COMPLEX HERBS

Preface

What is an herb? In botany the understanding of herb is a plant with a fleshy rather than a woody stem, which, after the plant has bloomed and set seed, dies down to the ground. However, the word “herb” has other meanings that expand the concept. The word is derived from the Old Sanskrit bharb, meaning “to eat;” this eventually became the Latin berba, used for “fodder.” The early English used the word herb as synonymous with vegetables. Later, this was restricted to parts of vegetables that grow above ground. In medicine an herb refers to a plant whose properties allow its use therapeutically. Some are also used as seasonings. In the culinary arts, compared to spices herbs are mild fresh or dried leaves, while spices involve more pungent seeds, roots, fruits, flowers, and bark. Generally, an herb is a plant or plant part valued for its medicinal, savory, or aromatic properties. In all of these cases, an herb is a fresh or dried plant or its useful part. Herbs descriptions all involve the intact substance of the plant, including its fiber but sometimes excluding the water. A plant extract is not an herb.

What is a drug? The term drug has different meanings in different times and contexts. Legal definitions and common understandings vary. Most people consider drugs as medicines or substances of abuse, as nonfood items that affect function and sometimes behavior. Herbs and their products are caught in the middle of this web of nomenclature. In the following discussions of herbal medicines, confusion may arise as to the proper designation of these products. A brief explanation is necessary to help guide the reader through this maze. The word ‘drug’ was derived from the Dutch work droog, meaning “dried,” and from the Anglo-Saxon drigan, indicating “to dry.” As recently as 100 years ago in the pharmaceutical profession, drugs were understood as the dried herbs from which medicinal extracts were produced. This is apparent in the many quotations taken from writings by the president of the American Pharmaceutical Association at that time, the Eclectic pharmacist John Uri Lloyd.

During this same period naturopaths were calling themselves drugless practitioners and using common dried herbs and their water extracts, considering them as foods. By naturopathic reckoning, toxic herbs, alcoholic tinctures, concentrated extracts and isolated compounds from botanical remedies were drugs. This belief was supported by the fact that during this time botanical agents comprised half of medications listed in the United States Pharmacopoeia (USP), the official American drug compendium. In addition, the USP contained many isolated compounds derived from plants. In the naturopathic context most nonaqueous derivatives of herbs used as official drugs were undesirable. Synthetic medications, referred to as “coal tar derivatives,” were anathema.

With the passage of time, many alcoholic extracts became accepted by naturopathic doctors as also providing in large part the desirable complex nature of the whole herb. Such preparations as juice, teas, and tinctures can be considered native extracts. Native extracts are liquid fractions prepared by simple extraction procedures from the fresh or dried herb and consumed without further alteration of this form. Another term often used to describe these native extracts is “crude extracts.” Nontoxic herbs and their native extracts are no longer considered as drugs, and their use remains commonplace among the general public. Ultimately, they became so popular that a law was passed to assure continuing access to these and other nutrients. In 1994 the Dietary Supplement Health and Education Act (DSHEA) included herb products under the official designation as dietary supplements in the United States. Herbs and their derivatives are now being included in the National Formulary, a publication of the USP Convention, even though they are not considered as drugs.

The past 50 years has seen an increased medicalization of American culture, along with an increased reliance upon synthesized pharmaceutical medications. Those botanical derivatives that are now officially designated as drugs in the USP are almost exclusively concentrated subfractions or isolated components, many of which have been altered at the molecular level for patent purposes. Even the use of concentrated extracts remains rare in American medicine, compared to European nations and Germany in particular. The emphasis on pharmaceutical extracts of botanicals in Europe has led to increasing clinical studies of these concentrates and has allowed for their official approval there as drugs. These phytopharmaceutical drugs are often concentrated subfractions of native extracts, produced by multiple purification steps using toxic chemical solvents. Yet, when these products are imported to the United States, they qualify under the DSHEA regulations as dietary supplements and are referred to as herbs. Such concentrated fractions for all intents and purposes are increasingly like conventional pharmaceutical drugs, the isolated compounds typically preferred in American medical practice.

