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St John’s wort has along history of medical treatment for many illnesses. Hypericum perforatum is a yellow flowering plant which is best described as stoloniferous or sarmentose by well renowned scientists. This perennial herb has its roots in Europe and lately, it has been spread to many temperate zones of the world where it is grown in numerous meadows. The actual situations or events that culminated until the herb was named St. John are unknown but many researchers point that the traditional name is linked to the traditional flowering and harvesting of the herb which usually takes place on the St. John’s day on 24th June of every year. On the other hand, the genus name Hypericum is derived from Greek philosophy that was linked with the herb. In Greek language, Hyper is used to mean something above or beyond, and eikon denotes a picture. The herb’s name was therefore derived from its Greek traditional use to ward off evils by being hanged on a religious icon that was stationed in the houses during the Saint John’s day. The herb’s species name also has meaning as the term perforatum is often used by scientists to mean the presence of small oil glands in plant leaves which can only be seen when the leaves are held straight against light rays.
Primary Clinical Applications of Hypericum perforatum
St. John’s wort has been phenomenal in treating various ailments since the time of its therapeutic discovery in Greek by Hippocrates who is widely regarded as the father of medicine. During its early discovery and especially during the time of the great Swiss physician, Paracellsns, St. John’s wort (SJW) was famously used to treat mental disorders that really affected the lives of many people in the world. It should be recorded that SJW faced a lot of challenges that came from the negative publicity the herb was accorded by many media houses leading to its obscurity. However, this negative situation was later changed when medical researches proved otherwise that the SJW was an important medicinal herb. This positive development was reflected in the year 2000 when the herb became the fifth best selling dietary supplement in the United States’ mainstream stores (Butterweck et.al 2000).
Contemporary medical research has discovered clinical applications of St. John’s wort in treating a wide variety of internal and external illnesses. For instance, modern pharmaceutical development in the United States has discovered that SJW is a crucial medicine for a wide range of infirmities with depression topping the list. This new development further reinforces the discovery of long time physicians such as Hippocrates who used it to treat mental disorders in their patients. Doctors have also found out that the complex chemical composition of the herb is detrimental and has been found to trigger certain infirmities that are closely related to depression such as chronic fatigue syndrome and PMS. Besides the small negative effect, Hypericum perforatum is broadly used to offset a wide range of diseases from the human system. Researches done to determine the effectiveness of the herb clearly states that approximately sixty seven percent of the patients suffering from mild to moderate depression actually recovered when they began to use the plant (Butterweck et.al 2000).
Hypericum perforatum has also been found to contain noble antibacterial and antiviral properties or characteristics which make it an ideal adjunctive medicine for treating any bacterial or viral infections. Besides bacterial and viral treatment, Hypericum perforatum has also continued to be used to treat a wide variety of internal disorders in the human, for instance, it is widely used to treat patients with pulmonary complications, dysentery, worms, urinary bladder blockage or any other trouble, and in reliving nervous complications. Hypericum perforatum has also been found to be clinically applicable in restoring and calming human serves besides increasing the flow of urine along the urinary bladder. Urinary flow is a vital metabolic reaction to remove excess urea from the body, any accumulation beyond the normal limit of urea is really dangerous for human survival and the use of Hypericum perforatum has been fund to really solve urinary complications (Butterweck et.al 2000).
Hypericum perforatum has been discovered to be a vital medicine for chest complications like in situations of bronchitis. In this regard, doctors have discovered a crucial use of the herb to relieve phlegm obstructions which are usually problems found within the human chest or lungs. This discovery is linked to the herb’s bacterial and antiviral qualities which are used to treat bacterial and viral infections in the body. This is in realization of the fact that bronchitis and phlegm obstructions are majorly caused by viral and bacterial infections that are ever present in the human environment. Medical and pharmaceutical discoveries have also found out that Hypericum perforatum serves the same purpose as Horsechestnut, which mainly is used for purposes of treating internal complications associated with bleeding. More so, the herb’s bacterial quality has been employed to heal and remove bacterially generated tumors and boils from the human body. St. John’s wort is currently being used to treat women’s menstruation complications by correcting and reducing the pain that is usual associated with the process, hence helping women a great deal. The herb is also being used extensively to reduce back pain complications, an area where SJW has been proved to be really effective. St John’s wort has been discovered to contain an important medical component called alkaloid acid which is used to stimulate human heart and artery in patients with heart problems (Calapai et.al 1999).
A major headway has been made by two world renowned institutions of New York University and the Weizman Institute of Science in Israel in regards to the two main components of the SJW that is, Hypercin and Pseudohypericin. The two institutions have found out that the two components of Hypericum perforatum reduce the growth of retroviruses such as HIV and AIDS virus in animals. Although the research has not reached its final conclusions, the results are quite positive and the world hopes that the same reaction can also happen on human beings in order to help the world come out of the dreaded HIV and AIDS pandemic. Doctors and pharmacists are of the view that the whole concept in reducing the growth of retroviruses is due to the production of oxygen free radicals which have the capacity to interfere with and damage the envelope surrounding the virus hence making the virus inactive (Calapai et.al 1999).
