Insight into the mechanism of Xiao-Chai-Hu-Tang alleviates irinotecan-induced diarrhea based on regulating the gut microbiota and inhibiting Gut ß-GUS.

BACKGROUND: Irinotecan (CPT-11, Camptosar@) is a first-line drug for metastatic colorectal cancer. CPT-11-induced diarrhea, which is closely related to the concentrations of ß-glucuronidase (ß-GUS) and SN-38 in the gut, largely limits its clinical application. PURPOSE: Herein, Xiao-Chai-Hu-Tang (XCHT), a traditional Chinese formula, was applied to mitigate CPT-11-induced toxicity. This study initially explored the mechanism by which XCHT alleviated diarrhea, especially for ß-GUS from the gut microbiota. METHODS: First, we examined the levels of the proinflammatory cytokines and the anti-inflammatory cytokines in the intestine. Furthermore, we researched the community abundances of the gut microbiota in the CPT-11 and XCHT-treated mice based on 16S rRNA high-throughput sequencing technology. Meanwhile, the level of SN-38 and the concentrations of ß-GUS in intestine were examined. We also resolved the 3D structure of ß-GUS from gut microbiota by X-ray crystallography technology. Moreover, we used virtual screening, SPR analysis, and enzyme activity assays to confirm whether the main active ingredients from XCHT could selectively inhibit ß-GUS. RESULTS: In XCHT-treated mice, the levels of the proinflammatory cytokines decreased, the anti-inflammatory cytokines increased, and the community abundances of beneficial Firmicutes and Bacteroidota improved in the gut microbiota. We also found that the concentrations of ß-GUS and the level of SN-38, the major ingredient that induces diarrhea in the gut, significantly decreased after coadministration of XCHT with CPT-11 in the intestine. Additionally, we revealed the structural differences of ß-GUS from different gut microbiota. Finally, we found that EcGUS had good affinity with baicalein and meanwhile could be selectively inhibited by baicalein from XCHT. CONCLUSIONS: Overall, XCHT could relieve the delayed diarrhea induced by CPT-11 through improving the abundance of beneficial gut microbiota and reduced inflammation. Furthermore, based on the three-dimensional structure, baicalein, especially, could be used as a candidate EcGUS inhibitor to alleviate CPT-11-induced diarrhea.

Xiao Chai Hu Tang alleviates the pancreatic tumorigenesis via improving the mtDNA N6-Methyladenine modification mediated mitochondrial dysfunction in Syrian hamster model.

BACKGROUND: Pancreatic intraepithelial neoplasia (PanIN) is the most common precursor lesion of pancreatic ductal adenocarcinoma (PDAC), which is a highly malignant tumor and lack of effective treatment. Although Xiao Chai Hu Tang (XCHT) has a good therapeutic effect on pancreatic cancer patients with advanced stage, the effect and mechanism of XCHT remains unclear in pancreatic tumorigenesis. PURPOSE: To assess the therapeutic effects of XCHT on the malignant transformation from PanIN to PDAC and to reveal its mechanisms of pancreatic tumorigenesis. METHODS: Syrian golden hamster were induced by N-Nitrosobis (2-oxopropyl) amine (BOP) to establish the pancreatic tumorigenesis model. The morphological changes of pancreatic tissue were observed by H&E and Masson staining; the Gene ontology (GO) analysis the transcriptional profiling changes; the mitochondrial ATP generation, mitochondrial redox status, mitochondrial DNA (mtDNA) N6-methyladenine (6mA) level and relative mtDNA genes expressions were examined. In addition, immunofluorescence detect the cell localization of 6mA in human pancreatic cancer PANC1 cell. Using the TCGA database, the prognostic effect of mtDNA 6mA demethylation ALKBH1 expression on pancreatic cancer patients was analyzed. RESULTS: We confirmed the mtDNA 6mA levels were gradually increased with the mitochondrial dysfunction in PanINs progression. XCHT showed the effect to inhibit the occurrence and development of pancreatic cancer in Syrian hamster pancreatic tumorigenesis model. In addition, the lack of ALKBH1 mediated mtDNA 6mA increase, mtDNA coded genes down-expression and abnormal redox status were rescued by XCHT. CONCLUSIONS: ALKBH1/mtDNA 6mA mediated mitochondrial dysfunction to induce the occurrence and progression of pancreatic cancer. XCHT can improve ALKBH1 expression and mtDNA 6mA level, regulate the oxidative stress and expression of mtDNA coded genes. This study investigated a new molecular mechanism of pancreatic tumorigenesis, and revealed the therapeutic efficacy of XCHT in pancreatic tumorigenesis for the first time.

