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Intestinal motility enhancing effect of Atractylodes lancea rhizome
Journul of Ethnopharmacology, Elsevier
Scientific
Publishers
29 (1990) 341-344 Ireland
341
Ltd.
Short communication
INTESTINAL
MOTILITY
ATRACTYLODES
JOHJI YAMAHARA, FUJIMURA
Kyoto Pharmaceutical (Accepted
LANCEA
HISASHI
University.
ENHANCING RHIZOME
MATSUDA,
EFFECT OF
QIRONG
HUANG,
YUHAO
LI and
HAJIME
Misasagi Yamaahina-Ku, Kyoto 607 Napad
March 1,199O)
Introduction
Previously, this laboratory has reported on the gastrointestinal motility enhancing effect of ginger and its active constituents (Yamahara et al., 19891. There are very few scientific reports dealing with the reported stomachic properties of Atructylodes lancea rhizome. Therefore, this plant was examined in the present paper in order to provide evidence substantiating or refuting the stomachic effect. Materials and Methods Plant material and drugs Dried rhizomes of Atractylodes
luncea Thunb. (Compositael were obtained from a local market in Osaka and this material was of Japanese pharmacopeial standard. After being powdered, the material was soaked in five volumes of acetone for 2 days, and filtered. This procedure was repeated three times. The filtrate was concentrated under reduced pressure below 40°C, and the solvent was completely eliminated. The yield of the extract was 9.8%. Fractionation of the active constituents and purification of /3-eudesmol and hinesol were carried out as shown in Fig. 1, and identification based on MS, NMR and IR spectra (Yamahara et al., 19771. Concentrations of the drugs were adjusted so that the volume of administration to mice was 10 ml/ kg of body weight. Commercially obtained atropine sulfate (Merck) and metoclopramide (Sigma) were used as reference drugs.
Experimental
procedure
Male ddy mice (Oriental Bio Service) weighing 20- 23 g (40 - 41 days old) were used (8- 11 mice in a group). Mice were fasted for 18 h (water intake 0373-8741/90/$01.75 0 1990 Elsevier Published and Printed in Ireland
Scientific
Publishers
Ireland
Ltd.
342
Atractylodes
lancea
rhizome
‘/:a;c::::c::
x) Acetone
ext.
(9.83%)
I
Fr,l
(4.8%)
,
/
Fr.2
::y:::,,,;:,
Fr.4
Fr.5
(2.2%)
(14.8%)
Fr.3
(10.4%)
(49.2%) 5%
AgN03
n-hexane
silica
gel
column
: AcOEt 10 : 1 -
5
:
1
I
I
1
B-eudosmol
hinesol
(58.8%)
(27.6%)
Fig.1. Flow diagram of extraction and fractionation rhizome. (I) indicates yield of fractions.
of an acetone extract
of Atractylodes
lancea
was permitted freely) prior to experimentation. Tested drugs were administered orally. Fifteen minutes thereafter, 0.2 ml of a charcoal meal (5% activated charcoal suspended in lo/b carboxymethylcellulose) was administered orally. Thirty minutes thereafter, the mice were killed by cervical dislocation and the abdomen immediately opened to excise the whole small intestine (the pylorus region to just above the cecum). The length of the small intestine (the pylorus region to the ileocecal region) and the distance between the pylorus region and the distance travelled by the tip of the charcoal meal were measured. For statistical analysis, the ratio of the distance that the charcoal meal moved to the whole length of the small intestine (charcoal transport ratio, %) was obtained and the differences between the control groups and drug groups were analyzed using Dunnett’s t-test. Results The acetone extract at 150 mglkg and 75 mgtkg significantly enhanced the charcoal transport by 72% and 35%, respectively (Table 1).
343 TABLE
1
EFFECTS OF A. LANCEA RHIZOME ACETONE EXTRACT AND ITS FRACTIONS ON INTESTINAL MOTILITY AS MEASURED BY PASSAGE OF AN ACTIVATED CHARCOAL MEAL IN MALE MICE Treatment
Oral dose
N
(mg/kgl
Vehicle (2% acacia)
-
Acetone extract
75 156 10 15 75 5 50 5 3
Fr. 1 Fr. 2 Fr. 3 Fr. 4 Fr. 5 Metoclopramide Atropine
8 10 9 9 9 9 8 9 9 9
Intestinal transport Charcoal passage (%k
Change (%l
45.6 + 3.5
-
61.6 78.4 64.9 60.5 70.0 56.4 62.8 72.4 29.2
+ 34.9 + 71.7 + 42.3 + 32.6 + 53.4 + 23.6 + 37.5 + 58.8 - 36.0
+ + + + f + + f f
5.3. 5.2** 6.1* 6.6 3.4** 5.2 6.0’ 2.6** 1.9**
*The distance that the charcoal had travelled from the pylorus was expressed as a percentage the length of the small intestine, and each tabular value represents the mean + S.E.M.
of
Significant difference from vehicle control: *P < 0.05. **P < 0.01.