The reduction of an intact complex herb to a native extract using water and/or ethanol represents the first level of fractionation of botanicals. A diminished complexity results, but these traditional selective liquid extracts are quite appropriate for specific conditions. The reduction of a native extract to a concentrated fraction allows a lower dose in exchange for even more limited activity. The final stage of reduction to a purified chemical compound provides a greater selective strength. Typically, an isolate is more rapidly absorbed and reaches greater tissue concentrations, but the greater bioavailability and potency is often associated with elevated risks as well.

Each person is confronted with important life choices each day. When it comes to health care and medicinal agents, such choices abound. Each individual must decide whether their preference should be for the greatest nutrient and phytochemical complexity as found in the whole herb and in a somewhat reduced content with native extracts. Or, are the concentrated fractions or their isolated drug constituents more desirable? It becomes more confusing when the extract is called a herb and the fraction is referred to as an extract. It is exasperating when the fraction is marketed as an herb. Dried herb, extract, fraction or isolate, each at some time likely to be called a drug, all have a living plant as their source. How close to the source do you want to be? This book provides information to help understand the differences, so that decisions can be made with a better grasp of the issues involved.

The second part of this book looks at examples of herbs whose products are popular in America. The uses of the different types of product forms are discussed from a historical perspective. This is intended to show both how our understanding of the herb, its extracts, and its fractions and isolated components has developed and how the uses of the various forms are in some ways similar and in other ways different. Emphasis on the acknowledged activities and uses for each of the forms provides a means for recognizing the unique features of each. While each form has some features that are similar, each also needs to be understood in terms of its own peculiar nature to appreciate its optimal applications in health care. Since the whole is greater than the sum of its parts, the potential found in the living plant remains the basis for each different form.

Introduction

MEDICINE AS FOOD

[The following is taken from end of this first section of the Introduction.]

Ultimately, the standard of high quality is the fresh plant part that contains the desirable features. This is the form that rightfully deserves to be described by the plant name. Whatever is made from the fresh part should be described in relation to this form. Dr. Ed Alstat likes to use a common food to illustrate this issue. Grapes (Vitis vinifera) are known to be powerful contributors to health as demonstrated by Johanna Brandt and her “grape cure,’ in which the whole fresh grape was consumed with its skin, pulp, and seeds. Visit any grocery store and find in the fruit aisle fresh red and green grapes with and without seeds. Another aisle has raisins, dark and golden. Moving through the store you can find white and Concord grape juices. In the condiment aisle will be red wine vinegar. In the freezers are found frozen concentrated grape juices. Many states allow a liquor section where many varieties and vintages of wine will be available, along with distilled brandy. Now, if grapes were like most herbs, these products would all be called “grapes.” Does it matter if it’s raisins or red wine that you put on your bran for breakfast?

What are some of the differences in these various forms of grapes? In 2000 Karadeniz and others found that compared to fresh Thompson Seedless grapes (Vitis vinifera cv. sultanina), loss of the major phenolic acids were on the order of 90% in sun-dried raisins and air-dried dark or golden (treated with sulfur dioxide - SO₂) raisins made from these grapes, with golden raisins retaining the most. Procyanidins and catechins in the raisin samples were completely degraded, while the flavonol content was not greatly influenced. Spanos and Wrolstad in 1990 looked at juice processing of Thompson Seedless grapes. They found that SO₂ addition gave higher levels of phenolic acids and procyanidins but not quercetin glycosides, while enzymatic clarification hydrolyzed the latter two. Heating during bottling and concentration reduced procyanidins, while storing concentrates for 9 months at room temperature markedly lowered phenolic acids and completely destroyed procyanidins and quercetin glycosides. Seedless grapes lack certain anti-oxidants to begin with. Of the 30 types of oligomeric procyanidins in grape seeds, Souquet and others found in 1996 that these are limited to the 7 in the skins of Merlot grapes (V. vinifera var. Merlot). Furthermore, the grape skin and seeds with their procyanidins and the skin’s anthocyanins, phenolic acids, and flavonols are removed in the production of white wine. These phenolics make up important taste and health components that vary among Bordeaux red wines such as Merlot, as described in 1984 by Salagoity-Auguste and Bertrand. Sources, parts, and processing matter greatly.

