Tong-Xie-Yao-Fang Research Articles

Regulating effect of TongXie-YaoFang on colonic epithelial secretion via Cl- and HCO3- channel.

AIMTo investigate the pharmacological effect of TongXie-YaoFang (TXYF) formula, a Chinese herbal formula, on Diarrhea-predominant irritable bowel syndrome (D-IBS) rats.METHODSIn a neonatal maternal separation plus restraint stress (NMS + RS) model of D-IBS, male Sprague Dawley rats were randomly divided into two groups (NMS + RS group and TXYF-formula group) with no handlings were used as controls (NH group). Starting from postnatal day 60, rats in TXYF-formula group were administered TXYF-formula (4.92 g/100 g bodyweight) orally twice a day for 14 consecutive days while NH group and NMS + RS group were given distilled water. Using short-circuit current technology, we observed 5-HT-induced changes of current across ion channels, such as cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel, epithelial Na+ channel (ENaC), Ca2+-dependent Cl- channel (CACC), Na+-K+-2Cl- co-transporter (NKCC), and Na+-HCO3- co-transporter (NBC), in the colonic epithelium of three groups after exposure to drugs and specific blockers with a Power Lab System (AD Instruments International).RESULTSUnder basal conditions, the changes of short-circuit current (∆Isc, µA/cm2) induced by 5-HT were similar in NH group and TXYF-formula group, and both higher than NMS + RS group (70.86 µA/cm2 ± 12.32 µA/cm2, 67.67 µA/cm2 ± 11.68 µA/cm2 vs 38.8 µA/cm2 ± 7.25 µA/cm2, P < 0.01, respectively). When CACC was blocked by 4,4′-diisothiocyanato-stilbene-2,2′-disulfonic acid, 5-HT-induced ∆Isc was smaller in NMS + RS group than in NH group and TXYF-formula group, respectively (48.41 µA/cm2 ± 13.15 µA/cm2 vs 74.62 µA/cm2 ± 10.73 µA/cm2, 69.22 µA/cm2 ± 11.7 µA/cm2, P < 0.05, respectively). The similar result could be obtained when ENaC was blocked by Amiloride (44.69 µA/cm2 ± 12.58 µA/cm2 vs 62.05 µA/cm2 ± 11.26 µA/cm2, 62.11 µA/cm2 ± 12.01 µA/cm2, P < 0.05, respectively). However, when CFTR Cl- channel was blocked by 1,1-dimethyl piperidinium chloride (DPC), 5-HT-induced ∆Isc did not significantly differ in three groups (42.28 µA/cm2 ± 10.61 µA/cm2 vs 51.48 µA/cm2 ± 6.56 µA/cm2 vs 47.75 µA/cm2 ± 7.99 µA/cm2, P > 0.05, respectively). The similar results could also be obtained in three groups when NBC and NKCC were respectively blocked by their blockers.CONCLUSIONTXYF-formula can regulate the Cl- and HCO3- secretion of colonic mucosa via CFTR Cl- channel, Cl-/HCO3- exchanger, NBC and NKCC co-transporters.

Evaluation of clinical effects of Jiawei Tongxie Yaofang decoction in treatment of irritable bowel syndrome based on brain-intestinal axis theory

Evaluation of clinical effects of Jiawei Tongxie Yaofang decoction in treatment of irritable bowel syndrome based on brain-intestinal axis theory

Tong Xie Yao Fang relieves irritable bowel syndrome in rats via mechanisms involving regulation of 5-hydroxytryptamine and substance P.