XCHT alleviates the pancreatic fibrosis via VDR/NLRP3 signaling pathway in a mouse model of CP.

ETHNOPHARMACOLOGICAL RELEVANCE: Xiao Chai Hu Tang (XCHT) derived from the classic medical book Shang Han Lun (Treatise on Febrile Diseases) in the Eastern Han Dynasty, which has been widely used in China and other Asian countries for the treatment of inflammation and fibrosis of chronic pancreatitis (CP), but the therapeutic mechanism of XCHT in pancreatic fibrosis remains unclear. AIM OF THE STUDY: This study aimed to evaluate the intervention effects and explore pharmacological mechanism of XCHT on inflammation and fibrosis in cerulein-induced CP model. MATERIALS AND METHODS: Fifty male C57BL/6 mice were randomly divided into five main groups, 10 animals in each: Control, CP model (50 µg/kg cerulein), high dose XCHT-treated CP group (60 g/kg XCHT), medium dose XCHT-treated CP group (30 g/kg XCHT) and low dose XCHT-treated CP group (15 g/kg XCHT). Different doses of XCHT were given to mice by gavage twice a day for 2 weeks after the CP model induction. Pancreatic tissues were harvested and the pancreatic inflammation and fibrosis were evaluated by histological score, Sirius red staining, and alpha-smooth muscle actin (α-SMA) immunohistochemical staining. ELISA, IHC and RT-qPCR were performed to detect the expression of Vitamin D3 (VD3) and Vitamin D receptor (VDR) in serum and pancreatic tissues, respectively. The expressions of NLRP3 inflammasome related genes and molecules were assayed by WB, IHC and RT-qPCR. RESULTS: The pathohistological results demonstrated that XCHT markedly inhibited the fibrosis and chronic inflammation of cerulein-induced CP, indicated by reduction of collagen I, collagen III, α-SMA, and NLRP3 expressions. XCHT significantly increased VD3 and VDR expression while reduced the pancreatic NLRP3 expression. Correspondingly, XCHT decreased the levels of NLRP3 downstream targets IL-1ß, TNF-α and IL-6. CONCLUSIONS: These results revealed that XCHT suppressed the pancreatic fibrosis and chronic inflammation in cerulein-induced CP model by enhancing the VD3/VDR expression and inhibiting the secretion of NLRP3-assoicated inflammatory factors.

Xiao-Chai-Hu-Tang ameliorates tumor growth in cancer comorbid depressive symptoms via modulating gut microbiota-mediated TLR4/MyD88/NF-κB signaling pathway.

