012 15060508
    [Google Scholar]
  105. AndrénL. AndreassonÅ. EggertsenR. Interaction between a commercially available St. John’s wort product (Movina) and atorvastatin in patients with hypercholesterolemia.Eur. J. Clin. Pharmacol.2007631091391610.1007/s00228‑007‑0345‑x 17701167
    [Google Scholar]
  106. MurphyP.A. KernS.E. StanczykF.Z. WesthoffC.L. Interaction of St. John’s Wort with oral contraceptives: Effects on the pharmacokinetics of norethindrone and ethinyl estradiol, ovarian activity and breakthrough bleeding.Contraception200571640240810.1016/j.contraception.2004.11.004 15914127
    [Google Scholar]
  107. McCance-KatzE.F. SullivanL.E. NallaniS. Drug interactions of clinical importance among the opioids, methadone and buprenorphine, and other frequently prescribed medications: A review.Am. J. Addict.201019141610.1111/j.1521‑0391.2009.00005.x 20132117
    [Google Scholar]
  108. HoY.F. HuangD.K. HsuehW.C. LaiM.Y. YuH.Y. TsaiT.H. Effects of St. John’s wort extract on indinavir pharmacokinetics in rats: Differentiation of intestinal and hepatic impacts.Life Sci.2009857-829630210.1016/j.lfs.2009.06.008 19559714
    [Google Scholar]
  109. NieminenT.H. HagelbergN.M. SaariT.I. NeuvonenM. LaineK. NeuvonenP.J. OlkkolaK.T. St John’s wort greatly reduces the concentrations of oral oxycodone.Eur. J. Pain201014885485910.1016/j.ejpain.2009.12.007 20106684
    [Google Scholar]
  110. IzzoA.A. Interactions between herbs and conventional drugs: Overview of the clinical data.Med. Princ. Pract.201221540442810.1159/000334488 22236736
    [Google Scholar]
  111. HebertM.F. ParkJ.M. ChenY.L. AkhtarS. LarsonA.M. Effects of St. John’s wort (Hypericum perforatum) on tacrolimus pharmacokinetics in healthy volunteers.J. Clin. Pharmacol.2004441899410.1177/0091270003261078 14681346
    [Google Scholar]
  112. MorimotoT. KotegawaT. TsutsumiK. OhtaniY. ImaiH. NakanoS. Effect of St. John’s wort on the pharmacokinetics of theophylline in healthy volunteers.J. Clin. Pharmacol.20044419510110.1177/0091270003261496 14681347
    [Google Scholar]
  113. WadaA. SakaedaT. TakaraK. HiraiM. KimuraT. OhmotoN. ZhouJ. NakamuraT. KobayashiH. OkamuraN. YagamiT. OkumuraK. Effects of St John’s wort and hypericin on cytotoxicity of anticancer drugs.Drug Metab. Pharmacokinet.200217546747410.2133/dmpk.17.467 15618698
    [Google Scholar]
  114. OdabasM.S. RadusieneJ. CirakC. CamasN. Prediction models for the phenolic contents in some Hypericum species from Turkey.Asian J. Chem.20082064792
    [Google Scholar]
  115. BeckerL.C. BergfeldW.F. BelsitoD.V. HillR.A. KlaassenC.D. LieblerD.C. MarksJ.G.Jr ShankR.C. SlagaT.J. SnyderP.W. AndersenF.A. Amended safety assessment of Hypericum perforatum-derived ingredients as used in cosmetics.Int. J. Toxicol.2014333_suppl)(Suppl.5S23S10.1177/109158181453335425297909
    [Google Scholar]
  116. ÇirakC.Ü. RadusieneJ. AksoyH.M. MackinaiteR. StaniusZ. CamasN. OdabasM.S. Differential phenolic accumulation in two Hypericum species in response to inoculation with Diploceras hypericinum and Pseudomonasputida.Plant Prot. Sci.201450311912810.17221/67/2012‑PPS
    [Google Scholar]
  117. SilvaA.R. TaofiqO. FerreiraI.C.F.R. BarrosL. Hypericum genus cosmeceutical application – A decade comprehensive review on its multifunctional biological properties.Ind. Crops Prod.202115911305310.1016/j.indcrop.2020.113053