Karadeniz F, et al. Polyphenolic compostition of raisins. J. Agric. Food Chem., 48:5343-50, 2000

Salagoity-Auguste M-H & Bertrand A. Wine phenolics – Analysis of low molecular weight components by high performance liquid chromatography. J. Sci. Foood Agric., 35:1241-7, 1984

Souquet J-M, et al. Polymeric proanthocyanidins from grape skins. Phytochem., 43(2):509-12, 1996

Spanos GA & Wrolstad RE. Influence of processing and storage on the phenolic composition of Thompson Seedless grape juice. J. Agric. Food Chem., 38:1565-71, 1990

The Challenge Of Complexity –

Distinctions Between Herb Products

Table 1.Herb Product Continuum from Most to Least Complex

The order in this list follows a steady reduction in content of plant compounds that may serve as adjuvants, agonists, antagonists, buffers, emulsifiers, enzymes, fiber, metabolism inducers and inhibitors, preservatives, stabilizers, synergists, etc. In general, some carriers (solvents, fillers, binders), preservatives, stabilizers, flavors, and/or other additives are present in most forms listed below. These additives usually range in relative content from the lesser amount with herbs (such as capsules) to greater amounts in native extracts (such as ethanol), simplified fractions and isolates.

MOST COMPLEX

HERB Common name(s)

Scientific binomial (Genus & species)

Plant part

Fresh

Frozen

Dried (freeze-dried > shade > sun > oven)

bulk

cut/sifted

powdered/capsule

NATIVE EXTRACTS Fresh extracts:

(Complex Fractions) fresh juice

bottled juice

freeze-dried juice

preserved juice

green tincture

homeopathic mother tincture (1:10)

Liquid extract of dried plant part:

decoction

infusion

cold influsion

tincture (hydro-alcoholic) (1:4 - 1:5)

spagyric extract (hydro-alcoholic + ash of marc)

fluid extract (1:1)

Solid extract

Standardized concentrate (2:1 – 10:1)

SIMPLIFIED FRACTIONS Standardized (multiple-solvent) fraction (10:1 – 50:1)

(Extract Subfractions) Fixed (nonvolatile) oils (50:1 – 100:1)

Aromatic (volatile) oils (50:1 – 100:1)

ISOLATED CONSTITUENTS Crystalline drug salts

(Purified Compounds)

LEAST COMPLEX

Glossary of Terms from Table 1 as Used in This Text

HERB – intact plant or utilized structures retaining fiber and complete phytochemical content

Common name(s) – describes herb or, sometimes, several similar herbs

Scientific name – identifies plant species distinct from generically similar plants

Plant part – medicinally active portion(s); often distinct parts have different activities

Fresh – recently separated from entire living plant; cells and tissues still alive and growing

Frozen –plant content preserved by suspending animation with extremely low temperature

Dried (1.freeze-dried > 2.shade > 3.oven > 4.sun) – removal of water to minimize changes

by: 1. freezing plant and slowly heating to remove water vapor in vacuum;

2. slowly drying away from intense light;

3. rapidly drying in high heat

4. rapidly drying in intense light

bulk – dry herb parts in whole uncut form

cut/sifted –dry herb parts chopped into slices or small pieces to increase surface area

powdered – dried herb parts ground into fine powder to greatly increase surface area

NATIVE EXTRACTS (Complex Fractions) – primary soluble portion of phytochemicals removed from the herb by a liquid solvent and/or heat and/or pressure, used to draw multiple types of compounds out of herb tissue matrix and into solution

Fresh extracts: liquid portions taken from living plant tissues

fresh juice – recently expressed watery liquid from one or more plant parts

freeze-dried juice – fresh juice frozen, then water slowly removed under a vacuum

frozen concentrate – juice with most water removed, then frozen

stabilized juice – bottled juice sealed under a vacuum, usually pasteurized (heated)

preserved juice – juice with additives (like alcohol) to prevent fermentation/degradation

green (specific) tincture – fresh plant part extracted at fresh herb weight to solvent volume ratio of 1:1 using a water/alcohol mixture

homeopathic mother tincture – fresh plant extract at 1:10 ratio with water/alcohol mixture

Liquid extracts of dried plant part: complex mixture of plant compounds removed with a solvent

decoction – solution from simmering cut herb in water at low heat for > 15 minutes

infusion – solution from soaking cut herb in hot (boiled) water for 5-15 minutes

cold infusion – solution from soaking cut herb in water at room-temperature for hours

tincture – extract of dried plant part, dry herb weight to solvent volume ratio usually 1:4 or 1:5, soaked in water/alcohol solvent for up to 14 days

spagyric extract – water/alcohol plant extract with ash from burnt plant marc added back

fluid extract – water/alcohol extract of powdered plant part, weight to volume ratio 1:1, first soaked and then slowly percolated over several days

