THE TWO NEW CHOLAGOGUES 
F.UONYMUS ATROPURPUREUS (WAHOO), 
AND 
IRIS VERSICOLOR (BLUE FLAG). 
An important and interesting paper, by Dr. J. R. Black, of Newark, 
Ohio, published in the Philadelphia Medical and Surgical Reporter for 
April 19, 1879, attracted attention to the valuable medicinal properties 
of the Fluid Extract of Euonymus Atropurpureus, or Wahoo, and 
especially to our preparation of it, which was the one employed by him. 
A largely increased demand upon us for this article was the result; and 
we were led to institute, through some of our ablest practitioners, ex- 
periments and investigations which have fully confirmed the assertions 
of Dr. B ack. We ascribe the superiority of the preparation supplied 
by us to the fact that we use in its manufacture the bark of the root 
only, employing a menstruum that we have found by experience, 
thoroughly extracts all the medicinal properties of the drug. The results 
attained with an article so prepared, are, according to all the testi- 
mony available, superior to those from the resinoid alone. Thus the 
favorable opinions expressed by Bartholow, Rutherford, and other writers, 
based upon the experience they had had with the resinoid, are of much 
greater force in support of our claims for our Elixir and Fluid Extract, 
which contain all the active principles of the plant. 
Our attention has also been drawn to the preparation, for medicinal 
use, of another vegetable product, of an analogous kind, viz.: the Iris 
Versicolor, or Blue Flag. Long known to the Indians, as a remedy, 
this plant has been extensively employed by eclectic practitioners, 
and only within a few years have the regular profession begun to recog- 
nize its virtues. These virtues are, according to the evidence of com- 
petent observers, superior to those of Podophyllin, which has acquired 
such favor as a cholagogue. We prepare this article in the same way, 
in the form of Elixir anil Fluid Extract, and claim the same superiority 
for it over the resinoid, as in the case of Wahoo. 
In regard to both these articles, we would say that we follow our 
inexorable rule of having the selection of the crude material made with 
the utmost care, and ol>serving the most scrupulous exactness in every 
stage of the manipulation, so as to produce an agent that shall not dis- 
appoint the preserver. 
Our claims, supported by authority such as that of Bartholow, 
Rutherford, Black, and others, will, we are confident, be borne out by 
the test of practice, which we ask physicians to institute; and we beg 
their careful perusal of the following statements in regard to the above 
named drugs. / 
Yours, very respectfully, \y 
JOHN WYETH & BRO. EUONYMUS ATROPURPUREUS. 
wjlieioq. 
The bark is the portion of the plant employed in the preparation 
of medicinal agents. The bark of the root, only, should be used in 
pharmaceutical processes, for this is richer in the active constituents 
than the bark of any other part of the shrub. 
History: Euonymus Europaeus has long been cultivated in 
gardens because of the brilliant red color of the fruit, which has given 
to the shrub one of its common names—burning bush. Euonymus 
Americanus has, also, been cultivated as an ornamental shrub. The 
latter has been used in preparing medicinal agents instead of E. Atropur- 
pureus, but although they possess analogous properties, such substitution 
must be regarded as a sophistication. According to the U. S. Dispen- 
satory, E. Europceus has been examined by Grundner, who found it to 
possess diuretic properties only; but an oil obtained from the seeds was 
used to destroy vermin and as a stimulating application to old ulcers. 
According to Griffith, “the seeds of these varieties are emetic and 
purgative, and the leaves are poisonous to sheep and other animals.” 
Through the West and South, under the name of Wahoo, E. Atro- 
purpureus has long been used in domestic practice. This name, as well 
as the knowledge of its uses was, doubtless, obtained from the Indians 
by the primitive settlers, in search of remedies for the diseases incident 
to a new country. It was used by them as a purgative, diuretic, and 
alterative, especially the last, because it was supposed to possess great 
powers as a “blood purifier.” We owe its introduction into medical 
practice to the Eclectic physicians, who have been diligent students of 
our indigenous Materia Medica. They adopted the aboriginal and 
domestic notions in regard to its use, and have for several years employed 
it as a purgative, diuretic, and alterative. Beside the Dispensatories, the 
works of the regular medical profession have only lately taken any 
notice of this, now, promising remedy. It is contained in the “Secondary 
List,” of the U. S. Pharmacopoeia. In Bartholow’s Treatise on Materia 
Medica and Therapeutics it is referred to and its powers defined briefly. 