    [Google Scholar]
  118. ButterweckV. BöckersT. KorteB. WittkowskiW. WinterhoffH. Long-term effects of St. John’s wort and hypericin on monoamine levels in rat hypothalamus and hippocampus.Brain Res.20029301-2212910.1016/S0006‑8993(01)03394‑7 11879791
    [Google Scholar]
  119. MenniniT. GobbiM. The antidepressant mechanism of Hypericum perforatum.Life Sci.20047591021102710.1016/j.lfs.2004.04.005 15207650
    [Google Scholar]
  120. SuzukiO. KatsumataY. OyaM. BladtS. WagnerH. Inhibition of monoamine oxidase by hypericin.Planta Med.198450327227410.1055/s‑2007‑969700 6484033
    [Google Scholar]
  121. KleberE. ObryT. HippeliS. SchneiderW. ElstnerE.F. Biochemical activities of extracts from Hypericum perforatum L. 1st Communication: Inhibition of dopamine-β-hydroxylase.Arzneimittelforschung1999492106109 10083977
    [Google Scholar]
  122. LiangC. HaoF. YaoX. QiuY. LiuL. WangS. YuC. SongZ. BaoY. YiJ. HuangY. WuY. ZhengL. SunY. WangG. YangX. YangS. SunL. LiY. Hypericin maintians PDX1 expression via the Erk pathway and protects islet β-cells against glucotoxicity and lipotoxicity.Int. J. Biol. Sci.20191571472148710.7150/ijbs.33817 31337977
    [Google Scholar]
  123. YuanX. YanF. GaoL.H. MaQ.H. WangJ. Hypericin as a potential drug for treating Alzheimer’s disease and type 2 diabetes with a view to drug repositioning.CNS Neurosci. Ther.202329113307332110.1111/cns.14260 37183545
    [Google Scholar]
  124. KubinA. WierraniF. BurnerU. AlthG. GrünbergerW. Hypericin--The facts about a controversial agent.Curr. Pharm. Des.200511223325310.2174/1381612053382287 15638760
    [Google Scholar]
  125. HudsonJ.B. Lopez-BazzocchiI. TowersG.H.N. Antiviral activities of hypericin.Antiviral Res.199115210111210.1016/0166‑3542(91)90028‑P 1650164
    [Google Scholar]
  126. KartnigT. GöbelI. HeydelB. Production of hypericin, pseudohypericin and flavonoids in cell cultures of various Hypericum species and their chemotypes.Planta Med.1996621515310.1055/s‑2006‑957796 8720388
    [Google Scholar]
  127. JainN. JainP. RajputD. PatilU.K. Green synthesized plant-based silver nanoparticles: Therapeutic prospective for anticancer and antiviral activity.Micro and Nano Systems Letters202191510.1186/s40486‑021‑00131‑6
    [Google Scholar]
  128. KitanovG.M. Hypericin and pseudohypericin in some Hypericum species.Biochem. Syst. Ecol.200129217117810.1016/S0305‑1978(00)00032‑6 11106845
    [Google Scholar]
  129. OdabasM.S. RadusieneJ. KarpavicieneB. CamasN. Prediction model of the effect of light intensity on phenolic contents in hypericum triquetrifolium turra.Izv. Him.2015472467471
    [Google Scholar]
  130. LiuY. WenF. LiJ. ZuoC. LiM. Transitions of multifocal electroretinography in patients with age-related macular degeneration after combination therapy with photodynamic therapy and intravitreal bevacizumab.Doc. Ophthalmol.2009119316316910.1007/s10633‑009‑9189‑2 20101800
    [Google Scholar]
  131. VantieghemA. XuY. DeclercqW. VandenabeeleP. DeneckerG. VandenheedeJ.R. MerlevedeW. de WitteP.A. AgostinisP. Different pathways mediate cytochrome c release after photodynamic therapy with hypericin.Photochem. Photobiol.200174213314210.1562/0031‑8655(2001)074<0133:DPMCCR>2.0.CO;2 11547546
    [Google Scholar]
