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CancerGuide: Alternative and Complementary Therapies

Evaluating Alternative Therapies
Separating The Wheat From the Chaff (will open in new window!)
Promising Therapies
+ PSK
Lesser Known Therapies
Hypericin References
Popular Therapies
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MedLine Search: Side Effects of Hypericin

Legacy MedLine Search

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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This CancerGuide Page By Steve Dunn. © Steve Dunn
Page Created: March, 1995, Last Updated: