St. John’s Wort

Effect of St. John’s wort on free radical production.
Hunt EJ, Lester CE, Lester EA, Tackett RL.
Life Sci. 2001 Jun 1;69(2):181-90.

 St. John’s wort (Hypericum perforatum) is an herbal compound used in the treatment of burns, bruises, swelling, anxiety, and most recently, mild to moderate depression. The present study was designed to evaluate the antioxidant properties of St. John’s wort in both cell-free and human vascular tissue. The experiment was performed initially in a cell-free system using Krebs buffer and a combination of xanthine/xanthine oxidase to initiate the production of the superoxide radical. Additionally, human placental vein was incubated in Krebs buffer without xanthine or xanthine oxidase to study the effects of St. John’s wort on human tissue in vitro. Commercially available formulations of St. John’s wort, standardized to either hypericin or hyperforin, were dissolved in an alkaline solution, and the following dilutions were made: 1:1, 1:2.5, 1:5, 1:7.5, 1:10, and 1:20. Lucigenin chemiluminescence was used to measure free radical production in both systems. A pro-oxidant effect was seen at the highest concentration, 1:1. Lower concentrations revealed antioxidant properties of the compound. All dilutions below 1:1 in both systems showed a dose-related inverse relationship of superoxide inhibition. The largest suppression was seen at the most dilute concentration, 1:20. The addition of 10(-3) M tiron inhibited the chemiluminescence signal, thereby confirming the production of superoxide. The results of this study suggest that St. John’s wort inhibits free radical production in both cell-free and human vascular tissue. PMID: 11441908

  St. John’s wort.
Lawvere S, Mahoney MC.
Am Fam Physician. 2005 Dec 1;72(11):2249-54.

 St. John’s wort has been used to treat a variety of conditions. Several brands are standardized for content of hypericin and hyperforin, which are among the most researched active components of St. John’s wort. St. John’s wort has been found to be superior to placebo and equivalent to standard antidepressants for the treatment of mild to moderate depression. Studies of St. John’s wort for the treatment of major depression have had conflicting results. St. John’s wort is generally well tolerated, although it may potentially reduce the effectiveness of several pharmaceutical drugs. PMID: 16342849

  Hypericum perforatum treatment: effect on behaviour and neurogenesis in a chronic stress model in mice.
Crupi R, Mazzon E, Marino A, La Spada G, Bramanti P, Battaglia F, Cuzzocrea S, Spina E.
BMC Complement Altern Med. 2011 Jan 27;11:7.

 Extracts of Hypericum perforatum (St. John’s wort) have been traditionally recommended for a wide range of medical conditions, in particular mild-to-moderate depression. The present study was designed to investigate the effect of Hypericum perforatum treatment in a mouse model of anxiety/depressive-like behavior, induced by chronic corticosterone administration. CD1 mice were submitted to 7 weeks corticosterone administration and then behavioral tests as Open Field (OF), Novelty-Suppressed Feeding (NSF), Forced Swim Test (FST) were performed. Cell proliferation in hippocampal dentate gyrus (DG) was investigated by both 5-bromo-2′-deoxyuridine (BrdU) and doublecortin (DCX) immunohistochemistry techniques and stereological procedure was used to quantify labeled cells. Golgi-impregnation method was used to evaluate changes in dendritic spines in DG. Hypericum perforatum (30 mg/Kg) has been administered for 3 weeks and then neural development in the adult hippocampus and behavioral changes have been examined. The anxiety/depressive-like state due to chronic corticosterone treatment was reversed by exogenous administration of Hypericum perforatum; the proliferation of progenitor cells in mice hippocampus was significantly reduced under chronic corticosterone treatment, whereas a long term treatment with Hypericum perforatum prevented the corticosterone-induced decrease in hippocampal cell proliferation. Corticosterone-treated mice exhibited a reduced spine density that was ameliorated by Hypericum perforatum administration. These results provide evidence of morphological adaptations occurring in mature hippocampal neurons that might underlie resilient responses to chronic stress and contribute to the therapeutic effects of chronic Hypericum perforatum treatment.PMID: 21272291