  132. AgostinisP. AssefaZ. VantieghemA. VandenheedeJ.R. MerlevedeW. De WitteP. Apoptotic and anti-apoptotic signaling pathways induced by photodynamic therapy with hypericin.Adv. Enzyme Regul.200040115718210.1016/S0065‑2571(99)00021‑7 10828351
    [Google Scholar]
  133. BenderO. Llorent-MartínezE.J. ZenginG. MollicaA. CeylanR. Molina-GarcíaL. Fernández-de CórdovaM.L. AtalayA. Integration of in vitro and in silico perspectives to explain chemical characterization, biological potential and anticancer effects of Hypericum salsugineum: A pharmacologically active source for functional drug formulations.PLoS One2018136e019781510.1371/journal.pone.0197815 29864137
    [Google Scholar]
  134. MauryaSK. DivakarS PatilUK. Potentials of plant derived products for the treatment of skin disorders.German J. Pharm. Biomater.202323931
    [Google Scholar]
  135. AgostinisP. VantieghemA. MerlevedeW. de WitteP.A.M. Hypericin in cancer treatment: More light on the way.Int. J. Biochem. Cell Biol.200234322124110.1016/S1357‑2725(01)00126‑1 11849990
    [Google Scholar]
  136. FiersW. BeyaertR. DeclercqW. Nature More than one way to die necrosis apoptosis ROS.Oncogene1999187719773010.1038/sj.onc.1203249 10618712
    [Google Scholar]
  137. ChenB. XuY. RoskamsT. DelaeyE. AgostinisP. VandenheedeJ.R. de WitteP. Efficacy of antitumoral photodynamic therapy with hypericin: Relationship between biodistribution and photodynamic effects in the RIF-1 mouse tumor model.Int. J. Cancer200193227528210.1002/ijc.1324 11410877
    [Google Scholar]
  138. TheodossiouT.A. HothersallJ.S. De WitteP.A. PantosA. AgostinisP. The multifaceted photocytotoxic profile of hypericin.Mol. Pharm.2009661775178910.1021/mp900166q 19739671
    [Google Scholar]
  139. ChenB. de WitteP.A. Photodynamic therapy efficacy and tissue distribution of hypericin in a mouse P388 lymphoma tumor model.Cancer Lett.2000150111111710.1016/S0304‑3835(99)00381‑X 10755394
    [Google Scholar]
  140. SchemppC.M. Simon-HaarhausB. TermeerC.C. SimonJ.C. Hypericin photo‐induced apoptosis involves the tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL) and activation of caspase‐8.FEBS Lett.20014931263010.1016/S0014‑5793(01)02268‑2 11277999
    [Google Scholar]
  141. DavidsL.M. KleemannB. KacerovskáD. PizingerK. KidsonS.H. Hypericin phototoxicity induces different modes of cell death in melanoma and human skin cells.J. Photochem. Photobiol. B2008912-3677610.1016/j.jphotobiol.2008.01.011 18342534
    [Google Scholar]
  142. ChenB. RoskamsT. de WitteP.A.M. Antivascular tumor eradication by hypericin-mediated photodynamic therapy.Photochem. Photobiol.200276550951310.1562/0031‑8655(2002)076<0509:ATEBHM>2.0.CO;2 12462645
    [Google Scholar]
  143. ChenB. ZupkóI. de WitteP. Photodynamic therapy with hypericin in a mouse P388 tumor model: Vascular effects determine the efficacy.Int. J. Oncol.200118473774210.3892/ijo.18.4.737 11251168
    [Google Scholar]
  144. MollicaA. ZenginG. LocatelliM. StefanucciA. MocanA. MacedonioG. CarradoriS. OnaolapoO. OnaolapoA. AdegokeJ. OlaniyanM. AktumsekA. NovellinoE. Anti-diabetic and anti-hyperlipidemic properties of Capparis spinosa L.: In vivo and in vitro evaluation of its nutraceutical potential.J. Funct. Foods201735324210.1016/j.jff.2017.05.001
    [Google Scholar]
  145. RafailovskaE. TushevskiO. ShijakovaK. SimicS.G. KjovkarovskaS.D. MiovaB. Hypericum perforatum L. extract exerts insulinotropic effects and inhibits gluconeogenesis in diabetic rats by regulating AMPK expression and PKCε concentration.J. Ethnopharmacol.2023302Pt A11589910.1016/j.jep.2022.11589936336219