Solid extract – powder obtained from liquid extract by removing solvent with heat and drying

standardized concentrate – contains most dissolved compounds found in a primary solvent extract and a consistent marker compound content, having ratio of original dry herb weight to final extract weight 2:1 – 10:1, along with excipients

SIMPLIFIED FRACTIONS (Extract Subfractions) – secondary extracts of complex fractions to concentrate select compounds; specific chemical portions separated from extracts

Standardized derivatives – multiple solvent extractions concentrate active component(s) to specific content; ratio of dry herb to final extract weight 10:1 – 50:1

Fixed or aromatic oils – lipid fraction removed by solvents (both) or cold pressure (fixed), or distilled with heat (aromatics); concentration ratio of dry herb to oil 50:1 – 100:1

ISOLATED CONSTITUENTS (Isolates; Purified Compounds) – phytochemicals that have been separated from their complex natural matrices; single molecular components removed from complex mixtures, often by fractionation followed by precipitation

Crystalline drug salts – single constituents altered through chemical processes that result in formation of drugs with ionic bonds that will dissolve in liquids

Table 2. Product Content Trends

When Moving From Whole Herb to Fractions to Isolates

MOST COMPLEX LEAST COMPLEX

Herb

(Complete Complexities)

Native

Extracts

(Complex

Fractions)

Simplified

Fractions

(Extract

Subfractions)

Isolated

Constituents

(Purified

Compounds)

Number of

Additives

XXXX

XXXXXX

Bioactive

Constituents

XXXXXX

XXXX

Constituents

Lost

XXXX

XXXXXX

COMPARATIVE DOSES

Concentrates

A mistaken assumption is constantly being promoted that a therapeutic equivalency exists between a certain weight of a whole herb and extracts made from that same weight. Based on the fact that any extract provides only a fraction of the total herb, and only some of any total component content, this clearly is not the case. Even if the whole herb contained only one biologically active component (a situation that is virtually unknown), no commercially employed extraction process will completely exhaust the herb of its content of the active compound. The most common means of making herbal liquid extracts (referred to as tinctures) is with a process known as maceration. When herbs are soaked (macerated) in a solvent made of a mixture of water and alcohol (ethanol), the extraction process stops when the concentration of a compound in the solvent equals the concentration remaining in the extracted herb (equilibrium), known as the marc. Relatively complete extraction of certain components in the herb can only occur under these conditions if the amount of solvent is great and little herb is used, resulting in an extract that is extremely weak. Even this will only occur if the compounds in the herb are completely soluble in the ratio of water to alcohol used. When using a water/alcohol mixture as the extracting solvent, a complete solubility, and therefore extraction, does not occur for any single compound, much less all of the components simultaneously.

The process that most closely approaches complete extraction of certain components of the herb is called percolation. Percolation is typically applied to the manufacture of concentrated fluid extracts. By allowing a slow, steady flow of solvent to pass through the ground herb loosely packed in a column, the fresh solvent added to the top of the column is much more effective in extracting the components than when it reaches the bottom of the column where it is concentrated with extracted components. Even using this method, to completely remove the remaining active components from the herb in the bottom of the column, the final portion of extract is so dilute that it must be concentrated after the extraction is complete. This process employs the application of heat to drive off the excess solvent and reduce the volume. Heating the extract is destructive to many compounds, thereby changing the content and rendering the extract less complex and less potent. As a consequence the extract does not provide all of the original component content and activity present in the whole herb amount that was extracted. Study of the essential oil content in thyme and its extracts has shown in general that the greater the degree of concentrating the extract, the lower the percentage of original content of the whole herb is contained in the final extract.

While this deficit in the retention of content by concentrating extracts is recognized and acknowledged, an associated error in logic is being propagated in the meantime. This faulty reasoning takes as a standard the effective dose of a concentrated herbal extract and then attempts to determine the equivalent dosage of the whole herb calculated on the basis of the degree of concentration by weight that has occurred. In other words, a 5:1 extract whose dosage quantity (for example, 100 mg) represents components extracted from a greater weight of whole herb (in this case, 500 mg) is regarded as five times more potent (a fallacy). As a consequence, it is believed that to get equivalent activity using the whole herb, five time as much of the herb must be used (a further fallacy). It is on this faulty premise that the proposed dosage equivalency of whole herbs compared to extracts is misrepresented to the public and practitioners alike.

