...at a talk presented by world class scientists, ...demonstrated  to me that standardization for hypericin content alone is at least misguided. ...even after .. plucking the plant apart into all its varied constituents,  it is the whole herb that does the work, and this still holds true.  Richo Cech, Horizon Herbs

 

Saint John's Wort, Hypericum perforatum

from The American Herbal Pharmacopoeia™  Analytical, Quality Control, and Therapeutic Monograph

Macroscopic Description
Physical Characteristics: The dried herb consists mainly of the flowering tops, including the leaves, unopened buds and flowers. The leaves are elliptical to oblong, small and oppositely set, without stalks, mainly green to pale green and glabrous with an entire margin. The flower petals are yellow to yellowish-brown and may still be present in the dried material either whole or fragmented in the chymes. Both petals and leaves are characterized by numerous, punctate glands approximately 0.5-1 mm in diameter. These can be readily observed with a 10X hand lens. The leaf glands appear translucent when held against the light. Those on the petals appear as black dots along the margins. The stems are pale green, cylindrical, and hollow with faint, longitudinal, opposing ribs that distinguish H. perforatum from other species. Powder: Greenish to yellowish-brown with the yellow becoming more pronounced as the percentage of flowers and unopened buds increases. Odor: Distinct, slightly sweet and aromatic, somewhat balsamic. Taste: Slightly sweet, mildly bitter, somewhat resinous and astringent (Bisset and Wichtl 1994; Bradlet 1983; Hobbs 1989).

COMMERCIAL SOURCES AND HANDLING
Collection
Concentrations of Hypericum's two primary classes of constituents, the naphthodianthrones (hypericin and pseudohypericin) and various flavonoids, vary greatly due to numerous factors, including varietal and species differences, harvesting and handling practices, moisture, altitude, and the different plant parts, The flowering tops should be gathered immediately before to immediately after opening and typically contain a mixture of buds and blossoms. The flowering tops contain the highest concentrations of naphthodianthrones and flavonoids, followed by the uppermost leaves and flowers during the budding and blooming period (Benigni and others 1971; Southwell and Campbell 1991).

ANALYTICAL
The primary compounds of interest as marker constituents include two naturally occurring pigments, hypericin and pseudohypericin (naphthodianthrones). These compounds are characteristic markers for this genus and are extracted in methanol. They both absorb visible light with a maximum absorption at 588 nm and are highly fluorescent in methanol when exposed to UV light. Both pigments are similar in their absorption and emission spectra, including their absorptivity. Separation of these two pigments is necessary to determine the concentration of each pigment. Flavonoids are also considered an important class of constituents in Hypericum. Methods are provided for both classes of compounds.

H. perforatum can be differentiated from adulterants by the presence of hyperforin and rutin, which are absent or negligible in other species. Adulteration can also be detected through thin-layer chromatography analysis. H. barbatum is distinguished by characteristic red-orange fluorescing flavonoid glycosides; H. hirsutum can be distinguished by the presence of the compound orientin; H. montanum contains a turquoise fluorescing vegetable acid (in addition to chlorogenic acid); and only H. maculatum and H. tetrapterum contain emodin (Berghofer and Holzl 1986).

THERAPEUTICS
Pharmacodynamics
Clinical Studies
Hypericum has become increasingly popular in Germany, where physicians routinely prescribe herbal medicines. In 1994, 66 million doses of Hypericum perforatum were prescribed for use in the treatment of depression (De Smet and Nolen 1996). This phytomedicine has been tested in more than 3,000 patients against placebo and various active medications (Hansgen and others 1994; Harrer and others 1994; Hubner and others 1994; Sommer and Harrer 1994; Vorbach and others 1994; Wolk and others 1994).

German researchers, along with a colleague from San Antonio, Texas, recently published a meta-analysis of 23 randomized trials of Hypericum with a total of 1,757 outpatients with mild to moderately severe depressive disorders. They concluded that the herb was significantly superior to placebo and appeared comparably effective to standard antidepressants (maprotiline, imipramine and amitriptyline) while producing fewer side effects (Linde and others 1996). The preparations used were all standardized to hypericin content (Table 11).