    [Google Scholar]
  146. CaoR. TianH. ZhangY. LiuG. XuH. RaoG. TianY. FuX. Signaling pathways and intervention for therapy of type 2 diabetes mellitus.MedComm202343e28310.1002/mco2.283 37303813
    [Google Scholar]
  147. FangC. PanJ. QuN. LeiY. HanJ. ZhangJ. HanD. The AMPK pathway in fatty liver disease.Front. Physiol.202213970292Epub ahead of print10.3389/fphys.2022.970292 36203933
    [Google Scholar]
  148. LiangC. LiY. BaiM. HuangY. YangH. LiuL. WangS. YuC. SongZ. BaoY. YiJ. SunL. LiY. Hypericin attenuates nonalcoholic fatty liver disease and abnormal lipid metabolism via the PKA-mediated AMPK signaling pathway in vitro and in vivo.Pharmacol. Res.202015310465710.1016/j.phrs.2020.104657 31982488
    [Google Scholar]
  149. Shaik Mohamed SayedU.F. MoshawihS. GohH.P. KifliN. GuptaG. SinghS.K. ChellappanD.K. DuaK. HermansyahA. SerH.L. MingL.C. GohB.H. Natural products as novel anti-obesity agents: Insights into mechanisms of action and potential for therapeutic management.Front. Pharmacol.202314118293710.3389/fphar.2023.1182937 37408757
    [Google Scholar]
  150. BrondzI. GreibrokkT. GrothP.A. AasenA.J. The relative stereochemistry of hyperforin-an antibiotic from hypericum perforatum L.Tetrahedron Lett.198223121299130010.1016/S0040‑4039(00)87088‑4
    [Google Scholar]
  151. SchemppC.M. WinghoferB. LangheinrichM. SchöpfE. SimonJ.C. Hypericin levels in human serum and interstitial skin blister fluid after oral single-dose and steady-state administration of Hypericum perforatum extract (St. John’s wort).Skin Pharmacol. Physiol.199912529930410.1159/000066256 10461100
    [Google Scholar]
  152. VossA. VerweijP.E. FiebichB.L. Antibacterial activity of hyperforin from St John’s wort.Lancet1999354918077710.1016/S0140‑6736(05)76018‑9 10475221
    [Google Scholar]
  153. PhulmogareG. RaniS. LodhiS. PatilU.K. SinhaS. Ajazuddin; Gupta, U. Fucoidan loaded PVA/Dextran blend electrospun nanofibers for the effective wound healing.Int. J. Pharm.202465012372210.1016/j.ijpharm.2023.123722 38110012
    [Google Scholar]
  154. LavagnaS.M. SecciD. ChimentiP. BonsignoreL. OttavianiA. BizzarriB. Efficacy of Hypericum and Calendula oils in the epithelial reconstruction of surgical wounds in childbirth with caesarean section.Farmaco2001565-745145310.1016/S0014‑827X(01)01060‑6 11482776
    [Google Scholar]
  155. SüntarI.P. AkkolE.K. YılmazerD. BaykalT. KırmızıbekmezH. AlperM. YeşiladaE. Investigations on the in vivo wound healing potential of Hypericum perforatum L.J. Ethnopharmacol.2010127246847710.1016/j.jep.2009.10.011 19833187
    [Google Scholar]
  156. N, Oztürk. Wound-healing activity of St. John’s Wort (Hypericum perforatum L.) on chicken embryonic fibroblasts.J. Ethnopharmacol.200711113339
    [Google Scholar]
  157. McDonnellA.M. DangC.H. Basic review of the cytochrome p450 system.J. Adv. Pract. Oncol.201344263268 25032007
    [Google Scholar]
  158. WanwimolrukS. PrachayasittikulV. Cytochrome P450 enzyme mediated herbal drug interactions (Part 1).EXCLI J.201413347391 26417265
    [Google Scholar]
  159. FinnerupN.B. KunerR. JensenT.S. Neuropathic pain: From mechanisms to treatment.Physiol. Rev.2021101125930110.1152/physrev.00045.2019 32584191