BACKGROUND: Depressive symptoms are thought to promote cancer development and depressive remission has been reported to be effective for defeating cancer. The herbal formula Xiao-Chai-Hu-Tang (XCHT), that has an anti-depressive efficacy, has been widely utilized in China. However, its anti-cancer effect and underlying mechanisms remain unclear. PURPOSE: The present study aims to investigate the effects of XCHT on the depression-associated tumor and its potential mechanisms. METHODS: A placebo-controlled trial was conducted in cancer patients comorbid with depressive symptoms to evaluate the effects of XCHT on depressive scales, tumor-related immune indicators, and gut microbial composition. A xenografted colorectal cancer (CRC) mouse model exposure to chronic restraint stress (CRS) was established to examine XCHT effects on tumorigenesis in vivo. Further, by manipulating gut bacteria with fecal microbial transplantation (FMT) or antibiotics-induced bacterial elimination in CRS-associated xenografted model, gut microbiota-mediated anti-tumor mechanism was explored. RESULTS: In cancer patients comorbid with depressive symptoms, XCHT showed substantial effects on improvement of depressive scales, system inflammatory levels and gut dysbiosis. In vivo, XCHT inhibited tumor growth and prolonged survival time in addition to showing anti-depressive effect. Similarly, in our clinical trial, XCHT partially reversed gut dysbiosis, particularly through reducing abundances of Parabacteroides, Blautia and Ruminococcaceae bacterium. Manipulation of gut bacteria in CRS-associated xenografted model further proved that the inhibition of XCHT on tumor progression was mediated by gut microbiota and that the underlying mechanism involves in downregulation of TLR4/MyD88/NF-κB signaling. CONCLUSIONS: We demonstrated that gut microbiota mediates the anti-tumor action of the formula XCHT in cancer patients and models that were comorbid with depressive symptoms. This study implies a novel clinical significance of anti-depressive herbal medicine in the cancer treatment and clarifies the important role of gut microbiota in treating cancer accompanied by depressive symptoms.

Could herbal medicine (Soshihotang) be a new treatment option for COVID-19?: a narrative review.

BACKGROUND: While the world struggles under the coronavirus disease 2019 (COVID-19) pandemic, a variety of antiviral agents and symptomatic treatments are being administered to patients and urgent clinical trials are underway. Under these circumstances, it is important to explore various possibilities for the treatment of COVID-19 including herbal medicines. Among various herbal medicines, Soshihotang (SSHT, Xiao Chai Hu Tang in Chinese) has been prescribed to treat various viral diseases and is used in combination with other herbal medicines depending on the patient's symptoms. METHODS: For conducting the present review, we searched electronic databases focusing on the antiviral effect of SSHT in experimental and clinical study until April 2020. The search keywords included SSHT, constituents of SSHT, and antiviral effect. We also searched for materials related to topic directly from websites and published books. Based on these search results, we summarized the results of the included materials in the form of a narrative review. RESULTS: In a number of recent clinical studies, treatment with SSHT improved the infection status of the respiratory and hepatobiliary systems, and experimental studies demonstrated the antiviral effect of SSHT and its components. Furthermore, SSHT are being used in China-where COVID-19 outbreak first took place-and offer a new option to treat COVID-19. CONCLUSION: Based on the present evidences, it is believed that SSHT is likely to be a new therapeutic option for COVID-19. Conducting further studies might provide improved understanding regarding the use of SSHT in treating COVID-19.

Xiao-Chai-Hu-Tang (XCHT) Intervening Irinotecan's Disposition: The Potential of XCHT in Alleviating Irinotecan-Induced Diarrhea.

BACKGROUND: Diarrhea is a severe side effect of irinotecan, a pro-drug of SN-38 used for the treatment of many types of cancers. Pre-clinical and clinical studies showed that decreasing the colonic exposure of SN-38 can mitigate irinotecan-induced diarrhea. OBJECTIVE: The purpose of this study is to evaluate the anti-diarrhea potential of Xiao-Chai-Hu-Tang (XCHT), a traditional Chinese herbal formula, against irinotecan-induced diarrhea by determining if and how XCHT alters the disposition of SN-38. METHODS: LC-MS/MS was used to quantify the concentrations of irinotecan and its major metabolites (i.e., SN-38, SN-38G). An Intestinal perfusion model was used to determine the effect of XCHT on the biliary and intestinal secretions of irinotecan, SN-38, and SN-38G. Pharmacokinetic (PK) studies were performed to determine the impact of XCHT on the blood and fecal concentrations of irinotecan, SN-38, and SN-38G. RESULTS: The results showed that XCHT significantly inhibits both biliary and intestinal excretions of irinotecan, SN-38, and SN-38G (range: 35% to 95%). PK studies revealed that the fecal concentrations of irinotecan and SN-38 were significantly decreased from 818.35 ± 120.2 to 411.74 ± 138.83 µg/g or from 423.95 ± 76.44 to 245.63 ± 56.72 µg/g (p<0.05) by XCHT, respectively, suggesting the colonic exposure of SN-38 is significantly decreased by XCHT. PK studies also showed that the plasma concentrations of irinotecan, SN-38, and SN-38G were not affected by XCHT. CONCLUSION: In conclusion, XCHT significantly decreased the exposure of SN-38 in the gut without affecting its plasma level, thereby possessing the potential of alleviating irinotecan-induced diarrhea without negatively impacting its therapeutic efficacy.