The controlled studies of Hypericum's efficacy in depression included in the above-mentioned meta-analysis were randomized, or "quasi-randomized", through alternation. Comparisons were made of the herb alone, or in combination with other plant extracts, to placebo, and/or a standard antidepressant. Twenty of the 23 trials were double-blind, one was single-blind, and two were open label. Most were 4 to 8 weeks in duration. The methodological quality of each study was assessed by at least two reviewers to determine eligibility for inclusion in the meta-analysis.

In each study, improvement in depressive symptoms had been evaluated with depression scales with interrater reliability, most commonly the Hamilton depression scale (HAM-D) and the clinical global impressions index (CGI). The daily dose of either hypericin, the reference substance for standardization, or of total extract varied considerably between studies, from 0.4 to 2.7 mg and 300 to 1000 mg, respectively.

In 13 studies comparing a single Hypericum preparation with placebo, 55.1 percent (225) patients receiving the herb improved, compared with 22.3 percent (94) responding to placebo. In the comparisons to standard antidepressants in three trials with single preparations and two with combinations, 63.9 percent (101) of patients responded to single preparations compared with 58.5 percent (93) to standard antidepressants and 67.7 percent (88) responded to combination extract products (Hypericum and Valeriana) compared with 50 percent (66) to standard antidepressants.

The researchers acknowledged the problems in drawing valid conclusions from the pooled data of quite heterogenous studies. These problems are compounded by the different amounts and preparations of the herb used across the studies (Table 11) and the possibility that hypericin is not the only active component.

These limitations aside, Linde and colleagues find sufficient evidence to conclude that Hypericum is better than placebo in treating some depressive disorders. These data were inadequate, however, to judge yet whether it is as effective as standard antidepressants, although it appears to cause fewer side effects. They consider that these initial indications of efficacy warrant the undertaking of longer controlled trials comparing several doses of different Hypericum preparations to standard antidepressants.

In separate commentary accompanying the meta-analysis, Netherlands researchers Peter De Smet and Willem Nolen agree that these data are promising, but not yet sufficient to accept Hypericum as an effective antidepressant preparation (De Smet and Nolen 1996). Aside from the need for dose standardization and adequate trial lengths, they call for studies in severely depressed patients and long-term studies to assess the risk of relapse and emergence of late side effects (De Smet and Nolan 1996).

Position on Ephedra (AHG)

Full (whole) herbal extracts - Often referred to as 'simple extracts', these are extracted in order to assure that the finished extract contains the broadest spectrum of an herb's chemical constituents in a similar ration to the crude herb.  Full extracts are produced using grain or fruit alcohol, water and/or plant glycerine, which are biodegradable and environmentally friendly.

Standardized herbal extracts are extracted to assure that the finished product contains a specific amount of one or a limited group of so-called "active " constituents.  The herb is selectively extracted in order to concentrate and quantify the active constituent (s), and  quite often its "inert" constituents are removed or reduced.  Standardized extracts are often extracted with acetone, benzene, methyl alcohol, butyl alcohol, carbon tetrachloride, and other synthetic chemicals which, although removed from the finished extract to some degree, can be harmful.

The most important considerations in achieving high quality herbal extracts are using the best quality herbs and a highly skilled extraction technique.  Altering, as little as possible the quality and ration of the herb's natural chemical profile.  A standardized extract is not a superior product.  It has only one out of many hundred of the herb's chemical constituents.  It does not offer superior health promoting or healing potential. The superior extract is the "balanced" extract which most fully represents the original herb from which it was made, in a more concentrated and optimally assimilable form.

Medicinal herbs contain a large complex of natural chemical constituents.  The therapeutic effects of an herb depend on the interaction of a number of the chemicals, not just one "active " constituent.  "Inert" constituents, while having no direct action of their own may potentiate or moderate the therapeutic effect of an "active" constituent by enhancing its stability or solubility, thus  facilitation its absorption, transport, or utilization.  Scientists frequently disagree about the "active" constituents of an herb.

 posted with permission from Ed Smith and Sara Katz of Herb-Pharm