Mechanism of Sijunzi Decoction in treatment of Alzheimer's disease based on UPLC-Q-TOF-MS, network pharmacology, and experimental verification / 中国中药杂志

The study identified the blood-entering components of Sijunzi Decoction after gavage administration in rats by UPLC-Q-TOF-MS/MS, and investigated the mechanism of Sijunzi Decoction in treating Alzheimer's disease by virtue of network pharmacology, molecular docking, and experimental verification. The blood-entering components of Sijunzi Decoction were identified based on the mass spectra and data from literature and databases. The potential targets of the above-mentioned blood-entering components in the treatment of Alzheimer's disease were searched against PharmMapper, OMIM, DisGeNET, GeneCards, and TTD. Next, STRING was employed to establish a protein-protein interaction(PPI) network. DAVID was used to perform the Gene Ontology(GO) annotation and the Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment. Cytoscape 3.9.0 was used to carry out visual analysis. AutoDock Vina and PyMOL were used for molecular docking of the blood-entering components with the potential targets. Finally, the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt) signaling pathway enriched by the KEGG analysis was selected for validation by animal experiments. The results showed that 17 blood-entering components were detected in the serum samples after administration. Among them, poricoic acid B, liquiritigenin, atractylenolide Ⅱ, atractylenolide Ⅲ, ginsenoside Rb_1, and glycyrrhizic acid were the key components of Sijunzi Decoction in treating Alzheimer's disease. HSP90AA1, PPARA, SRC, AR, and ESR1 were the main targets for Sijunzi Decoction to treat Alzheimer's disease. Molecular docking showed that the components bound well with the targets. Therefore, we hypothesized that the mechanism of Sijunzi Decoction in treating Alzheimer's disease may be associated with the PI3K/Akt, cancer treatment, and mitogen-activated protein kinase(MAPK) signaling pathways. The results of animal experiments showed that Sijunzi Decoction significantly attenuated the neuronal damage in the hippocampal dentate gyrus area, increased the neurons, and raised the ratios of p-Akt/Akt and p-PI3K/PI3K in the hippocampus of mice. In conclusion, Sijunzi Decoction may treat Alzheimer's disease by activating the PI3K/Akt signaling pathway. The findings of this study provide a reference for further studies about the mechanism of action and clinical application of Sijunzi Decoction.

Huangqi Sijunzi decoction for treating cancer-related fatigue in breast cancer patients: a randomized trial and network pharmacology study / 南方医科大学学报

OBJECTIVE@#To evaluate the clinical efficacy of Huangqi Sijunzi decoction (HQSJZD) for treating cancer-related fatigue (CRF) of spleen and stomach Qi deficiency type after chemotherapy in patients with breast cancer.@*METHODS@#A total of 94 breast cancer patients who developed CRF of spleen and stomach Qi deficiency type after chemotherapy were randomized into chemotherapy group (n=47) and traditional Chinese medicine (TCM) + chemotherapy group (n=47). The patients in chemotherapy group received the AC or EC regimen and non-drug interventions including psychological counseling, and those in TCM + chemotherapy group received oral administration of HQSJZD in addition to chemotherapy for 21 days as a treatment cycle, after which improvement of fatigue was assessed using Modified Piper Fatigue Scale. The active ingredients and targets of HQSJZD were screened using the TCM System Pharmacology Analysis Platform (TCMSP); the CRF- and breast cancer-related disease targets were retrieved based on data from the GeneCards, NCBI gene and OMIM databases to construct the component-target network and the protein-protein interaction (PPI) network. GO functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes KEGG pathway enrichment analysis of the target genes were performed to construct the component-disease-pathway-target biological network. The binding strength of the major drug ingredients and CRF key targets were predicted using AutoDock software.@*RESULTS@#The scores for somatic fatigue, emotional fatigue and cognitive fatigue, along with the overall fatigue score, showed more significant improvements in TCM+chemotherapy group than in chemotherapy group (P < 0.001), and the response rate reached 89.4% in the combined treatment group. We identified 250 targets for HQSJZD, 2653 CRF-related genes, 15 329 breast cancer-related genes and 161 prescription-disease intersected targets, from which topological analysis identified 66 potential key targets. GO and KEGG enrichment analyses predicted multiple pathways related with the disease. Molecular docking results suggested that the core ingredients of HQSJZD showed high affinities to the key targets AKT1, CASP3, IL6, JUN and VEGFA, among which AKT1 might be the most important target for HQSJZD to treat CRF.@*CONCLUSION@#HQSJZD can obviously improve CRF symptoms in breast cancer patients possibly by regulating multiple signaling pathways including PI3K-Akt through AKT1.