It has been the subject of investigation by several pharmaceutists, 
Wenzell and Clothier; its physiological actions have been studied by 
Rutherford, and its medical properties have been set forth in a special 
memoir by Dr. J. R. Black. 3 
Composition and Properties: The first systematic study of its 
composition was made by Mr. William P. Clothier, who in 1861, pub- 
lished an inaugural essay in The American Journal of Pharmacy, o. 490. 
He ascertained that it contained starch, sugar, gum, pectin, indifferent 
substances, an oleo-resin, and a bitter principle crystallizing in “yellow, 
acicular crystals.” A year subsequent to jnese researches, Mr. W. T. 
Wenzel 1 undertook the examination of the bark anew, and as his pro- 
cesses were better, it is probable that his results are more to be depended 
on. Beside various unimportant ingredients, Wenzell separated a bitter, 
non-crystallizable principle, neutral in reaction, which he named, Euony- 
min\ he also discovered a principle identical with Asparagin, an oteo- 
resin of complex constitution, an acid peculiar to Euonymus, which he 
termed Euonic acid, and various other constituents. (American Journal 
of Pharmacy, 1862, p. 390, Vol. 34.) 
These analyses are very important, as they demonstrate the nume- 
rous and valuable constituents found in Euonymus, and afford abundant 
support to the theory of its utility in disease. A drug possessed of such 
constituents must have important uses. 
We learn from domestic practice and from the experience of those 
physicians who have tried it, that it acts as a purgative of a peculiar kind. 
Some liken it to Rhubarb, some to Castor oil, but as we shall see, it differs 
from both of these in important particulars. Most of the trials have 
been made with the preparation introduced by the Eclectic practitioners, 
and known as Euonymine, which is not an active principle, but consists 
of the oleo-resin mixed with variable proportions of Euonymin and 
Asparagin. The Eclectic “ Euonymine ” is obtained by precipitation 
of a concentrated tincture by water—the precipitate consisting of the 
parts named above, and when dried, is a brownish powder having an 
intensely bitter taste. When this Euonymine is taken in doses of about 
five grains, it causes free evacuations, characterised by certain peculiarities 
to be mentioned hereafter. It is obvious, however, that this preparation 
does not represent the full powers of the remedy. Much of the active 
principle, and other important ingredients, are lost in this process. A 
properly made fluid extract of the bark of the root is the true preparation, 
for in this are retained all of the constituents. A fluid extract of the bark 
of the root will contain not only the purgative principle, but the diuretic 
and so called alterant properties. 
The valuable uses of Euonymus are set forth briefly by Barthorow, 
the first one to indicate the precise nature of its powers, as a remedy 
acting similarly to rhubarb and possessed of special activity as a hepatic 
stimulant. (Practical Treatise on Materia Medica and Therapeutics, 4 
3d Ed., p. 484.) The most important contribution yet made to our 
knowledge of the physiological action of Euonymus, is the research of 
Rutherford and Vignal, undertaken for the British Medical Association. 
Amongst the cholagogues examined by them, Euonymine, the Eclectic 
preparation, stands in almost the first position as an agent stimulating the 
hepatic secretion. ( The British MedicalJournal, June, 1877). Mr. C. A. 
Santos, in some remarks on the chemical properties of Euonymus, states 
that it is a “ diuretic, tonic, antiperiodic, and hydragogue cathartic,” and 
that it has “beneficial effects in the different forms of dropsy.” Accord- 
ing to Mr. Clothier this remedy was introduced in Philadelphia by Mr. 
G. W. Carpenter as a remedy for dropsy, he having ascertained that it 
was largely used in the West for this purpose. 
A recent and most important contribution to the therapeutical use 
of Euonymus is that of Dr. J. R. Black, of Newark, Ohio, {The Medical 
and Surgical Reporter, April 19, 1879,) who points out that “it acts as 
a gastric tonic, cholagogue and mild cathartic, and usually within two 
hours after its administration. Its action is unattended by nausea, 
griping, or any debilitating influence.” Furthermore, he says, “the 
stools indicate the large presence of bile,” which is a striking clinical 
confirmation of the laboratory experiments of Rutherford and Vignal. 
