MedLine Search: Side Effects of Hypericin
Hypericin is the active ingredient of Saint John’s Wort. This search emphasizes references that mention toxicity. Since its documented clinical use has been in the treatment of AIDS, most of these references are on the treatment of AIDS patients rather than cancer patients.
This MedLine Search of the technical medical literature is from the early days of CancerGuide so it may not include the latest research. The articles referenced are still relevant but more recent ones may also be available. For more information on the incredibly powerful and freely available MedLine database see my Article on MedLine.
In all cases I have selected the references that looked most interesting to me. These are searches with a point of view! There could be references on this same subject that I didn’t include that you would have. For both of these reasons as well as the age of the search, you may want to consider doing your own search on this subject after looking at mine.
Finally, keep in mind that the abstracts presented here are only summaries of the actual articles. If you want to delve deeper you may want to get some of these articles from a Medical Library or an online document delivery service, as is provided with all MedLine accesses (usually for a fairly substantial fee).
FRI MAR 10,1995 9:11 AM PaperChase Contains 8,691,829 References -- All References Found in the Following Databases of the National Library of Medicine and the National Cancer Institute*. You are searching all four databases simultaneously. Database Indexing Began Updated Current through MEDLINE 1966 weekly April 1995 Update, Part 4 HEALTH 1975 monthly March 1995 Update AIDSLINE 1980 monthly December 1994 Update *CANCERLIT 1980 monthly February 1995 Update LIST REFERENCES LIST REFERENCES A) HYPERICIN 50 C) *ON A&B; 20 B) HUMAN 5408867 *****PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES***** (REFERENCE 1 OF 6) 88276931 Meruelo D Lavie G Lavie D Therapeutic agents with dramatic antiretroviral activity and little toxicity at effective doses: aromatic polycyclic diones hypericin and pseudohypericin. In: Proc Natl Acad Sci U S A (1988 Jul) 85(14):5230-4 Two aromatic polycyclic diones hypericin and pseudohypericin have potent antiretroviral activity; these substances occur in plants of the Hypericum family. Both compounds are highly effective in preventing viral-induced manifestations that follow infections with a variety of retroviruses in vivo and in vitro. Pseudohypericin and hypericin probably interfere with viral infection and/or spread by direct inactivation of the virus or by preventing virus shedding, budding, or assembly at the cell membrane. These compounds have no apparent activity against the transcription, translation, or transport of viral proteins to the cell membrane and also no direct effect on the polymerase. This property distinguishes their mode of action from that of the major antiretro-virus group of nucleoside analogues. Hypericin and pseudohypericin have low in vitro cytotoxic activity at concentrations sufficient to produce dramatic antiviral effects in murine tissue culture model systems that use radiation leukemia and Friend viruses. Administration of these compounds to mice at the low doses sufficient to prevent retroviral-induced disease appears devoid of undesirable side effects. This lack of toxicity at therapeutic doses extends to humans, as these compounds have been tested in patients as antidepressants with apparent salutary effects. Our observations to date suggest that pseudohypericin and hypericin could become therapeutic tools against retroviral-induced diseases such as acquired immunodeficiency syndrome (AIDS). Institutional address: Department of Pathology New York University Medical Center NY 10016. *****INTERNATIONAL CONFERENCE ON AIDS***** (REFERENCE 2 OF 6) 92401654 Gulick R Lui H Anderson R Kollias N Hussey S Crumpacker C Human hypericism: a photosensitivity reaction to hypericin (St. John's Wort). In: Int Conf AIDS (1992 Jul 19-24) 8(2):B90 (abstract no. PoB 3018) INTRO: Hypericin (HY) is a polycyclic quinone which is found in plants from the genus Hypericum, and