    [Google Scholar]
  160. GaleottiN. FarzadM. BianchiE. GhelardiniC. PKC-mediated potentiation of morphine analgesia by St. John’s Wort in rodents and humans.J. Pharmacol. Sci.2014124440941710.1254/jphs.13226FP 24739262
    [Google Scholar]
  161. SpiessD. AbeggV.F. ChauveauA. RathJ. TreyerA. ReinehrM. KuoniS. OufirM. PotteratO. HamburgerM. Simões-WüstA.P. Transplacental passage of hyperforin, hypericin, and valerenic acid.Front. Pharmacol.202314112319410.3389/fphar.2023.1123194 37063288
    [Google Scholar]
  162. CamposL.V. VieiraV.A. SilvaL.R. JasminJ. GuerraM.O. PetersV.M. SáR.C.S. Rats treated with Hypericum perforatum during pregnancy generate offspring with behavioral changes in adulthood.Rev. Bras. Farmacogn.201727336136810.1016/j.bjp.2017.01.004
    [Google Scholar]
  163. JendželovskáZ. JendželovskýR. KuchárováB. FedoročkoP. Hypericin in the light and in the dark: Two sides of the same coin.Front. Plant Sci.2016756010.3389/fpls.2016.00560 27200034
    [Google Scholar]
  164. SørensenM.G. KarsdalM.A. DziegielM.H. BoutinJ.A. NosjeanO. HenriksenK. Screening of protein kinase inhibitors identifies PKC inhibitors as inhibitors of osteoclastic acid secretion and bone resorption.BMC Musculoskelet. Disord.201011125010.1186/1471‑2474‑11‑250 20977756
    [Google Scholar]
  165. MansouriP. MirafzalS. NajafizadehP. Safaei-NaraghiZ. Salehi-SurmaghiM.H. HashemianF. The impact of topical Saint John’s Wort (Hypericum perforatum) treatment on tissue tumor necrosis factor-alpha levels in plaque-type psoriasis.J. Postgrad. Med.201763421522010.4103/0022‑3859.201423 28272075
    [Google Scholar]
  166. YanB.X. ChenX.Y. YeL.R. ChenJ.Q. ZhengM. ManX.Y. Cutaneous and systemic psoriasis: Classifications and classification for the distinction.Front. Med.2021864940810.3389/fmed.2021.649408 34722555
    [Google Scholar]
  167. WendelboeA.M. RaskobG.E. Global burden of thrombosis.Circ. Res.201611891340134710.1161/CIRCRESAHA.115.306841 27126645
    [Google Scholar]
  168. WeiL.H. ChenT.R. FangH.B. JinQ. ZhangS.J. HouJ. YuY. DouT.Y. CaoY.F. GuoW.Z. GeG.B. Natural constituents of St. John’s Wort inhibit the proteolytic activity of human thrombin.Int. J. Biol. Macromol.201913462263010.1016/j.ijbiomac.2019.04.181 31047931
    [Google Scholar]
  169. VargasonA.M. AnselmoA.C. MitragotriS. The evolution of commercial drug delivery technologies.Nat. Biomed. Eng.20215995196710.1038/s41551‑021‑00698‑w 33795852
    [Google Scholar]
  170. WuJ.J. ZhangJ. XiaC.Y. DingK. LiX.X. PanX.G. XuJ.K. HeJ. ZhangW.K. Hypericin: A natural anthraquinone as promising therapeutic agent.Phytomedicine202311115465410.1016/j.phymed.2023.154654 36689857
    [Google Scholar]
  171. de MoraisF.A.P. De OliveiraA.C.V. BalbinotR.B. Lazarin-BidóiaD. Ueda-NakamuraT. de Oliveira SilvaS. da Silva Souza CampanholiK. da SilvaJuniorR.C. GonçalvesR.S. CaetanoW. NakamuraC.V. Multifunctional nanoparticles as high-efficient targeted hypericin system for theranostic melanoma.Polymers202215117910.3390/polym15010179 36616529
    [Google Scholar]
  172. GaoY. WangK. ZhangJ. DuanX. SunQ. MenK. Multifunctional nanoparticle for cancer therapy.MedComm202341e18710.1002/mco2.187 36654533
    [Google Scholar]
  173. Zeisser-LabouèbeM. LangeN. GurnyR. DelieF. Hypericin-loaded nanoparticles for the photodynamic treatment of ovarian cancer.Int. J. Pharm.20063261-217418110.1016/j.ijpharm.2006.07.012 16930882