To investigate whether the Chinese medicine Tong Xie Yao Fang (TXYF) improves dysfunction in an irritable bowel syndrome (IBS) rat model. Thirty baby rats for IBS modeling were separated from mother rats (1 h per day) from days 8 to 21, and the rectum was expanded by angioplasty from days 8 to 12. Ten normal rats were used as normal controls. We examined the effects of TXYF on defection frequency, colonic transit function and smooth muscle contraction, and the expression of 5-hydroxytryptamine (5-HT) and substance P (SP) in colonic and hypothalamus tissues by Western blot and RT-PCT techniques in both normal rats and IBS model rats with characterized visceral hypersensitivity. Defecation frequency was 1.8 ± 1.03 in normal rats and 4.5 ± 1.58 in IBS model rats (P < 0.001). However, the defecation frequency was significantly decreased (3.0 ± 1.25 vs 4.5 ± 1.58, P < 0.05), while the time (in seconds) of colon transit function was significantly increased (256.88 ± 20.32 vs 93.36 ± 17.28, P < 0.001) in IBS + TXYF group rats than in IBS group rats. Increased colonic smooth muscle tension and contract frequency in IBS model rats were significantly decreased by administration of TXYF. Exogenous agonist stimulants increased spontaneous activity and elicited contractions of colon smooth muscle in IBS model rats, and all of these actions were significantly reduced by TXYF involving 5-HT and SP down-regulation. TXYF can modulate the activity of the enteric nervous system and alter 5-HT and SP activities, which may contribute to the symptoms of IBS.

Observation of the clinical curative effect when adopt smoothing liver and invigorating spleen treatment to cure diarrhea-predominant irritable bowel syndrome

Objective To evaluate the clinical effects and safety when adopt smoothing liver and invigorating spleen treatment to cure diarrhea- predominant irritable bowel syndrome(D- IBS)characterized by liver stagnation with spleen deficiency. Methods 71 patients met the inclusion criteria of D- IBS were randomly divided into the treatment group(36 cases)and control group(35 cases), the treatment group used Shugan Jianpi therapy, traditional Chinese medicine Tongxieyao Fang and additive Shenlingbaishu Decoction; the control group taking Lactobacillus Complex Capsules treatment. Two groups of the time of taking medicine for 4 weeks.Observation and analysis of comprehensive effects and D- IBS symptom score before and after treatment. Results There was no statistical significance in the two groups before treatment, symptom total score difference, after the treatment group and the control group of symptom score were(4.83±3.30),(7.00±3.96), with a significant difference between the two groups(t= 2.51,P< 0.05); the total effective rate of treatment group was 91.67%, which was higher than 68.57% in the control group(χ2= 5.98,P< 0.05). Conclusion The adoption of the smoothing liver and invigorating spleen treatment characterized by the use of Tong Xie Yao Fang and additive Shen LingBaiZhu decoction to cure D- IBS patients with liver stagnation and spleen deficiency has a relatively satisfactory clinical curative effect. Key words: Smoothing liver and invigorating spleen treatment; Irritable bowel syndrome

Inhibitory effect of TongXie-YaoFang formula on colonic contraction in rats.

To investigate the pharmacological effect of TongXie-YaoFang (TXYF) formula and its underlying mechanisms. A neonatal maternal separation plus restraint stress (NMS + RS) model of diarrhea-predominant irritable bowel syndrome was developed by subjecting male Sprague-Dawley rats to daily maternal separation from postnatal days 2 to 21 plus restraint stress from days 50 to 59. Rats were randomly divided into two groups (NMS + RS and TXYF formula), and rats with no handling or separation were used as normal controls. Starting from postnatal day 60, rats were administered TXYF formula (9.84 g/100 g body weight) orally twice daily for 14 consecutive days, while the normal and NMS + RS groups were given distilled water. The distinctions of movement index (MI, area under the curve of contraction intensity/min, mg/min) and contraction frequency (CF, number of contractions/min, times/min) of isolated colonic longitudinal smooth muscle strips (CLSMs) in the three groups before and after treatment were observed with a Power Lab system. Different inhibitors were applied, and then 10(-4) mol/L acetylcholine chloride (Ach) was added to CLSMs to induce muscle contraction. Before treatment, the MI of CLSMs in the NMS + RS and TXYF formula groups was similar and both higher than that in the normal group (545.49 ± 73.66 mg/min vs 245.76 ± 34.44 mg/min and 551.09 ± 54.29 mg/min vs 245.76 ± 34.44 mg/min, P < 0.01, respectively). After treatment, the MI in the TXYF formula group was lower than that in the NMS + RS group (261.39 ± 38.59 mg/min vs 533.9 ± 61.63 mg/min, P < 0.01). In the same way, the CF of CLSMs in the NMS + RS and TXYF formula groups was similar and both higher than that in the normal group (3.42 ± 0.25 times/min and 3.31 ± 0.21 vs 1.1 ± 0.17 times/min, P < 0.01) before treatment. After treatment, the CF in the TXYF formula group was lower than that in the NMS + RS group (1.42 ± 0.87 times/min vs 3.11 ± 0.82 times/min, P < 0.01) and similar to that in the normal group (1.42 ± 0.87 times/min vs 1.09 ± 0.13 times/min). When 8-(N,N-diethylamino)octyl 3,4,5-trimethoxybenzoate hydrochloride and 4-aminopyridine were added to the bath and equilibrated for 30 min, respectively, and 10(-4) mol/L Ach was added to CLSMs to induce muscle contraction, MI of the CLSMs in the TXYF formula group was lower than that in the normal group (666 ± 36.32 mg/min vs 747.77 ± 49.47 mg/min, and 686.53 ± 39.17 mg/min vs 750.45 ± 29.39 mg/min; P < 0.01, respectively). The MI of CLSMs in the TXYF formula group was lower than that in the normal group after treatment with nifedipine (689.48 ± 30.84 mg/min vs 741.65 ± 32.41 mg/min; P < 0.05). TXYF formula inhibits colon contraction in rats. This may be related to activation of specific potassium channels and inhibition of extracellular calcium internal flow.