TABLE
2
EFFECTS OF 6EUDESMOL AND HINESOL ON INTESTINAL MOTILITY BY PASSAGE OF AN ACTIVATED CHARCOAL MEAL IN MALE MICE Treatment
Oral dose
N
(mglkgl
Vehicle (2% acacia) /I-Eudesmol
-
/%Eudesmol
30 60
Vehicle (2% acacia) Hines01
30
Vehicle (2%) acacia) Hinesol Metoclopramide
60 5
-
-
AS MEASURED
Intestinal transport Charcoal passage (%p
Change (O/o)
48.6 + 3.7
-
49.4 -c 4.8 64.5 f 5.7*
+1.6 + 32.7
9 10
52.2 f 65.2 f
1.7 4.3*
_
8 8 8
48.6 f
3.7
-
73.0 f 74.6 f
6.0** 3.7**
+ 50.2 + 53.5
8 8 8
+ 25.0
‘-The distance that the charcoal had travelled from the pylorus was expressed as a percentage the length of the small intestine, and each tabular value represents the mean f S.E.M. Significant difference from respective vehicle control: *P < 0.05, **P < 0.01.
of
344
In order to examine further the active constituents, the acetone extract was fractionated into Fr. 1 to Fr. 5 as shown in Fig. 1. Fr. 3 at 75 mgikg p.o. significantly enhanced the charcoal transport as shown in Table 2. Each of the fractions were given at dosages determined by their respective yield from the acetone extract. As shown in Fig. 1, Fr. 3 was further fractionated and p-eudesmol and hinesol were obtained. fi-Eudesmol and hinesol at 60 mglkg had significant effects but hinesol appeared to be more effective than 6-eudesmol. Discussion A. lancea rhizome, a Chinese medicinal plant affecting digestive tract function, has already been reported to have an anti-ulcer effect (Kubo et al., 19831and to increase the secretion of bile ~Yamaharaet al., 19831. The effect of A. Zuncea on intestinal motility was examined in order to provide evidence substantiating the stomachic effect of A. Zuncea rhizome. There are relatively large amounts of volatile oils present belonging to the terpenoids, such as /3-eudesmol and hinesol. Such terpenoids may be regarded as important constituents affecting intestinal motility. There are many drugs which enhance gastrointestinal motility (King et al., 19881.Among natural stomach&, one of the effects may be considered to be a gastrointestinal motility enhancing action, but only a few cases have been clearly proven. In the present study, /3-eudesmol and hinesol, belonging to the sesquiterpenoids, clearly enhanced intestinal charcoal transport in mice. This finding not only gives a clue for the development of new types of intestinal motility enhancing drugs but also tends to substantiate the medicinal use of A. luncea Currently, other aspects of the intestinal motility enhancing action of /3-eudesmol and hinesol are being investigated. References King, F.D. and Sanger, G.J. (19881 Gastrointestinal motility enhancing agents. Annual Reports i?z Medical Chemistry 23,201- 210. Kubo, M., Nogami, M., Nishimura. M., Moriura, T. and Arichi, S. (1983) Studies of crude drugs about their origin, process and quality. I: the preventive effects of Chinese crude drug “Zhu” on experimental stomach ulcer and its pharmacological evaluation. Yukugukv Zusshi 103, 442 - 448. Yamahara, J., Sawada. T., Tani, T., Nishino, T., Kitagawa, 1. and Fujimuea, H. Wi’7) Hiolo~~lly active principles of crude drugs: Pharmacological evaluation of the crude drug “Zhu”. Yakugaku Zaashi 97,873-079.
Yamahara, J., Matsuda, H., Kobayashi, M., Sawada, T. and Fujimura, H. (19831Biologically active principles of crude drugs: Pharmacological evaluation of “Baizbu” and “Chongzhu”: II. Shoyakgaku Zasshi 37.17 - 20.
Yamahara, J., Huang, Q.R., Li, Y.H.. Xu, L. and Fujimura, H. (1990) Gastrointestinal motility enhancing effect of ginger and its active constituents. C~ern~cal and Pha~~eut~c~l R~l~et~n 38,430 - 431.
