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St. John’s Wort Rachael Krob, Melissa Morrison & Katie Wooten St. John’s Wort • Hypericum perforatum from the family Hypericaceae – genus Hypericum – 400 species worldwide • Common Name: Goatweed Klamath Weed Amber Touch-and-Heal Blood of Christ Hardhay Guttiferae Tipton weed Botanical Description • SJW is an aromatic perennial herb, usually growing between 1-3 feet -small oblong leaves dotted with glandular trichomes containing essential oils -flowers are yellow with an abundance of bushy stamens - 5 petals with black dots on the periphery • Native to Europe, Asia and parts of Africa • Widespread in the U.S. and can be found in sunny places such as fields, meadows, and roadsides Ethnobotany -What’s in a name? • “wort”- English word for plant • “perforatum”- Latin word for hole • Legend of SJW • Origin of name dates back to the Middle Ages -believed the red resin was blood from the beheaded St. John the Baptist -flowers have brightest appearance on June 24th, John the Baptist’s birthday Ethnobotany • Gaelic tradition • Food flavoring • Crop blessings – Soaked plant in olive oil until “blood” was released – Red oil used to bless crops • Pre-Christian Religious practices – Protect from evil spirits and banish witches – Sleeping with plant provided blessings – “herba demonis fuga”: herb that chases away the devil Historical Usage • Used by various countries to treat: – – – – – – – – – Depression Kidney disorders Wound treatment Antibacterial Anti-viral (AIDS) GI disorders Diuretic Night terrors Cancer Historical Uses • Many early herbalist/physicians recommended SJW – Hippocrates, Gerard, Pliny the Elder, Dioscorides • Medicinal usage well document with 1st written record dating back to 1st century A.D. – Pliny the Elder • Dioscorides recommended SJW in his medical text for the treatment of sciatica and burns • First suggested by Paracelsus to treat mental illnesses – Work led to centuries of research in this area – 1630: Agelo Sala mentioned SJW’s excellent reputation for treating “illnesses of the imagination, melancholia, and anxiety” Historical Usage • SJW continued to spread and was eventually introduced to the American Indians – Used to treat tuberculosis and other breathing conditions • Today, SJW is best known for anti-depressive activities, but research continues in many areas, especially cancer and AIDS • Currently, SJW is listed in national pharmacopoeias of France, Poland, Czechoslovakia, Russia, Germany and Romania Current Medical Uses • Depression • Cancer • HIV/AIDS ***(Further research and trials is needed to confirm effectiveness) • Burns, cuts, and herpes (painful blisters of genital herpes). Methods of Use •Capsules •Tinctures •Teas (powder) •Depremin and Depesin : contains 0.5 mg Hypericin •Natrol •Kira or Jarsin 300 Depression • In any given 1-year period, 9.5 percent of the population, or about 18.8 million American adults, suffer from a depressive illness (Robins) • “In Germany, it is prescribed twenty times more often than popular pharmaceutical drugs Zoloft and Prozac” • Effectiveness of St John's Wort. in Major Depression (Shelton et al. 1978-1986) • St.John’s wort for depression-an overview and metaanalysis of randomised clinical trials (Linde et al. 253-258) Cancer • Compounds from St.John’s Wort have anticancer properties • St.John’s Wort More Implications for Cancer Patients (Mansky et al. 1187-1188) • Anti-cancer Activities of Hypericin in the Dark (Blank et al. 120-125) • Antivascular Tumor Eradication by Hypericinmediated Photodynamic Therapy (Chen et al. 509-513) HIV/AIDS • Hypericin seems to interfere with the reproduction of retroviruses • Further research is needed • P27SJ, a novel protein in St John's Wort, that suppresses expression of HIV-1 genome (Sarkissian et al. 288-295) Side Effects • Anxiety, dry mouth dizziness, gastrointestinal symptoms, fatigue, headache, or sexual dysfunction. • Research shows that St. John’s Wort interacts with some drugs. • Indinavir, Irinotecan, Cyclosporine, Digoxin, Warfarin, Birth control pills, and Antidepressants. Compounds • SJW contains naphtodiantrons, flavonoids, phloroglucinols, phenolic acids, and essential oils • The active compounds are: – Hypericin, pseudohypericin (naphtodiantrons) • Cancer – Hyperforin (phloroglucinol) • Used for depression Compound Structures Mode of Action - Depression • Hyperforin – major component • Inhibits the 3H-GABA transporter GAT1 and the 3H-L-glutamate transporter EAAC1 • Monensin, a Na+ ionophore, inhibits reuptake of these, serotonin, and dopamine • Hyperforin does not act on this channel, but it appears to act on a sodium conductive pathway (Wonnemann, 2000) • 2003 study – upregulates serotonin 5-HT(2) receptors in mice (Butterweck, 2003) Mode of Action - Cancer • Study by F. Pajonk, 2005 – Hypericin inhibits NF-κB, a major transcription factor influencing apoptosis – Leads to premature apoptosis • Study by B. Chen, 2002 – Photodynamic therapy and hypericin – Destroys vascular cells in tumors – Has potential for use in solid tumors Mode of Action – HIV/AIDS • Protein from SJW - p27SJ • Binds to C/EBPβ – inhibits its interaction with DNA • p27SJ decreases level of viral replication in HIV infected cells (Darbinian-Sarkissian , 2006) Contraindications • Hyperforin – May activate pregnane X receptor – PXR induces CYP3A4 transcription – Results in quicker metabolism of certain xenobiotics (Moore, 2000) Work Cited Blank, Michael, Mathilda Mandel, Sadick Hazan, and Yona Keisari. "ANTI-cancer Activities of Hypercin in the Dark." Photochemistry and Photobiology May 2001: 120-125. Chen, Bin, Tania Roskams, and Peter A.M. de Witte. "Antivascular Tumor eradication by Hypericin-mediated Photodynamic Therapy." Photochemistry and Photobiology 76.5 (2002): 509-513. Linde, Klaus, Gilbert Ramirez, Cynthia Mulrow, and Dieter Melchart. "St. John's wort for depression- an overview and meta-analysis of randomised clinical trials." BMJ 313 (1996): 253-258. Mansky, Patrick, and Stephen Straus. "St.John's Wort: More Implications for Cancer Patients." Journal of the National Cancer Institute Aug 2002: 1187-1188. Shelton, Richard, Martin Keller, Alan Gelenberg, and David Dunner. "Effectiveness of St John's Wort in Major Depression." JAMA 285.15 (2001): 1978-1986. "St. John's Wort." July 2005. National Center for Complementary and Alternative Medicine. 10 Apr. 2006 Robins LN, Regier DA (Eds). Psychiatric Disorders in America, The Epidemiologic Catchment Area Study, 1990; New York: The Free Press. Rosenthal, Norman. St.John's Wort: the herbal way to feeling good. New York: HarperCollins, 1998. Sarkissian, N Darbinian, A Darbinyan, J Otte, and S Radhakrishnan. "P27SJ, a novel protein in St John's Wort, that suppresses expression of HIV-1 genome." Gene Therapy 13 (2005): 288-295.