Effect of modified Sijunzi Decoction on myelosuppression in moderate- and advanced-stage lung cancer patients with Qi and Yin deficiency and investigation of the underlying mechanism / 中国基层医药

Objective:To investigate the effects of modified Sijunzi Decoction on myelosuppression in moderate- and advanced-stage lung cancer patients with Qi and Yin deficiency and analyze the underlying mechanism. Methods:A total of 100 moderate- and advanced-stage lung cancer patients with Qi and Yin deficiency who received treatment in Lishui Hospital of Traditional Chinese Medicine, China were included in this study. They were randomly assigned to receive chemotherapy with paclitaxel combined with cisplatin (control group, n = 50) or treatment with modified Sijunzi Decoction based on chemotherapy with paclitaxel combined with cisplatin (observation group, n = 50). Myelosuppression, traditional Chinese medicine symptom score, cellular immune function, serum levels of granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor, and the dosage of recombinant human granulocyte-colony stimulating factor. Results:After treatment, the incidence of leucopenia, thrombocytopenia, hemoglobinopenia and neutropenia in the observation group were 60% (30/50), 18% (9/50), 18% (9/50) and 62% (31/50), respectively, which were significantly lower than those in the control group [90% (45/50), 30% (15/50), 32% (16/50) and 92% (46/50), χ2 = 6.979, 7.025, 6.534, 6.134, all P < 0.001]. The complete remission rate in the observation group was significantly higher than that in the control group [30% (15/50) vs. 8% (4/50), χ2 = 9.018, P < 0.001]. The traditional Chinese medicine symptom score in the observation group was significantly lower than that in the control group ( t = 6.982, P < 0.05). CD 8+, CD 4+ and CD 3+ levels in the observation group were (25.16 ± 2.87)%, (38.76 ± 4.16)%, (48.83 ± 5.61)%, respectively, and they were (28. 89 ± 4.02)%, (34.10 ± 4.59)%, (41.12 ± 77)%, respectively in the control group. There were significant differences in CD 8+, CD 4+ and CD 3+ levels between the observation and control groups ( t = 6.392, 6.235, 5.983, all P < 0.05). The dosage of recombinant human granulocyte-colony stimulating factor in the observation group was significantly lower than that in the control group [(2 567.34 ± 308.25) μg vs. (3 917.82 ± 411.67) μg, t = 11.258, P < 0.05]. Serum levels of granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor were (25.53 ± 7.86) ng/L and (278.34 ± 28.74) ng/L, which were significantly higher than those in the control group [(21.30 ± 3.12) ng/L, (204.17 ± 11.98) ng/L, t = 9.136, 8.856, both P < 0.05]. Conclusion:Modified Sijunzi Decoction for the treatment of moderate- and advanced-stage lung cancer patients with Qi and Yin deficiency can decrease the incidence of myelosuppression possibly through increasing serum levels of granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor and improving the immune function.

Inhibition of Sijunzi Decoction extract on human breast cancer cells MDA-MB-468 / 中草药

Objective: To investigate the effect of Sijunzi Decoction extract (SDE) on the growth of human triple negative breast cancer (TNBC) cell line MDA-MB-468. Methods: MDA-MB-468 cells were treated with different concentrations of SDE. The effect of SDE on the proliferation and migration of the cells were detected by CCK-8 assay and the cell wound healing assay. The colony formation assay was performed to analyze the effect on the ability of colony formation of the cells with SDE. Hoechst 33342 staining technique and flow cytometry (FCM) were used to detect apoptosis and cell cycle of the cells. Western blotting was used to detect the expression levels of STAT3, which was related with the proliferation and apoptosis of cells. Results: Compared with the control group, SDE had a certain inhibitory effect on MDA-MB-468 cells (P < 0.05), and it was dependent on the concentration and time. Cloning formation experiments showed that SDE inhibited the clonality of the cells. The cell migration experiment showed that the wound healing ability of the cells could be weakened by the extract with the medium and high dosage (P < 0.001). The results of FCM showed that the apoptosis rate of all SDE dosage increased gradually in a dose-dependent manner. And SDE with the medium and high dosage induced apoptosis of the cells significantly (P < 0.01 and 0.001). Cell cycle was affected by SDE with the obvious reduction of the cells in G2 phase (P < 0.01). The results of Western blotting showed that the expression level of STAT3 was decreased significantly. Conclusion: SDE inhibited the proliferation and clonal formation of MDA-MB-468 cells, inhibited migration, promoted apoptosis and decreased the cells of G2 phase. which may be related to the regulation of STAT3 pathway.

