Planta Med 2014; 80(02/03): 109-120
DOI: 10.1055/s-0033-1351019
Reviews
Georg Thieme Verlag KG Stuttgart · New York

Topical Application of St. Johnʼs Wort (Hypericum perforatum)

Ute Wölfle
1   Section skintegral, Department of Dermatology, University Medical Center Freiburg, Freiburg, Germany
,
Günter Seelinger
2   Medical Services Dr. Seelinger, Berlin, Germany
,
Christoph M. Schempp
1   Section skintegral, Department of Dermatology, University Medical Center Freiburg, Freiburg, Germany
› Author Affiliations
Further Information

Publication History

received 28 June 2013
revised 26 September 2013

accepted 27 September 2013

Publication Date:
08 November 2013 (online)

Abstract

St. Johnʼs wort (Hypericum perforatum) has been intensively investigated for its antidepressive activity, but dermatological applications also have a long tradition. Topical St. Johnʼs wort preparations such as oils or tinctures are used for the treatment of minor wounds and burns, sunburns, abrasions, bruises, contusions, ulcers, myalgia, and many others. Pharmacological research supports the use in these fields. Of the constituents, naphthodianthrones (e.g., hypericin) and phloroglucinols (e.g., hyperforin) have interesting pharmacological profiles, including antioxidant, anti-inflammatory, anticancer, and antimicrobial activities. In addition, hyperforin stimulates growth and differentiation of keratinocytes, and hypericin is a photosensitizer which can be used for selective treatment of nonmelanoma skin cancer. However, clinical research in this field is still scarce. Recently, sporadic trials have been conducted in wound healing, atopic dermatitis, psoriasis, and herpes simplex infections, partly with purified single constituents and modern dermatological formulations. St. Johnʼs wort also has a potential for use in medical skin care. Composition and stability of pharmaceutical formulations vary greatly depending on origin of the plant material, production method, lipophilicity of solvents, and storage conditions, and this must be regarded with respect to practical as well as scientific purposes.

 
  • References

  • 1 Pliny the Elder (23-79 A.D.). The natural history. Book XXVI, Chapter LXXX. Cited after: Bostock J, Riley HT, editors. London: Taylor and Francis; 1855. The perseus digital library. Available at: http://www.perseus.tufts.edu/hopper/text?doc=Perseus%253atext%253a1999.02.0137 Accessed April 5, 2013
  • 2 Blaschek W, Ebel S, Hackenthal E, Holzgrabe U, Keller K, Reichling J, Schulz V. Hagers Handbuch der pharmazeutischen Praxis. Berlin, Heidelberg: Springer Verlag; 2008
  • 3 WHO. WHO-Monographs on selected medical plants. Geneva: World Health Organization; 2002
  • 4 EMEA (European Medicines Agency). HMPC Community herbal monograph on Hypericum perforatum L., herba (Traditional use). EMEA/HMPC/745582/2009. Wien Med Wochenschr 2010; 160: 557-563
  • 5 Isacchi B, Bergonzi MC, Carnevali F, van der Esch SA, Vincieri FF, Bilia AR. Analysis and stability of the constituents of St. Johnʼs wort oils prepared with different methods. J Pharm Biomed Anal 2007; 45: 756-761
  • 6 German Pharmacopoeia, EB6 (Deutsches Arzneibuch. Suppl., 6th edition). Bonn: Phytopharmaceutical Corporation; 1941: 409