is particularly abundant in H. perforatum (St. John's Wort). HY has antiretroviral activity both in vitro and in animal studies. Hypericism, described in veterinary medicine, is a state of skin sensitivity induced by visible light, caused by ingestion of HY-containing plants and feed. METHODS: As part of the AIDS Clinical Trial Group phase I study of intravenous, synthetic HY (ACTG #150), we enrolled 4 patients (3 men, 1 woman; all white, 1 of Mediterranean descent), 2 at 0.25 mg/kg and 2 at 0.50 mg/kg. RESULTS: The 2 patients at the higher HY dose experienced facial pain/erythema after 5-10 minutes of sunlight exposure (direct or through glass) after 2-3 doses of drug. The patient of Mediterranean descent experienced severe hand pain/erythema after 13 weeks of lower dose HY. To further evaluate this toxicity, the fourth patient underwent formal phototesting to establish the minimal erythema dose (smallest amount of light that produces erythema) before and after HY: TABULAR DATA, SEE ABSTRACT VOLUME. CONCLUSIONS: Hypericin is a potent photosensitizing agent. This photosensitivity represents the first description of human hypericism. Institutional address: Beth Israel Hosp. Boston. (REFERENCE 3 OF 6) 3207191 Furner V Bek M Gold J A Phase I/II unblinded dose ranging study of hypericin in HIV- positive subjects. In: Int Conf AIDS (1991 Jun 16-21) 7(2):199 (abstract no. W.B.2071) OBJECTIVE: To perform a preliminary assessment of the toxicity and possible anti-HIV activity in seropositive persons of hypericin. METHODS: This is an observational study. All subjects are homosexual men attending our clinic. There is no CD4 cell count criteria for entry. Four levels of hypericin (0.5 mg, 2.0mg, 4.0mg, and 8.0mg) are being administered to cohorts of ten HIV-infected persons each for a period of 12 weeks. Regular assessments are made of clinical, haematological and biochemical toxicities, and standard immunological markers of HIV activity. RESULTS: Preliminary analysis has been performed on the first two cohorts. Possible toxicities discovered include mild diarrhoea and indigestion, an infrequent itchy mainly trunkal rash, and fatigue/depression. An idiosyncratic, reversible elevation of hepatic transaminases has been observed. No early, marked anti-HIV activity has been found. DISCUSSION AND CONCLUSIONS: Administration of hypericin to HIV-infected individuals, at least at a dose of 2.0mg per day, appears to be safe for the majority of subjects observed so far. However, regular biochemical and clinical monitoring is required. Institutional address: Albion St (AIDS) Centre NSW Health Dept Sydney Australia (REFERENCE 4 OF 6) 40206390 Cooper WC James J An observational study of the safety and efficacy of hypericin in HIV+ subjects. In: Int Conf AIDS (1990 Jun 20-23) 6(2):369 (abstract no. 2063) OBJECTIVE: To assess clinical and laboratory changes in patients (pts) self-administering hypericin (HY) herbal extracts available over-the-counter (OTC). METHODS: HIV+ pts at any stage of the disease who were starting to use HY (approximately 1 mg per day) received baseline and 4 monthly measurements, including physical exam, T-cell subsets, p24 antigen, beta 2 microglobulin, and Merieux skin testing. Concomitant use of AZT and other treatments was permitted. RESULTS: 31 pts were enrolled and 26 completed the 4-month study. Toxicities were limited to reversible liver enzyme elevations in 5 pts; all levels returned to baseline after 1 month without HY. P24 antigenemia disappeared in 2 of 6 initially positive pts, both also using AZT. CD4 changes differed depending on AZT usage. In the subgroup of 10 pts who took no AZT either before or during the study ("AZT virgins"; none had AIDS), the mean CD4 count increased 13 percent from baseline after 1 month on HY and maintained this increase for 4 months. These increases were not statistically significant. By contrast, CD4 counts of those using AZT throughout the study (N=10) fell significantly after an initial mild rise (see table). TABULAR DATA, SEE ABSTRACT VOLUME. No change occurred in beta 2 microglobulin, or delayed hypersensitivity by Merieux testing. CONCLUSIONS: OTC herbal extracts