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
Meruelo D  Lavie G  Lavie D
Therapeutic agents with dramatic antiretroviral activity and little
toxicity at effective doses: aromatic polycyclic diones hypericin and
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.
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)
Hypericin is a potent photosensitizing agent. This photosensitivity
represents the first description of human hypericism.
Institutional address:
Beth Israel Hosp.
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
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
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.
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.

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