Encyclopedia of

Feverfew (Tanacetum parthenium) 213
newspaper accounts of favorable responses in sufferers
whose condition was resistant to conventional medication.
[11] The stimulus for this burgeoning attention was
the experience of Ann Jenkins, a Welsh doctor’s wife,
who in 1973 at age 68, upon the suggestion of the
elderly father of a friend of her sister’s, had begun
experimenting with feverfew; the old gentleman,
interestingly enough, had found feverfew helpful in
treating his arthritis. After increasing the dose from
one small leaf to three, after 5 mo, the vomiting associated
with the migraine attacks stopped. She also
required less of her conventional migraine treatment,
ergotamine. After 6 mo, she went for an entire month
without a migraine attack, and after 10 mo, the attacks
ceased. [15]
The Questionnaire
With the assistance of Mrs. Jenkins, Dr. E. Stewart
Johnson, associated with the City of London Migraine
Clinic, solicited participants in an epidemiological survey
on the use and value of feverfew. A questionnaire
was provided inquiring as to whether headaches during
use of the herb were less frequent, more frequent, less
painful, more painful, or unchanged. Of the roughly
300 responders, 253 were judged to be suffering from
true migraine, 93% having been diagnosed by a doctor.
Of these, 72% reported reduced frequency of migraine
attacks, while 26% felt that their headaches worsened.
This success rate was virtually identical for participants
whether or not they were suffering from other ailments
or taking other medications. A further assessment of
242 patients for actual numbers of attacks each month
before and during feverfew treatment revealed that
33% no longer suffered any migraine attacks while
taking the herb and 76% had fewer monthly episodes.
Eighty percent of those who stopped taking feverfew
reported recurrence of severe migraine within a week
or two. A polling of feverfew users on their experience
with conventional migraine preventive drugs produced
very interesting results. Clonidine, the pharmaceutical
most commonly tried, was deemed ineffective by 72%
of feverfew users, while ergotamine, the most helpful
of the other drugs, was judged helpful by 62%.
Most of the other drugs were found less than 50%
effective. Curiously, about 40% of feverfew users attributed
pleasant side effects to the plant: relief from the
symptoms of coexisting arthritis, less muscular tension,
more restful sleep, and the like. Responders to the
questionnaire had been taking feverfew for an average
of two-and-a-half years. [15] Traditionally, feverfew users
take 2–4 small or 1–2 large leaves per day, often in a
bread-and-butter sandwich, sometimes mixing honey
with the crushed leaves to further mask the bitter
taste. [11]
CHEMICAL CONSTITUENTS
The main chemical constituents that have received
attention regarding biological activity fall into three
categories, namely, essential oil, STLs, and flavonoids.
The flavonoids of feverfew are the lipophilic flavonols
di- and trimethylethers of 6-hydroxykaempferol and
quercetagetin, and the hydrophilic flavone glycosides
apigenin-7-glucuronide, luteolin-7-glucuronide, and
chrysoeriol-7-glucuronide. [18] The trimethylether of
6-hydroxykaempferol, originally named tanetin, and
characterized as 3,7,4 0 -substituted, was later determined
to be the known flavonol santin, a 3,6,4 0 -trimethylether.
Santin, 6-hydroxykaempferol-3,6-dimethylether, and
quercetagetin-3,6-dimethylether (axillarin) are the three
main flavonol constituents. Two further minor lipophilic
flavonols have been identified unequivocally:
quercetagetin-3,6,3 0 -trimethylether (jaceidin) and
quercetagetin-3,6,4 0 -trimethylether (centaureidin). [19]
The volatile essential oil is dominated by camphor
(43–44%) and chrysanthenyl acetate (24%), accompanied
by lesser amounts of spiroketal enol ether diynes,
camphene, germacrene-D, p-cymene and terpinen-4-ol.
The dominant STL, parthenolide, is also released in
the volatile oil, as are the ubiquitous phytosterols
sitosterol and stigmasterol. [20–22] No significant infraspecific
variation has been observed in the composition
of the volatile oil. [23]
STLs have until recently been the prime focus of
chemical and biological attention among feverfew
constituents. The germacranolide (10-membered carbon
ring), parthenolide, dominates the STL chemotype
that has been subjected to clinical evaluation. The most
comprehensive analysis of the chemical content of
feverfew leaf has been conducted by Bohlmann and
Zdero. [24] Parthenolide comprises more than 80% of
the total STL content of this chemotype, in concentrations
as high as 2% of dry weight in individual
plants. [25] At least two other STL chemotypes of feverfew
have been recognized, devoid of parthenolide. [26]
The most prominent STLs accompanying parthenolide
in the clinically efficacious STL chemical profile are
3b-hydroxyparthenolide, the isomeric guaianolide
(5=7-carbobicyclic) bis-epoxides, canin (a) and artecanin
(b), the endoperoxide precursor of canin,
tanaparthin-a-peroxide, and the cyclopentenone secotanaparthenolide
A, all containing an a-methylene-gbutyrolactone
moiety. [16,27]
Respecting the historical identification of feverfew
STLs, it should be noted that there is a serious question
concerning the presence of unusually structured compounds
such as chrysanthemonin, chrysanthemolide,
and partholide, [28] which are not identified elsewhere
as feverfew constituents and are likely the result of
degradation during protracted refluxing 1 week and subsequent
processing; chrysanthemonin, a trisesquiterpene
F