    [Google Scholar]
  174. YoussefT. FadelM. FahmyR. KassabK. Evaluation of hypericin-loaded solid lipid nanoparticles: Physicochemical properties, photostability and phototoxicity.Pharm. Dev. Technol.201217217718610.3109/10837450.2010.529148 21047275
    [Google Scholar]
  175. SicilianoG. MonteduroA.G. TurcoA. PrimiceriE. RizzatoS. DepaloN. CurriM.L. MaruccioG. Polydopamine-coated magnetic iron oxide nanoparticles: From design to applications.Nanomaterials2022127114510.3390/nano12071145 35407264
    [Google Scholar]
  176. HanX. TaratulaO. TaratulaO. XuK. St LorenzA. MosesA. JahangiriY. YuG. FarsadK. Biodegradable hypericin-containing nanoparticles for necrosis targeting and fluorescence imaging.Mol. Pharm.20201751538154510.1021/acs.molpharmaceut.9b01238 32212709
    [Google Scholar]
  177. de MoraisF.A.P. GonçalvesR.S. VilsinskiB.H. de OliveiraÉ.L. RochaN.L. HiokaN. CaetanoW. Hypericin photodynamic activity in DPPC liposome. PART I: Biomimetism of loading, location, interactions and thermodynamic properties.J. Photochem. Photobiol. B201919011812710.1016/j.jphotobiol.2018.11.019 30513414
    [Google Scholar]
  178. Abu DayyihA. AlawakM. AyoubA.M. AminM.U. Abu DayyihW. EngelhardtK. DuseL. PreisE. BrüßlerJ. BakowskyU. Thermosensitive liposomes encapsulating hypericin: Characterization and photodynamic efficiency.Int. J. Pharm.202160912119510.1016/j.ijpharm.2021.121195 34673168
    [Google Scholar]
  179. WangY. ZhangY. JinM. LvY. PeiZ. PeiY. A hypericin delivery system based on polydopamine coated cerium oxide nanorods for targeted photodynamic therapy.Polymers2019116102510.3390/polym11061025 31185679
    [Google Scholar]
  180. KimY. KimH. KangH.W. Enhancement of gold nanorods‐assisted photothermal treatment on cancer with laser power in stepwise modulation.Lasers Surg. Med.202254684185010.1002/lsm.23549 35419820
    [Google Scholar]
  181. GalinariC.B. ConradoP.C.V. AritaG.S. MoscaV.A.B. MeloR.C. BianchiT.P. FariaD.R. SakitaK.M. MalacarneL.C. GonçalvesR.S. PereiraP.C.S. CesarG.B. CaetanoW. de SouzaM. da Silva PaláciosR. BaessoM.L. SvidzinskiT.I.E. CoticaÉ.S.K. Bonfim-MendonçaP.S. Nanoencapsulated hypericin in P-123 associated with photodynamic therapy for the treatment of dermatophytosis.J. Photochem. Photobiol. B202121511210310.1016/j.jphotobiol.2020.112103 33383558
    [Google Scholar]
  182. LazzaraS. MilitelloM. CarrubbaA. NapoliE. SaiaS. Arbuscular mycorrhizal fungi altered the hypericin, pseudohypericin, and hyperforin content in flowers of Hypericum perforatum grown under contrasting P availability in a highly organic substrate.Mycorrhiza201727434535410.1007/s00572‑016‑0756‑6 27999964
    [Google Scholar]
  183. de MoraisF.A.P. GonçalvesR.S. VilsinskiB.H. Lazarin-BidóiaD. BalbinotR.B. TsuboneT.M. BrunaldiK. NakamuraC.V. HiokaN. CaetanoW. Hypericin photodynamic activity in DPPC liposomes – part II: Stability and application in melanoma B16-F10 cancer cells.Photochem. Photobiol. Sci.202019562063010.1039/c9pp00284g 32248218
    [Google Scholar]
  184. MaH.L. VarandaL.C. PerussiJ.R. CarrilhoE. Hypericin-loaded oil-in-water nanoemulsion synthesized by ultrasonication process enhances photodynamic therapy efficiency.J. Photochem. Photobiol. B202122311230310.1016/j.jphotobiol.2021.112303 34509718
    [Google Scholar]
