Ž . Immunopharmacology 46 2000 247–251 www.elsevier.comrlocaterimmpharm ž / The effects of St. John’s Wort Hypericum perforatum on NK cell activity in vitro C.M. Helgason a , J.L. Wieseler Frank b , D.R. Johnson a,c, ) , M.G. Frank a , S.E. Hendricks b,d a Department of Pathology and Microbiology, College of Medicine, Omaha, NE, USA b Department of Psychology, UniÕersity of Nebraska at Omaha, Omaha, NE, USA c Eppley Institute for Research in Cancer and Related Diseases, Omaha, NE, USA d Department of Psychiatry, UniÕersity of Nebraska Medical Center, Omaha, NE, USA Accepted 15 November 1999 Abstract Ž . St. John’s Wort Hypericum perforatum; H. perforatum is a popular herbal supplement used to treat mild to moderate Ž . depression. H. perforatum possesses serotonergic properties such as inhibition of serotonin 5-hydroxytryptamine; 5-HT reuptake. Serotonergic pharmacotherapy is associated with amelioration of depression as well as increases in natural killer Ž . Ž . NK cell activity NKCA . Also, 5-HT and 5-HT analogs augment NKCA in vitro. Considering the serotonergic properties Ž . of H. perforatum, the effects of H. perforatum on NKCA were assessed in vitro. Mononuclear cells MNCs from normal Ž . donors were exposed in vitro to an extract of H. perforatum LI160s or established 5-HT stimulators of NKCA. After an overnight incubation, cells were washed and a standard 51 Cr-release cytotoxicity assay performed to assess NKCA. LI160s at all concentrations failed to augment NKCA. However, in corroboration of previous studies, 5-HT, the selective serotonin Ž . reuptake inhibitors SSRIs , paroxetine and norfluoxetine, and a-interferon augmented NKCA above control levels. Though an efficacious treatment for mild to moderate depression, H. perforatum differs from commonly prescribed serotonergic antidepressants insofar as H. perforatum fails to enhance NKCA in vitro. Therefore, the present results are consistent with pharmacologic studies indicating that H. perforatum possesses, at best, weak serotonergic activity. q 2000 Elsevier Science B.V. All rights reserved. Keywords: Hypericum perforatum; Natural killer cells; Serotonin; Antidepressants AbbreÕiations: H. perforatum, Hypericum perforatum; 5-HT, 5-hydroxytryptamine; SSRI, selective serotonin reuptake inhibitor; NKCA, natural killer cell activity; FBS, fetal bovine serum; PBS, phosphate buffered saline; MNC, mononuclear cells; LU, lytic unit; CRH, corticotropin releasing hormone ) Corresponding author. UNMC, Department of Pathology and Microbiology, 986495 Nebraska Medical Center, Omaha, NE 68198-6495, USA. Fax: q 1-402-559-4077; e-mail: drjohnso@unmc.edu 1. Introduction Ž St. John’s wort Hypericum perforatum; H. per- . foratum is a popular herbal supplement with pur- Ž ported antidepressant effects Linde et al., 1996; Cott . and Fugh-Berman, 1998 . Possessing serotonergic properties similar to 5-HT receptor agonists and antidepressants such as selective serotonin reuptake Ž . inhibitors SSRI , H. perforatum potentially modu- 0162-3109r00r$ - see front matter q 2000 Elsevier Science B.V. All rights reserved. Ž . PII: S0162-3109 99 00187-3