|
Research Publications on "Sho-saiko-to" (1990-2001)
|
|
Is your "Sho-saiko-to" manufactured under the same quality standard as the ones approved by the Japanese Ministry of Health, Welfare, and Labor? Find out more... |
|
<5> Authors
Li C. Homma M.
Oka K. Institution
Department of Clinical Pharmacology, School of Pharmacy, Tokyo
University of
Pharmacy and Life Science, Japan. Title
Characteristics of delayed excretion of flavonoids in human urine
after
administration of Shosaiko-to, a herbal medicine. Source
Biological & Pharmaceutical Bulletin.
21(12):1251-7, 1998 Dec. Abstract
There has been little explanation of herbal medicines by modern
medical
sciences, including pharmacokinetics, whereas physicians follow
empirical
indications written in classical literature. Recent reports of
herb-induced
adverse reactions compelled us to proceed the investigation of a
herbal
medicine Shosaiko-to (TJ-9) from a pharmacokinetic point of
view. To five healthy volunteers, a single 5 g dose of TJ-9,
consisting of 7
herbs, was administered. We conducted HPLC analysis of the
timed-urine
specimens to disclose the type and amount of compounds excreted.
Excretion
rate-time curves were analyzed individually. Four flavonoids,
liquiritigenin,
baicalein, wogonin and oroxylin A, were found both in the urine and
TJ-9. The
glycosides in TJ-9 were absorbed after microflora hydrolysis.
Davidigenin,
which was not found in TJ-9, was an intestinal metabolite of
liquiritigenin.
Also, two flavanones, S-dihydrowogonin and S-dihydrooroxylin A, were
identified as the metabolites of wogonin and oroxylin A,
respectively.
Excretion rate-time curves of the flavonoids were divided into three
types of
structure-dependent absorption, i.e. (1) the fast absorption of
herbal-origin
aglycons, (2) the moderately-delayed absorption of aglycons derived
from
herbal glycosides, and (3) markedly-delayed absorption after the
molecular
transformation of herbal compounds. Individual excretion profiles
seemed to
depend on microflora activities. Two types of flavanones, S-dihydrowogonin
and S-dihydrooroxylin A, were found in a half of the volunteers,
suggesting
there might be two kinds of volunteers, namely, rapid and poor
metabolizers
of flavonoids. <6> Authors
Nakahata N. Kutsuwa M.
Kyo R. Kubo M.
Hayashi K. Ohizumi Y. Institution
Department of Pharmaceutical Molecular Biology, Faculty of
Pharmaceutical
Sciences, Tohoku University, Sendai, Japan. Title
Analysis of inhibitory effects of scutellariae radix and baicalein on
prostaglandin E2 production in rat C6 glioma cells. Source
American Journal of Chinese Medicine.
26(3-4):311-23, 1998. Abstract
Inhibitory mechanism of the water extract of Scutellariae Radix on
prostaglandin E2 (PGE2) release was examined in C6 rat glioma cells.
Scutellariae Radix reduced a Ca2+ ionophore A23187-induced PGE2
release by
inhibition of arachidonic acid (AA) liberation. Sho-saiko-to
and San'o-shashin-to, which contain Scutellariae Radix, also
inhibited PGE2
release. A23187 caused phosphorylation of mitrogen-activated protein
kinase
(MAPK), resulting in activation of cytosolic phospholipase A2
(cPLA2).
Scutellariae Radix and baicalein inhibited the phosphorylation of
MAPK.
Baicalein, but not baicalin, inhibited A23187-induced PGE2 release.
These
results suggest that baicalein in Scutellariae Radix reduces AA
liberation
through the inhibition of the MAPK-cPLA2 pathway. <7> Authors
Kyo R. Nakahata N.
Sakakibara I. Kubo M.
Ohizumi Y. Institution
Department of Pharmaceutical Molecular Biology, Faculty of
Pharmaceutical
Sciences, Tohoku University, Aramaki, Sendai, Japan. Title
Effects of Sho-saiko-to, San'o-shashin-to and Scutellariae
Radix on intracellular Ca2+ mobilization in C6 rat glioma cells. Source
Biological & Pharmaceutical Bulletin.
21(10):1067-71, 1998 Oct. Abstract
Glial cells are able to support neurons physically and functionally.