Again — “ it is preeminently, the most unobjectionable of cathartics to 
overcome habitually loaded abdominal viscera * * especially is it 
of eminent service, when, from a variety of causes, hepatic and intestinal 
torpor are confirmed. * * Continued use does not habituate and blunt 
the system to its energy, consequently, the dose does not require to be 
increased. Black finds that “ the fluid extracts of this drug in the market 
are of unequal strength,” and that made from the bark of the root, is 
twice the strength of that prepared from the bark of the shrub. In 
this Dr. Black is undoubtedly correct, as all testify on this point who 
have made chemical investigations of both the bark of the root, and 
bark of the shrub. 
“In summing up,” says, Dr. Black, “ it may be said that in Euony- 
mus we have an invaluable gastric tonic, mild cholagogue. pleasant laxa- 
tive or cathartic, according to the dose.” 
We have called on a practical therapeutist of much experience for 
an opinion as to the real value of this remedy, which we subjoin : 
“Physiological experiment and clinical experience agree in the 
view that Euonymus is a stimulant to the liver,—a cholagogue—of 
special power. It is therefore a very satisfactory remedy in cases of 
torpor of the liver, in congestion of the liver, in jaundice from catarrh 
of the bile ducts, in ascites from obstructive disease of the liver. It is 5 
much more effective than mercurials, and entirely free from their objec- 
tionable features. 
“Asa bitter, it acts as a tonic to the stomach, promotes appetite and 
digestion, and is peculiarly valuable because, as a hepatic stimulant, it 
promotes the intestinal digestion, the solution and absorption of fats, etc. 
Kuonvmus is, for these reasons, specially desirable in the gastro intestinal 
and hepatic disorders succeeding to attacks of malarial fever. It 
possesses quite considerable antiperiodic power, and is therefore a valua- 
able adjunct to quinia in the treatment of intermittent and remittent 
fevers. That it is a serviceable diuretic, there can be no doubt. It is 
useful in the dropsy of malaria, and in cardiac dropsy, but its most 
important application in this direction is as a remedy for ascites, and as 
a hydragogue.” 
Since the above was in print the following in regard to Euonymus 
has appeared in the Lancet, from Dr. \V. M. Collins, of London: 
Having recently made a trial of Euonymin in some cases of 
hepatic derangement, with defective secretion of bile, I am induced to 
offer a few brief remarks on its action as a cholagogue. 
Euonymin, which has lately been brought into notice by the experi- 
ments of Dr. Rutherford, as a hepatic stimulant, is a resinous substance 
obtained from a species of Euonymus (Wahoo Bark). It differs from 
most of the ordinary so-called cholagogues, in not producing any intes- 
tinal irritation, its action on the liver being direct. It, theref. re, does not 
give rise to the colicky pains and discomfort which so often attend the 
use of Bodophyllin, and which tend to prove that the latter drug acts 
only indire tly on the liver by the irritation it sets up in the duodenum, 
for which portion of the intestine it has a special affinity. Euonymin is 
particularly serviceable in cases of hepatic dyspepsia, or what are com- 
monly called attacks of “biliousness,” with furred tongue, pale stools, 
' usitude, and general malaise, and under its use the tongue cleans, the 
stools become dirker, and the feeling of languor and heaviness disappears. 
Its action is slow, and its effects experienced most about forty-eight 
hours after it has been taken. In too large or too frequent doses it may 
cause some depression. In most classifications of remedies met with in 
therapeutical works there is no special division made of cholagogues, 
but those remedies which are supposed to act on the liver are classified 
under other heads; e. g., Podophyllin is included with the cathartics, 
and, perhaps, properly so, as this remedy only exercises a secondary 
action on the liver by catharsis. But Euonymin, and probably Iridin 
also, as shown by the recent experiments of Dr. Rutherford, may be 
considered as true cholagogues or hepatic stimulants, since they act 
directly on the liver. IRIS VERSICOLOR 
BLUE FLAG. 