  • 7 Schmidt AH. Use of an on-line, precolumn photochemical reactor in high-performance liquid chromatography of naphthodianthrones in Hypericum perforatum preparations. J Chromatogr A 2003; 987: 181-187
  • 8 Maisenbacher P, Kovar KA. Analysis and stability of Hyperici oleum . Planta Med 1992; 58: 351-354
  • 9 Verotta L, Appendino G, Jakupovic J, Bombardelli E. Hyperforin analogues from St. Johnʼs wort (Hypericum perforatum). J Nat Prod 2000; 63: 412-415
  • 10 Arsić I, Zugić A, Tadić V, Tasić-Kostov M, Mišić D, Primorac M, Runjaić-Antić D. Estimation of dermatological application of creams with St. Johnʼs Wort oil extracts. Molecules 2011; 17: 275-294
  • 11 Orhan IE, Kartal M, Gülpinar AR, Cos P, Matheeussen A, Maes L, Tasdemir D. Assessment of antimicrobial and antiprotozoal activity of the olive oil macerate samples of Hypericum perforatum and their LC-DAD-MS analyses. Food Chem 2013; 138: 870-875
  • 12 EMEA (European Medicines Agency). HMPC assessment report on Hypericum perforatum L., Herba. EMA/HMPC/101303/2008. London: EMEA; 2009
  • 13 Gaedcke F. Herstell- und Qualitätsaspekte pflanzlicher Extrakte. Pharmazie in unserer Zeit 2003; 3: 192-202
  • 14 Kacerovská D, Pizinger K, Majer F, Smíd F. Photodynamic therapy of nonmelanoma skin cancer with topical Hypericum perforatum extract–a pilot study. Photochem Photobiol 2008; 84: 779-785
  • 15 Tardivo JP, Wainwright M, Baptista MS. Local clinical phototreatment of herpes infection in São Paulo. Photodiagnosis Photodyn Ther 2012; 9: 118-121
  • 16 Schempp CM, Lüdtke R, Winghofer B, Simon JC. Effect of topical application of Hypericum perforatum extract (St. Johnʼs wort) on skin sensitivity to solar simulated radiation. Photodermatol Photoimmunol Photomed 2000; 16: 125-128
  • 17 Schempp CM, Windeck T, Hezel S, Simon JC. Topical treatment of atopic dermatitis with St. Johnʼs wort cream – a randomized, placebo controlled, double blind half-side comparison. Phytomedicine 2003; 10 (Suppl. 04) 31-37
  • 18 Cecchini C, Cresci A, Coman MM, Ricciutelli M, Sagratini G, Vittori S, Lucarini D, Maggi F. Antimicrobial activity of seven Hypericum entities from central Italy. Planta Med 2007; 73: 564-566
  • 19 Gibbons S, Ohlendorf B, Johnsen I. The genus Hypericum – a valuable resource of anti-Staphylococcal leads. Fitoterapia 2002; 73: 300-304
  • 20 Bystrov NS, Dobrynin VN, Kolosov MN, Chernov BK, Chervin II. [Structure of the chromophoric part of hyperforin]. Dokl Akad Nauk SSSR 1975; 225: 1327-1328
  • 21 Schempp CM, Pelz K, Wittmer A, Schöpf E, Simon JC. Antibacterial activity of hyperforin from St Johnʼs wort, against multiresistant Staphylococcus aureus and gram-positive bacteria. Lancet 1999; 353: 2129
  • 22 Yow CM, Tang HM, Chu ES, Huang Z. Hypericin-mediated photodynamic antimicrobial effect on clinically isolated pathogens. Photochem Photobiol 2012; 88: 626-632
  • 23 Borchardt JR, Wyse DL, Sheaffer CC, Kauppi KL, Fulcher RG, Ehlke NG, Bicsboer DD, Bey RF. Antimicrobial activity of native and naturalized plants of Minnesota and Wisconsin. J Med Plants Res 2008; 2: 98-110
  • 24 Avato P, Raffo F, Guglielmi G, Vitali C, Rosato A. Extracts from St Johnʼs Wort and their antimicrobial activity. Phytother Res 2004; 18: 230-232
