Volume 4, Number 1 | Spring 2009

Kampo Medicine - Current Research
Varieties of Effects of Shakuyakukanzoto
Hiromichi Yasui
Japan Institute of TCM Research

Shakuyakukanzotois the formula first
appeared in “Shan Han Lung”. This has a simple
composition comprising peony root and licorice
root. Despite the simple makeup, it has powerfuland potential medicinal benefits and versatile
applications across therapeutic categories.
Shakuyakukanzoto known in Japan as a magicbullet for so-called “komuragaeri (muscle cramps)”
has also useful prophylactic efficacy against it.
Thus, sports lovers as well as other people
habitually use it. For instance, they often take it
before golf competitions, going hiking, and long
distance bicycle touring in order to prevent muscle
fatigue in the lower extremity muscle fatigue;
mothers who learn of their child having a footballgame give this formula to him on the night before
the game. Moreover, this formula has the actionsof preventing or resolving striated muscle fatigue
or cramps, relieving colicky pain caused by thecontraction of smooth muscles, and improving
hyperprolactinemia. It is also used for preventing
acne.
Varieties of effects of shakuyakukanzoto andthe results of clinical trials will be introduced as
below based on the clinical results:
1. Muscle cramps
Since it is too basic that shakuyakukanzoto iseffective for muscle cramps, only a few reports
have been published. Muscle cramps occur mostly
during night. One pack (2.0 – 2.5g) dose before
sleep has the preventive effect. Even after theoccurrence, cramps will be relieved promptly with
one pack dosing. In this chapter, a study will be
introduced on the use of the formula for thepatients with hepatocirrhosis who had the onset ofkomurogaeri (muscle cramps) when they were2

undergoing artificial dialysis.
Kumakura, et al. administered on demand theExtract of shakuyakukanzoto 2.5g to 23
hemodialytic patients (male 10, female 13,
aggregated number of patients 61) immediately
after they claimed the onset of muscle cramps
while undergoing artificial dialysis. Muscle
cramps disappeared in 54 patients (88.5%), and an
average time taken to achieve the dissipation ofpain was 5.4±3.9 minutes. The amount ofphysiological saline solution per dialysis needed
for the cramp treatment was reduced to about one
thirds (p<0.0001) from that before the use of
shakuyakukanzoto1).
Kumada, et al. divided 101 patients with thediagnosis

ofhepatocirrhosis

who

had

the

experience of muscle cramps twice or more duringa week (four times or more during two weeks) inthe positive drug group (52 patients: male 21 andfemale 31) and the control group (49 patients:
male

26

and

female23).

Extractofshakuyakukanzoto (7.5g/day) was administered in
the positive drug group for two weeks, whereas
placebo (7.5g/day) was used in the control groupfor two weeks. In the group of Extract of

shakuyakukanzoto, the frequency of muscle
cramp occurrence was markedly improved in 4
patients, improved in 31, remained unchanged in
14, and worsened in 3 with the overall result of
improved or above in 67.3% of the patients. In theplacebo group, the frequency was markedly
improved in 5 patients, improved in 13, remained
unchanged in 22, and worsened in 8 with theoverall result of improved or above in 37.5%. The
effect in the positive drug group was significantly
superior (p ＜0.05) to that in the placebo group.
And the overall improvement rate was also higher
in the positive drug group2).

The Journal of Kampo, Acupuncture and Integrative Medicine (KAIM)

Volume 4, Number 1 | Spring 2009

2. Dysmenorrhea
Dysmenorrhea is a syndrome associated withmenstruation characterized mainly by spasm-like
acute pain in the lower abdomen and backache. It
has two types – functional dysmenorrhea andorganic dysmenorrhea. Shakuyakukanzoto is used
for both of them. Studies that have been reported
until now are as follows:month’s menstruation and at the time of hospital
visit were compared based on VAS values. Vasvalues declined and effects were sustained in 6
patients (42.9%); effects in each menstrual cycle
were not consistent in 4 patients (28.6%); although
VAS values declined, effects were not identifiablein 2 (14.3%); and ineffective in 2 (14.3%)4).