Scientific
Publishers
29 (1990) 341-344 Ireland
341
Ltd.
Short communication
INTESTINAL
MOTILITY
ATRACTYLODES
JOHJI YAMAHARA, FUJIMURA
Kyoto Pharmaceutical (Accepted
LANCEA
HISASHI
University.
ENHANCING RHIZOME
MATSUDA,
EFFECT OF
QIRONG
HUANG,
YUHAO
LI and
HAJIME
Misasagi Yamaahina-Ku, Kyoto 607 Napad
March 1,199O)
Introduction
Previously, this laboratory has reported on the gastrointestinal motility enhancing effect of ginger and its active constituents (Yamahara et al., 19891. There are very few scientific reports dealing with the reported stomachic properties of Atructylodes lancea rhizome. Therefore, this plant was examined in the present paper in order to provide evidence substantiating or refuting the stomachic effect. Materials and Methods Plant material and drugs Dried rhizomes of Atractylodes
luncea Thunb. (Compositael were obtained from a local market in Osaka and this material was of Japanese pharmacopeial standard. After being powdered, the material was soaked in five volumes of acetone for 2 days, and filtered. This procedure was repeated three times. The filtrate was concentrated under reduced pressure below 40°C, and the solvent was completely eliminated. The yield of the extract was 9.8%. Fractionation of the active constituents and purification of /3-eudesmol and hinesol were carried out as shown in Fig. 1, and identification based on MS, NMR and IR spectra (Yamahara et al., 19771. Concentrations of the drugs were adjusted so that the volume of administration to mice was 10 ml/ kg of body weight. Commercially obtained atropine sulfate (Merck) and metoclopramide (Sigma) were used as reference drugs.
Experimental
procedure
Male ddy mice (Oriental Bio Service) weighing 20- 23 g (40 - 41 days old) were used (8- 11 mice in a group). Mice were fasted for 18 h (water intake 0373-8741/90/$01.75 0 1990 Elsevier Published and Printed in Ireland
Scientific
Publishers
Ireland
Ltd.
342
Atractylodes
lancea
rhizome
‘/:a;c::::c::
x) Acetone
ext.
(9.83%)
I
Fr,l
(4.8%)
,
/
Fr.2
::y:::,,,;:,
Fr.4
Fr.5
(2.2%)
(14.8%)
Fr.3
(10.4%)
(49.2%) 5%
AgN03
n-hexane
silica
gel
column
: AcOEt 10 : 1 -
5
:
1
I
I
1
B-eudosmol
hinesol
(58.8%)
(27.6%)
Fig.1. Flow diagram of extraction and fractionation rhizome. (I) indicates yield of fractions.
of an acetone extract
of Atractylodes
lancea
was permitted freely) prior to experimentation. Tested drugs were administered orally. Fifteen minutes thereafter, 0.2 ml of a charcoal meal (5% activated charcoal suspended in lo/b carboxymethylcellulose) was administered orally. Thirty minutes thereafter, the mice were killed by cervical dislocation and the abdomen immediately opened to excise the whole small intestine (the pylorus region to just above the cecum). The length of the small intestine (the pylorus region to the ileocecal region) and the distance between the pylorus region and the distance travelled by the tip of the charcoal meal were measured. For statistical analysis, the ratio of the distance that the charcoal meal moved to the whole length of the small intestine (charcoal transport ratio, %) was obtained and the differences between the control groups and drug groups were analyzed using Dunnett’s t-test. Results The acetone extract at 150 mglkg and 75 mgtkg significantly enhanced the charcoal transport by 72% and 35%, respectively (Table 1).
343 TABLE
1
EFFECTS OF A. LANCEA RHIZOME ACETONE EXTRACT AND ITS FRACTIONS ON INTESTINAL MOTILITY AS MEASURED BY PASSAGE OF AN ACTIVATED CHARCOAL MEAL IN MALE MICE Treatment
Oral dose
N
(mg/kgl
Vehicle (2% acacia)
-
Acetone extract
75 156 10 15 75 5 50 5 3
Fr. 1 Fr. 2 Fr. 3 Fr. 4 Fr. 5 Metoclopramide Atropine
8 10 9 9 9 9 8 9 9 9
Intestinal transport Charcoal passage (%k
Change (%l
45.6 + 3.5
-
61.6 78.4 64.9 60.5 70.0 56.4 62.8 72.4 29.2
+ 34.9 + 71.7 + 42.3 + 32.6 + 53.4 + 23.6 + 37.5 + 58.8 - 36.0
+ + + + f + + f f
5.3. 5.2** 6.1* 6.6 3.4** 5.2 6.0’ 2.6** 1.9**
*The distance that the charcoal had travelled from the pylorus was expressed as a percentage the length of the small intestine, and each tabular value represents the mean + S.E.M.
of
Significant difference from vehicle control: *P < 0.05. **P < 0.01.