A sensitive UPLC–MS/MS method for simultaneous determination of eleven bioactive components of Tong-Xie-Yao-Fang decoction in rat biological matrices

There is a growing concern for the sensitive quantification of multiple components using advanced data acquisition method in herbal medicines (HMs). An improved and rugged UPLC-MS/MS method has been developed and validated for sensitive and rapid determination of multiply analytes from Tong-Xie-Yao-Fang (TXYF) decoction in three biological matrices (plasma/brain tissue/urine) using geniposide and formononetin as internal standards. After solid-phase extraction, chromatographic separation was performed on a C18 column using gradient elution. Quantifier and qualifier transitions were monitored using novel Triggered Dynamic multiple reaction monitoring (TdMRM) in the positive ionization mode. A significant peak symmetry and sensitivity improvement in the TdMRM mode was achieved as compared to conventional MRM. The reproducibility (RSD%) was ≤7.9% by applying TdMRM transition while the values were 6.8-20.6% for MRM. Excellent linear calibration curves were obtained under TdMRM transitions over the tested concentration ranges. Intra- and inter-day precisions (RSD%) were ≤14.2% and accuracies (RE%) ranged from -9.6% to 10.6%. The validation data of specificity, carryover, recovery, matrix effect and stability were within the required limits. The method was effectively applied to simultaneously detect and quantify 1 lactone, 2 monoterpene glucosides, 1 alkaloid, 5 flavonoids and 2 chromones in plasma, brain tissue and urine after oral administration of TXYF decoction. In conclusion, this new and reliable method is beneficial for quantification and confirmation assays of multiply components in complex biological samples.

The inhibitory effect of tongxieyaofang on rats with post infectious irritable bowel syndrome through regulating colonic par-2 receptor

BackgroundThe aims of this study were to evaluate the effect and mechanism of a traditional Chinese medicine formula: Tongxieyaofang (TXYF) on Rats with Post Infectious Irritable Bowel Syndrome (PI-IBS).MethodsSD male rats in adult were used to model PI-IBS and treated with TXYF at three dosage for 14 consecutive days, and then visceral sensation and the frequency of stool in PI-IBS rats were investigated. In addition, the contents of SP, TNF- α and IL-6 in colonic mucosal were analyzed by ELISA. Moreover faecal serine protease activity and PAR-2 mRNA expression were measured by ultraviolet spectrophotometry and RT-PCR, respectively.ResultsOur study showed that TXYF attenuated visceral hyperalgesia and inhibited stool frequency in Campylobacter-stimulated Post Infectious Irritable Bowel Syndrome (PI-IBS) rats. Furthermore, TXYF decreased the colonic SP, TNF- α and IL-6 content in PI-IBS rats. In addition, the up-regulated colonic mucosa PAR-2 mRNA expression in PI-IBS rats was significantly suppressed by orally TXYF.ConclusionsTXYF attenuated PI-IBS symptom by attenuating behavioral hyperalgesia and anti-diarrhea, the underlying mechanism was mediated by inhibiting PAR-2 receptor expression, reducing the levels of SP, TNF- α and IL-6 in colonic mucosa and decreasing faecal serine protease activity.