The
present study was undertaken to determine the effects of Kampo
medicines on
glial cell function, especially Ca2+ mobilization. C6 rat glioma
cells
expressed H1-histamine, muscarinic cholinergic and adrenergic
alpha1-receptors, stimulation of which resulted in phosphoinositide
hydrolysis and increase in intracellular Ca2+ concentrations
([Ca2+]i). The
water extracts of Sho-saiko-to and San'o-shashin-to, Kampo
medicines which contain Scutellariae Radix (Ogon, the root of
Scutellaria
baicalensis GFORGI), inhibited histamine (100 microM)-induced
increase in
[Ca2+]i in a concentration-dependent manner. The water extract of
Scutellariae Radix potently decreased [Ca2+]i in a
concentration-dependent
manner. Sho-saiko-to, San'o-shashin-to and Scutellariae
Radix significantly inhibited histamine-induced accumulation of total
[3H]inositol phosphates, consistent with their inhibition of the
increase in
[Ca2+1]i. These results suggest that Sho-saiko-to,
San'o-shashin-to and Scutellariae Radix inhibit Ca2+ mobilization
mediated
via an inhibition of phospholipase C. The inhibitory effect may be
important
in interpreting the pharmacological actions of above Kampo medicines. <8> Authors
Kayano K. Sakaida I.
Uchida K. Okita K. Institution
First Department of Internal Medicine, Yamaguchi University, School
of
Medicine, Ube City, Japan. Title
Inhibitory effects of the herbal medicine Sho-saiko-to
(TJ-9) on cell proliferation and procollagen gene expressions in
cultured rat
hepatic stellate cells. Source
Journal of Hepatology. 29(4):642-9,
1998 Oct. Abstract
BACKGROUND/AIMS: It is of extreme importance to prevent liver
fibrosis and
subsequent progression to liver cirrhosis. The aim of our study was
to
elucidate in vitro whether Sho-saiko-to exerted inhibitory
effects on hepatic stellate cells. METHODS: Hepatic stellate cells
were
isolated from male Wistar rats. Water-soluble ingredients of
Sho-saiko-to were obtained at concentrations of 10, 100,
250, 500 and 1000 microg/ml. Morphological transformation was
observed under
a phase-contrast microscope. Flow cytometric analysis was performed
on day 4
after culture to evaluate the potential to proliferate of the
stellate cells
by analyzing cell cycles. Northern blot analysis was carried out on
day 3
after culture to determine the expressions of type I and type III
procollagen
mRNAs. RESULTS: (i) Sho-saiko-to 500 and 1000 microg/ml
inhibited morphological transformation of the stellate cells to
myofibroblast-like cells. (ii) Sho-saiko-to 500 and 1000
microg/ml significantly (p<0.0001) accumulated the cells in the
G0/G1 phase
(118.8+/-0.7%, 119.2+/-0.5%, respectively as compared with control)
and
significantly (p<0.0001) decreased cell numbers subsequently in
G2/M phase
(47.5+/-8.1%, 48.9+/-2.0%, respectively). (iii) Sho-saiko-to
500 and 1000 microg/ml also significantly (p<0.05 or p<0.0001)
suppressed
procollagen mRNA expression of type I to 51.5+/-6.4%, 34.9+/-3.7%,
respectively, and type III to 51.3+/-12.3%, 46.7+/-11.4%,
respectively.
CONCLUSIONS: We have clarified the inhibitory effects of
Sho-saiko-to on hepatic stellate cells in vitro.
Sho-saiko-to could be a potent inhibitor in the pathogenesis
of liver fibrosis. <9> Authors
Matsumoto T. Shibata T. Institution
Department of Otolaryngology, Izumiotsu Municipal Hospital, Osaka,
Japan. Title
The ex vivo effect of the herbal medicine sho-saiko-to on
histamine release from rat mast cells. Source
European Archives of Oto-Rhino-Laryngology.
255(7):359-64, 1998. Abstract
A traditional Japanese herbal medicine, Shosaiko-to (SST),
has been used orally to treat several chronic diseases. Since these
have
included allergic rhinitis and bronchial asthma, we investigated the
effect
of SST on histamine release and the intracellular Ca2+ response in
mast cells
ex vivo. A single dose of 1.0 g/kg SST was administered orally to
immunized
rats 2-12 h before death. Mast cells were then separated from
peritoneal
lavages and stimulated with antigen. SST at 3 h after oral
administration
most significantly inhibited histamine release. This inhibitory
effect was
dose-dependent and was weaker than that of tranilast. In contrast,
SST at 3 h
had no effect on the antigen-induced Ca2+ response of the mast cells
and
failed to inhibit compound 48/80-induced histamine release. Our
findings show
that SST indeed has an active anti-allergic effect. We suggest that
SST
inhibits IgE receptor-associated protein phosphorylation in the
histamine
release pathway. <10> Authors
Kato M. Liu W.