Inoue, et al. measured effects, using a pain
scale, of the Extract of shakuyakukanzoto in 42
patients who suffered from dysmenorrhea ofmoderate to severe degrees (age 14-49, averageage 30.4: functional dysmennorhea-18, organic
dysmenorrheal-24): the administration of theformula 2.5g/day was commenced from 5 to 7 days
before the expected first date of theirmenstruation period and then 7.5g/day for 2-3
days after the start of menstruation, and pains
were assessed by 5 pain intensity scales fromextreme pain to pain free. (Pain improved by 3
scales is assessed as prominently effective;
improved by 2 scales is effective; improved by not
more than 1 is ineffective.) The results were thatprominently effective was 31.0%, effective 57.1%,
and ineffective 11.9%, and the overall
effectiveness was 88.1%. There was no significant
difference between the group of functional
dysmenorrheal (88.9%) and the group of organic
dysmenorrheal (87.5%)3).

Tanaka, et al. report that they administered theOhta, et al. administered the Extract of
shakuyakukanzoto (7.5g/day divided in 3 doses) to
25 patients with dysmenorrhea of moderate tosevere degrees (age 17-37, average 25.2±5.2) for 10
days from the expected commencement date of
menstruation. Pains were assessed three times
using the VAS scale at the time of registration(previous menstrual pain was registered at thehospital), at the time of menstruation, and at thetime of hospital visit. For 14 patients after
excluding those whose pains could not
appropriately be grasped, pains at the time of each

References
Extract of shakuyakukanzoto (7.5g/day divided in 3
doses) to 12 patients with functional dysmenorrheal
and organic dysmenorrhea of moderate to severe
degrees (age: 22-46, average 33.0±8.7, functional-4 andorganic-8). The administration was commenced from 7
days before their expected first day of menstruation
until

the

last

Subsequently,

day

of

their

menstrualthepreparation

7.5/day

period.
wascontinuously administered until 7 days prior to thestart of their next expected menstrual cycle, resulting
in prominent effects in 12 patients after threemenstrual cycles5).

3. Hypertestosteronemia and hyperprolactinemia
Recentstudieshave
elucidated
that
shakuyakukanzoto
haseffectsonHypertestosteronemia and hyperprolactinemia.
As a result, this preparation is believed to haveapplications for any disorders developed byhormonal abnormalities. Especially, there areseveral documents reported in the gynecologies
that it was useful for the patients who complainedof anovulation or infertility due to hormonal
abnormalities.
Yaginuma, et al. administered the Extract of
shakuyakukanzoto (7.5g/day) to 110 patients(anovulation 78, rare occurrence of ovulation 15,
normal menstrual cycle 17) out of 128 patientswith high blood levels of testosterone of 0.7ng/ml
or higher (age 26.7±0.4), after excluding those
who were not appropriate to have evaluations.
After 16-week administration, blood levels of
testosterone, estrone (El), estradiol, cortisol, FSH,

The Journal of Kampo, Acupuncture and Integrative Medicine (KAIM)

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Volume 4, Number 1 | Spring 2009