  185. PriyadarshiniM. RajN.A.N. Green synthesis and in vitro photodynamic efficacy of hypericin: Cytotoxicity assessment on MCF-7 breast cancer cells.Photodiagn. Photodyn. Ther.20245010441110.1016/j.pdpdt.2024.104411 39579841
    [Google Scholar]
  186. Abd-El-AzimH. AbbasH. El SayedN. MousaM.R. ElbardisyH.M. ZewailM. Hypericin emulsomes combined with hollow microneedles as a non-invasive photodynamic platform for rheumatoid arthritis treatment.Int. J. Pharm.202465312387610.1016/j.ijpharm.2024.123876 38331331
    [Google Scholar]
  187. Abd-El-AzimH. TekkoI.A. AliA. RamadanA. NafeeN. KhalafallahN. RahmanT. McdaidW. AlyR.G. VoraL.K. BellS.J. FurlongF. McCarthyH.O. DonnellyR.F. Hollow microneedle assisted intradermal delivery of hypericin lipid nanocapsules with light enabled photodynamic therapy against skin cancer.J. Control. Release202234884986910.1016/j.jconrel.2022.06.027 35728715
    [Google Scholar]
  188. ZimathP. PintoS. DiasS. RafachoA. SarmentoB. Zein nanoparticles as oral carrier for mometasone furoate delivery.Drug Deliv. Transl. Res.202313112948295910.1007/s13346‑023‑01367‑y 37208563
    [Google Scholar]
  189. AbdelsalamA.M. SomaidaA. AmbreenG. AyoubA.M. TariqI. EngelhardtK. GaridelP. FawazI. AminM.U. WojcikM. BakowskyU. Surface tailored zein as a novel delivery system for hypericin: Application in photodynamic therapy.Mater. Sci. Eng. C202112911242010.1016/j.msec.2021.112420 34579929
    [Google Scholar]
  190. MerueloD. LavieG. LavieD. Therapeutic agents with dramatic antiretroviral activity and little toxicity at effective doses: Aromatic polycyclic diones hypericin and pseudohypericin.Proc. Natl. Acad. Sci. USA198885145230523410.1073/pnas.85.14.5230 2839837
    [Google Scholar]
  191. OdabasM.S. KayhanG. ErgunE. SenyerN. Using artificial neural network and multiple linear regression for predicting the chlorophyll concentration index of Saint John’s wort leaves.Commun. Soil Sci. Plant Anal.201647223724510.1080/00103624.2015.1104342
    [Google Scholar]
  192. WurglicsM. WesterhoffK. KaunzingerA. WilkeA. BaumeisterA. DressmanJ. Schubert-ZsilaveczM. Comparison of German St. John’s wort products according to hyperforin and total hypericin content.J. Am. Pharm. Assoc.200141456056610.1016/S1086‑5802(16)31280‑3 11486982
    [Google Scholar]
  193. SchwarzD. KisselevP. RootsI.St. John’s wort extracts and some of their constituents potently inhibit ultimate carcinogen formation from benzo[a]pyrene-7,8-dihydrodiol by human CYP1A1.Cancer Res.2003632280628068 14633740
    [Google Scholar]
  194. MannelM. Drug interactions with St John’s wort: Mechanisms and clinical implications.Drug Saf.2004271177379710.2165/00002018‑200427110‑00003 15350151
    [Google Scholar]
  195. FornalC. MetzlerC.W. MirescuC. SteinS.K. JacobsB.L. Effects of standardized extracts of St. John’s wort on the single-unit activity of serotonergic dorsal Raphe neurons in awake cats: Comparisons with fluoxetine and sertraline.Neuropsychopharmacology200125685887010.1016/S0893‑133X(01)00297‑4 11750179
    [Google Scholar]
  196. AdamsJ. SteelA. BroomA. FrawleyJ. Eds.; Women’s health and complementary and integrative medicine.LondonRoutledge2019
    [Google Scholar]
  197. AdamsJ. SteelA. BroomA. FrawleyJ. Eds.; Women’s health and complementary and integrative medicine.LondonRoutledge2019
    [Google Scholar]