STANDARDIZED EXTRACTS

Confusion in the ranks – Standardization claims for products of popular herbs

Echinacea [Example discussing one genus taken from this section.]

A final example of standardization illustrates how its use can be misconstrued in evaluating the quality, and even the identity, of products. In an attempt to assess the validity of label claims, in 2003 Gilroy and others obtained 59 preparations sold as echinacea in the Denver metropolitan area. The investigators decided to use thin layer chromatography (TLC) as a means of determining the legitimacy of content claims for these products. They based the interpretation of their findings on the assumption that the relative content of Echinacea purpurea could be determined by the cichoric acid yield. They also assayed echinacoside as the marker for E. angustifolia to differentiate these two species.

The third commercial echinacea species, E. pallida, also contains echinacoside, therefore this marker could not be used as a means of distinguishing this species from E. angustifolia. Five of the 59 samples were identified on their labels as E. pallida, but the authors state that differentiating between it and E. angustifolia “was never a concern.” Unfortunately, the authors failed to note claims about the part of the plant used. Normally, E. pallida and E. angustifolia roots are the parts used for such products. If this is true for these samples, species identification can be made by the caffeoyl phenolic compound cynarin present in E. angustifolia roots but absent in E. pallida roots (and E. purpurea as well), as shown by Perry and others in 2001.

The roots can also be easily distinguished due to E. pallida root’s lack of the tongue-tingling isobutylamides that typify E. angustifolia (and E. purpurea). Isobutylamides and the polyacetylene or 2-ketoalkenes and 2-ketoalkyne components found in E. pallida are readily demonstrable by TLC. The authors referenced the research by Bauer and Remiger in 1989 that describe these differences with TLC, but surprisingly use this means to only identify the phenolic markers. In addition, Cheminat and others determined in 1988 that cichoric acid was the main phenolic product in E. pallida flowers and leaves, with some was present in the root as well. Likewise, Perry and others in 2001 found cichoric acid in E. angustifolia roots, making this a nonspecific marker for absolutely identifying E. purpurea.

The inadequacy of using the phenolics, cichoric acid and echinacoside, as suitable echinacea markers, as well as not characterizing the processed forms of the samples, come to bear on the issue of evaluating E. purpurea products. The juice of the aerial plant preserved with 22% ethanol is an established remedy, and the most researched echinacea product on the market. In 1999 both Bauer and Kreuter indicated that the enzyme polyphenol oxidase rapidly breaks down cichoric acid in the cold-pressed fresh juice. Kreuter pointed out that clinical research had employed the cold-pressed and unheated E. purpurea plant juice, so only this juice with little or no cichoric acid has been proven clinically effective. When the juice is heated to destroy the enzyme, cichoric acid will be consistently retained. However, in 1999 Bauer found that heat-stabilized juice products had much lower isobutylamide content on average. The isobutylamide components are believed to be more therapeutically active as immune enhancers than the cichoric acid.

Arnason reported that in 1998 Bauer observed that cichoric acid declines in tinctures in six days. Livesey and others indicated in 1999 that cichoric acid diminished in tinctures with 55% alcohol at room temperature after 7 months but was stable in powder during this time even at higher temperatures. Nusslein and others in 2000 showed cichoric acid could be preserved in aqueous extracts over four weeks by adding 50 mM ascorbic acid or 40% ethanol. Thus, it is obviously necessary to characterize the form of the product when assessing relative cichoric acid content, rather than generalizing average content to all forms.

In their evaluation Gilroy and others did not identify these products as powdered root/plant or extracts, but simply reported that 9 were tablets, 32 were capsules, 4 were softgels, and 14 were liquids. Only 21 of the products were standardized, but their forms were not specified. The standardized products had much lower recommended doses, suggesting that these were solid extracts rather than the root. It is obvious that the softgels and liquids were extracts, as were likely some of the tablets and capsules. Whether these were processed as pressed plant juice, its dried powder, or as liquid or solid solvent extracts of fresh or dried roots cannot be deduced. Nonetheless, not all extracts are standardized, so we don’t know from the information given what the forms of the standardized products were. Calling all of the products simply echinacea is inherently misleading, since they represent many possible identities: root, aerial plant, juice, or their solvent extracts and concentrates.

