Combined Traditional and Modern Medicine Open Access
Copyright ©The Author(s) 1998. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 15, 1998; 4(6): 544-547
Published online Dec 15, 1998. doi: 10.3748/wjg.v4.i6.544
A comparison between Zhishi Xiaopiwan and cisapride in treatment of functional dyspepsia
Jiang Lin, Gan Cai, Jia-Yu Xu
Jiang Lin, Gan Cai, Department of Gastroenterology, Shuguang Hospital, Shanghai Traditional Chinese Medicine University, Shanghai 200021, China
Jia-Yu Xu, Department of Gastroenterology, Ruijin Hospital, Shanghai Second Medical University, Shanghai 200025, China
Jiang Lin, born on June 21, 1969, graduated from Shanghai Traditional Chinese Medicine University in 1997 with Ph.D., now attending physician, engaged in the study of chronic atrophic gastritis and gastrointestinal motility, having 4 papers published.
Author contributions: All authors contributed equally to the work.
Correspondence to: Dr. Jiang Lin, Department of Gastroenterology, Shuguang Hospital, Shanghai Traditional Chinese Medicine University, Shanghai 200021, China.
Telephone: +86-21-53821650-291
Received: November 9, 1998
Revised: November 20, 1998
Accepted: November 28, 1998
Published online: December 15, 1998


AIM: To compare the therapeutic effect of the herbal medicine Zhishi Xiaopi with that of Cisapride in the treatment of functional dyspepsia (FD).

METHODS: Fifty-one FD patients were randomized into Herbal group (n = 27) and Cisapride group (n = 24). Two two groups were given a four-week treatment of Zhishi Xiaopiwan 100 mL, tid, a.c. and Cisapride 5 mg, tid, a.c. respectively. Patients’ symptoms were assessed and 39 patients’ (22 of Herbal group and 17 of Cisapride group) gastric liquid emptying times were measured with ultrasonography before and after the treatment.

RESULTS: The therapeutic effective rates of Herbal group and Cisapride group were 81.49% and 87.50% (P > 0.05). The half gastric emptying time (GET50) and gastric emptying time (GET) of healthy controls and FD patients were 36.12 min ± 10.22 min vs 52.95 min ± 13.49 min and 87.07 min ± 21.11 min vs 120.74 min ± 23.08 min (P < 0.001). The GET50 and GET of Herbal group before and after the treatment were 51.63 min ± 13.15 min vs 45.62 min ± 10.82 min and 117.34 min ± 23.29 min vs 103.26 min ± 22.19 min (P < 0.01). The results of Cisapride group were 54.66 min ± 14.14 min vs 40.95 min ± 11.29 min and 125.12 min ± 24.47 min vs 95.49 min ± 22.31 min (P < 0.01). The differences in values (median) of GET50 and GET for Herbal group and Cisapride group before and after treatment were 5.75 min vs 17.18 min and 13.22 min vs 33.54 min (P < 0.05).

CONCLUSION: Delayed gastric emptying is one of the pathogenesis of FD. Both Zhishi Xiaopi pills and Cisapride can effectively alleviate the symptoms of FD and accelerate gastric liquid emptying. The effect of Zhishi Xiaopiwan on enhancing gastric motility is comparable with but less than that of Cisapride.

Key Words: Dyspepsia/therapy, Zhishi xiaopi, cisapride, gastric emptying


Dyspepsia is a common syndrome, Outpatients in gastrointestinal clinics complaining of dyspeptic symptoms amount to about 30%-40% of the total visits. Among them, more than half have no organic lesions after examination. So it is called functional dyspepsia (FD). Some of the patients with FD present symptoms suggestive of delayed gastric emptying. So gastrointestinal hypomotility is considered one of the pathogenesis. In this study, we compared the therapeutic effect of Zhishi Xiaopiwan made of (herbal medicine) with Cisapride in the treatment of FD by assessing symptomatic improvement and measurement of gastric liquid emptying time.

Diagnosis of functional dyspepsia

Epigastric pain, discomfort or bloating, postprandial fullness, eructation, nausea and other upper abdominal symptoms lasting at least for 4 weeks; esophagitis, peptic ulcer, upper gastrointestinal erosion and neoplasm were excluded by endoscopy; diseases of liver, gallbladder, pancreas and lower gastrointestinal tract by laboratory, ultrasound and X-ray examinations; and diabetes, hyperthyroidism, connective tissue diseases and history of abdominal surgery were excluded.

