Research Proposal Paper Sample: Evaluation of Hypericin Herb-Drug Interactions

Abstract:

Extracts of St. John's wort (SJW) prepared from the stem apex of Hypericum perforatum contain myriad pharmacologically active ingredients, such as flavonoids, phloroglucinols derivatives, and naphthodianthrones (for example hypericin and its derivatives). These derivatives are used widely for the treatment interventions for mild-to-moderate depression. SJW, as a monotherapy, has been found to have a relatively promising safety profile. However, in some cases, and relevant, life-threatening interactions continue to be reported, especially with medications that are substrates of P-glycoprotein and cytochrome P450. Well documented interactions of SJW include serotonin syndrome, low blood cyclosporine levels, unwanted pregnancies on women on oral contraceptives, reduced drug concentration of anticancer and antiretroviral drugs. Hypericin is believed to be the contributor of the antidepressant action of SJW and responsible for the above interactions.

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A growing proportion of the population is increasingly using herbal products for therapeutic and preventive purposes. Annual retail sales for herbal products reflect the increased consumer interest. The wide range usage of herbal products can be attributed to the popular perspective that equates natural to safety. SJW and its active derivative hypericin have been demonstrated to inhibit the reabsorption of neurotransmitters, such as noradrenaline, serotonin, glutamate, gamma-aminobutyric acid and dopamine.

Considering the widespread application of SJW and given the implications of herb-drug interaction for safety concerns, research on the interaction between prescribed medicine and herbal remedy is proposed. The Department of Chemistry and Biochemistry is well-equipped to support the proposed investigation thanks to the advanced analytical instrumentation useful for the assessment of the toxicological effects of biological molecules.

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Introduction

Herbal remedies are generally viewed as natural and hence their safety is unquestioned. In part, the perspective has contributed to the wide acceptance and increased use of such products. The increase is estimated to be by three hundred and eight percent between 1990 and 1997 within the United States (Linde, Berner, Egger & Mulrow, 2005). The increased usage, however, has helped mirror the concerns related to these seemingly safe herbal remedies, such as adverse reactions and interactions. Within American and European jurisdictions, SJW is classified as an over-the-counter drug for treating a range of conditions. The drug is considered safe because their clinicians are rarely informed of their use and the associated undesired effects. However, recent reports show that the product interacts with various medicines, resulting in potentially severe adverse reactions. SJW extracts have for long been known for their medicinal properties. Traditionally, they have been used to treat wounds, burns, fevers and nervous conditioning, as well as depression. Presently, subject to some conditions, unlicensed herbal remedies may be supplied or sold as herbal medicines. There are no specific quality or safety requirements for un-licensing herbal remedies, as well as no written labels on the intended use of the product considering it is sold under the said exceptions.

There are nine classes of compounds that contribute to the pharmacological effect of SJW. Although the pharmacological effects of most of these compounds remain a subject of continued research, the effect of SJW on the central nervous system is well-known. The extract is known to have a potent affinity for serotonin, adenosine, gh-aminobutyric acid and benzodiazepine receptors and partially inhibit monoamine oxidase. The antidepressant activity of SJW has been postulated to be due to its action on interleukin-6. Contrary to the popular view, however, the herbal drug can result in significant side effects, particularly the herb-drug interactions. Over the past decade, there has been a growing concern over interactions between the constituent of top-selling herbal antidepressant medication, Hypericum perforatum, and pharmaceutical drugs. Hypericum perforatum, commonly as SJW, is a herbaceous perennial plant, whose extracts sourced from the apex, have been recommended for various medical conditions. The commonest present-day application of SJW commercial extract is as the treatment intervention for depression. Multiple systematic reviews report SJT as a more effective treatment than placebo, as well as equally equivalent in efficacy as synthetic antidepressants in the treatment of depressive disorders in the short-term, including chronic depression.

Hypericin, the constituent of SJW is possibly the closest candidate for the antidepressant effects and may have significant implications for the therapeutic effect of the herbal remedy (Linde et al., 2005). Despite the research gap on the various constituents of SJW, hypericin concentration is widely used in the standardization of SJW products however the concentration of the constituent varies significantly across the various parts of the plant depending on seasonality and growth conditions. Furthermore, hypericin is perhaps one of the numerous relevant constituents. Therefore, it is possible that the distinct preparations differ in the content of the constituents leading to the SJW antidepressant effects (Clement, Covertson, Johnson & Dearing, 2006). Therefore, and hence there is a possibility for different SJW products to varying in terms of efficacy and adverse reaction profiles.

