Hypericum Extract And Its Effect On Heart, Catecholamine, HPA Axis And Anticancer Drugs
St johns wort or Hypericum perforatum extract was tested for its effect on some biochemicals and neurotransmitters. Its effect was also seen on the activity of anticancer drug Gleevec.
Sixteen double blind clinical studies were reviewed for their quality and they demonstrated definite and significant superiority of hypericum extract over placebo. Another meta-analysis of clinical studies also concluded with similar results.
Some researchers criticized the clinical studies related with hypericum extract and these are the points that should be paid due attention. However now there are sufficiently large number of studies are available outside Germany.
In vitro study of hypericum extract was carried out to evaluate its effect on Catecholamine and cardiovascular regulation through biochemical and physiological tests. The effects of hypericum extract were compared with positive control group taking Imipramine.
Another study is related with the effect of hypericum extract over HPA axis – the major hormonal pathway that is associated with stress, anxiety and depression. Flavonoids in hypericum extract exerted positive influence on HPA axis that contributes toward antidepressant activity.
In another study with anticancer drug Gleevac, hypericum extract was found to reduce its concentration in blood by 42% and therby diminishing its effect.
16 Studies Comparing Hypericum With Placebo:
Sixteen double blind randomized clinical studies are compared here that tested hypericum against the placebo.
Thirteen studies showed difference between effects of hypericum and placebo. Two studies had been of low quality. Side effects profile had been comparable in placebo as well as hypericum.
Hypericum was found to be better even against the secondary symptoms of depression like anxiety, sweating, palpitation, headache and insomnia.
These studies suggest a clear superiority of hypericum for beneficial effects in depression.
St. John’s Wort And Somatoform Disorders:2004
184 patients of somatoform disorders, somatoform autonomic dysfunction but without major depression were taken into this randomized, double blind, placebo controlled trial. They were given either st. john’s wort or matching placebo for six weeks.
Results found considerable efficacy of st. john’s wort (45%) over placebo (20%) and equal safety in treating somatoform disorders. This study affirms a previous study of same nature.
Psychosom Med. 2004 Jul-Aug;66(4):538-47.
St. John’s Wort As An Antidepressant:
After a detailed computerized search for quality clinical studies of hypericum therapy, some studies were selected from 1980 to 1994.
Fourteen studies were included and all of them concluded with efficacy of hypericum in depression. These studies compared antidepressant effect of hypericum with either imipramine or maprotiline.
Criticism Of Clinical Studies:
- Most of these studies were published in Germany.
- There had been relative lack of data about adverse drug reactions and side effects.
- There had been no reporting of toxicity of hypericum with its overdosage. Though it is just normal with hypericum as toxicity is not present in st. john’s wort extract like that of antidepressant drugs that report 30.1 deaths per million prescriptions. (Henry et al 1995)
- Another point that was raised against these studies was that some of these appeared too good to be true. Many of them concluded that hypericum is effective against a broad range of disorders.
AU – Ernst ESO – Fortschritte der Medizin 1995 Sep 10;113(25):354-5
Catecholamine Turnover, Cardiovascular Regulation And St. John’s Wort (2004):
In vitro studies of hypericum extract showed earlier that its effect is partially due to Monoamine oxidase inhibitor activity. This randomized double blind, placebo controlled study was carried out on 16 patients taking either a placebo or hypericum extract (300 mg thrice a day). Positive control was served by Imipramine taken in 50 mg dose thrice a day.
After seven days of treatment, the physiological and biochemical tests were done like plasma catecholamine levels, graded head up-tilting exercises, cardiovascular reflex testing.
Results of this study demonstrated that the use of hypericum extract didn’t have any effect on blood pressure and heart rate and their variability. There had been no effect on plasma concentrations of norepinephrine and its metabolites. The concentration of DOPAC (Dihydrophenylacetic acid) – the metabolite of dopamine concentration was found increased.
Researchers concluded that this trial found that the use of st. john’s didn’t change norepinephrine uptake or MAO activity in vivo. The inhibitory effect on dopamine is mild and should be further studied. Whereas the positive control group taking imipramine was found with increased resting blood pressure, heart rate and orthostatic tachycardia (increased heart beating on lying down).
Clin Pharmacol Ther. 2004 Nov;76(5):480-9.
Flavonoids Of St. John’s Wort Pacifies HPA Axis In Rats (2004):
Hypothalamic-Pituitary-Adrenaline axis is found over active in major depression patients with hypersecretion of ACTH (Adrenocorticotropic hormone) and cortisol. Modern pharmacologic drugs like imipramine slows down this overactivity of HPA axis.
Earlier studies showed that hypericin slowed down the activity of HPA axis while hyperforin was inactive in this regard. This study tried to find the effect of flavonoids on HPA axis and the possibility of their role in antidepressant effect of hypericum extract.
In this trial, imipramine, hypericin, hyperoside, isoquercitrin and miquelianin were given daily by gavage for two weeks. After two weeks, the plasma levels of ACTH and corticosterone were found 40-70% lower. However, none of these tested compound demonstrated any effect of ACTH and corticosterone after 8 weeks of therapy.
Researchers concluded that this study confirmed the role of flavonoids in antidepressant activity of st. john’s wort and over the HPA axis.
Planta Med. 2004 Oct;70(10):1008-11.
St. John’s Wort & AntiCancer Drug Gleevec:
Gleevec or Glivec is one of the newer anticancer drug that is used to treat blood cancer chronic myeloid leukemia. The use of st. john’s wort with this drug cause 42% lowering of its concentration that is enough to result in its failure. So this drug is also added to the list of drugs that have interactions with st. john’s wort.
Journal Of Pharmacology.