Patients and healthy controls

Fifty-one patients meeting the above diagnostic criteria were randomly divided into two groups: Herbal group, 27 patients (average age, 45.1 ± 9.67 year; range, 25-63 years; a ratio of men/women, 10 ± 17) and Cisapride group, 24 patients (aveaage age, 48.5 ± 12.9 years; range, 26-72 year; a ratio of men/women, 13:11). Healthy control group consisted of 10 volunteers without gastrointestinal symptoms (average age, 41.4 ± 11.75 years; range, 25-58 year; a ratio of men/women, 7:3).

Symptom assessment

Five symptoms (epigastric pain or discomfort, bloating, postprandial fullness, eructation and nausea) were assessed for each patient once a week or two weeks. Symptoms were assessed according to Stanghellini criteria[1]: 0 = absent, 1 = occasionally present and not affecting patients¡ä daily activities; 2 = present moderately often, slightly affecting their activities; 3 = present moderately or more often, affecting considerably patients’ activities. The symptom complex index (SCI) was calculated by dividing the summation of all presenting symptoms’ scores with the number of symptoms.

Therapeutic efficacy assessment criteria

Noticeable efficiency (NE): SCI was less than pre-treatment value by 2 or more; efficiency: SCI was less than pre-treatment value by 1 or more but less than 2; and inefficiency: SCI was less than pre-treatment value by less than 1.

Measurement of gastric liquid emptying

Gastric liquid emptying was measured in one vertical section of antrum with real time ultrasonography as used by Marizo[2]. All medication was stopped for 3 days and the patients were fasted for 12 h before the test. Milk of 250 mL with a total caloric value of 597 KJ, prewarmed to 37 °C, was used as a testing meal.


Herbal group was treated with Zhishi Xiaopiwan in the form of decoction (100 mL three times a day before meal) for 4 weeks. Zhishi Xiaopiwan consisted for the following ingredients:Citrus aurantium L.15 g, Officinal Magnolia Bark 12 g, Tangshen Asiabell Root 10 g, Largehead Atractylodes Rhizome 10 g, Poria 12 g, Ternate Pinellia Tuber 10 g, Golden Thread Rhizome 3 g, Nardostachys Rhizome and Root 6 g, etc. If pain was severe, Paniclate Swallowwort Root 10 g and Corydalis yanhusuo W.T.Wang 15 g were added. If bloating was severe, Finger Citron 10 g, Akebi Fruit 10 g and Costus Root 10 g were supplemented. If eructation and nausea were severe, Inula Flower 10 g and Bamboo Shavings 5 g were added. If there was regurgitation, Ark Shell 30 g and Cuttle Bone 30 g were used Cisapride group was treated with Cisapride (5 mg three times a day before meals) for 4 weeks.

Statistical analysis

Student’s t test, χ2 test, rank sum test and linear regression were used and P values less than 0.05 were considered significant.

Therapeutic efficiency of symptoms

Both Zhishi Xiaopiwan and Cisapride could effectively alleviate patients’ symptoms (Table 1, Table 2, Table 3). There were no significant difference between the efficencies of the two medications on the symptoms of the FD, and in improvement SCI between two groups after treatment. The total efficacy rates (NE + E) of Herbal group and Cisapride group were 81.49% and 87.5% respecitively (P > 0.05). During treatment, 3 patients of Cisapride group had fewer gastrointestinal symptoms (1 with lower abdominal pain, 2 with loose stool). Patient in Herbal group had no side reactions, but with no statistical significance (χ2 = 3.59, P > 0.05).

Table 1 Comparision of the theraputic efficiency for symptoms relief.
SymptomsGroupCasesNEa (n)Ea (n)IEa (n)EFa (%)
Epigastic painHerbal16110568.75b
Postprandial fullnessHerbal1998289.47b
Table 2 Comparision of symptoms complex index.
GroupCasesBefore treatmentAfter treatmentDifferential values
Herbal272.28 ± 0.321.02 ± 0.60a1.26 ± 0.56b
Cispride242.19 ± 0.400.71 ± 0.55a1.49 ± 0.56
Table 3 Comparision of the clinical theraputic efficiency rate.
GroupCasesNEa rate % (n)Ea rate % (n)IEa rate % (n)
Herbal2725.93 (7)b55.56 (15)b18.51 (5)b
Cisapride2437.50 (9)50.00 (12)12.50 (3)
Gastric liquid emptying

Gastric liquid emptying tests were done in 10 healthy volunteers and 39 FD patients. Half gastric emptying time (GET-50) and total gastric emptying time (GET) of health controls were 36.12 min ± 10.22 min and 87.07 min ± 21.11 min. Those of FD patients were 52.95 min ± 13.49 min and 120.74 min ±23.80 min, both of which were longer than those of healthy controls (P < 0.001). If the normal GET50 range was set as from 16.09 to 56.15 (mean ± 1.96 SD), there were 14 (35.90%) patients with delay of gastric emptying.