  • 25 Dadgar T, Asmar M, Saifi A, Mazandarani M, Bayat H, Moradi A, Bazueri M, Ghaemi E. Antibacterial activity of certain medicinal plants against methicillin resistant and methicillin sensitive Staphylococcus aureus . Asian J Plant Sci 2006; 5: 861-866
  • 26 Lasik M, Nowak J, Stachowiak B, Czarnecki Z. Evaluation of the antagonistic properties of natural antibacterial substances extracted from herbs: poster presentation. Eurobiotech 2007; 54: 10 (cited after Saddiqe 2010)
  • 27 Reichling J, Weseler A, Saller R. A current review of the antimicrobial activity of Hypericum perforatum L. Pharmacopsychiatry 2001; 34 (Suppl. 01) S116-S118
  • 28 Mortensen T, Shen S, Shen F, Walsh MK, Sims RC, Miller CD. Investigating the effectiveness of St Johnʼs wort herb as an antimicrobial agent against Mycobacteria . Phytother Res 2012; 26: 1327-1333
  • 29 Peeva-Naumovska V, Panovski N, Grdanovska T, Fredro-Kumbaradzi E. Formulations of St. Johnʼs Wort oil ointment and evaluation of its antibacterial effect. Available at http://www.amapseec.org/cmapseec.1/papers/pap-p067.htm 2000. Accessed April 28, 2013
  • 30 Saddiqe Z, Naeem I, Maimoona A. A review of the antibacterial activity of Hypericum perforatum L. J Ethnopharmacol 2010; 131: 511-521
  • 31 Birt DF, Widrlechner MP, Hammer KD, Hillwig ML, Wei J, Kraus GA, Murphy PA, McCoy J, Wurtele ES, Neighbors JD, Wiemer DF, Maury WJ, Price JP. Hypericum in infection: Identification of anti-viral and anti-inflammatory constituents. Pharm Biol 2009; 47: 774-782
  • 32 Klemow KM, Bartlow A, Crawford J, Kocher N, Shah J, Ritsick M. Medical attributes of St. Johnʼs Wort (Hypericum perforatum). In: Benzie IFF, Wachtel-Galor S, editors Herbal medicine: biomolecular and clinical aspects. 2nd edition. Boca Raton: CRC Press; 2011. (Chapter 11)
  • 33 Takahashi I, Nakanishi S, Kobayashi E, Nakano H, Suzuki K, Tamaoki T. Hypericin and pseudohypericin specifically inhibit protein kinase C: possible relation to their antiretroviral activity. Biochem Biophys Res Commun 1989; 165: 1207-1212
  • 34 Gulick RM, McAuliffe V, Holden-Wiltse J, Crumpacker C, Liebes L, Stein DS, Meehan P, Hussey S, Forcht J, Valentine FT. Phase I studies of hypericin, the active compound in St. Johnʼs Wort, as an antiretroviral agent in HIV-infected adults. AIDS Clinical Trials Group Protocols 150 and 258. Ann Intern Med 1999; 130: 510-514
  • 35 Maury W, Price JP, Brindley MA, Oh C, Neighbors JD, Wiemer DF, Wills N, Carpenter S, Hauck C, Murphy P, Widrlechner MP, Delate K, Kumar G, Kraus GA, Rizshsky L, Nikolau B. Identification of light-independent inhibition of human immunodeficiency virus-1 infection through bioguided fractionation of Hypericum perforatum . Virol J 2009; 6: 101
  • 36 López-Chicón P, Paz-Cristobal MP, Rezusta A, Aspiroz C, Royo-Cañas M, Andres-Ciriano E, Gilaberte Y, Agut M, Nonell S. On the mechanism of Candida spp. photoinactivation by hypericin. Photochem Photobiol Sci 2012; 11: 1099-1107
  • 37 Khosa RL, Bhatia N. Antifungal effect of Hypericum perforatum Linn. J Sci Res Plant Med 1982; 3: 49-50
  • 38 Hunt EJ, Lester CE, Lester EA, Tackett RL. Effect of St. Johnʼs wort on free radical production. Life Sci 2001; 69: 181-190