Yi H. Asai N.
Hayakawa A. Kozaki K.
Takahashi M.
Nakashima I. Institution
Department of Immunology, Nagoya University School of Medicine,
Aichi, Japan. Title
The herbal medicine Sho-saiko-to inhibits growth and
metastasis of malignant melanoma primarily developed in
ret-transgenic mice. Source
Journal of Investigative Dermatology.
111(4):640-4, 1998 Oct. Abstract
Sho-saiko-to is the most popular herbal medicine in Japan.
We investigated the anti-tumor and anti-metastatic effects of
Sho-saiko-to and its chemically defined ingredients on the
primary skin melanoma that developed in a metallothionein-I (MT)/ret
transgenic mouse line and on a melanoma cell line (Mel-ret), which
was
derived from a primary tumor developed in a MT/ret transgenic mouse.
In
vitro, Sho-saiko-to suppressed the growth of Mel-ret cells
more strongly than any single ingredient of Sho-saiko-to,
although baicalin as one of several ingredients tested also
suppressed it
significantly. In vivo, Sho-saiko-to (i) significantly (p <
0.02) prolonged the onset of tumor development (1.5 mo), (ii)
definitely
retarded the transition to malignancy, (iii) significantly decreased
the
incidence of distant metastasis to brain (p < 0.002), kidney (p
< 0.05), and
liver (p < 0.05) at the malignant stage, and (iv) significantly (p
< 0.02)
prolonged life span (2.6 mo). Moreover, Sho-saiko-to and
baicalin down-regulated the matrix metalloproteinase-2 and -9
expression
levels, and upregulated their inhibitor expression level in both the
primary
tumors and Mel-ret cells. In conclusion, Sho-saiko-to
displayed anti-tumor and anti-metastatic effects on melanoma with
regulation
of the balance of matrix metalloproteinase and tissue inhibitor of
the matrix
metalloproteinase levels. <11> Authors
Li C. Homma M.
Oka K. Institution
Department of Clinical Pharmacology, School of Pharmacy, Tokyo
University of
Pharmacy and Life Science, Japan. Title
Chiral resolution of four major flavanones in post-administrative
urine of
Chinese herbal medicines by HPLC on macroporous silica gel coated
with
cellulose tris(3,5-dimethylphenylcarbamate). Source
Biomedical Chromatography. 12(4):199-202,
1998 Jul-Aug. Abstract
Direct chiral resolution of four major flavanones recovered from
post-administrative urine of the traditional Chinese medicines
Daisaiko-to
and Shosaiko-to was achieved by high-performance liquid
chromatography (HPLC) on macroporous silica gel coated with cellulose
tris(3,5-dimethylphenylcarbamate), Chiralcel OD. Chromatographic
conditions
were optimized so as to attain satisfactory enantiomeric resolution
of the
polysubstituted flavanones. Urinary liquiritigenin and naringenin
were
considerable mixtures of R and S-enantiomers, while S-enantiomers of
dihydrowogonin and dihydrooroxylin A were predominantly excreted. Our
chiral
HPLC techniques can be applied to pharmacokinetical evaluation of the
chiral
flavanone enantiomers following oral administration of the herbal
medicines. <12> Authors
Liu W. Kato M.
Akhand AA. Hayakawa A.
Takemura M. Yoshida S.
Suzuki H.
Nakashima I. Institution
Department of Immunology, Nagoya University School of Medicine,
Nagoya
466-8550, Japan. Title
The herbal medicine sho-saiko-to inhibits the growth of
malignant melanoma cells by upregulating Fas-mediated apoptosis and
arresting
cell cycle through downregulation of cyclin dependent kinases. Source
International Journal of Oncology.