Modified Tong Xie Yao Fang in the treatment of 60 patients with irritable bowel syndrome

Objective To observe the clinical efficacy of Modified Tong Xie Yao Fang for irritable bowel syndrome.Methods 120 patients with irritable bowel syndrome were randomly divided into treatment group and control group,with 60 cases in each.The treatment group were treated with Modified Tong Xie Yao Fang dialectically,and the control group were treated with western medicine.Results The treatment group had a 61.7％ cure rate and a 96.7％ total effective rate,and the control group had 33.3％ in cure rate and 85.0％ in total effective rate,so the differences were significant ( P ＜ 0.05 ).Conclusions Modified Tong Xie Yao Fang is effective in the treatment of irritable bowel syndrome,which is worth being generalized clinically. Key words: Irritable bowel syndrome; Dialectical treatment; Modified tong xie yao fang

Qualitative and quantitative analysis of chemical constituents in traditional Chinese medicinal formula Tong-Xie-Yao-Fang by high-performance liquid chromatography/diode array detection/electrospray ionization tandem mass spectrometry

Tong-Xie-Yao-Fang (TXYF), a famous traditional Chinese medicine formula, has efficient effects on treatment of the diarrhea-predominant irritable bowel syndrome (D-IBS), a disease with high incidence worldwide. However, the active principles for this complex formula have not been fully explored so far. In this paper, high-performance liquid chromatography coupled with diode array detection and electrospray ionization tandem mass spectrometry (HPLC-DAD-ESI-MS/MS) was applied for the qualitative and quantitative analysis of major chemical constituents in TXYF. Two monoterpene glycosides, one chromone and five polymethoxylated flavones were tentatively characterized based on the retention times, UV spectra and MS data. Fifteen compounds were unambiguously identified by comparison with reference standards. Constituents such as lactone and steroidal, which could not be found by single HPLC method due to the low content in the formula, were identified in this paper. Seven compounds (gallic acid, prim- O-β- d-glucosylcimifugin, paeoniflorin, cimifugin, naringin, hesperidin and 4′- O-β- d-glucosyl-5- O-methylvisamminol) were quantified by HPLC-DAD using a C18 column and gradient elution with acetonitrile and water–0.1% formic acid. The method exhibited intra- and inter-day precision of less than 2.35% and 3.14%, respectively. The LODs and the LOQs for the analytes were less than 0.47 and 1.82 μg ml −1, respectively. The overall recoveries ranged from 96.82% to 102.47%, with the R.S.D. ranging from 1.17% to 3.94%. These results demonstrated that our present method was effective and reliable for comprehensive quality evaluation of TXYF. Meanwhile, the study might provide the chemical evidence for revealing the material basis of its therapeutic effects.

Tongxie Yaofang inhibits the contraction of colonic smooth muscle isolated from rats through a mechanism related to calcium mobilization

To study the relationship between the inhibitory effects of Tongxie Yaofang, a compound traditional Chinese herbal medicine, on the contraction of the colonic smooth muscle isolated from rats and calcium mobilization. By measuring the tension of the isolated colonic smooth muscle strips, the inhibitory effects of Tongxie Yaofang on the contraction induced by acetylcholine (ACh), KCl and exhausting Ca(2+) of internal calcium store were assessed respectively. Tongxie Yaofang could concentration-dependently inhibit the contraction of isolated rat colonic smooth muscle strips induced by KCl and exhausting the Ca(2+) of internal calcium store. Tongxie Yaofang could also inhibit the tension of the second contractile phase induced by ACh (P<0.01, vs control), but had no influence on the first contractile phase. Tongxie Yaofang can inhibit the contraction of isolated rat colonic smooth muscle strips mainly by preventing the influx of extracellular Ca(2+), which may be associated with blocking voltage-dependent channel, store-operated channel and receptor-operated channel, but not by preventing the release of internal Ca(2+) from calcium store.