Both Zhishi Xiaopiwan and Cisapride could shorten the gastric liquid emptying time (Table 4). After treatment, there was still significant difference between the gastric emptying time of Herbal group and control group (P < 0.05), but there was no significant difference between those of Cisapride group and control group (P > 0.05). The median difference of GET50 and GET of Herbal group before and after treatment were 5.75 min and 13.22 min respecitively, and those of Cisapride group were 17.18 min and 33.54 min (0.25 < P < 0.05). So the effect of Zhishi Xiaopiwan in enhancing gastric emptying is less than that of Cisapride.

Table 4 Comparision of gastric emptying time between before and after treatment.
GroupCasesGET50 (min)GET (min)
Control1036.12 ± 10.2287.07 ± 21.11
HerbalBefore treatment2251.63 ± 13.15a117.34 ± 23.29a
After treatment2245.62 ± 10.82bc103.26 ± 22.19bc
CisaprideBefore treatment1754.66 ± 14.14a125.01 ± 24.47a
After treatment1740.95 ± 11.29bd95.49 ± 22.31bd

In this study, we found 35.9% of FD patients had delayed gastric liquid emptying, which is similiar to the results of 23%-55% reported previously[3,4]. This indicates that quiet a few FD patients have gastric hypomotility. Gastrointestinal manometric techniques[1,5] showed that during fasting, the cycles of Migrating Motor Complex (MMC) of FD patients are less than those of healthy subjects. No matter during fasting or digestive period, the amplitude and frequency of the contractions of antrum and duodenum of FD patients are all less than those of healthy subjects. During digestive period, the numbers of duodenal propulsive peristalsis and the coordinating contractions between antrum and duodenum are less than those of healthy subjects. Ultrasonographic techniques[6] also showed that the postprandial antrum contractions of FD patients are incomplete with small waves of irregular rhythm, as compared to the complete, even and rhythmical peristalsis of healthy subjects. The gastrointestinal hypomotility and the incoordination between antrum and duodenum may induce delay of gastric emptying. As an agonist of 5-HT4 receptor, Cisapride can act on the receptors of the intermediate and terminal neurons of myenteric nerve plexus in gastrointestinal smooth muscle and improve the gastrointestinal motility by promoting cholinergic nerves to release acetylcholine. It can increase the amplitude and freqauency of the gastric contractions and the numbers of coordinating contractions between antrum and duodenum to accelerate gastric emptying.

Symptomatology of FD is very similar to that of “Piman Zheng”, a name of disease in Traditional Chinese medicine with bloating as the chief complaint. Zhishi Xiaopiwan is the commonly used Chinese medicine for “Piman Zheng”. So we chose this medicine to treat FD and compared it with Cisapride. The results showed that Zhishi Xiaopiwan could effectively ameliorate the symptoms of FD, and its total efficiency rate (81.49%) was not significantly different from that of Cisapride (87.5%). Gastric emptying examinations indicated that Zhishi Xiaopiwan also could accelerate the gastric liquid emptying, although its effect was less than that of Cisapride. Its effect on enhancing gastrointestinal motility was proven in previous animal exeriments. The main ingredient of Zhishi Xiaopiwan-Citrus aurantium L. could prolong the cavine intestinal active duration of MMC by reducing the duration of the phase I and prolonging the duration of the phase II[7]. Other ingredients, such as Tangshen Asiabel Root, Rhizome Atracty lodes macrocephalae, Ternate Pinellia Tuber and Golden Thread Rhizome, could increase the frequency of rat gastric electric spikes and amplitude of gastric contractions and regulate the disturbance of gastric electric rhythm. Rhizome Atractylodes macrocephalae might act on cholinergic receptors to activate the gastric movement[8,9].

Not all FD patients had delayed gastric emptying. This indicates that gastrointestinal hypomotility is not the sole pathogensis of FD, other factors such as hypersensitiveness of gastric mucosa, disturbance of gastric accomodation and failure of gallbladder contraction might also be involved in the pathogenesis[10]. The inconsistency between the symptomatic relief and improvement of gastric emptying by Zhishi Xiaopian also suggests that the action of the herbal medicine to improve symptoms might be through mechanisms other than promoting gastric motility, which shoujld be further studied in the future.

In conclusion, we found that delay of gastric emptying was one of the pathogenetic factors of FD, and both Zhishi Xiaopiwan and Cisapride could ameliorate the symptoms of FD and accelerate the gastric liquid emptying in certain percentage of patients. In this aspect, Cisapride is better than the herbal medicine we used.

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