  • 39 Benedi J, Arroyo R, Romero C, Martin-Aragon S, Villar AM. Antioxidant properties and protective effects of a standardized extract of Hypericum perforatum on hydrogen peroxide-induced oxidative damage in PC12 cells. Life Sci 2004; 75: 1263-1276
  • 40 Jang MH, Lee TH, Shin MC, Bahn GH, Kim JW, Shin DH, Kim EH, Kim CJ. Protective effect of Hypericum perforatum Linn (St. Johnʼs wort) against hydrogen peroxide-induced apoptosis on human neuroblastoma cells. Neurosci Lett 2002; 329: 177-180
  • 41 Sagratini G, Ricciutelli M, Vittori S, Oztürk N, Oztürk Y, Maggi F. Phytochemical and antioxidant analysis of eight Hypericum taxa from Central Italy. Fitoterapia 2008; 79: 210-213
  • 42 Rainha N, Lima E, Baptista J. Comparison of the endemic Azorean Hypericum foliosum with other Hypericum species: antioxidant activity and phenolic profile. Nat Prod Res 2011; 25: 123-135
  • 43 Zou Y, Lu Y, Wei D. Antioxidant activity of a flavonoid-rich extract of Hypericum perforatum L. in vitro . J Agric Food Chem 2004; 52: 5032-5039
  • 44 Meinke MC, Schanzer S, Haag SF, Casetti F, Müller ML, Wölfle U, Kleemann A, Lademann J, Schempp CM. In vivo photoprotective and anti-inflammatory effect of hyperforin is associated with high antioxidant activity in vitro and ex vivo. Eur J Pharm Biopharm 2012; 81: 346-350
  • 45 Onoue S, Seto Y, Ochi M, Inoue R, Ito H, Hatano T, Yamada S. In vitro photochemical and phototoxicological characterization of major constituents in St. Johnʼs Wort (Hypericum perforatum) extracts. Phytochemistry 2011; 72: 1814-1820
  • 46 Schempp CM, Müller K, Winghofer B, Schulte-Mönting J, Simon JC. Single-dose and steady-state administration of Hypericum perforatum extract (St Johnʼs Wort) does not influence skin sensitivity to UV radiation, visible light, and solar-simulated radiation. Arch Dermatol 2001; 137: 512-513
  • 47 Traynor NJ, Beattie PE, Ibbotson SH, Moseley H, Ferguson J, Woods JA. Photogenotoxicity of hypericin in HaCaT keratinocytes: implications for St. Johnʼs Wort supplements and high dose UVA-1 therapy. Toxicol Lett 2005; 158: 220-224
  • 48 Schmitt LA, Liu Y, Murphy PA, Petrich JW, Dixon PM, Birt DF. Reduction in hypericin-induced phototoxicity by Hypericum perforatum extracts and pure compounds. J Photochem Photobiol B 2006; 85: 118-130
  • 49 Boiy A, Roelandts R, van den Oord J, de Witte PA. Photosensitizing activity of hypericin and hypericin acetate after topical application on normal mouse skin. Br J Dermatol 2008; 158: 360-369
  • 50 Sosa S, Pace R, Bornancin A, Morazzoni P, Riva A, Tubaro A, Della Loggia R. Topical anti-inflammatory activity of extracts and compounds from Hypericum perforatum L. J Pharm Pharmacol 2007; 59: 703-709
  • 51 Kang BY, Chung SW, Kim TS. Inhibition of interleukin-12 production in lipopolysaccharide-activated mouse macrophages by hpyericin, an active component of Hypericum perforatum . Planta Med 2001; 67: 364-366
  • 52 Albert D, Zündorf I, Dingermann T, Müller WE, Steinhilber D, Werz O. Hyperforin is a dual inhibitor of cyclooxygenase-1 and 5-lipoxygenase. Biochem Pharmacol 2002; 64: 1767-1775
  • 53 Hammer KD, Hillwig ML, Solco AK, Dixon PM, Delate K, Murphy PA, Wurtele ES, Birt DF. Inhibition of prostaglandin E(2) production by anti-inflammatory Hypericum perforatum extracts and constituents in RAW264.7 Mouse Macrophage Cells. J Agric Food Chem 2007; 55: 7323-7331