12(6):1321-6, 1998 Jun. Abstract
The anti-tumor effect and its mechanism of the herbal medicine
sho-saiko-to were investigated on a murine malignant
melanoma cell line (Mel-ret). Sho-saiko-to induced apoptotic
cell death of Mel-ret cells with a definite increase of cell surface
Fas
antigen and Fas ligand (FasL). Sho-saiko-to arrested Mel-ret
cells in G1 phase by decreasing the expression of cyclin-dependent
kinase
(cdk) 4 and its homologue cdk6. Kinase activities of cdk4 and cdk6
were
identified to be downregulated by sho-saiko-to. Ingredient
analysis revealed that baicalin is likely the main active constituent
in the
upregulation of Fas antigen and Fas ligand, while glycyrrhizin is the
main
constituent in the inhibition of cdks. <13> Authors
Li C. Homma M.
Ohkura N. Oka K. Institution
Department of Clinical Pharmacology, School of Pharmacy, Tokyo
University of
Pharmacy and Life Science, Japan. Title
Stereochemistry and putative origins of flavanones found in
post-administration urine of the traditional Chinese remedies
shosaiko-to and daisaiko-to. Source
Chemical & Pharmaceutical Bulletin.
46(5):807-11, 1998 May. Abstract
Optically active flavanones, dihydrowogonin and dihydrooroxylin A,
were found
in the urine of healthy volunteers who orally received the
traditional
Chinese remedies Shosaiko-to and Daisaiko-to on separate
occasions. These remedies, which consisted of dried extracts of
Scutellariae
Radix and other herbs, contained the metabolic precursors of the
flavanones,
but not the flavanones themselves, in stoichiometrically sufficient
amounts.
Structures and stereochemistry of the flavanones were elucidated by
UV,
circular dichroism (CD), electron impact (EI)-MS and 1H-NMR analyses,
showing
that the biotransformations from the corresponding flavones, wogonin
and
oroxylin A, were stereoselective with a preference for the
S-enantiomers. The
putative origins of the flavanones were confirmed in terms of
pharmacokinetics. Renal excretion-time data of the flavanones and the
flavones suggested that the stereoselective transformations might
have
occurred in the intestinal tract as a result of microfloral
metabolism before
absorption. <14> Authors
Kojima K. Mizukami H.
Tazawa T. Nose M.
Inoue M. Ogihara Y. Institution
Faculty of Pharmaceutical Sciences, Nagoya City University, Nagoya,
Japan. Title
Long-term administration of "sho-saiko-to" increases
cytochrome P-450 mRNA level in mouse liver. Source
Biological & Pharmaceutical Bulletin.
21(4):426-8, 1998 Apr. Abstract
Simplified differential display of mRNA was applied to isolate and
identify
genes transcriptionally regulated in mouse liver by
sho-saiko-to administration. A cDNA fragment up-regulated by
sho-saiko-to was isolated and characterized. cDNA sequencing
and subsequent database analysis revealed that the fragment showed
significant sequence similarity with mouse testosterone
16-alpha-hydroxylase
(cytochrome P-450[16alpha]) cDNA. The increased level of mRNA
expression of
cytochrome P-450(16alpha) in association with sho-saiko-to
administration suggests the molecular mechanism of the
chemopreventive effect
of sho-saiko-to. This result indicates the usefulness of the
mRNA differential display technique to investigate the molecular
mechanism of
Kampo medicine. <15> Authors
Nishimura N. Naora K. Hirano
H. Iwamoto K. Institution
Department of Pharmacy, Shimane Medical University Hospital, Izumo,
Japan. Title
Effects of Sho-saiko-to on the pharmacokinetics and
pharmacodynamics of tolbutamide in rats. Source
Journal of Pharmacy & Pharmacology.
50(2):231-6, 1998 Feb. Abstract
Although Sho-saiko-to (Xiao Chai Hu Tang), a major Chinese
traditional medicine, is frequently prescribed with other synthetic
or
biotechnological drugs for the treatment of various chronic diseases,
there
is a dearth of information about interactions between
sho-saiko-to and co-administered drugs. This paper reports
the effects of Sho-saiko-to on the pharmacokinetics and
glucose responses of a sulphonylurea hypoglycaemic agent,
tolbutamide, after
their oral administration in rats. After oral administration of
tolbutamide
(50 mg kg(-1)) with or without Sho-saiko-to extract powder
(300 mg kg(-1)) to male Sprague-Dawley rats cannulated in the jugular
vein,
plasma tolbutamide and glucose levels were periodically measured.