Effect of Tongxie Yaofang (痛泻要方) Granule in treating diarrhea-predominate irritable bowel syndrome

To study the clinical effect of Tongxie Yaofang (TXYF) Granule in treating diarrhea-predominate irritable bowel syndrome (D-IBS) and its possible mechanism. A total of 120 patients were assigned to two groups using stratified block randomization, 80 in the intervention group and 40 in the control group. To the intervention group the TXYF granule was given at one package each time, twice a day; the control group was treated with Miyarisan three times a day, two tablets each time. The course of treatment was 4 weeks for both groups. The total efficacy in them was compared, and data of scoring on stool (Bristol method), abdominal pain, abdominal distension, and mental condition were collected before treatment and 2 and 4 weeks after treatment. The activation of mast cells (MCs) of six patients chosen from each group was detected as well before and after treatment. No significant difference between the two groups in terms of the total efficacy or the scores of symptoms before and after treatment was found (P>0.05). The number of activated MCs was decreased in the intervention group after treatment, showing significant difference as compared with that before treatment as well as with that in the control group after treatment (P<0.01). TXYF is an effective preparation for the treatment of D-IBS. It can quickly lessen abdominal pain and distention, improve the property of stool, and improve mental tension and depression in patients. Its mechanism of action might be through the adjustment of MCs activation to decrease visceral hypersensitivity.

The Alleviating Pain Effect of Aqueous Extract from Tong-Xie-Yao-Fang, on Experimental Visceral Hypersensitivity and Its Mechanism

Tong-Xie-Yao-Fang (TXYF) is a prescription in traditional chinese medicine (TCM), used for relieving abdominal pain associated with irritable bowel syndrome. The aim of the present study was to investigate the effects and mechanism of TXYF on experimental visceral hypersensitivity (VH) models. TXYF affected the abdominal withdrawal reflex produced by colonic distention in maternal separation-induced visceral hypersensitivity rats, in a dosage-dependent manner. TXYF significantly decreased serotonin (5-HT) levels in serum and corticotrophin releasing factor (CRF) concentrations in the brain. Moreover, it was found that VH alleviation by TXYF was dependent on the substance P (SP) expression in the colon mucosa. These results suggest that TXYF attenuates behavioral hyperalgesia by regulating substance associated with the brain-gut axis, including decreasing the expression of 5-HT and SP in the periphery and that of CRF in the center.

Effectiveness of the Chinese Herbal Formula TongXieYaoFang for Irritable Bowel Syndrome: A Systematic Review

Irritable bowel syndrome (IBS) is a common problem, but treatment is unsatisfactory. Although Chinese herbal medicines have been tried, there are limited data to support their usage. The authors set out to systematically review the effectiveness of the Chinese herbal medicine TongXieYaoFang (TXYF) and TXYF with different Chinese herbal additions (TXYF-A) in the management of IBS in order to make evidence-based recommendations. The authors searched the literature to identify randomized trials of TXYF or TXYF-A for patients with IBS by using MEDLINE, EMBASE, the Cochrane Controlled Trials Register (CCTR), the Cochrane Complementary Medicine Fields Specialized Register from 1966 to 2004, the CMB Disc database from January 1978 to December 1988, and the Full Text Chinese Journal database from January 1994 to December 2004. Standard forms regarding study design, treatment course, outcome measures, and adverse events were used to abstract data. Studies were assigned a quality score based on published methodology. Relative risk (RR) and 95% confidence interval (CI) were analyzed. Twelve studies (n = 1125) that met the criteria for review were identified. There was heterogeneity in the studies with regard to herbal formulas, control medicine, treatment course, and outcome measurement. The quality of all studies was low. The pooled analyses of effectiveness for the near-term (immediately after finishing the treatment course), short-term (3 months after finishing the treatment course), and long-term (6 months or more after finishing the treatment course) effectiveness showed that the effect of TXYF-A was better than that of conventional medicine in four, two, and six studies, respectively. The RRs were 1.34 (95% CI 1.16-1.54, p < 0.05), 1.39 (95% CI 1.17-1.64, p < 0.05), and 1.34 (95% CI 1.12-1.61, p < 0.05), respectively. Overall, combining all data from the 12 studies, the effectiveness of TXYF-As was higher than that in control groups, with statistical significance and RR of 1.35 (95% CI 1.21-1.50, p < 0.05). There is evidence to indicate the potential usefulness of TXYF-A for IBS patients. The results were limited by the poor quality and heterogeneity of these studies. Further studies with carefully designed, randomized double-blinded placebo-controlled trials will be needed to confirm the effectiveness of TXYF or TXYF-A for IBS.