  Update on St. John’s Wort.
Howland RH.
J Psychosoc Nurs Ment Health Serv. 2010 Nov;48(11):20-4

 Herbal preparations for depression are often preferred over pharmaceutical drugs because they are available without prescription and because they are commonly assumed to be safe. St. John’s wort (SJW) is one of the best-known and best-selling herbal therapies for depression. Meta-analyses of randomized controlled trials of SJW for major depression suggest that SJW is superior to placebo, is similarly effective compared with conventional antidepressant drugs, and tends to have fewer side effects compared with antidepressant agents, but there is a large degree of heterogeneity among the placebo-controlled studies, and trials from German-speaking countries tend to report more favorable findings. A small number of studies suggest SJW is safe to use during pregnancy and breastfeeding. Although SJW is relatively well tolerated, it is prone to many important drug-drug interactions. PMID: 21053786

  Efficacy and tolerability of Hypericum extract for the treatment of mild to moderate depression.
Kasper S, Caraci F, Forti B, Drago F, Aguglia E.
Eur Neuropsychopharmacol. 2010 Nov;20(11):747-65

Depression is a common condition in the community with a significant impact on affected individuals, their relatives and society. Many patients with depression do not seek treatment and are often concerned about the possible adverse effects of antidepressant drugs. Extract of Hypericum perforatum (St. John’s wort) has long been recognized as a treatment for depression. Several published trials and meta-analyses have demonstrated the efficacy and tolerability of Hypericum extract for mild to moderate depression. Recent comparative trials of Hypericum extract and other antidepressants, including selective serotonin reuptake inhibitors (SSRIs), provide support for Hypericum extract efficacy. However, since the constituents of Hypericum extract differ between the individual manufacturers, the efficacy cannot be extrapolated from one extract to another. In this review, WS 5572, LI 160, WS 5570 and ZE 117 Hypericum extracts have been shown to be significantly more effective than placebo with at least similar efficacy and better tolerability compared to standard antidepressant drugs. PMID: 20708905
Copyright © 2010 Elsevier B.V. and ECNP. All rights reserved.

  St. John’s wort components and the brain: uptake, concentrations reached and the mechanisms underlying pharmacological effects.
Caccia S, Gobbi M.
Curr Drug Metab. 2009 Nov;10(9):1055-65.

 Hypericum perforatum L. (St. John’s wort) extracts have gained popularity as an alternative to conventional antidepressant drugs for mild to moderate forms of depressive disorders. New potential psychiatric uses for extracts in obsessive-compulsive disorder, generalised anxiety disorder and alcohol dependence have also been suggested on the basis of animal studies. The neurochemical mechanisms of these central actions are still debated but several components have antidepressant-like and anxiolytic-like effects in animals, or interact with neurotransmitter systems believed to be causally involved in depression, anxiety and in psychiatric illness generally. However, these data should interpreted taking account of the pharmacokinetic data on the main components, particularly those of their brain distribution and concentrations and the relationships with blood concentrations; the (scant) data so far suggest that the acylphloroglucinol hyperforin, the flavonol quercetin and its glycosylated forms and their metabolites, the biflavones amentoflavone and its I3,II8-analog biapigenin and the naphthodianthrones hypericin and pseudohypericin pass the blood-brain barrier poorly in animals. The brain concentrations of all these high-molecular weight, poorly water-soluble compounds after pharmacologically effective doses of the extracts are therefore far below those effective on neurotransmitter receptors and the mechanisms which are obviously important in the central effects of conventional, pharmacologically related drugs. Additional pharmacokinetic data on the brain concentrations of these and other constituents and their metabolites are therefore required for a more meaningful interpretation of the central effects of St. John’s Wort extracts. PMID: 20214594