Co-administration of Sho-saiko-to tended to elevate the
plasma tolbutamide concentration in the absorption phase. A
two-compartment
lag-time model was found to describe the plasma tolbutamide
concentration-time data. The maximum concentration of tolbutamide was
significantly increased and time to reach the maximum concentration
was
reduced to about 70% by co-administration with Sho-saiko-to.
There was no significant change in area under the curve or in the
elimination
half-life of tolbutamide. The extent of the lowering effect of
tolbutamide on
plasma glucose levels was increased up to 0.75 h and decreased after
5 h
after co-administration of Sho-saiko-to. In conclusion,
these studies suggest that sho-saiko-to slightly hastens the
gastrointestinal absorption of tolbutamide. Furthermore, it is
considered
that elevation of the gastrointestinal absorption rate by
Sho-saiko-to might potentiate the hypoglycaemic effect of
this sulphonylurea in the early period after oral administration. <16> Authors
Sakaida I. Matsumura Y.
Akiyama S. Hayashi K.
Ishige A. Okita K. Institution
First Department of Internal Medicine, School of Medicine, Yamaguchi
University, Japan. Title
Herbal medicine Sho-saiko-to (TJ-9) prevents liver fibrosis
and enzyme-altered lesions in rat liver cirrhosis induced by a
choline-deficient L-amino acid-defined diet. Source
Journal of Hepatology. 28(2):298-306,
1998 Feb. Abstract
BACKGROUND/AIM: A herbal medicine, Sho-saiko-to (TJ-9), has
recently been orally administered to patients with chronic liver
disease in
Japan and has been reported to inhibit the development of
hepatocellular
carcinoma. The aim of this study was to investigate whether TJ-9 has
an
inhibitory effect on the development of preneoplastic lesions and
liver
fibrosis in rats. METHODS: The effects of the TJ-9 were examined
using the
choline-deficient L-amino acid-defined (CDAA) diet-induced liver
fibrosis
model in 16-week-old male Wistar rats. RESULTS: TJ-9 (1% w/w)
prevented
fibrosis, as indicated by reduced hydroxyproline content in the liver
and
inhibition of the increase in a serum marker of fibrosis (hyaluronic
acid),
without reducing the increase in serum alanine aminotransferase and
aspartate
aminotransferase. TJ-9 also reduced the expression of type III
procollagen
alpha 1 mRNA in the liver, as well as the proliferation of
myofibroblast-like
cells (activated stellate cells, activated Ito cells). Furthermore,
TJ-9
reduced the number of preneoplastic lesions, detected as
enzyme-altered
(glutathione S-transferase placental form-positive) lesions, in the
liver.
CONCLUSIONS: These results indicate that the herbal medicine
Sho-saiko-to (TJ-9) prevents fibrosis as well as
preneoplastic lesions, not by inhibiting hepatocyte cell death but by
inhibiting the activation of stellate cells, which are considered to
be the
main collagen-producing cells, leading to a reduction in the
development of
preneoplastic lesions. <17> Authors
Miyamura M. Ono M.
Kyotani S. Nishioka Y. Institution
Department of Pharmacy, Kochi Medical School Hospital, Kohasu, Japan. Title
Effects of sho-saiko-to extract on fibrosis and regeneration
of the liver in rats. Source
Journal of Pharmacy & Pharmacology.
50(1):97-105, 1998 Jan. Abstract
Sho-saiko-to, one of the most widely used Chinese herbal
preparations, has long been used for the treatment of chronic liver
diseases.
We have investigated its effect in retarding the process of liver
fibrosis
and accelerating liver regeneration, especially its effect on Ito
cells that
are thought to be deeply involved with liver fibrosis.
Sho-saiko-to extract and its active constituents were orally
administered to rats with dimethylnitrosamine-induced liver-injury.
After
treatment with sho-saiko-to extract hepatic function
improved, histopathological results confirmed repair of liver tissue,
and
retinoid levels increased. On the other hand, when active
constituents of
sho-saiko-to extract were administered alone, liver retinoid
levels remained low, implying that interaction among active
constituents of
the extract was suppressing Ito cell activation. When
sho-saiko-to extract was administered to 70% hepatectomized
normal and liver-injured rats, liver weight, the number of
S-phase-cells and
retinoid levels increased with time. However, these changes were
different
for normal and liver-injured rats, suggesting that the site of action
of
sho-saiko-to extract in regenerating liver is different for
normal and liver-injured rats. These results show that
sho-saiko-to extract was useful for suppressing the
activation of Ito cells.
|
|
|