Pharmacology of Hypericum perforatum
Latest pharmaceutical researchers have found Hypericum perforatum to be a unique and different kind of antidepressant from the rest in the same category. This uniqueness is more evident in the herb’s pharmacology in that it exhibits or displays pharmacology of many classes of antidepressants coupled with new mechanisms that in normal circumstances are not found with standard antidepressants. One of the critical and important pharmacological actions of Hypericum perforatum is its unique ability of moderate to high potency for human inhibition in the reuptake of elements such as monoamines, serotonin and dopamine, among others. It is important to note that unlike the standard inhibitors which carry out their reuptake process competitively, hypericum does it the other way round by using intracellular Na+ ion concentrations to conduct a non-competitive reuptake. The most interesting thing in the pharmacology of Hypericum perforatum is its actions at the receptor level. At this level, any chronic treatment with hypericum will lead to two outcomes of down-regulating b1-adrenoceptor, up-regulating post-synaptic 5-HT1A receptors and 5-HT2 receptors. Although several pharmaceutical and medical researches have linked SJW antidepressant effects to the hyperforin component, new studies have expounded on that component and found out that several other constituents are at play. For instance, hypericin, pseudohypericin, andflavonoid are all thought to have a stake in the antidepressant nature of SWZ (Calapai et.al 1999).
Effects of monoamine oxidase A activity
The first formal and logical study that carried out to determine the antidepressant action of hypericum was commissioned in the year 1984 by a scientist named Suzuki who late reported that in deed hypericum is an antidepressant. The study particularly found out that hypericin which is a constituent of hypericum plays a noble duty of reversing the inhibitor called monoamine oxidase A activity (MAOI). Because of this scientific evidence, hypericin came to be considered the standard and active component of hypericum which subsequently meant that all hypericum extracts were to be standardized in reference to the hypericin as the standard formula or yard stick. However subsequent researchers conducted to test the same effects of hypericin have not found any links to support Suzuki’s conclusions. But it should be taken into consideration that the sample of hypericum used by Suzuki only had 80% purity with either one or two components in the remaining 20% being responsible for inhibition of MOA. This assumption was further reinforced by the discovery of Bladt and Wagner in 1994 where they found out that MOA inhibition was imminent in those constituents that contained high amounts of flavonoids. Although many scientific discoveries have found elements such as flavonoids, quercetin and quercitrin to have inhibiting effects on MAO, their therapeutic action has been widely criticized and doubted by many discoveries that have found them to have low plasma levels (Calapai et.al 1999).
Hypericum as a non-selective reuptake inhibitor
Hypericum effects on reuptake inhibition of monoamines can be traced to the year 1995 when a scholar by the name Muller commissioned a study to realize the connection between the two variables. The study by the scholar found out that clinically used hypericum just like any other common and conventional antidepressant concentration functions to inhibit the synaptic reuptake of serotonin (5-HT), noradrenaline and dopamine that contains IC50 of approximately 2 μg/ml. One important conclusion that comes from the studies of many doctors and pharmacists is that while all other antidepressants have absolutely the same affinity in their reactions towards either 5-HT or noradrenaline or any other compound in the same genre in reuptake inhibition, none of them actually displays the same kind of potency for all the three available uptake systems (Heal et.al, 1989).
Generally, several medical studies authored by different institutions and scholars pointed to the fact that hyperforin, a component of hypericum has got an immense capacity and potential to potently inhibit the reuptake of all three monoamines in a concentration range of 80–200 nmol/l, a property that seems missing in all other depressants. The same researches on hypericum have also found hyperforin to have the same antidepressant property even in animal models of depression, further making Hypericum perforatum to be a distinct type of antidepressant. Further proofs found hyperforin to exists in several chemical compounds, for instance, alcoholic compound was discovered to also contain hyperforin (Heal et.al, 1989).
In deed several researches conducted by medical institutions all point to the fact that hypericum is a distinct kind of antidepressant from the rest in the same genre. For instance, it becomes crystal clear that unlike other antidepressants that fundamentally rely on gluing or binding to the monoamine transporters to inhibit reuptake, hyperforin component adopts a totally different kind of action to perform the same action. For instance, it becomes clear that hypericum’s effects and actions on reuptake are different as it adopts a non competitive process which is usually estimated to be within the range of (decrease in Vmax and Km). This hypericum pattern should be seen in comparison to other antidepressants which as mentioned above adopts a competitive inhibition process (increase in Km, no change in Vmax). Furthermore, many pharmaceutical researches make it clear that increasing free intracellular Na+ ion concentrations are perfect mediators that can hasten hyperforin’s actions and effects on monoamine general uptake (Heal et.al, 1989).