Action mechanism of Sijunzi Decoction in treatment of type 2 diabetes mellitus based on network pharmacology / 中草药

Objective: The main active components and targets of Sijunzi Decoction for type 2 diabetes mellitus (T2DM) treatment were predicted by network pharmacology, and the potential mechanism of multi-component-multi-target-multi-pathway was discussed, and INSR and PI3K in the AMPK signal pathway were verified in animal experiment. Methods: Based on TCM system pharmacology database and analysis platform (TCMSP), literature mining and previous studies of our research group, the chemical components of Sijunzi decoction and its four herbs Codonopsis pilosula, Atractylodes macrocephala, Poria cocos, Glycyrrhiza uralensis were screened. Three conditions of oral absorption rate (OB), drug-like (DL), half-life (HL) were used to screen the active components of the drug; The targets of active components were predicted through the Swiss Target Prediction database; TTD, Drupe and DisGNET databases were used to screen the targets of T2DM. After mapping the component target and disease target, the interaction network of the target proteins of the active components was constructed by using the software of Cytoscape 3.2.1. Through topological analysis of the network, the nodes with degree of freedom ≥ average degree of freedom were screened out, and the core target network of core active ingredient was obtained, while using the String database to draw core-target protein-protein interaction (PPI) networks, using DAVID database for GO analysis and KEGG analysis of core target genes to construct core active components-core target-metabolism Path network diagram to explore the potential mechanism of Sijunzi Decoction against T2DM. The system docking site was used for molecular docking of the top 5 components and the top 3 proteins. Further, animal experiments were used to verify. SD rats were fed with high-sugar high-fat diet combined with low-dose streptozotocin (STZ) to induce T2DM model, and administrated with 5.65 g/kg Sijunzi Decoction for 28 d, and the levels of blood glucose (FBG) and oral glucose tolerance (OGTT) of each group of mice were determinated. The InsR, PI3K mRNA expression in AMPK signaling pathway was detected by RT-PCR. Results: A total of 113 chemical components were selected from Sijunzi Decoction, involving 47 targets for the treatment of T2DM. Twenty-two core components and 27 core targets were screened according to node degree of freedom ≥ average degree of freedom. The GO analysis results showed that it involved seven biological processes such as blood glucose homeostasis, positive regulation of adipose tissue development, four molecular functions including steroid hormone receptor activation and drug binding, and cell composition including the plasma membrane and nuclear chromatin. The results of KEGG analysis showed that it might treat diabetes through 14 signaling pathways, such as AMPK signaling pathway, PPAR signaling pathway and insulin resistance. A total of 60% of the molecules had intense binding activity and 40% had stronger binding activity. The results of animal experiments showed that Sijunzi Decoction could significantly improve OGTT (P < 0.001), and decrease FBG (P < 0.01) in T2DM rats, and significantly increase the expression of INSR mRNA (P < 0.001) and PI3K mRNA (P < 0.001). Some of the predicted results of network pharmacology were verified. Conclusion: This study reflects that Sijunzi Decoction can treat type 2 diabetes mellitus through multi-target and multi-channel, which lays a foundation for the future study of molecular mechanism.

Optimization of water extracting and refining procession of Sijunzi Decoction Granules by orthogonal design and pharmacodynamics test / 中草药

Objective: To optimize the water extracting and refining procession of Sijunzi Decoction Granules (SDG). Methods: The orthogonal test method was used to study the four factors including the soak time, amount of water added, extraction time and frequency by taking the dry extract yield of the medicinal materials and contents of ginsenoside Rg1, Re, Rb1, glycyrrhizic acid, and liquiritin as indicators to optimize the water extracting process of SDG. To optimize the alcohol precipitation process of SDG, the factors including the concentration of the medicinal materials, alcohol content, and time of alcohol precipitation were investigated. The extracts before and after alcohol precipitation were compared by intervening spleen deficiency syndrome pharmacodynamics experiment. Results: The best water extracting procession of SDG was soaked for 60 min with 10 times of water, decocted three times, 30 min for each time. The optimal water extraction by alcohol sedimentation process was to concentrate the filtrate of water extraction to 1 mL, which was equivalent to 0.5 g of the original medicinal materials, with 80% alcohol content and 12 h alcohol precipitation time. Compared with the model group, the activity of salivary amylase and the conent of serum gastrin in the water extracting group and water extracting by alcohol sedimentation group of SDG were significantly increased and could improve the absorption function of xylose in small intestine of rats with spleen deficiency syndrome (P 0.05). Conclusion: The alcohol precipitation process is not suitable for refining of SDG. So the water extracting process is finally selected as the best extraction process of SDG.

