Evaluation of the cytotoxicity, mutagenicity and antimutagenicity of a natural antidepressant, Hypericum perforatum L. (St. John’s wort), on vegetal and animal test systems

BMC Complementary and Alternative Medicine

Veronica Elisa Pimenta Vicentini¹  Mário Sérgio Mantovani³  Elisângela Düsman¹  Igor Vivian de Almeida¹  Rosinete Gonçalves Mariucci¹  Ana Paula Peron² 

[1] Department of Biotechnology, Genetics and Cell Biology, State University of Maringá, Maringá, Paraná, Brazil;Department of Biotechnology, Genetics and Cell Biology, State University of Maringá, Avenida Colombo 5790, Bloco H67 (11), Jardim Universitário, Maringá, Paraná CEP: 87020-900, Brazil;Department of General Biology, State University of Londrina, Londrina, Paraná, Brazil

关键词: Mitotic index;    Allium cepa L.;    Medicinal plant;    Wistar rats;    Pharmacological action;    Chromosomal aberration;   

Others  :  1229967
DOI  :  10.1186/1472-6882-13-97

 received in 2012-11-05, accepted in 2013-05-02,  发布年份 2013

【 摘 要 】

Background

St. John’s wort (Hypericum perforatum L.) is an herbaceous plant that is native to Europe, West Asia and North Africa and that is recognized and used worldwide for the treatment of mild and moderate depression. It also has been shown to be therapeutic for the treatment of burns, bruises and swelling and can be used for its wound healing, antiviral, antimicrobial, antioxidant, analgesic, hepato-protective and anxiolytic properties. The aim of this study was to evaluate the potential cytotoxic, mutagenic and antimutagenic action of H. Perforatum.

Methods

Meristematic cells were used as the test system for Allium cepa L., and bone marrow cells from Rattus norvegicus, ex vivo, were used to calculate the mitotic index and the percentage of chromosomal aberration. Statistical analysis was performed using the chi-square test.

Results

This medicinal plant had no cytotoxic potential in the vegetal test system evaluated. In the animal test system, none of the acute treatments, including intraperitoneal gavage and subchronic gavage, were cytotoxic or mutagenic. Moreover, this plant presented antimutagenic activity against the clastogenic action of cyclophosphamide, as confirmed in pre-treatment (76% reduction in damage), simultaneous treatment (95%) and post-treatment (97%).

Conclusions

Thus, the results of this study suggest that the administration of H. perforatum, especially by gavage similar to oral consumption used by humans, is safe and with beneficial antimutagenic potential.