Effects on monoamine receptors
Medical doctors have discovered that using antidepressant for chronic treatment of patients has reduction effects in terms of changes to the brain receptors as shown in table 1. To achieve this long-term change in the brain receptors, doctors usually rely on the use of b1-adrenoceptors which are subjected to a rigorous down-regulation mechanism. Several studies confirm to the fact that the use of antidepressants and electroconvulsive therapy (ECP) for purposes of chronic and not acute treatment has the inevitable of down-regulating b1-adrenoceptors in certain animals such as in the rat forebrain. Similarly, doctors have found hypericum to have the same down-regulating effects the same described above. For instance, medical reports points out that hypericum has the potential of down-regulating b1-adrenoceptors in the frontal context of the human brain while at the same time causing no change in the receptor affinity (Hubner et.al, 1994).
It should be remembered that chronic and not acute treatment using the commercially available hypericum extracts in many shopping outlets has the effect of up-regulating post-synaptic 5-HT1A while at the same time causing no deviating in the receptor affinity. However, this action stands as a contrast to what usually happens when other antidepressants are administered for chronic treatments, where down-regulation of 5-HT2 comes out as the end result. However, studies have found hypericum to react differently to 5-HT2 receptors leading to the conclusion that different constituents of might be each responsible for the different reaction of hypericum on 5-HT2 (Hubner et.al, 1994).
Evidence of efficacy
Several evidences from both clinical and pharmaceutical studies point to the fact that hypericum extracts have a superior efficacy as compared to several other similar medicines in the same genre. One of those studies clearly evidences facts to prove that hypericum extracts have a superior efficacy when compared to placebo in treating mild to moderate depressions in patients. Several other studies carried out in the recent pasts have also found hypericum to have the same efficacy as tricyclic antidepressants (TCA) like nmaprotiline and imipramine. Most importantly, systemic analyses by renowned scientists have explicitly identified that hypericum had a response rate of 63.9%, much higher than 58.5% and 22.3% for other antidepressants and placebo respectively (Hubner et.al, 1994).
The clinical and pharmaceutical evidences of hypericum efficacy have been reinforced by many pre-clinical studies especially, those conducted in animal models of depression. For instance, the famous forced swim test (FST) in rats has been used to provide vital behavioral animal model that can be used effectively to determine the efficacy of antidepressant drugs such as hypericum. Several other effective animal models such as the learned helplessness test and the chronic escape deficit model have all been used and proved that in deed hypericum has a higher efficacy compared to several other antidepressants (Johne et.al, 1999).
In the former studies to determine hypericum efficacy, hyperforin constituent of the antidepressant was considered to be the major component that determines its whole efficacy leading to conclusions that hyperforin is the fundamental ingredient of hypericum. However, later researches found out new knowledge that highly enriched the use of hypericum. For instance, it was discovered that other constituents of hypericum like flavonoids and xanthones are actively used in the FST (Johne et.al, 1999).
It should be noted that despite the earlier and subsequent pre-clinical and clinical proofs of hypericum efficacy, its main mode of action is still obscure to many scientists and pharmacists who are working all day and night to determine this obscurity. This complexity in hypericum’s mode of action should be understood out of the fact that it has a unique medical pharmacology that incorporates those of the other classes and new mechanisms that are usually not associated with standard antidepressants. More so, this complexity can be in part attributed to the assumption that the multiple bioactive components of hypericum have the potential to independently or synergistically have their own pharmacological application.
Presentation of Current Clinical and Scientific Research
Presentation of current research on hypericum can be traced to the year 1995 when modern and systematic review of twelve randomized controlled trials (RCTs) was commissioned to determine the herb’s efficacy. From the study research it was clearly indicated that hypericum has a higher and effective efficacy than placebo and more so, is an effective drug to be used in reducing depression levels in patients. However, the 1995 reviewed studies were carried out in Germany where individualized and subjective methods of research were imminent in psychiatric studies of patients with psychological problems, as opposed to the objective methods that yield objective and reliable results. Duet to the possibility of bias in the already commissioned studies, it was advised that subsequent studies should take into consideration rigorous methods that are objective and reliable in order to ascertain the accuracy and efficacy of the earlier results of the extract (Kaehler et.al, 1999).
A more synthesized meta-analytic study was carried out in the year 1996 using twenty three randomized controlled trials (RCTs) on a study population of 1757 outpatients. This study, which was done on patients with moderate to mild depressions, came up with important and fundamental conclusions about the application of hypericum. One of the conclusions as already mentioned is that hypericum has a higher efficacy than placebo whose efficacy value was found to be three times lower. The second conclusion emphasized the fact that hypericum’s effectiveness was equivalent to that of tricyclic antidepressants (TCAs) hence making it more appropriate for treating depressions. The third conclusion made it clear that hypericum was better off than tricyclic antidepressants (TCAs?) which had severity and unfriendly side effects. However, these conclusions might not be valid as claimed by several other researchers who argue that the methods adopted were subjective and therefore lacks the objective character (Kaehler et.al, 1999).
From the literatures and evidences provided in this paper, it is explicitly clear that hypericum is real and should be considered a trusted antidepressant brand for people who still doubt its safety and efficacy. Hypericum is found to be more effective than the usual antidepressants like TCAs that have been used extensively to treat or reduce depression levels in many patients.
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