Effect of Sijunzi Decoction on regulation of Aβ-related proteins across blood-brain barrier / 中国中药杂志

According to traditional Chinese medicine, "spleen transport" is closely related to the metabolism of substance and energy. Studies have shown that Alzheimer's disease(AD) is a disease related to glucose and lipid metabolism and energy metabolism. The traditional Chinese medicine Jiangpi Recipe can improve the learning ability and memory of AD animal model. Sijunzi Decoction originated from Taiping Huimin Hefang Prescription is the basic prescription for strengthening and nourishing the spleen, with the effects of nourishing Qi and strengthening the spleen. In this experiment, human brain microvascular endothelial cells(HBMEC) and Sijunzi Decoction water extract(0.25, 0.5, 1 mg·L~(-1)) were pre-incubated for 2 h, and then Aβ_(25-35) oligomers(final concentration 40 μmol·L~(-1)) was added for co-culture for 22 hours. The effect of Sijunzi Decoction on the activity of Aβ_(25-35) oligomer injured cells and the expression of related proteins were investigated. Q-TOF-LC-MS was used first for principal component analysis of Sijunzi Decoction water extract. Then MTT assay was used to investigate the effect of Sijunzi Decoction water extract on the proliferation of HBMEC cells. Real-time fluorescence quantitative PCR(RT-qPCR) was employed to detect the mRNA expression of GLUT1, RAGE, and LRP1. The expression of Aβ-related proteins across blood-brain barrier(RAGE, LRP1) was detected by Western blot. The results showed that 40 μmol·L~(-1) Aβ_(25-35) oligomers could induce endothelial cell damage, reduce cell survival, increase expression of RAGE mRNA and RAGE protein, and reduce expression of GLUT1 mRNA, LRP1 mRNA, and LRP1 protein. Sijunzi Decoction water extract could reduce the Aβ_(25-35) oligomer-induced cytotoxicity of HBMEC, decrease the expression of RAGE mRNA and RAGE protein, and increase the expression of GLUT1 mRNA, LRP1 mRNA and LRP1 protein. The results indicated that Sijunzi Decoction could reduce the injury of HBMEC cells induced by Aβ_(25-35) oligomer, and regulate the transport-related proteins GLUT1, RAGE and LRP1, which might be the mechanism of regulating Aβ_(25-35) transport across the blood-brain barrier.

Chinmedomics facilitated quality-marker discovery of Sijunzi decoction to treat spleen qi deficiency syndrome / 医学前沿

Sijunzi decoction (SJZD) is a Chinese classical formula to treat spleen qi deficiency syndrome (SQDS) and has been widely used for thousands of years. However, the quality control (QC) standards of SJZD are insufficient. Chinmedomics has been designed to discover and verify bioactive compounds of a variety of formula rapidly. In this study, we used Chinmedomics to evaluate the SJZD's efficacy against SQDS to discover the potential quality-markers (q-markers) for QC. A total of 56 compounds in SJZD were characterized in vitro, and 23 compounds were discovered in vivo. A total of 58 biomarkers were related to SQDS, and SJZD can adjust a large proportion of marker metabolites to normal level and then regulate the metabolic profile to the health status. A total of 10 constituents were absorbed as effective ingredients that were associated with overall efficacy. We preliminarily determined malonyl-ginsenoside Rb2 and ginsenoside Ro as the q-markers of ginseng; dehydrotumulosic acid and dihydroxy lanostene-triene-21-acid as the q-markers of poria; glycyrrhizic acid, isoglabrolide, and glycyrrhetnic acid as the q-markers of licorice; and 2-atractylenolide as the q-marker of macrocephala. According to the discovery of the SJZD q-markers, we can establish the quality standard that is related to efficacy.

