Volume 4, Number 4 | Winter 2009

Kampo Medicine - Current Research
Effect of Goreisan on Cerbral Infarction－From the Goreisan Symposium 2010”－
Hiroshi Kimoto, Internist
Saito Clinic, Medical Corporation Eizukai

Introduction
Goreisan, whose source is “shang han lun”, haslong been known as a common agent in Chinese
herbal medicine. It is considered to be an
aquaretic drug and alleviates aqueous moisturemetabolic abnormality. Using this medicine totreat headaches has recently come to light in(1)Japan. In this paper, we review the indications
for goreisan on cerebral infarction, a pathologic
condition in cerebral stroke. At present, its
application for cerebral infarction is being
conducted only by the author, and there is a(3)clinical comparison
with the 2002 Japan(2)Standard Stroke Registry Study (JSSRS), as
described later.
Background
Acute cerebral infarction is a disease that isclassified into types of cerebral stroke and itself is
a risk factor in elderly persons. A guideline forthe treatment of cerebral stroke has been
published by the Cerebral Stroke Joint Guideline
Committee (the Committee), starting in 2003 and(4)continuing in 2003, 2004, and 2009. At each of
those times, treatment based on scientificfoundations was recommended. In the process,various drugs such as thrombolytics and radicalscavengers have been developed, which hasresulted in a greater number of patients withfavorable prognoses. On the other hand,statistically, many patients have residualdisabilities such as paralysis, which reduces apatient’s quality of life (QOL) and causes socialproblems such as patient care. Thus, further
development of drugs and treatment for thedisease has been desired.
In Japan, the use of Chinese herbal medicines

8for cerebral stroke has been described in various(5)Whiledaisaikoto,historicalliterature.
san’oshashinto, and zokumeito, etc., are indicatedfor treatment at the acute stage, a record of theuse of goreisan has not been found. The reason ispresumed to be because its diagnostic findings in
Chinese medicine varied historically due to alarge number of hemorrhagic pathologic
conditions such as cerebral hemorrhage, whichmight result in various prescriptions of Chinese
herbal medicines; it was also impossible tounderstand the lesions in the brain in detail as
can now be done by CT or MRI, etc., andconsequently, it was impossible to detect cerebral
edema, a pathologic condition induced by cerebral
stroke in many cases.
In cerebral infarction, signals are detected on
diffusion images of MRI at the initial stage orlater after onset, and thus the local pathologic
condition of cerebral edema at the lesion appears.
It is expected that controlling the edematous
condition will enable protection from necrosis ofcerebral nervous tissue induced by the infarction,
which indicates the great contribution to aprognosis. However, only edaravone, which isavailable as a cerebral protector, has a certain
effect, but it is not a cure-all.
Process till application of goreisan
In 2000, the author reported a case of a patientwith external hydrocephalus secondary totraumatic subarachnoid hemorrhage and theprognosis could be controlled favorably byadministration of aquaretic drugs such as
inchingoreisan and shinbuto. In addition,
aquaretic drugs of Chinese herbal medicine wereapplicable for an edematous pathologic condition(6)
in the cranium.
Taking these findings and the above-describedpathologic conditions of cerebral infarction intoconsideration, the author devised a method inwhich Western drugs and Chinese herbal

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

Volume 4, Number 4 | Winter 2009
(7–9)

medicines were combined
and the treatment
was described in case reports during the period
from 2001 to 2002. The outline of the method is asfollows:
A small dose of argatroban (10 mg/day; aprescribed dose is 60 mg/day for the first two daysand 20 mg/day for the subsequent five days) andgoreisan extract (7.5 mg/day) were combined for
all cases, and for abdominal symptoms,
saikokeishito, san’oshashinto, orengedokuto, etc.,
were added (see reference for details). The
functional prognoses after discharge weresufficiently satisfactory.
Comparison with the 2002 Japan Standard
Stroke Registry Study
Based on the above-described case report, theauthor describes a comparative study of theseverity at admission and findings in follow-up
observations after discharge of 14 inpatients withlacunar and atherothrombosis cerebral infarction
who were treated by a combined therapy withChinese herbal medicines at the author’s clinic
during the period from October 2000 to October
2002, and those findings were compared withthose in the 2002 Japan Standard Stroke(2,3)
Registry Study (JSSRS).
The subjects were 14 patients (seven males
and seven females aged 68–99; mean age,78.0±9.1), of whom 9 had a lacunar type disease, 4
had an atherothrombotic type disease, and 1 wasunknown. The time until consultation at theclinic ranged from one to 84 hours after onset(mean time, 19.3±26.6 hours).
In diagnosing the disease, except for one case,the infarct site becoming a culprit lesion wasdetermined by neurological symptoms anddetectable lesion sites on diffusion images of MRI
performed two to three hours after onset. Theseverity at admission was evaluated according to
the Japan Stroke Scale (JSS), the clinicalevaluation at discharge was determined by thedegree of neurological improvement on the JSS,