THE HERBAL MIXTURE XIAO-CHAI-HU TANG (XCHT) INDUCES APOPTOSIS OF HUMAN HEPATOCELLULAR CARCINOMA HUH7 CELLS IN VITRO AND IN VIVO.

BACKGROUND: Xiao-Chai-Hu Tang (XCHT) is an extract of seven herbs with anticancer properties, but its mechanism of action is unknown. In this study, we evaluated XCHT-treated hepatocellular carcinoma (HCC) for anti-proliferative and pro-apoptotic effects. MATERIALS AND METHODS: Using a hepatic cancer xenograft model, we investigated the in vivo efficacy of XCHT against tumor growth by evaluating tumor volume and weight, as well as measuring apoptosis and cellular proliferation within the tumor. To study the effects of XCHT in vitro, we measured the cell viability of XCHT-treated Huh7 cells, as well as colony formation and apoptosis. To identify a potential mechanism of action, the gene and protein expression levels of Bax, Bcl-2, CDK4 and cyclin-D1 were measured in XCHT-treated Huh7 cells. RESULTS: We found that XCHT reduced tumor size and weight, as well as significantly decreased cell viability both in vivo and in vitro. XCHT suppressed the expression of the proliferation marker Ki-67 in HCC tissues and inhibited Huh7 colony formation. XCHT induced apoptosis in HCC tumor tissues and in Huh7 cells. Finally, XCHT altered the expression of Bax, Bcl-2, CDK4 and cyclin-D1, which halted cell proliferation and promoted apoptosis. CONCLUSION: Our data suggest that XCHT enhances expression of pro-apoptotic pathways, resulting in potent anticancer activity.

A Network-Based Pharmacology Study of the Herb-Induced Liver Injury Potential of Traditional Hepatoprotective Chinese Herbal Medicines.

Herbal medicines are widely used for treating liver diseases and generally regarded as safe due to their extensive use in Traditional Chinese Medicine practice for thousands of years. However, in recent years, there have been increased concerns regarding the long-term risk of Herb-Induced Liver Injury (HILI) in patients with liver dysfunction. Herein, two representative Chinese herbal medicines: one-Xiao-Chai-Hu-Tang (XCHT)-a composite formula, and the other-Radix Polygoni Multiflori (Heshouwu)-a single herb, were analyzed by network pharmacology study. Based on the network pharmacology framework, we exploited the potential HILI effects of XCHT and Heshouwu by predicting the molecular mechanisms of HILI and identified the potential hepatotoxic ingredients in XCHT and Heshouwu. According to our network results, kaempferol and thymol in XCHT and rhein in Heshouwu exhibit the largest number of liver injury target connections, whereby CASP3, PPARG and MCL1 may be potential liver injury targets for these herbal medicines. This network pharmacology assay might serve as a useful tool to explore the underlying molecular mechanism of HILI. Based on the theoretical predictions, further experimental verification should be performed to validate the accuracy of the predicted interactions between herbal ingredients and protein targets in the future.

Serum metabonomics study of anti-depressive effect of Xiao-Chai-Hu-Tang on rat model of chronic unpredictable mild stress.