  • 54 Koeberle A, Rossi A, Bauer J, Dehm F, Verotta L, Northoff H, Sautebin L, Werz O. Hyperforin, an Anti-Inflammatory Constituent from St. Johnʼs Wort, Inhibits Microsomal Prostaglandin E(2) Synthase-1 and Suppresses Prostaglandin E(2) Formation in vivo . Front Pharmacol 2011; 2: 7
  • 55 Feisst C, Pergola C, Rakonjac M, Rossi A, Koeberle A, Dodt G, Hoffmann M, Hoernig C, Fischer L, Steinhilber D, Franke L, Schneider G, Rådmark O, Sautebin L, Werz O. Hyperforin is a novel type of 5-lipoxygenase inhibitor with high efficacy in vivo . Cell Mol Life Sci 2009; 66: 2759-2771
  • 56 Heilmann J, Winkelmann K, Sticher O. Studies on the antioxidative activity of phloroglucinol derivatives isolated from Hypericum species. Planta Med 2003; 69: 202-206
  • 57 Cabrelle A, DellʼAica I, Melchiori L, Carraro S, Brunetta E, Niero R, Scquizzato E, DʼIntino G, Calzà L, Garbisa S, Agostini C. Hyperforin down-regulates effector function of activated T lymphocytes and shows efficacy against Th1-triggered CNS inflammatory-demyelinating disease. J Leukoc Biol 2008; 83: 212-219
  • 58 Schempp CM, Winghofer B, Lüdtke R, Simon-Haarhaus B, Schöpf E, Simon JC. Topical application of St Johnʼs wort (Hypericum perforatum L.) and of its metabolite hyperforin inhibits the allostimulatory capacity of epidermal cells. Br J Dermatol 2000; 142: 979-984
  • 59 Schempp CM, Simon-Haarhaus B, Simon JC. Phototoxic and apoptosis-inducing capacity of pseudohypericin. Planta Med 2002; 68: 171-173
  • 60 Schempp CM, Simon-Haarhaus B, Termeer CC, Simon JC. Hypericin photo-induced apoptosis involves the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and activation of caspase-8. FEBS Lett 2001; 493: 26-30
  • 61 Sharma KV, Davids LM. Hypericin-PDT-induced rapid necrotic death in human squamous cell carcinoma cultures after multiple treatment. Cell Biol Int 2012; 36: 1261-1266
  • 62 Sharma KV, Davids LM. Depigmentation in melanomas increases the efficacy of hypericin-mediated photodynamic-induced cell death. Photodiagnosis Photodyn Ther 2012; 9: 156-163
  • 63 Menichini G, Alfano C, Marrelli M, Toniolo C, Provenzano E, Statti GA, Nicoletti M, Menichini F, Conforti F. Hypericum perforatum L. subsp. perforatum induces inhibition of free radicals and enhanced phototoxicity in human melanoma cells under ultraviolet light. Cell Prolif 2013; 46: 193-202
  • 64 Huntosova V, Nadova Z, Dzurova L, Jakusova V, Sureau F, Miskovsky P. Cell death response of U87 glioma cells on hypericin photoactivation is mediated by dynamics of hypericin subcellular distribution and its aggregation in cellular organelles. Photochem Photobiol Sci 2012; 11: 1428-1436
  • 65 Ritz R, Scheidle C, Noell S, Roser F, Schenk M, Dietz K, Strauss WSL. In vitro comparison of hypericin and 5-aminolevulinic acid-derived protoporphyrin IX for photodynamic inactivation of medulloblastoma cells. PLoS ONE 2012; 7: e51974
  • 66 Šemeláková M, Mikeš J, Jendželovský R, Fedoročko P. The pro-apoptotic and anti-invasive effects of hypericin-mediated photodynamic therapy are enhanced by hyperforin or aristoforin in HT-29 colon adenocarcinoma cells. J Photochem Photobiol B 2012; 117: 115-125