History: Iris Versicolor, or Blue Flag, is indigenous to this 
country. Although belonging to the same family as Iris Florentina and 
other species of Iris growing in the south of Europe, it possesses very 
different powers. The portion of the plant employed in the preparation 
of pharmaceutical products, is the rhizoma, or root stalk, which is most 
active in the fresh state. This has long been known to possess cathartic 
and diuretic properties, but a careful investigation of its real properties 
has been made only recently. As was the case with its congener Euony- 
mus, the knowledge of its uses was obtained by the pioneers from the 
Indians, who had learned by experience of its curative effects in certain 
conditions of disease. Since the first settlement of this continent Iris 
has been used more or less by regular physicians, cognizant of its powers, 
but its actual introduction into practice and its popularization as a 
remedy we owe to the Eclectics. These practitioners have always 
maintained that Iris had special power as a cholagogue, or bile stimulant, 
and have used it with success in disease of the liver, as a stomachic tonic, 
and as a diuretic. After all, this application of Iris is a mere confirma- 
tion of the notions entertained by the aborigines of its properties. It 
has been recognized by the U. S. Pharmacopoeia, as a remedy, but is 
borne on the Secondary List as a substance of secondary importance. 
The U. S. Dispensatory gives the uncertain and desultory opinions of 
various practitioners in respect to its properties and uses. Bartholow is 
the only one amongst our systematic authors, who appears to have correct 
notions of the real utility of this ageut. He remarks “There is much 
evidence tending to show that this remedy is really serviceable when the 
stools are clay-colored, and the skin jaundiced, in consequence of duo- 
denal catarrh and obstruction of the biliary ducts. It is said that mala- 
rial jaundice may be cured by this drug, and that in bilious remittent 
fever and in chronic malarial poisoning it exerts a favorable influence.” 
(.Practical Treatise on Materia Medic a and Therapeutics, p. 484b A 
writer on the editorial corps of the London Lancet had so long ago as 
1862, Lancet, Aug. 30, 1862 , correctly indicated the range of its pow- 7 
ers. Speaking of Iridin, he says,—“Its action is that of a mild aperient 
cholagogue, and it is alleged to be diuretic, and indeed to excite all of 
the secretory organs. ‘Physicians,’ says one writer, ‘occasionally meet 
with patients upon whom podophyllin, even in small doses, exerts a 
powerful and long-continued influence, not easily obviated: in such cases 
Iridin seems to be more especially, indicated.’ In our hands Iridin has 
produced effects very similar to those occasioned by a combination of 
blue pill, rhubarb, and aloes. It seldom fails to produce mild catharsis 
with bilious evacuations; and appears to possess the advantages of (i) 
not requiring the addition of a mercurial, (2) not irritating the rectum 
as aloes is apt to do, and (3) it has no astringency, and therefore does 
not produce subsequent costiveness like rhubarb when given alone. In 
a sluggish state of the bowels arising from torpidity ot the liver, or when 
the stools are pale, particularly as we find them in the intervals of overt 
attacks in gouty persons, we have found the Iridin one of the best aperi- 
ents—much gentler than podophyllin, and more reliable when a slight 
cholagogue action is required to be maintained for a lengthened period.” 
It is remarkable how this strong testimony to the peculiar powers 
and properties of Iris, derived from clinical experienc c ami observation, 
is supported by physiological experiment. In that remarkable series of 
investigations into the action of cholagogues, undertaken by Rutherford, 
and which has thrown so much light on the actions of Euonymus, Iris 
was also examined into with the same care and accuracy, and with results 
that entirely confirm the deductions of clinical experience. We quote 
from the report ( The British AfedicalJournal, June, 1877). “Iridin 
* * very powerfully stimulated the liver. * * It is also a decided stimu- 
lant of the intestinal glands. Judging from these experiments its irritant 
effects on the intestinal mucous membrane are decidedly less than those 
of podophyllin, while the purgative effects are greater than in the case of 
Euonymin. It is, also, more powerful in its effects on the liver than 
Euonymin. There seems every reason why this substance should be 
removed from its present obscurity and placed in a prominent position 
in practical medicine.” 
In a recent article ( The Practitioner,—London,—November, 1879,) 
on the “Physiological Actions of Drugs on the Secretion of Bile,” 
Rutherford sums up anew his conclusions on the actions and relative 
merits of Euonymin and Iridin. 