Study on the Improvement Effects of Sijunzi Decoction on Chronic Kidney Disease-protein Energy Wasting Model Mice and Its Mecranism / 中国药房

OBJECTIVE：To study the improvement effects of Sijunzi decoction on skeletal muscle atrophy in chronic kidney disease-protein energy wasting （CKD-PEW）model mice ，and to explore its potential mechanism . METHODS ：A total of 80 mice were randomly divided into sham operation group （n＝10）and modeling group （n＝70）. CKD-PEW model was established by removing 5/6 kidneys and giving a low-protein diet （4％ casein）for mice in modeling group. Totally 50 modeled mice were randomly divided into model group ，Sijunzi decoction low-dose ，medium-dose and high-dose groups [ 2.34，4.68，9.36 g/（kg·d）， by crude drug] ，Compound α-ketoacid tablets group [positive control ，1 g/（kg·d）]，with 10 mice in each group. Administration groups were given relevant medicine intragastrically ；sham operation group and model group were given constant volume of normal saline intragastrically ，once a day ，for consecutive 14 d. After last medication ，body weight of mice and wet mass of left tibialis anterior muscle （TA）were weighed ；TA cross-sectional area was determined ；protein synthesis and decomposition metabolism ability of TA were detected ；mRNA expressions of Bcl-2，Bax and Caspase-3 in TA were detected by Real-time PCR ；protein expressions of muscular dystrophin Fbox- 1 （Atrogin-1），myofloin-1 （MuRF-1），Rho-related protein kinase 1 （ROCK1）， phosphorylated PTEN （p-PTEN），phosphatidylinositol-3-kinase（PI3K）and phosphorylated Akt （p-Akt）in TA were detected by Western blotting. RESULTS ：Compared with the sham operation group ，the body weight ，TA wet weight ，protein synthesis metabolism ability of TA as well as protein expressions of PI 3K and p-Akt were decreased significantly in model group （P＜0.05）； the cross-sectional area of TA decreased significantly （P＜0.05）；protein decomposition metabolism ability of TA ，Bax/Bcl-2 ratio， Caspase-3 mRNA expression ，protein expressions of Atrogin- 1，MuRF-1，ROCK1 and p-PTEN were increased significantly （P＜ 0.05）. Compared with model group ，above indexes of mice were all improved significantly in Sijunzi decoction medium-dose ， high-dose groups and Compound α-ketoacid tablets group （P＜0.05）. CONCLUSIONS ：Sijunzi decoction can increase the body weight of CKD-PEW model mice and alleviate the skeletal atrophy ；the mechanism may be related to regulating ROCK 1/PTEN/Akt signaling pathway activity ，inhibiting the expression of Atrogin- 1 and MuRF- 1.

Mechanism and experimental verification of Sijunzi Decoction in treatment of ulcerative colitis based on network pharmacology / 中国中药杂志

To explore the mechanism of Sijunzi Decoction in the treatment of ulcerative colitis(UC) based on network pharmacology. The active components and corresponding targets of Sijunzi Decoction were extracted with Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), and the targets were standardized with the help of Uniprot database. The related targets of UC were obtained through GeneCards database and Disgenet database, and the intersection targets of drugs and diseases were screened by R language. The visual regulation network of "active ingredient-disease target" of Sijunzi Decoction was constructed by Cytoscape software, and the protein-protein interaction network was constructed by STRING database. The functional enrichment analysis of gene ontology(GO) and the enrichment analysis of Kyoto encyclopedia of genes and genomes(KEGG) pathway were carried out on Bioconductor platform, and some of the targets were verified by animal experiments. Through database analysis, a total of 135 active components of Sijunzi Decoction, 114 predicted targets and 80 common targets with UC were obtained. The core target proteins included interleukin 6(IL-6), caspase-3(CASP3), vascular endothelial growth factor A(VEGFA), epidermal growth factor receptor(EGFR) and so on. GO functional enrichment analysis involved 102 items, which mainly affected transcription factor activity, enzyme activity, receptor activity and biochemical process regulation. KEGG pathway enrichment analysis showed that 120 items were involved in human cytomegalovirus infection, cancer, apoptosis, inflammation and other pathways. Mouse experiments showed that Sijunzi Decoction could down-regulate the expression of target proteins IL-6 and caspase-3 and inhibit intestinal epithelial cell apoptosis. The treatment of UC with Sijunzi Decoction is the result of the interaction among multi-components, multi-targets and multi-pathways. It is proved by experiments that Sijunzi Decoction may play an effective role by regulating the expression of IL-6 and caspase-3, and getting involved in apoptosis, inflammation and other pathways.