LH, and prolactin were compared before and after
the administration. For 10 patients who showed
the blood prolactin levels were 25ng/ml or above,fluctuations in its level were also reviewed. The
results were that from two-week administration
onward, the blood levels of testosterone and El
were significantly reduced (p＜0.001, p＜0.05 foreach) and 78 patients with anovulation (42.3%)
recovered the regular ovulation cycle. Moreover,the blood prolactin levels in 10 patients weresignificantly reduced (p＜0.05)7).
Takahashi, et al. administered the Extract of
shakuyakukanzoto (7.5g/day) for 24 weeks to 34
patients of the group of polycystic ovary syndrome,
who had polycystic swellings in both ovaries foundon an ultrasonic examination with the blood
testosterone levels of 100ng/dl and compared thelevels of the testosterone before and after theadministration, resulting in reduced levels in 30
patients (91%). Average testosterone levels
dropped in the 4th week from the preadministration levels of 137.1±27.6ng/dl to 85.3
± 38.3ng/dl (p ＜ 0.001). Similarly, the levels
reduced in 12th week and 24th week8).
Itoh, et al. administered the Extract of
shakuyakukanzoto (7.5g/day) to 51 patients who
visited our facility with the complaint of infertility
and was diagnosed as having occulted
hyperprolactinemia by a TRH test, and compared
the TRH prolactin levels at 30-min time points
before the administration and after 8 weeks
administration. The patients who had theadministration for 8 weeks or more and was able
to have re-tests of TRH loading was 22, of which
16 (72.7%) showed reduced blood prolactin.
Furthermore, the overall blood prolactin levels
dropped significantly from 79.1±14.9ng/ml to
65.3±20.9ng/ml (p＜0.001)9).

prolactin. If shakuyakukanzoto is administered
for those in the normal ranges, they will not belowered more than necessary.
4. Abdominal pain

Shakuyakukanzoto is used for pain thatsuddenly occurs. Especially, this preparation has
many applications for abdominal pain induced byspasms of smooth muscles. Case reports on theuse of this preparation for biliary stones, urinarystones, and irritable bowel syndrome have beenreported and reports of case series, although
limited, have been submitted.
Nagata, et al. assessed the intensity of
abdominal
pain
before
and
after
the
administration of shakuyakukanzoto in 45
patients (irritable bowel syndrome-29 patients,
biliary dyskinesia-7, bladder stones-2, kidneystones-3, abdominal pain after taking a medicine4): Pain intensity before the administration wasclassified into most serious, serious, moderate,
mild and symptom-free. The results showed aneffectiveness rate of 79.3% with an ineffectivenessrate of 20.7% in the irritable bowel syndromegroup and an effectiveness rate of 71.4% with anineffectiveness rate of 28.6% in the biliary
dyskinesia group. In the group of bladder stones,
one patient had effects while one patient did nothave effects. In the group of kidney stones, twopatients had effects and one patient did not haveeffects. In the group of abdominal pain after
taking medicine, two patients had effects while
two patients did not have effects10).
For the purpose of reference
Katsura, et al. made an observation to compare
effects between the two medicines of Kanzoto andshakuyakukanzoto in 130 patients who visited
Pediatric Outpatients because of common cold,
acute gastroenteritis or other disorders (maleIt may be considered from these reports thatshakuyakukanzoto has the action of loweringhigh levels of blood testosterone and blood4

children-69 patients, female children-61, adults-7).
Each of the group of kanzoto and the group of

shakuyakukanzoto was divided into the subgroup

The Journal of Kampo, Acupuncture and Integrative Medicine (KAIM)

Volume 4, Number 1 | Spring 2009of internal use and the subgroup of oral use. In theConcerning blood hormone levels, testosterone (T)shakuyakukanzotoofwas significantly reduced from 37.8±13.3ng/dl

internal use had an effectiveness rate of 97.5%

before the administration to 30.7±16.2 ng/dl afterwith one patient excluded, and the subgroup of

the administration (p<0.01). Free testosterone

oral use had an effectiveness rate of 97.9% with(FT) was also lowered significantly although no

one

of

significant differences were observed between

shakuyakukanzoto, all patients of the subgroup of

before and after the administration in the levels ofinternal use had effects and the subgroup of oral

dehydrotestosterone,

dehydroepiandosterone,

use had an effectiveness rate of 92.9 with two

dehydroepiandosterone

sulfate,patients excluded. In the 4 subgroups, pains

binding globlin12).

patients

group,

excluded.

theIn

subgroup

the

group

disappeared within 1-3 minutes in 50% of thepatients and within 5 minutes and 30 seconds insexhormoneTanaka, et al. administered shakuyakukanzoto

80%11).

to the patients with acne vulgarizes (2 males and5. Acne vulgaris

assessment after 2 months. There were no

11 females from 16 to 32 years old) and made anappropriate

patients who had hyperandrogenemia. The results

indication for acne. Reports on seijobofuto andwere markedly effective in 1 patient, effective in 4,

keigairengyoto can be seen quite often. Kampo

ineffective in 4, and drop-out 4. Significant

preparations are effective enough for pustularchanges in the levels of blood androgens were notacne vulgarises. However they are less responsive.

observed13).