【 授权许可】

   
2013 Peron et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

【 参考文献 】

• [1]Linde K: St. John’s wort – an overview. Forsch Komplementmed 2009, 16:146-155.
• [2]Bilia AR, Gallori S, Vincieri FF: St. John’s wort and depression efficacy, safety and tolerability – an update. Life Sci 2002, 70:3077-3096.
• [3]Di Carlo G, Borrelli F, Ernst E, Izzo AA: St John’s wort: Prozac from the plant kingdom. Trends Pharmacol Sci 2001, 22:292-298.
• [4]Mennini T, Gobbi M: The antidepressant mechanisms of Hypericum perforatum. Life Sci 2004, 75:1021-1027.
• [5]Guedes AP, Franklin G, Fernandes-Ferreira M: Hypericum sp.: essential oil composition and biologic activities. Phytochemestry Rev 2012, 11:127-152.
• [6]Prado B, Rabanal R, Sánchez-Mateo C: Evaluation of the central properties of several Hypericum species from the Canary Islands. Phytother Res 2002, 16:740-744.
• [7]Pieroni A, Quave CL, Santoro RF: Folk pharmaceutical knowledge in the territory of the Dolomiti Lucane, inland southern Italy. J Ethnopharmacol 2004, 95:373-384.
• [8]Ferreira A, Proença C, Serralheiro MLM, Araújo MEM: The in vitro screening for a acetylcholinesterase inhibition and antioxidant activity of medicinal plants from Portugal. J Ethnopharmacol 2006, 108:31-37.
• [9]Gaedcke F: St John’s wort herb extracts: Manufacturing, standardization and characterization. In Hypericum: the genus Hypericum. London: E. Ernst. Taylor & Francis; 2003:49-64.
• [10]Nogueira T, Duarte F, Venâncio F, Tavares R, Lousã M, Bicchi C, Rubiolo P: Aspectos quimiotaxonómicos do género Hypericum L. em Portugal. Silva Lusitana 1998, 6:55-61.
• [11]Jakovljević V, Popović M, Mimica-Dukić N, Sabo A, Gvozdenović LJ: Pharmacodynamic study of Hypericum perforatum L. Phytomedicine 2000, 7:449-453.
• [12]Popović M, Jakovljević V, Mimica-Dukić N, Kaurinović B, Ćebović T: Effects of different extracts of Hypericum perforatum L. on the CCl4-induced hepatotoxicity in rats. Oxid Communications 2002, 25:273-278.
• [13]Camejo-Rodrigues J, Ascensão L, Bonet MA, Vallés J: An ethnobotanical study of medicinal and aromatic plants in the natural park of “Serra de São Mamede” (Portugal). J Ethnopharmacol 2003, 89:199-209.
• [14]Ivanova D, Gerova D, Chervenkov T, Yankova T: Polyphenols and antioxidant capacity of Bulgarian medicinal plants. J Ethnopharmacol 2005, 96:145-150.
• [15]Jaric S, Popovic Z, Macukanovic-Jocic M, Djurdjevic L, Mijatovic M, Karadzic B, Mitrovic M, Pavlovic P: An ethnobotanical study on the usage of wild medicinal herbs from Kopaonik Mountain (Central Serbia). J Ethnopharmacol 2007, 111:160-175.
• [16]Kültür S: Medicinal plants used in KIrklareli Province (Turkey). J Ethnopharmacol 2007, 111:341-364.
• [17]Radulović N, Stankov-Jovanović V, Stojanović G, Šmelcerović A, Spiteller M, Asakawa Y: Screening of in vitro antimicrobial and antioxidant activity of nine Hypericum species from the Balkans. Food Chemestry 2007, 20:315-321.
• [18]Spiteller M, Ozen T, Šmelcerović A, Zuehlke S, Mimica-Dukić N: Phenolic constituents and the in vitro antioxidant activity of the flowers of Hypericum venustum. Fitoterapia 2008, 79:191-193.
• [19]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, 6:1-12. BioMed Central Full Text
• [20]Greeson JM, Sanford B, Monti DA: St. John’s wort (Hypericum perforatum): a review of the current pharmacological, toxicological, and clinical literature. Psychopharmacol 2001, 153:402-414.
• [21]Bhatia A, Arora S, Singh B, Kaur G, Nagpal A: Anticancer potential of Himalayan plants. Phytochemestry Rev 2011, 10:309-323.
• [22]Nahrstedt A, Butterweck V: Biologically active and other chemical constituents of the herb of Hypericum perforatum. Pharmacopsychiatry 1997, 30:129-134.
• [23]Müller WE: Current St. John’s wort research from mode of action to clinical efficacy. Phamacol Res 2003, 47:101-1093.
• [24]Butterweck V, Schmidt M: St. John’s wort: role of active compounds for its mechanism of action and efficacy. Wien Med Wochenschr 2007, 157:356-361.
• [25]Fiskesjö G: The Allium test as a standard in environmental monitoring. Hereditas 1985, 102:99-112.
• [26]Ford CE, Hamerton JL: A colchicine, hypotonic citrate, squash sequence for mammalian chromosomes. Stain Technol 1956, 31:247-251.
• [27]Schempp CM, Winghofer B, Ludtke R: Topical application of St. John’s wort (Hypericum perforatum L.) and of its metabolite hyperforin inhibits the allostimulatory capacity of epidermal cells. Br J Dermatol 2000, 142:979-984.
• [28]Schempp C, Pelz K: Wittmer A. Antibacterial activity of hyperforin from St. John’s wort, against multiresistant Staphylococcus aureus and gram-positive bacteria. Lancet 1999, 353:21-29.
• [29]Alecu M, Ursaciuc C, Halalau F: Photodynamic treatment of basal cell carcinoma and squamous cell carcinoma with hypericin. Anticancer Res 1998, 18:4651-4654.
• [30]Patocka J: The chemistry, pharmacology, and toxicology of the biologically active constituents of the herb Hypericum perforatum L. J Appl Biomedicine 2003, 1:61-70.