  • 67 Schempp CM, Kirkin V, Simon-Haarhaus B, Kersten A, Kiss J, Termeer CC, Gilb B, Kaufmann T, Borner C, Sleeman JP, Simon JC. Inhibition of tumour cell growth by hyperforin, a novel anticancer drug from St. Johnʼs wort that acts by induction of apoptosis. Oncogene 2002; 21: 1242-1250
  • 68 Merhi F, Tang R, Piedfer M, Mathieu J, Bombarda I, Zaher M, Kolb JP, Billard C, Bauvois B. Hyperforin inhibits Akt1 kinase activity and promotes caspase-mediated apoptosis involving Bad and Noxa activation in human myeloid tumor cells. PLoS One 2011; 6: e25963
  • 69 Hostanska K, Reichling J, Bommer S, Weber M, Saller R. Hyperforin a constituent of St Johnʼs wort (Hypericum perforatum L.) extract induces apoptosis by triggering activation of caspases and with hypericin synergistically exerts cytotoxicity towards human malignant cell lines. Eur J Pharm Biopharm 2003; 56: 121-132
  • 70 Schempp CM, Kiss J, Kirkin V, Averbeck M, Simon-Haarhaus B, Kremer B, Termeer CC, Sleeman J, Simon JC. Hyperforin acts as an angiogenesis inhibitor. Planta Med 2005; 71: 999-1004
  • 71 Dajas F. Life or death: neuroprotective and anticancer effects of quercetin. J Ethnopharmacol 2012; 143: 383-396
  • 72 Romagnolo DF, Selmin OI. Flavonoids and cancer prevention: a review of the evidence. J Nutr Gerontol Geriatr 2012; 31: 206-238
  • 73 Mukherjee PK, Verpoorte R, Suresh B. Evaluation of in-vivo wound healing activity of Hypericum patulum (Family: Hypericaceae) leaf extract on different wound model in rats. J Ethnopharmacol 2000; 70: 315-321
  • 74 Süntar IP, Akkol EK, Yilmazer D, Baykal T, Kirmizibekmez H, Alper M, Yeşilada E. Investigations on the in vivo wound healing potential of Hypericum perforatum L. J Ethnopharmacol 2010; 127: 468-477
  • 75 Castro FC, Magre A, Cherpinski R, Zelante PM, Neves LM, Esquisatto MA, Mendonça FA, Santos GM. Effects of microcurrent application alone or in combination with topical Hypericum perforatum L. and Arnica montana L. on surgically induced wound healing in Wistar rats. Homeopathy 2012; 101: 147-153
  • 76 Öztürk N, Korkmaz S, Ozturk Y. Wound-healing activity of St. Johnʼs Wort (Hypericum perforatum L.) on chicken embryonic fibroblasts. J Ethnopharmacol 2006; 111: 33-39
  • 77 Hostanska K, Rostock M, Melzer J, Baumgartner S, Saller R. A homeopathic remedy from arnica, marigold, St. Johnʼs wort and comfrey accelerates in vitro wound scratch closure of NIH 3 T3 fibroblasts. BMC Complement Altern Med 2012; 12: 100
  • 78 Leuner K, Kraus M, Woelfle U, Beschmann H, Harteneck C, Boehncke WH, Schempp CM, Müller WE. Reduced TRPC channel expression in psoriatic keratinocytes is associated with impaired differentiation and enhanced proliferation. PLoS One 2011; 6: e14716
  • 79 Müller M, Essin K, Hill K, Beschmann H, Rubant S, Schempp CM, Gollasch M, Boehncke WH, Harteneck C, Müller WE, Leuner K. Specific TRPC6 channel activation, a novel approach to stimulate keratinocyte differentiation. J Biol Chem 2008; 283: 33942-33954
  • 80 Chen WC, Liou SS, Tzeng TF, Lee SL, Liu IM. Effect of topical application of chlorogenic acid on excision wound healing in rats. Planta Med 2013; Apr 8. [Epub ahead of print]
  • 81 CEBM – Oxford Centre for Evidence Based Medicine. Levels of evidence. March 2009. Available at http://www.cebm.net/?o=1025 Accessed April 30, 2013