Herbal medicines for treatment of irritable bowel syndrome

Traditional herbal therapies have been used for a long time to treat gastrointestinal disorders including irritable bowel syndrome, and their effectiveness from clinical research evidence needs to be systematically reviewed. To assess the effectiveness and safety of herbal medicines in patients with irritable bowel syndrome. We searched the following electronic databases till July 2004: The Cochrane Library (CENTRAL), MEDLINE, EMBASE, AMED, LILACS, the Chinese Biomedical Database, combined with hand searches of Chinese journals and conference proceedings till end of 2003. No language restriction was used. Randomised controlled trials of herbal medicines compared with no treatment, placebo, pharmacological interventions were included. Data were extracted independently by two authors. The methodological quality of trials was evaluated using the components of randomisation, allocation concealment, double blinding, and inclusion of randomised participants. Seventy-five randomised trials, involving 7957 participants with irritable bowel syndrome, met the inclusion criteria. The methodological quality of three double-blind, placebo-controlled trials was high, but the quality of remaining trials was generally low. Seventy-one different herbal medicines were tested in the included trials, in which herbal medicines were compared with placebo or conventional pharmacologic therapy. Herbal medicines were also combined with conventional therapy and compared to conventional therapy alone.Compared with placebo, a Standard Chinese herbal formula, individualised Chinese herbal medicine, STW 5 and STW 5-II, Tibetan herbal medicine Padma Lax, traditional Chinese formula Tongxie Yaofang, and Ayurvedic preparation showed significantly improvement of global symptoms. Compared with conventional therapy in 65 trials testing 51 different herbal medicines, 22 herbal medicines demonstrated a statistically significant benefit for symptom improvement, and 29 herbal medicines were not significantly different than conventional therapy. In nine trials that evaluated herbal medicine combined with conventional therapy, six tested herbal preparations showed additional benefit from the combination therapy compared with conventional monotherapy. No serious adverse events from the herbal medicines were reported. Some herbal medicines may improve the symptoms of irritable bowel syndrome. However, positive findings from less rigorous trials should be interpreted with caution due to inadequate methodology, small sample sizes, and lack of confirming data. Some herbal medicines deserve further examination in high-quality trials.

Effects of four regulating-intestine prescriptions on pathology and ultrastructure of colon tissue in rats with ulcerative colitis

To observe different histomorphologic changes of ulcerative colitis (UC) rats that were treated with four regulating-intestine prescriptions (FRIP), to investigate the curative effects of FRIP and to analyze their treatment mechanism. The UC rat model was made by the method of 2,4-dinitro chloro benzene (DNCB) immunity and acetic acid local enema. Ninety-eight SD rats were randomly divided into seven groups, namely, the normal control group, model group, salicylazosulfapyridine (SASP) group, Wumeiwan (WMW) group, Baitouwengtang (BTWT) group, Senglingbaishusan (SLBSS) group, and Tongxieyaofang (TXYF) group. Each group had 14 rats (with equal ratio of male and female). The six animal model groups of UC -SASP, TXYF, WMW, BTWT, SLBSS, TXYF-were treated by distilled water except the normal control group. Changes of the rat's general conditions after treatment were respectively observed, the colon tissue damage scores were given out, the pathology of colonic mucosa and changes of ultrastructure were analyzed. Different pathological changes on histology were shown after treatment by FRIP. The colon tissue damage score in model group was higher than that of FRIP groups and SASP group (q = 4.59, 4.77, P<0.05 or q = 5.48, 6.25, 5.97, P<0.01). The scores of WMW group, BTWT group and SLBSS group were lower than that of SASP (q = 4.13, P<0.05 or q = 5.31, 5.12, P<0.01). There was no remarkable difference between the damage score of TXYF group and SASP group (q = 3.75, P>0.05). In addition, some apoptosis cells were found in the pathologic control group. The model made with DNCB and acetic acid was successful, and FRIP had better curative effect and WMW was the best curative effect, BTW, SLBSS and TXYF were similar to SASP, and we discovered that apoptosis was possibly related to UC.