TABLE
2
EFFECTS OF 6EUDESMOL AND HINESOL ON INTESTINAL MOTILITY BY PASSAGE OF AN ACTIVATED CHARCOAL MEAL IN MALE MICE Treatment
Oral dose
N
(mglkgl
Vehicle (2% acacia) /I-Eudesmol
-
/%Eudesmol
30 60
Vehicle (2% acacia) Hines01
30
Vehicle (2%) acacia) Hinesol Metoclopramide
60 5
-
-
AS MEASURED
Intestinal transport Charcoal passage (%p
Change (O/o)
48.6 + 3.7
-
49.4 -c 4.8 64.5 f 5.7*
+1.6 + 32.7
9 10
52.2 f 65.2 f
1.7 4.3*
_
8 8 8
48.6 f
3.7
-
73.0 f 74.6 f
6.0** 3.7**
+ 50.2 + 53.5
8 8 8
+ 25.0
‘-The distance that the charcoal had travelled from the pylorus was expressed as a percentage the length of the small intestine, and each tabular value represents the mean f S.E.M. Significant difference from respective vehicle control: *P < 0.05, **P < 0.01.
of
344
In order to examine further the active constituents, the acetone extract was fractionated into Fr. 1 to Fr. 5 as shown in Fig. 1. Fr. 3 at 75 mgikg p.o. significantly enhanced the charcoal transport as shown in Table 2. Each of the fractions were given at dosages determined by their respective yield from the acetone extract. As shown in Fig. 1, Fr. 3 was further fractionated and p-eudesmol and hinesol were obtained. fi-Eudesmol and hinesol at 60 mglkg had significant effects but hinesol appeared to be more effective than 6-eudesmol. Discussion A. lancea rhizome, a Chinese medicinal plant affecting digestive tract function, has already been reported to have an anti-ulcer effect (Kubo et al., 19831and to increase the secretion of bile ~Yamaharaet al., 19831. The effect of A. Zuncea on intestinal motility was examined in order to provide evidence substantiating the stomachic effect of A. Zuncea rhizome. There are relatively large amounts of volatile oils present belonging to the terpenoids, such as /3-eudesmol and hinesol. Such terpenoids may be regarded as important constituents affecting intestinal motility. There are many drugs which enhance gastrointestinal motility (King et al., 19881.Among natural stomach&, one of the effects may be considered to be a gastrointestinal motility enhancing action, but only a few cases have been clearly proven. In the present study, /3-eudesmol and hinesol, belonging to the sesquiterpenoids, clearly enhanced intestinal charcoal transport in mice. This finding not only gives a clue for the development of new types of intestinal motility enhancing drugs but also tends to substantiate the medicinal use of A. luncea Currently, other aspects of the intestinal motility enhancing action of /3-eudesmol and hinesol are being investigated. References King, F.D. and Sanger, G.J. (19881 Gastrointestinal motility enhancing agents. Annual Reports i?z Medical Chemistry 23,201- 210. Kubo, M., Nogami, M., Nishimura. M., Moriura, T. and Arichi, S. (1983) Studies of crude drugs about their origin, process and quality. I: the preventive effects of Chinese crude drug “Zhu” on experimental stomach ulcer and its pharmacological evaluation. Yukugukv Zusshi 103, 442 - 448. Yamahara, J., Sawada. T., Tani, T., Nishino, T., Kitagawa, 1. and Fujimuea, H. Wi’7) Hiolo~~lly active principles of crude drugs: Pharmacological evaluation of the crude drug “Zhu”. Yakugaku Zaashi 97,873-079.
Yamahara, J., Matsuda, H., Kobayashi, M., Sawada, T. and Fujimura, H. (19831Biologically active principles of crude drugs: Pharmacological evaluation of “Baizbu” and “Chongzhu”: II. Shoyakgaku Zasshi 37.17 - 20.
Yamahara, J., Huang, Q.R., Li, Y.H.. Xu, L. and Fujimura, H. (1990) Gastrointestinal motility enhancing effect of ginger and its active constituents. C~ern~cal and Pha~~eut~c~l R~l~et~n 38,430 - 431.