  • 82 Saljic J. Ointment for the treatment of burns. Ger Offen 1975; 2: 406-452
  • 83 Lomagno P, Lomagno RC. Activity of Hypericum perforatum oil in the treatment of the bed sores in old people. Fitoterapia 1979; 50: 201-205
  • 84 Kundaković T, Milenković M, Zlatković S, Nikolić V, Nikolić G, Binić I. Treatment of venous ulcers with the herbal-based ointment Herbadermal®: a prospective non-randomized pilot study. Forsch Komplementmed 2012; 19: 26-30
  • 85 Lavagna SM, Secci D, Chimenti P, Bonsignore L, Ottaviani A, Bizzarri B. Efficacy of Hypericum and Calendula oils in the epithelial reconstruction of surgical wounds in childbirth with caesarean section. Farmaco 2001; 56: 451-453
  • 86 Samadi S, Khadivzadeh T, Emami A, Moosavi NS, Tafaghodi M, Behnam HR. The effect of Hypericum perforatum on the wound healing and scar of cesarean. J Alternat Complement Med 2010; 16: 113-117
  • 87 Läuchli S, Hafner J, Wehrmann C, French LE, Hunziker T. Post-surgical scalp wounds with exposed bone treated with a plant-derived wound therapeutic. J Wound Care 2012; 21: 228 230, 232–233
  • 88 Najafizadeh P, Hashemian F, Mansouri P, Farshi S, Surmaghi MS, Chalangari R. The evaluation of the clinical effect of topical St Johns wort (Hypericum perforatum L.) in plaque type psoriasis vulgaris: a pilot study. Australas J Dermatol 2012; 53: 131-135
  • 89 Mannel M, Koytchev R, Dundarov S. Oral hypericum extract LI 160 is an effective treatment of recurrent herpes genitalis and herpes labialis. Phytomedicine 2000; 7 (Suppl. 02) 17
  • 90 Clewell A, Barnes M, Endres JR, Ahmed M, Ghambeer DK. 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. J Drugs Dermatol 2012; 11: 209-215
  • 91 Alecu M, Ursaciuc C, Hãlãlãu F, Coman G, Merlevede W, Waelkens E, de Witte P. Photodynamic treatment of basal cell carcinoma and squamous cell carcinoma with hypericin. Anticancer Res 1998; 18: 4651-4654
  • 92 Dirschka T and AK-CT002 Study Group. Photodynamic therapy with BF-200 ALA for the treatment of actinic keratosis: results of a multicentre, randomized, observer-blind phase III study in comparison with a registered methyl-5-aminolaevulinate cream and placebo. Br J Dermatol 2012; 166: 137-146
  • 93 Heinrich U, Tronnier H. Wirksamkeit und Verträglichkeit eines Johanniskraut-Extraktes zur Pflege der atopischen Haut. Kosmetische Med 2003; 124: 133-136
  • 94 Arndt S, Haag SF, Kleemann A, Lademann J, Meinke MC. Radical protection in the visible and infrared by a hyperforin-rich cream – in vivo versus ex vivo methods. Exp Dermatol 2013; 22: 354-357
  • 95 Haag SF, Tscherch K, Arndt S, Kleemann A, Gersonde I, Lademann J, Rohn S, Meinke MC. Enhancement of skin radical scavenging activity and stratum corneum lipids after the application of a hyperforin-rich cream. Eur J Pharm Biopharm 2013; Jun 26 [pii: S0939–6411(13)00235-X]. DOI: 10.1016/j.ejpb.2013.06.016. [Epub ahead of print]
  • 96 CIR – Cosmetic Ingredient Review. Final report on the safety assessment of Hypericum perforatum extract and Hypericum perforatum oil. Int J Toxicol 2001; 20 (Suppl. 02) 31-39
  • 97 Reuter J, Huyke C, Scheuvens H, Ploch M, Neumann K, Jakob T, Schempp CM. Skin tolerance of a new bath oil containing St. Johnʼs wort extract. Skin Pharmacol Physiol 2008; 21: 306-311