Anti-tumor and immune-modulating effect of decoction in mice bearing hepatoma H22 tumor / 南方医科大学学报

OBJECTIVE@#To investigate the antitumor activity of decoction and study its liver and kidney toxicity and its effect on the immune system in a tumor-bearing mouse model.@*METHODS@#Hepatoma H22 tumor-bearing mouse models were randomized into model group, cyclophosphamide (CTX) group, and low-, moderate-, and high-dose decoction groups (JW-L, JW-M, and JW-H groups, respectively). The antitumor activity of decoction was assessed by calculating the tumor inhibition rate and pathological observation of the tumor tissues. Immunohistochemistry was used to detect the expressions of Bax, Bcl-2, Bax/Bcl-2 and caspase-3 in the tumors. The liver and kidney toxicity of decoction was analyzed by evaluating the biochemical indicators of liver and kidney functions. The immune function of the tumor-bearing mice were assessed by calculating the immune organ index, testing peripheral blood routines, and detection of serum IL-2 and TNF-α levels using enzyme-linked immunosorbent assay.@*RESULTS@#Compared with that in the model group, the tumor mass in CTX, JW-M and JW-H groups were all significantly reduced ( < 0.05) with cell rupture and necrosis in the tumors. Immunohistochemistry revealed obviously up-regulated expressions of Bax and caspase-3 and down- regulated expression of Bcl-2 protein with an increased Bax/Bcl-2 ratio in CTX, JW-M and JW-H groups. Treatment with decoction significantly reduced Cr, BUN, AST and ALT levels, improved the immune organ index, increased peripheral blood leukocytes, erythrocytes and hemoglobin levels, and up-regulated the levels of TNF-α and IL-2 in the tumor-bearing mice. These changes were especially significant in JW-H group when compared with the parameters in the model group ( < 0.01).@*CONCLUSIONS@# decoction has a strong anti-tumor activity and can improve the liver and kidney functions of tumor-bearing mice. Its anti-tumor effect may be attributed to the up-regulation of Bax, caspase-3, TNF-α and IL-2 levels and the down-regulation of Bcl-2 expression as well as the enhancement of the non-specific immune function.

Professor Liu Guangxian's experience in treatment of cholangiocarcinoma by Yinchenhao decoction combined with Xiaoshi Fanshi powder / 中国中西医结合急救杂志

Professor Liu Guangxian used traditional Chinese medicine (TCM) for the treatment of patient with cholangiocarcinoma after surgery achieved unique effect. On the one hand, the classical prescriptions Yinchenhao decoction and Xiaoshi Fanshi powder combined with processed pangolin scales and cremastrae pseudobulbus were used to promote diuresis and clear jaundice, eliminate phlegm and resolve static blood, and soften hard mass and remove stagnation, in order to eliminate the pathogens; on the other hand, Sijunzi decoction was used as the main prescription to invigorate the spleen and benefit qi to strengthen vital qi, in order to protect the spleen and stomach and strengthen the body resistance. After more than 3 months of treatment for a patient with cholangiocarcinoma, the patient had significant improvement in symptoms, signs, imaging findings, and laboratory results.

Clinical research of Huangqi-Sijunzi decoction combined with conventional western medicine for gestational diabetes mellitus / 国际中医中药杂志

Objective To evaluate the efficacy of Huangqi-Sijunzi decoction combined with conventional western medicine in treatment of gestational diabetes mellitus(GDM). Methods A total of 103 patients with GDM who met the inclusion criteria were randomly divided into control group and treatment group (52 in each group).The control group was treated with GDM standardized treatment, and the treatment group was addedHuangqi-Sijunzi decoction on the basis of the control group. Both groups were treated for 14 days. The ELISA was used to detect serum CRP and adiponectin, and Mg2+ was detected by automatic biochemical analyzer. Pregnancy outcome observed and recorded, and the adverse reaction was recorded. Results After the treatment, the levels of FPG, 2 hPG and HbAlc in the treatment group were significantly lower than those in the control group (t=7.352,17.962, 9.713, P<0.01); and the level of CRP in the treatment group was significantly lower than that in the control group. While the Mg2+ and adiponectin were significantly higher than those in the control group (t=9.275, 4.206,6.021, P<0.01). After the treatment, the incidence of abortion, fetal macrosomia, cesarean section and polyhydramnios in the treatment group were significantly lower than that in the control group (χ2=5.358, 7.262, 3.992, 6.116, P<0.05).Conclusions The Huangqi-Sijunzi decoction combined with conventional western medicine can improve the blood sugar level of GDM patients, reduce the incidence of adverse pregnancy outcomes, and improve the clinical efficacy.