Xiao-Chai-Hu-Tang (XCHT) has been proven to be effective for the clinical treatment of depression. However, the mechanisms of definite antidepressant-like effects and detailed metabolic biomarkers were still unclear in this prior study. Here, we have investigated the metabolic profiles and potential biomarkers in a chronic unpredictable mild stress model after treatment with XCHT. Metabonomics based on ultra-high performance liquid chromatography coupled with mass spectrometry was used to profile the metabolic fingerprints of serum obtained from a rat model with chronic unpredictable mild stress with and without XCHT treatment. The model rats showed a significant decrease in sucrose preference and food consumption, and these depression-like symptoms were significantly improved by XCHT. Through principal component analysis (PCA), nine potential biomarkers of tryptophan, uric acid, phenylalanine, cholic acid and lysophosphatidylcholine (C18:0 LPC, C16:0 LPC, C16:1 LPC, C18:1 LPC, C20:4 LPC) were characterized as potential biomarkers involved the pathogenesis of depression. The therapeutic effect of XCHT on depression may involve in amino acid metabolism, lipid metabolism, oxidative stress and inflammation response. The present investigation highlights that metabonomics is a valuable tool for studying the essence of depression as well as evaluating the efficacy of the corresponding drug treatment.

Experimental study of effect of Xiao Chai Hu Tang on C6 glioma / 中国免疫学杂志

Objective:To investigate the inhibitory effect and mechanism of different doses of Xiao Chai Hu Tang on C6 glioma cells cultured in vitro. Methods:C6 glioma cells were inoculated in 96 holes,24 holes and 6 holes,each culture plate was divided into 4 groups:control group, low dose group, middle dose group and high dose group, when the cells covered the bottom of culture plate 80%-90%,began adding,cultured for 24 hours after the ter mination of training. Cell proliferation activity,cell viability,protein content and protein positive expression intensity of VEGF and ESM-1,cell apoptosis in early and late stage were detected by CCK-8,in vivo staining,ELISA, immunocytochemistry and flow cytometry. Results: CCK-8 assay showed that the growth of C6 glioma cells was inhibited by low,medium and high dose group;ELISA and immunocytochemistry showed that the expression of VEGF and ESM-1 was lower in the lower, middle and high dose groups, and the levels of protein expression and protein levels were decreased. The flow cytometry showed that the low dose of small radix,middle and high dose group could promote the cell apoptosis. Inverted microscope ob-servation showed that with the increase of dose,the number of cells increased gradually,and the number of dead cells increased,and all kinds of detection methods showed that the inhibition effect increased with dose and dose dependence. The difference between the two groups was statistically significant(P<0. 01). Conclusion:The growth of C6 glioma cells was significantly inhibited by Xiao Chai Hu Tang. It may play a role in inhibiting tumor growth by down regulating ESM-1 and VEGF protein level and promoting cell apoptosis.

Simultaneous determinations of 17 marker compounds in Xiao-Chai-Hu-Tang by LC-MS/MS: Application to its pharmacokinetic studies in mice.

The purpose of this study is to develop and validate an UPLC-MS/MS method to quantify different marker compounds from Xiao-Chai-Hu-Tang (XCHT, a Chinese traditional herbal) in biological samples and apply the method to pharmacokinetic study. A Waters BEH C18 UPLC column was used with acetonitrile/0.1% formic acid mobile phases. The mass analysis was performed in a triple quadrupole mass spectrometer using multiple reaction monitoring (MRM) with positive scan mode. A one-step protein precipitation by methanol was used to extract the analytes from blood. Seventeen commercially available compounds from the different compositing herbals were selected as markers. The results revealed that all of the calibration curves showed good linear regression (r(2)>0.9918). The intra-day and inter-day precisions (RSD) of all of these markers at three different levels were less than 15.0% and the bias of the accuracies ranged from -13.5% to 16.6%.The extraction recoveries of all of these 17 markers were from 70.8% to 113.7% and the matrix effects ranged from 71.8% to 114.8%. The stabilities of these compounds in blood were evaluated by analyzing three replicates of QC samples at three different concentrations following storage at 25°C for 6h, 4°C for 24h, and -80°C for 30 days. All the samples displayed 85-115% precision and accuracy after various stability tests. The validated method was successfully applied to pharmacokinetic study in A/J mouse with oral administration of XCHT. All of these markers were detected and the pharmacokinetic parameters of 8 compounds were able to be calculated. This method is sensitive and reproducible that can be used for XCHT's in vivo study.