The authors’ premise in assessing the content of the particular caffeoyl phenolic markers is understandable, since these compounds are typically used to “standardize” products of these species. They addressed those products that claimed to be standardized to specific phenolics. Of the nine samples that identified either echinacoside or cichoric acid as markers, none matched the label claim. Rather, seven had on average only 26% of the label claims, and the other two contained no measurable amounts. Ten product labels made claims to be standardized to total phenolics, but this fails to distinguish between particular species markers. In his talk at an international echinacea conference in 1999 Arnason noted that even though the total phenolic content had been the common echinacea standard for years, it was a “completely, utterly useless measure, in the opinion of all the phytochemists in the room, as to the quality of echinacea products.”

Gilroy and others assayed phenolic marker content of standardized products as well as those whose identifying label claim was simply the species used in the product. It is interesting to note that, based on their phenolic evaluation approach, 21 of 30 (70%) of the nonstandardized products matched the label species claim, while only 10 of 19 (53%) of the standardized products were presumably the appropriate species. For those products containing cichoric acid, the nonstandardized yielded on average about 2.5 times more than the standardized samples. In the products with echinacoside, the content of nonstandardized samples averaged more than 3 times the yield of those that were standardized. The doses of nonstandardized products were about twice those of standardized.

Finally, Gilroy and others claim that only four of the products (7%) met the four FDA labeling requirements. They observe that the better compliance score for standardized than nonstandardized products was due to the presence of the “Supplements Facts” box. However, products that do not make standardization or structure/function activity claims and companies that have less than 100 employees are exempt from this label requirement. The authors’ conclusion that the “claim of “standardization” does not mean the preparation is accurately labeled, nor does it indicate less variability in concentration of constituents of the herb,” is an appropriate assessement of these echinacea products. One could accurately state that standardization claims provide no basis for determination of quality of these products in terms of therapeutic efficacy. Trying to evaluate echinacea products on the basis of phenolic markers without specifying the plant part and form of each preparation being assessed is meaningless. Even knowing those features is of little value beyond limited characterization of the product. Quality is a function of effect, not just identity.

Arnason JT. North American raw materials: the case for an isobutylamide standardized product. Echin. Past, Present Future Internat. Conf. 1999 Proc., Session Three, pp. 4-5 & slide 40, Skamania, Wash., June 10-12, 1999

Bauer R. Standardization of Echinacea purpurea expressed juice with reference to cichoric acid and alkamides. J. Herbs, Spices Med Plants, 6(3):51-62, 1999

Bauer R & Remiger P. TLC and HPLC analysis of alkamides in echinacea drugs. Planta Med., 55:367-71, 1989

Cheminat A et al. Caffeoyl conjugates from Echinacea species: structures and biological activity. Phytochem., 27(9):2787-94, 1988

Gilroy CM et al. Echinacea and truth in labeling. Arch. Int. Med., 163:699-704, 2003

Kreuter M. Echinacea purpurea substances, characteristics and immunological active principles. Echin. Past, Present Future Internat. Conf. 1999 Proc., Session Two, p. 3 & slide 7, Skamania, Wash., June 10-12, 1999

Livesey J et al. Effect of temperature on stability of marker constituents in Echinacea purpurea root formulations. Phytomed., 6(5):347-9, 1999

Nusslein B et al. Enzymatic degradation of cichoric acid in Echinacea purpurea preparations. J. Nat. Prod., 63:1615-1618, 2000

Perry NB et al. Echinacea standardization: Analytical methods for phenolic compounds and typical levels in medicinal species. J. Agric. Food Chem., 49:1702-6, 2001

Table 3. Echinacea Products of Different Types*

(X = Commercially Available Product)

WHOLE HERB
Common name	Echinacea	Echinacea	Echinacea	Echinacea	Echinacea
Scientific names	Echinacea angustifolia	Echinacea pallida	Echinacea purpurea	Echinacea purpurea	Echinacea purpurea
Plant part	Root	Root	Whole plant	Aerial plant	Root
Fresh, living			X
Freeze-dried	X			X	X
Air/oven dried: bulk	X	X