Research progress on intestinal immunoregulation and mechanism of Sijunzi Decoction polysaccharide / 中草药

Sijunzi Decoction polysaccharide (SJZDP) is the active component contributing to the function of intestinal immunoregulation, which is the highest content in Sijunzi Decoction. SJZDP can activate immunological response in peyer’s patch, mesenteric lymph nodes, intestinal epithelial cells and intestinal intraepithelial lymphocytes, but the mechanism is unknown. The reported mechanisms of SJZDP’s intestinal immunoregulation activity are related to its regulation of intestinal flora and polyamine signaling pathway. This review is to give a comprehensive summary of information regarding the intestinal immunoregulation of SJZDP and mechanism to help us take the action for reasonable clinical utilization and further researches.

Content Comparison of Total Saponins and Total Polysaccharides between Formula Granules and Traditional Decoction of Sijunzi Decoction / 中国药师

Objective: To compare the content of total saponins and total polysaccharides between formula granule and traditional decoction of Sijunzi decoction.Methods: UV spectrophotometry was used to determine the content of total saponins and total polysaccharides in formula granule and traditional decoction of Sijunzi decoction respectively at the wavelength of 540 nm and 488 nm.Results: The absorbance of ginsenoside Re had a good linear correlation with the concentration within the range of 10.909-65.454 μg · ml-1 (r=0.999 7), and the average recovery was 98.49%(RSD=0.85%, n=6);the absorbance of D-anhydrous glucose had a good linear correlation with the concentration within the range of 2.160-12.960 μg · ml-1 (r=0.999 7), and the average recovery was 99.46%(RSD=0.73%, n=6).The contents of total saponins from 3 batches of formula granule were slightly higher than those from traditional decoction,and that of total polysaccharides in formula granule was slightly lower than that in traditional decoction,and there was no significant difference between the two groups (P>0.05)Conclusion: The difference of material basis between formula granule and traditional decoction of Sijunzi decoction is small, and formula granule is more feasible for clinical application.

Analysis of Medication Principles of Professor Liu Fengbin for Treatment of Irritable Bowel Syndrome / 广州中医药大学学报

In this study,we collected the prescriptions of Professor Liu Fengbin used for the out-patients with irritable bowel syndrome(IBS),counted the usage frequency of the herbs and core-combination herbs in the prescriptions,analyzed the medication principles of Professor Liu Fengbin,and mined the new recipes for IBS by the methods of association rule mining and complex system entropy clustering presented in the Traditional Chinese Medicine Inheritance Support System.The results showed that Professor Liu is experienced in treating IBS based on liver-spleen differentiation,mainly applying the therapies of invigorating spleen and replenishing qi,soothing liver and regulating qi,also using the methods of resolving dampness,alleviating depression,relieving pain and activating blood,and prescribing the basic recipe of Chai Shao Sijunzi Decoction.The medication principles of Professor Liu Fengbin for the treatment of IBS will be beneficial to the further exploration of the syndrome pattern distribution of IBS and new recipes for IBS.