Understanding the polypharmacological anticancer effects of Xiao Chai Hu Tang via a computational pharmacological model.

Xiao Chai Hu Tang (XCHT), a traditional herbal formula, is widely administered as a cancer treatment. However, the underlying molecular mechanisms of its anticancer effects are not fully understood. In the present study, a computational pharmacological model that combined chemical space mapping, molecular docking and network analysis was employed to predict which chemical compounds in XCHT are potential inhibitors of cancer-associated targets, and to establish a compound-target (C-T) network and compound-compound (C-C) association network. The identified compounds from XCHT demonstrated diversity in chemical space. Furthermore, they occupied regions of chemical space that were the same, or close to, those occupied by drug or drug-like compounds that are associated with cancer, according to the Therapeutic Targets Database. The analysis of the molecular docking and the C-T network demonstrated that the potential inhibitors possessed the properties of promiscuous drugs and combination therapies. The C-C network was classified into four clusters and the different clusters contained various multi-compound combinations that acted on different targets. The study indicated that XCHT has a polypharmacological role in treating cancer and the potential inhibitory components of XCHT require further investigation as potential therapeutic strategies for cancer patients.

Xiao-Chai-Hu Tang in treating model mice with D-galactosamine-induced liver injury.

This study explored the effects of a classical Chinese medicine formula- Xiao-Chai-Hu Tang(XCHT) on the model mice with D-galactosamine -induced liver injury. Sixty male imprinting control region (ICR) mice were used in the present study, and they were separated randomly into 6 groups: a normal control group (Group A, n=10), a model control (Group B, n=10), a positive control (Group C, n=10), a low dose of XCHT group (Group D, n=10), a medium dose of XCHT group (Group E, n=10), and a high dose of XCHT group (Group F, n=10). ELISA was used to detect the IL-6 and TNF-α levels in the serum. Real-time PCR was performed to assess the expression of FasmRNA, Fas-LmRNA, Bcl-2mRNA of the liver tissues. Western blotting was used to detect the Bax protein expression of the liver tissues. The serum IL-6 and TNF-α levels of Group B were significantly higher than the other groups (P<0.05). The expression of Fas mRNA, Fas-LmRNA, and Bax protein of the liver tissues of Group B were significantly higher than those of the other groups (P<0.05). The expression of Bcl-2 mRNA of the liver tissues of Group B was significantly lower than other groups (P<0.05). Both of XCHT and biphenyl dicarboxylate significantly decreased the serum IL-6 and TNF-α levels and FasmRNA, FasLmRNA, Bax protein expression and increased the Bcl-2 mRNA expression of the liver tissues of model mice (P<0.05). It may be through decreasing the serum IL-6 and TNF-α levels and FasmRNA, FasLmRNA, Bax protein expression and increasing the Bcl-2 mRNA expression of the liver tissues that XCHT significantly relieved the D-galactosamine -induced liver injury.

Pathogenesis and Treatment of Shao Yang Disease Learned in the Shang Han Lun / 日本東洋医学雑誌

The Shaoyang lies next to the Interior of the Taiyang and to the Exterior of the Yangming, and is located in the half exterior and half interior position, containing both the parts and its physiological function which belong to the Gallbladder Channel of Foot-Shaoyang and the Triple Warmer Channel of Hand-Shaoyang. The Gallbladder Channel of Foot-Shaoyang controls the dispersing and discharging function of the vital energy (qi), and the Triple Warmer Channel of Hand-Shaoyang controls the function which distributes and transports the vital energy (qi), the fire and the water. When the wind-cold pathogen enters Shaoyang, anti-pathogenic vital-qi and exopathogen conflict each other, the distribution and the transport of the vital energy (qi), the fire and the water in the Triple Warmer Channel is obstructed due to the impairment of the dispersing and discharging function of the Gallbladder Channel of Foot-Shaoyang, the malfunction of Shaoyang pivots is then occured and results in the Shaoyang disease which is characteristic of the symptom complex such as bitter taste in the mouth, dryness of the throat, blurring of vision, alternate fever and chills, fullness in the chest and hypochondrium, hypochondria and anorexia, restless in mind, incessant vomiting, wiry and thready pulse and so on. This syndrome is treated by using Xiao chai fu tang which can harmonize Shaoyang. If various inproper treatments are given repeatedly to the Shaoyang disease, the syndrome to which Xiao chai hu tang must be given disappears, and a delirium as a deteriorated case appears newly, it is important to make clear what kind of inproper treatments were given, and the most appropriate treatment must be done in accordance with different present syndromes.