Proposed Research

The dramatic increase in the use of herbal medications including SJW implies the increased exposure of patients to traditional medicines. These forms of remedies are barely reported to clinicians, and hence little information on the intended use and the resulting outcomes. Most patients consider herbal remedies as safe because they are natural. Most of the interactions associated with conventional herbal remedies are often associated with efficacy. Continued consumer and healthcare professional education on the possible herb-drug interactions is necessary to ensure these interactions are addressed. Research list interactions of SJW as serotonin syndrome, low blood cyclosporine levels, unwanted pregnancies on women on oral contraceptives, reduced drug concentration of anticancer and antiretroviral drugs. Scholars propose that Hypericin is the possible contributor to the antidepressant action of SJW and responsible for the above interactions. The herb-drug interactions possess a significant threat to public health and hence the objective of the present research (Trepanier, 2006).

Evidence exists to prove that the administration of SJW preparations may result in pharmacodynamics or pharmacokinetic interactions, which present a significant risk to patients. At present, data are insufficient to demonstrate to indicate the extent of use of the various products of SJW and the related dosages that may produce a wide-ranging outcome with respect to adverse and severe reactions. At present, all the pharmacokinetic interaction already identified point toward the reality that SJW constituent(s) induce various drug-metabolizing enzymes, as well as transport proteins. However, evidence associating SJW with pharmacodynamic interactions remains scanty. Notwithstanding, because of the widespread application of the products, and hence there is a high possibility of occurrence of fatal adverse reactions. As such, these interactions need to be taken into consideration as potential safety hazards. Patients barely include their use of over-the-counter prescriptions into their medical histories, which makes it difficult to understand the existing trend adverse reactions as far as SJW is concerned. The study will review adverse interactions and reactions associated with SJW as a herbal remedy to ascertain its safety as a treatment intervention.

Some herbal remedies have been associated with serious and fatal adverse reactions. Persons experiencing such reactions barely link them to their use of the natural preparations. The scenario is further complicated by the self-prescription of herbal remedies and the lack of reporting to consulting physicians, and hence the adverse reactions linked to the herbal remedies are often under-reported. The commonly reported contra-indications for SJW are allergic reactions, gastrointestinal symptoms, confusion and dizziness, sedation and tiredness and dry mouth, and they are all considered to range from the mold, temporary or moderate. The most adverse and fatal reaction affecting the skin is photosensitivity reactions linked to SJW. Recent findings suggest that these reactions are dosage related to higher doses associated with increased sensitivity. The principal body of evidence, however, is from the anecdotal evidence from grazing mammals.

Clinically significant pharmacodynamics and pharmacokinetic interactions have been cited widely, and herbs have a high potential to impact metabolic deposition of agents with toxicological and clinical relevance (Capasso, Gaginella, Grandolini & Izzo, 2003). The constituent responsible for such interactions is yet to be studied systematically and hence it is difficult to identify the responsible extracts. Extracts vary in composition and it is impossible to explore whether a given preparation is possible the cause of the interactions. Since only a single constituent of the SJW is often standardized, it is impossible to generalize in vitro data. Further research is a necessary and specific assessment of the effect of lengthy exposure of SJW on various biological processes. The scholarly endeavor will be particularly significant because the use of SJW in mild-to-moderate depression is in line with long-term use.

References

Capasso, F., Gaginella, T. S., Grandolini, G., & Izzo, A. A., (2003). Phytotherapy. A quick reference to herbal medicine. Berlin: Springer;

Clement, K., Covertson, C. R., Johnson M. J., & Dearing K. (2006). St. John's wort and the treatment of mild to moderate depression: a systematic review. Holist Nurse Practice. 20:197-203.

Linde, K., Berner, M., Egger, M., & Mulrow, C. (2005). St John's wort for depression: meta-analysis of randomized controlled trials. Br J Psychiatry. 186: 99-107. doi: 10.1192/bjp.186.2.99.

Trepanier, L. A. (2006). Cytochrome P450 and its role in veterinary drug interactions. Vet Clinical North American Small Animal Practice. 36: 975-985. doi: 10.1016/j.cvsm.2006.05.003.