and the degree of recapitulative functional
improvement was evaluated based on theModified Rankin Scale.
The results obtained could not undergo a testof significant difference between both sets of databecause the number of cases was insufficient andindividual data in JSSRS were not available. In
the group treated with combined Chinese herbal
medicines, the ages of the subjects were higher(78.0±9.1 years vs. 68.0±11.4 in JSSRS lacunar
type and 68.0±10.2 in JSSRS atherothrombotictype), and the period (days) of hospitalization was
shorter (29±18 vs. 33±25 in JSSRS lacunar typeand 36±23 in JSSRS atherothrombotic type). The
JSS at admission was higher (8.9±5.9 vs. 2.1±3.5in JSSRS lacunar type and 4.9±6.5 in JSSRS
atherothrombotic type), indicating a severer
condition, and the JSS at discharge was lower(0.3±1.2 vs. 1.3±4.1 in JSSRS lacunar type and3.6±6.6 in JSSRS atherothrombotic type),
indicating a neurological improvement. As for theModified Rankin Scale at discharge, theproportion of the scores of 0 or 1 that indicatesnormal or very slight pathologic condition without
any clinical problem, was 93% versus 67% inJSSRS lacunar type and 45% in JSSRS
atherothrombotictype,whichisanunquestionably favorable outcome. As for theclinical results from the different treatment
methods, the variation in JSS was 8.6±6.20 in thegroup treated with combined Chinese herbal
medicines versus 2.7±6.11 in the group treatedwith argatroban in JSSRS and 1.7±4.44 in thegroup with ozagrel in JSSRS, which was a morefavorable result than the groups treated witheach single Western drug. As for safety, no side
effect or harmful event was found in thetreatment with combined Chinese herbal
medicines.
Subsequent reports
Based on a search of the literature, no clinicalstudies appear to have been published after theThe Journal of Kampo, Acupuncture and Integrative Medicine (KAIM)

9Volume 4, Number 4 | Winter 2009

above-described report. However, the author
presented a report at the end of 2003, in which amechanism for the effect related to the above(10)
The report was about aresults is indicated.
patient with atherothrombotic cerebral infarctionin the anterior cerebral arterial region, where thevariations in the lesion on an MRI three hours
and seven days after onset were compared. The
results revealed that the extent of the infarctlesion seven days after onset was far less than theexpected range in an untreated case, whichstrongly indicates a cerebral protective action of
the combined Chinese herbal medicines. Theauthor also presented data (in this journal) from acomparison of variations in urinary volume
during treatment with goreisan administered topatients with other diseases such as vertigo.
According to the report, the urinary volume
increased significantly with the treatment for
cerebral infarction, which strongly indicates acause and effect relationship between thetreatment effect and the administration of anaquaretic drug, namely goreisan, for cerebral
infarction.
The author hasn’t presented further clinicalstudies and similar additional reports about
cerebral infarction have also not been presented.
Therefore, further studies are required.
Viewpoint of current medicine for cerebral edema
In 2004–2005, Nagai et al. from Kumamoto
University and Isohama et al. presented thetreatment effects of goreisan on fatal cerebral
edema induced by water intoxication in rats,
reporting that the mechanism for this is due tothe active inhibition of aquaporin 4, and the basisof the inhibitors of aquaporin 4 were mineralcomponents such as manganese contained incang-shu and zhu-ling, both of which areconstituent crude drugs of goreisan (see reference11). Subsequently, the relationship between
cerebral edema with various pathologic
conditions and the pharmacokinetics of aquaporin

10(12)

Although the
4 was studied and reported.
mechanism cannot always be explained only by
the action of aquaporin 4, clinically, evidence ofthe effects of Western drugs such as glyceol on
cerebral edema have not been apparent and therole of goreisan as an anti-cerebroedema drug isthus anticipated.
Summary
Although no additional reports have currently
been presented with respect to cerebral infarction,
there have been clinical reports on cerebral
edemas induced by chronic intradural hematoma,(13–15)
As such,dialysis uneven syndrome, etc.
recently, the efficacy of goreisan on various
cerebral edemas has been strongly indicated byclinical reports and animal experiments fromindependent facilities. Accordingly, goreisan is
now considered to be effective for treatment ofedematous pathologic conditions accompanying
various cerebral diseases. There is currently noeffective Western drug for the treatment ofcerebral edema, but the clinical applications forgoreisan have been strongly indicated and they
therefore remain to be clarified by future studies.
References(1)

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(2)

Kobayashi S. et al.: A Study on Structure ofDatabase of Patients with Acute Cerebral
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Cerebral Infarction: Japan Standard Stroke
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Shinohara Y. et al.: Edition: 2009 Guideline fortreatment of cerebral stroke. Kyowa Project,
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Kimoto H.: Three Treatment Cases byCombined Chinese Herbal Preparation for
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