Influence of Fu Fang Xiao Chai Hu Tang on level of interleukin-2 and value of CD4~+/CD8~+ in mice bearing Ehrlish ascites carcinoma / 中国病理生理杂志

AIM:To investigate the effects of Fu Fang Xiao Chai Hu Tang(FFXCHT)on level of Interleukin-2 and value of CD4+/CD8+ in mice bearing Ehrlish ascites carcinoma(EAC).METHODS:The effects of FFXCHT on the EAC were observed and index of thymus and spleen were observed.The method of [3H]-TdR incorporation was used to measure the IL-2 level,and the value of CD4+/CD8+ was assayed by ELITE calibur flow cytometry.RESULTS:Compared with the model group,FFXCHT inhibited the growth of EAC(P

Differences between the Effects of Sho-saiko-to, Gorei-san and Toki-shakuyaku-san on the Sphincter of Oddi. An intraoperative cholangiomanometric study / 日本東洋医学雑誌

Female patients suffering from gallbladder stone disease were administered Sho-saiko-to (Xiao-Chai-Hu-Tang), Gorei-san (Wu-Ling-San) or Toki-shakuyaku-san (Dang-Gui-Shao-Yao-San) preoperatively, and were examined by cholangiomanometry during operation. Perfusion pressure was significantly elevated, when Sho-saiko-to or Gorei-san were administered, meaning that the pressure threshold of the sphincter of Oddi for volume load in the bile duct was lowered. This phenomenon tended to be more obvious in Gorei-san group, and will prevent duodenal fluid from transpapillary reflux. Parameters concerning the declining curve (T_1/2, T_1/4, T_1/5) showed a significantly rapid relaxation of the sphincter of Oddi only in Sho-saiko-to group, which will result in a prevention of stasis of bile. These modulating functions of Sho-saiko-to and Gorei-san for the sphincter of Oddi would be one of the main reasons why these formulas are used for hypochondriac fullness and distress or excessively accumulated intestinal fluid. Toki-shakuyaku-san showed no such effects on the sphincter of Oddi.

VALIDITY OF XIAO CHAI HU TANG IN THE RADIOTHERAPY FOR SQUAMOUS CARCINOMA OF THE ESOPHAGUS-A RANDOMIZED TRIAL ON 66 CASES / 中华放射肿瘤学杂志

Xiao Chai Hu Tang (XCHT), a blended decoction of multiple chinese medicinal herbs, was tested in combination with radiation therapy for moderate or advanced squamous carcinoma of the esophagus. A total of 66 such patients were randomized into a combined group (33 patients, XCHT + radiotherapy) and a radiation only group (33 patients, RT). Telecobalt irradiation, D T 40～70 Gy, was given to the RT group. Similar telecobalt, D T 40～68 Gy with concomitant XCHT, I dose po/day to a total of 28～50 doses, was given to the combined group. The grades Ⅰ+Ⅱresponse rate of the combined group were higher than that of the RT group. The 1-, 3-and 5 year survival rates of the combined group (69.7%, 40.9%, 25.0%) also surpassed those of the RT group (45.5%, 14.3%, 9.1%). There was statistical significance in the differences in the 1-and 3-years survival rates between the combined and RT groupsFurthermore, XCHT was able to alleviate some of the toxic reactions of radiotherapy for esophageal carcinoma.