Kampo

medicines

have

an

One of the causes of acne vulgaris is said to be
hyperandrogenemi and there are several studies
on applications of the effect of shakuyakukanzoto
that can improve this clinical condition.

It is clear from two studies above thatshakuyakukanzoto is effective for acne vulgaris.
Concerning blood androgens, T and FT showed
highlevelsin

somepatients.

However,

Aaizawa administered shakuyakukanzoto to

shakuyakukanzoto works to lower high levels of

19 female patients with Kligman classificationthese although it will hardly change levels thatstage II acne vulgarises (age: 14-30, average 25)

are in the normal range from the beginning. And

and compared improvements in the condition andit can be understood that the preparation works

changes in blood hormone levels before and after

effectively for acne. It seems that the preparation

the administration. The administration period

does not reduce the number of papulars but

was about 2 weeks from the 7th day from the date

reduces the number of comedones and thereby

menstruation started (mid follicular phase) to theresolve acne.
6. Others

mid follicular phase after a menstrual cycle. The
results showed that the number of papules

Shakuyakukanzoto is often used for spasmodic

remained unchanged, the number of comedones

pains of smooth and skeletal muscles. In order toapply this effect, a study was conducted on
analgesic potency for hemorrhoid pain.
Endo, et al. made a comparative clinical trial of
the effect of ointment alone and in combination of
ointment and shakuyakukanzoto with thesubjects of 100 patients who visited the facility forsignificantly reduced, and subjective symptoms ofseborrhea were markedly improved in 4 patients,
moderately improved in 6, mildly

improved in 5,

and remained unchanged in 4 ． The results ofclinical effect assessment were that 11 out of 19(60%) had moderate or more improvements.

The Journal of Kampo, Acupuncture and Integrative Medicine (KAIM)

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Volume 4, Number 1 | Spring 2009

the treatment of anal fissure and non-surgicaltreatment was considered appropriate (male 48,
female 52). Of these patients, 50 were assigned to
the group of ointment alone treatment and theremaining 50 patients were assigned to the groupof combination therapy of ointment andshakuyakukanzoto. The group of ointment alone
received Tribenoside-lidocaine ointment injections
into the anus twice/day and the group of the
combination medication received Tribenosidelidocaine Ointment and the Extract of
shakuyakukanzoto 6g in 3 doses before or between
meals. The administration continued at least for
17 days.
The intensity of pain was assessed by VAS
scales, and the nature of pain, time, influence of
pain on everyday life, the severity of hemorrhage,
and the number of defecations was assessed using
questionnaire sheets. The severity of pain was
significantly improved after 10 days in the groupof ointment alone administration, whereas it wassignificantly improved after 3 days. Influence on
everyday life was also significantly superior in thegroup of combination use. There were no
significant differences in the severity ofhemorrhage and the number of defecations. Aboutsatisfaction after treatment, satisfied or more was
32% in the group of ointment alone and 78% in thegroup of combination use. About overall
improvement, improved or more was 32% in thegroup of ointment alone and 78% in the group of
combination use14).