  198. CostacheI.I. MironA. HăncianuM. AursuleseiV. CostacheA.D. AprotosoaieA.C. Pharmacokinetic interactions between cardiovascular medicines and plant products.Cardiovasc. Ther.20192019111910.1155/2019/9402781 32089733
    [Google Scholar]
  199. NobakhtS.Z. AkaberiM. MohammadpourA.H. Tafazoli MoghadamA. EmamiS.A. Hypericum perforatum: Traditional uses, clinical trials, and drug interactions.Iran. J. Basic Med. Sci.202225910451058 36246064
    [Google Scholar]
  200. RookA.H. WoodG.S. DuvicM. VonderheidE.C. TobiaA. CabanaB. A phase II placebo-controlled study of photodynamic therapy with topical hypericin and visible light irradiation in the treatment of cutaneous T-cell lymphoma and psoriasis.J. Am. Acad. Dermatol.201063698499010.1016/j.jaad.2010.02.039 20889234
    [Google Scholar]
  201. TatsisEC. ExarchouV TroganisAN. GerothanassisIP. 1H NMR determination of hypericin and pseudohypericin in complex natural mixtures by the use of strongly deshielded OH groups.Anal. Chim. Acta20086072219226
    [Google Scholar]
  202. WilliamsonE.M. Drug interactions between herbal and prescription medicines.Drug Saf.200326151075109210.2165/00002018‑200326150‑00002 14640772
    [Google Scholar]
  203. DelcanaleP. UriatiE. MariangeliM. MussiniA. MorenoA. LelliD. CavannaL. BianchiniP. DiasproA. AbbruzzettiS. ViappianiC. The interaction of hypericin with SARS-CoV-2 reveals a multimodal antiviral activity.ACS Appl. Mater. Interfaces20221412140251403210.1021/acsami.1c22439 35302731
    [Google Scholar]
  204. WaqarM.A. ZamanM. HameedH. JamshaidM. IrfanA. ShazlyG.A. Paiva-SantosA.C. Bin JardanY.A. Formulation, characterization, and evaluation of β-Cyclodextrin functionalized hypericin loaded nanocarriers.ACS Omega2023841381913820310.1021/acsomega.3c04444 37867680
    [Google Scholar]
  205. GalinariC.B. BiachiT.P. GonçalvesR.S. CesarG.B. BergmannE.V. MalacarneL.C. Kioshima CoticaÉ.S. Bonfim-MendonçaP.S. SvidzinskiT.I.E. Photoactivity of hypericin: From natural product to antifungal application.Crit. Rev. Microbiol.2023491385610.1080/1040841X.2022.2036100 35171731
    [Google Scholar]
  206. TaşkonakB. AylazG. AndacM. GüvenE. OzkahramanB. PerçinI. Kılıç SüloğluA. Hypericin-loaded chitosan nanoparticles for enhanced photodynamic therapy in A549 lung cancer cells.Bionanoscience202313235236410.1007/s12668‑023‑01099‑w
    [Google Scholar]
  207. BuľkováV. VargováJ. BabinčákM. JendželovskýR. ZdráhalZ. RoudnickýP. KošuthJ. FedoročkoP. New findings on the action of hypericin in hypoxic cancer cells with a focus on the modulation of side population cells.Biomed. Pharmacother.202316311482910.1016/j.biopha.2023.114829 37146419
    [Google Scholar]
  208. OlekM. Machorowska-PieniążekA. CzubaZ.P. CieślarG. Kawczyk-KrupkaA. Immunomodulatory effect of hypericin-mediated photodynamic therapy on oral cancer cells.Pharmaceutics20231614210.3390/pharmaceutics16010042 38258051
    [Google Scholar]
  209. WoźniakM. Nowak-PerlakM. Hypericin-based photodynamic therapy displays higher selectivity and phototoxicity towards melanoma and squamous cell cancer compared to normal keratinocytes in vitro.Int. J. Mol. Sci.202324231689710.3390/ijms242316897 38069219
    [Google Scholar]
/content/journals/ctmc/10.2174/0115680266330142250224101958
Loading
/content/journals/ctmc/10.2174/0115680266330142250224101958
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test