• [31]Kusari S, Zühlke S, Kosuth J, Cellárová E, Spiteller M: Light-independent metabolomics of endophytic Thielavia subthermophila provides insight into microbial hypericin biosynthesis. J Nat Prod 2009, 72:1825-1835.
• [32]Xu CS, Leung AWN: Light-activated hypericin induces cellular destruction of nasopharyngeal carcinoma cells. Laser Phys Lett 2010, 7:68-72.
• [33]Ferraz A, Faria DH, Benneti MN, Brondani da Rocha A, Schwartsmann G, Henriques A, Von Poser GL: Screening for antiproliferative activity of six southern Brazilian species of Hypericum. Phytomedicine 2005, 12:112-115.
• [34]Hostanska K, Bommer S, Weber M, Krasniqi B, Saller R: Comparison of the growth-inhibitory effect of Hypericum perforatum L. extracts, differing in the concentration of phloroglucinols and flavonoids, on leukaemia cells. J Pharm Pharmacol 2003, 55:973-980.
• [35]Tanaka N, Kashiwada Y, Kim SY, Hashida W, Sekiya M, Ikeshiro Y, Takaishi Y: Acylphloroglucinol, biyouyanagiol, biyouyanagin B, and related spiro-lactones from Hypericum chinense. J Nat Prod 2009, 72:1447-1452.
• [36]Tanaka N, Kashiwada Y, Kim SY, Sekiya M, Ikeshiro Y, Takaishi Y: Xanthones from Hypericum chinense and their cytotoxicity evaluation. Phytochemistry 2009, 70:1456-1461.
• [37]Moon HI: Antiplasmodial and cytotoxic activity of Phloroglucinol derivatives from Hypericum erectum Thunb. Phytother Res 2010, 24:941-944.
• [38]Hammerness P, Basch E, Ulbricht C, Barrette EP, Foppa I, Basch S, Bent S, Boon H, Ernst E: John’s Wort: a systematic review of adverse effects and drug interactions for the Consultation Psychiatrist. Psychosom 2003, 44:271-282.
• [39]Rayburn WF, Christensen HD, Gonzalez CL: Effect of antenatal exposure to Saint John’s wort (Hypericum) on neurobehavior of developing mice. Am J Obstet Gynecol 2000, 183:1225-1231.
• [40]Rayburn WF, Gonzalez CL, Christensen HD, Stewart JD: Effect of prenatally administered hypericum (St John’s wort) on growth and physical maturation of mouse offspring. Am J Obstet Gynecol 2001, 184:191-195.
• [41]Okpanyi SN, Lidzba H, Scholl BC, Miltenburger HG: Investigations into the genotoxicity of a standardized extract of Hypericum perforatum. Arzneim.-Forsch/Drug Res 1990, 40:851-855.
• [42]Ndhlala AR, Finnie JF, Van Staden J: Plant composition, pharmacological properties and mutagenic evaluation of a commercial Zulu herbal mixture: Imbiza ephuzwato. J Ethnopharmacol 2011, 133:663-674.
• [43]Miadokova E, Chalupa I, Vlckova V, Sevcovicova A, Nadova S, Kopaskova M, Hercegova A, Gasperova P, Alfoldiova L, Komjatiova M, Csanyiova Z, Galova E, Cellarova E, Vlcek D: Genotoxicity and antigenotoxicity evaluation of non-photoactivated hypericin. Phytother Res 2010, 24:90-95.
• [44]Alonso J: Hipérico. (Hypericum perforatum L.). Rev Fitociência 1997, 1:20-29.
• [45]Stolf A, Dreifuss A, Vieira FL: Apostila do Curso de Verão em Farmacologia. 2011. http://insightltda.com.br/images/dinamica/pdf_7fe1310c8e894324299fcfd3b8f760ef webcite
• [46]Tolan V, Toker Z, Ozdemir S, Demirci O, Otludil B, Oezen HC: Mutagenicity of Hypericum lysimachioides extracts. Pharm Biol 2009, 47:1035-1041.
• [47]Bhatia A, Arora S, Singh B, Nagpal A: Evaluation of in vitro antimutagenic activity of Hypericum perforatum Linn. in Ames assay. Pharmacologyonline 2010, 1:167-175.
• [48]Schwarz D, Kisselev P, Roots I: 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 2003, 63:8062-8068.
• [49]Hostanska K, Reichlingb J, Bommerc S: Constituent of St John’s wort (Hypericum perforatum L.) extract induces apoptosis by triggering activation of caspases and with hypericin synergistically exerts cytotoxicity towards human malignant cell lines. J Pharmacol Biopharmacol 2003, 56:121-132.
• [50]Theodossiou TA, Hothersall JS, De Witte PA, Pantos A, Agostinis P: The multifaceted photocytotoxic profile of Hypericin. Mol Pharm 2009, 6:1775-1789.
• [51]Kada T, Morita K, Inoue T: Anti-mutagenic action of vegetable factor(s) on the mutagenic principle of tryptophan pyrolysate. Mutat Res 1978, 53:351-353.
• [52]Kojima H, Konishi H, Kuroda Y: Combined mutagenicity of methyl methanesulfonate and ethyl methanesulfonate in chinese hamster V79 cells. Mutat Res 1992, 266:171-180.
• [53]Kuroda Y, Jain AK, Tekuza H, Kada T: Antimutagenicity in cultured mammalian cells. Mutat Res 1992, 267:201-209.
• [54]Hunt EJ, Lester CE, Lester EA, Tackett RL: Effect of St. John’s wort on free radical production. Life Sci 2001, 69:181-190.
• [55]Jang MH, Lee TH, Shin MC, Bahn GH, Kim JW, Shin DH, Kim EH, Kim CJ: Protective effect of Hypericum perforatum Linn (St. John’s wort) against hydrogen peroxide-induced apoptosis on human neuroblastoma 3. Neurosci Lett 2002, 329:177-180.
• [56]Zou YP, Lu YH, Wei DZ: Protective effects of a flavonoid-rich extract of Hypericum perforatum L. against hydrogen peroxide-induced apoptosis in PC12 cells. Phytother Res 2010, 24:S6-S10.
• [57]An RB, Jeong GS, Beom JS, Sohn DH, Kim Y: Chromone glycosides and hepatoprotective constituents of Hypericum erectum. Arch Pharm Res 2009, 32:1393-1397.