6

References
1) KUMAKURA
Miyuki,HYODOToru,
TOYOMICHI Eriko, et al.: Ketuekitoseki
Kanjyano
Kinkeiren
nitaisuru
Shakuyakukanzoto no Sokkousei. The Japanese
Journal of Dialysis & Caring, 6：75-79, 2000.
2) KUMADA Takashi, KUMADA Hiromitsu,
YOSHIBA Makoto, et al.: TJ-68Tsumura
Shakuyakukanzoto no Kinkeirei (Kankouhen ni
tomonaumono) ni taisuru Placebo Taishou Nijyu
moukengunkanhikakushiken. Journal of clinicaltherapeutics & medicine, 15(3):499-523.
3) OTA Hirotaka, TANAKA Toshinobu, KUSHIMA
Osamu:
Gekkeikonnanshou
eno
Keishibukuryogan no Gekkeiji-tankitouyohou(New method of dosage of Chinese medicine fordysmenorrhea. Dosage of gui-zhi-fu-ling-wan for
short-term menstrual period). Sanfujinka
Kampou Kenkyuno Ayumi, 17：48-50、2000。
4) INOUE Shuji, TAKEUCHI Yuzuru, KAMITANI
Naoyuki, et al.: A treatment of dysmenorrhea by
Shakuyakukanzoto. Sanfujinka Kampo Kenkyu
no Ayumi, 12:65-71, 1995.
5) OHTA
Hiroaki,
TAKAMATSU
Kiyoshi,
HORIGUCHI
Fumi,
et
al.:
Kinousei
Gekkeikonnanshou nitaisuru visual analgue
scale
(VAS)
no
Yuyousei
to
TJ-68(Shakuyakukanzoto) no Chintsukouka ni
kansuru Kentou. Sanfujinka Kampou Kenkyuno
Ayumi, 13：25-29, 1996
6) TANAKA Tetsuji: Ninshin wo Kibousuru
Jyushou-Gekkeikonnanshou-Kanjya nitaisuru
Atarashii Kampo Ryouhou.. Science of Kampo
Medicine, 26：69-73, 2002.
7) YAGINUMA Tsutomu, OKAMURA Takashi,
TAKEUCHI Toru, et al.: Shakuyakukanzoto (S-K)
no Hypertestosteronemia-Fujin niokeru Kecchuu
androgens
no
Noudo
no
Teika,
Hairanhouhatsukouka
toAnzensei–A
multicenter collaborative study.Japanese Journalof Fertility and Sterility. 33:606-616, 1988.

The Journal of Kampo, Acupuncture and Integrative Medicine (KAIM)

Volume 4, Number 1 | Spring 20098) TAKAHASHI

Kentaro,KITAO

Manabu:Polycystic ovary symdrome (PCOS) and Kampo.
Sanfujinka no Sekai, 42:201-208, 1990.
9) ITO Kimihiko, KOMI Yuriko, INAGAKI Noboru,
et

al.:

Senzaisei

Koupurorakuchinkesshou(hyperprolactinemea) wo Yusuru Funin-Fujin
nitaisuru Shakuyakukanzoto no Shiyoukeiken.
Obstetrical and Gynecological Practice, 49:11611164, 2000.
10) NAGATA

Katsutaro,

KAMANO

Yasuaki,

KAMANO Seiko, et al.: Treatment of Abdominal
Pain with Shakuyakukanzoto. Pain and Kampo
Medicine, 2:30-37, 1992
11) KATSURA Toshio: The Remarkable Effect ofKanzo-toandShakuyakukanzoto,

in

the

Treatment of Acute Abdominal Pain. Japanese
Journal of Oriental Medicine, 46:293-299, 1995
12) AIZAWA

Hiroshi:

Shakuyakukanzoto

Zasou
no

Kampo Practice Journal

nitaisuru

Rinshouteki-kouka,
15(6):25-28, 1996

13) TANAKA Genichi, SEKIFUJI Narifumi: Zasou
nitaisuru Shakuyakukanzoto no Shiyoukeiken,
Journal of Traditional Medicines, 6,515-517,
199914) ENDO

Takeshi:

RetukouniyoruNaikoumonkatsuyakukin no Keiren nitomonau
Toutsunitaisuru

Shakuyakukanzoto

noRinshou-seiseki. Journal of New Remedies andClinics, 49:712-719, 2000.

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