containing HY may be hepatotoxic; tests of liver function should be monitored in patients taking HY preparations. Improvement of CD4 counts seen in "AZT virgin" patients justifies controlled trials of pure HY (non-hepatotoxic in animal tests) in HIV+ subjects, to assess its antiviral activity in human use. Institutional address: Community Research Alliance San Francisco California USA (REFERENCE 5 OF 6) 93335618 Steinbeck-Klose A Wernet P Successful long term treatment over 40 months of HIV-patients with intravenous Hypericin. In: Int Conf AIDS (1993 Jun 6-11) 9(1):470 (abstract no. PO-B26-2012) In an open pilot study 18 HIV patients (3 with the CDC II, 8 with CDC III, 4 with CDC IV B and 3 with CDC IV C1 classification) were treated solely with Hyperforat (Klein), i.v. 2x2 mL weekly plus 3x2 Hypericum tablets (Jossa) per day. The 16/18 patients with good study compliance in their majority showed stable or even increasing counts of absolute CD4 values for helper T cells over the 40 months of observation until now. It is remarkable that this trend was apparently not dependent on the level of the absolute CD4 count at the beginning of the Hypericum treatment. Also the CD4/CD8 ratio showed an improvement in the majority of these patients. Clinically, it was noteworthy that only two of these 16 patients encountered an opportunistic infection during the 40 months of observation. The other 14/16 patients remained clinically stable and are active in work and life with a Karnovsky-Index of 100. This steady state situation of the HIV infection also correlated with stable values of hemoglobin, leukocytes and platelets. Furthermore, none of the otherwise known viral complications due to CMV, herpes or EBV was encountered in these 16 patients. Also in no instance a toxoplasmosis nor neurological symptoms became apparent. Hypericum perforatum is presented as a novel effective anti-viral substance of broader activity, though with an hitherto unknown mode of action. It should be noted that no side effects have been seen or measured in any of these 16 patients until now. On this basis an extended trial with more patients in all CDC categories seems warranted now. *****NEUROSURGERY***** (REFERENCE 6 OF 6) 95107491 Couldwell WT Gopalakrishna R Hinton DR He S Weiss MH Law RE Apuzzo ML Hypericin: a potential antiglioma therapy. In: Neurosurgery (1994 Oct) 35(4):705-9; discussion 709-10 Hypericin, a polycyclic aromatic dione isolated from plants, is presently being clinically evaluated as an antiviral agent in the treatment of human immunodeficiency virus (HIV) infection. In addition, it is known to be a potent protein kinase C inhibitor. To evaluate its potential as an inhibitor of glioma growth, an established (U87) and low-passage glioma line (93-492) were treated with hypericin in tissue culture for a period of 48 hours after passage. Hypericin inhibited the glioma growth in a dose-related manner, with a marked inhibition of growth in the low-micromolar concentration range (e.g., in line U87 and low-passage line 93-492, a concentration of hypericin of 10 mumol/L produced 62 and 76% decreases in [3H]thymidine uptake, respectively). Because the reported inhibitory effects of protein kinase C are enhanced by visible light, [3H]thymidine uptake was measured in both the presence and the absence of visible light. In glioma line A172, the presence of light slightly increased the inhibitory effect of hypericin. Moreover, an apoptosis (i.e., programmed cell death) assay was performed to determine whether the treatment of glioma cells with hypericin was cytostatic or cytocidal. Cells were harvested, and purified deoxyribonucleic acid (DNA) was analyzed by agarose gel electrophoresis. DNA from cells treated with hypericin for 48 hours exhibited a classical "ladder" pattern of oligonucleosome-sized fragments characteristic of apoptosis. These data suggest that the proven safe drug hypericin may have potential as an antiglioma agent; we suggest clinical trials. Institutional address: Department of Neurological Surgery University of Southern California School of Medicine Los Angeles.
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