“ These two substances are prepared respectively from the roots of 
the Iris Versicolor and Euonymus Atropurpureus. Both powerfully 
stimulate the liver, while they do not powerfully stimulate the intestine 8 
of the dog. Although not so powerful as podophyllin, they will both 
doubtless be preferred in many cases to that substance, because of their 
far milder excitement of the intestines. For not only is the latter in most 
cases advantageous on its own account, but also because the action on 
the liver is far less liable to be hampered and diminished by the intesti- 
nal stimulation. This, as we have seen, is apt to be the case with 
podophyllin. Our experiments on the dog have led us, and have led 
many others, to try the effect of these substances on man, and they are 
of great value. The average dose of Iridin is four grains, of Euonymin 
two grains. In either case two grains of extract of hyoscyamus should 
be added, and taken at bed time, for without this some persons ex- 
perience griping. Neither substance produces any sickness or headache. 
In some persons the above doses of both substances produce a sufficient 
purgative effect; but in other cases the purgation is insufficient or de- 
layed, and griping is then apt to ensue. The most beneficial result is 
obtained by following the dose of these remedies by a mild, saline 
aperient, such as Piillna or Carlsbad Water, on the following morning, 
so that the bile secreted during the night may be fully and quickly re- 
moved. I have in my own case noticed slight depression after four 
grains of Iridin, which I have never observed after two grains of Euony- 
min. I therefore inferred that the latter is preferable when repeated 
stimulation of the liver is desirable. It is, however, important to remem- 
ber that although Euonymin usually suffices to quickly remove a slight 
feeling of biliousness, Iridin is, I am convinced, the more powerful 
remedy of the two, when the tongue is decidedly yellow. I have been 
in such a case, more than once surprised to find that on awaking in the 
morning after taking four grains of Iridin the previous night the yellow 
tongue and bilious sensations were entirely gone. Since the publication 
of our results these remedies have come into very general use. Mr. 
Hardyman of Cardiff, {The British Medical Journal, July, 12, 1879,) 
states that he has used Euonymin in two grain doses at bed-time in over 
fifty cases of biliary derangement and sick headache, and finds it of much 
value. Finding that in most cases one dose is sufficient, he gives two 
grains at bed-tim2 on two successive nights, following it each morning 
with a saline purge. ” 
Composition: The active constituent is an oleo-resin. Whether 
it contains a distinct principle or alkaloid, is not known, but it is highly 
probable that such is the case. The important constituent is the oleo- 
resin, and on the presence of this depends its powers as a hepatic stimu- 
lant. It may be administered in the form of tincture, or fluid extract, 9 
or solid extract. The so-called Iridin is the oleo-resin, precipitated from 
a saturated tincture by the addition of water, and mixed with some 
indifferent powder. 
Notwithstanding there is but little tendency to griping manifest in 
its action, it may be desirable to indicate some method of obviating this. 
Rutherford suggests the addition of the extract of hyoscyamus—two 
grains to each dose. One-fourth to one-half grain of extract of bella- 
donna may also l>e used. A little capsicum seems to be effective. A 
small quantity of oil of anise, will no doubt accomplish the same object. 
As, however, delayed action seems to be a cause of the griping, a more 
active preparation will render any addition to prevent this effect un- 
necessary. Much of the so-called “Iridin” found in commerce but 
inadequately represents the real powers and capabilities of the remedy. 
llartholow says:— 
“ It is consequently extremely desirable to have a suitable prepara- 
tion made which shall contain all of the constituents of the drug. A 
properly prepared fluid extract, made from the bark of the fresh root, 
is the only preparation which can adequately represent either Euonymus 
or Iris. Such a fluid extract will, under all circumstances, accomplish 
the results expected from these remedies, whilst the imperfectly prepared 
Iridin or Euonymin, will often disappoint. Valuable remedies con- 
stantly fall into disfavor, because the preparations do not contain all the 
principles to be found in them, or in consequence of faulty methods of 
manufacture, prove to be inert. This statement is eminently true of 
Iridin and Euonymin. These resinoids represent these plants in part, 
only, and hence there cannot be obtained from them the therapeutical 
results produced by the fluid extracts, which represent these plants in 
their entirety.”