Effects of traditional herbal formulae on human CYP450 isozymes / 中国结合医学杂志

<p><b>OBJECTIVE</b>To assess the effects of traditional herbal formulae Sijunzi Decoction (, Sagunja-tang, SJZD), Siwu Decoction (, Samul-tang, SWD), Bawu Decoction (, Palmul-tang, BWD) and Shiquan Dabu Decoction (, Sipjeondaebo-tang, SDD) on the activities of human cytochrome P450 (CYP450), a drug-metabolizing enzyme.</p><p><b>METHODS</b>Herbal formula water extracts were filtered and lyophilized after the powder extracts were dissolved in distilled water. The activities of major human CYP450 isozymes (CYP3A4, CYP2C19, CYP2D6 and CYP2E1) were measured using in vitro fluorescence-based enzyme assays. The inhibitory effects of the herbal formulas on the activities of CYP450 were characterized as half maximal inhibition concentration (IC) values.</p><p><b>RESULTS</b>All the tested herbal formulae inhibited CYP2C19 activity (IC: SJZD, 83.28 μg/mL; SWD, 235.54 μg/mL; BWD, 166.82 μg/mL; SDD, 178.19 μg/mL); SJZD (IC= 196.46 μg/mL), SWD (IC= 333.42 μg/mL) and SDD (IC= 163.42 μg/mL) inhibited CYP2E1-mediated metabolism; whereas BWD exhibited comparatively weak inhibition of CYP2E1 (IC= 501.78 μg/mL). None of the four herbal formulas significantly affected CYP3A4 or CYP2D6.</p><p><b>CONCLUSIONS</b>These results suggest that SJZD, SWD, BWD and SDD could potentially inhibit the metabolism of co-administered synthetic drugs whose primary route of elimination is via CYP2C19. In addition, clinically relevant pharmacokinetic interactions could occur when SJZD, SWD or SDD is co-administered with drugs metabolized by CYP2E1. Our findings provide information for the safety and effective clinical use of these four classic herbal formulas.</p>

Research progress on chemical constituents and pharmacological effects of Sijunzi Decoction / 中草药

Sijunzi Decoction (SJZD) is a classical prescription for curing spleen deficiency in traditional Chinese medicine, consisting of Ginseng Radix et Rhizoma, Atractylodes Macrocephalae Rhizoma, Poria, and Glycyrrhizae Radix et Rhizoma Praeparate cum Melle. Modern pharmacological experiments have proved that sponin, flavonoid, and polysaccharide are the most active ingredients in SJZD. SJZD has been used to regulate gastrointestinal function and enhance immunity ability. Effects on tumor cell apoptosis and anti-aging have also been reported. But few report on SJZD polysaccharide and its therapeutic basis research was found. This review is to give a comprehensive summary of information regarding the chemical constituents and pharmacological effects of SJZD to help us take the action for reasonable clinical utilization and further researches of SJZD.

Effect of cerebrospinal fluid contained Sijunzi Decoction on function of colon mucosa lymphocytes of ulcerative colitis in vitro / 中国免疫学杂志

Objective:To explore the effects of cerebrospinal fluid contained Sijunzi Decoction on function of colon mucosa lymphocytes of ulcerative colitis in vitro. Methods: Prepared the rat cerebrospinal fluid contained Sijunzi Decoction or Mesalamine. Collected colon mucosa of the 12 healthy ( as normal group ) and 18 ulcerative colitis, then isolated and obtained lymphocytes from these samples. The lymphocytes were divided into pathological group, IL-12 group, cerebrospinal fluid group cerebrospinal fluid contained Sijunzi Decoction group, cerebrospinal fluid contained Mesalamine group. After exposing to various treatment,the proliferative capacity was measured by CCK-8,the cell cycle and the ratio of CD4+T was analyzed by flow cytometry (FCM), the content of IL-1, IL-6, TNF-α was detected by ELISA. The expression of IL-2 were detected by Western blot analysis. Results:Compared the cerebrospinal fluid contained Sijunzi Decoction group with the IL-12 group or cerebrospinal fluid group,the proliferative capacity and the percentage of CD4+T was decreased, the cells significantly arrested at G0/G1 phase, the secretory capability of IL-1, IL-6, TNF-α were obviously reduced; the expression of IL-2 was also significantly down-regulated. Conclusion:The cerebrospinal fluid contained Sijunzi Decoction could decrease the function of colon mucosa lymphocytes of ulcerative colitis,the mechanism involved in may be Sijunzi Decoction regulating the secretory capability of IL-1,IL-6 and TNF-α.

Observation of the clinical effects of modified treatment with sijunzi decoction and shenqi pills for primary hypothyroidism / 中国基层医药

Objective To observe the clinical curative effect of sijunzi decoction composite with shenqi pills in the treatment of spleen and kidney yang deficiency syndrome in patients with primary hypothyroidism(hypothyroid-ism).Methods 62 spleen kidney yang deficiency patients with hypothyroidism were randomly divided into 30 cases in the control group and 32 cases in the treatment group.Patients in the control group were given L-thyroxine tablets orally,once a day;patients in the treatment group were given sijunzi decoction combined with shenqi pills for decoc-tion,daily 1 agent,3 times a day orally,on the basis of the control treatment group.Two groups treatment cycle were 4 months,and the clinical efficacy of the two groups were observed.Results The treatment group total effective rate was 96.9%,which was higher than that in the control group 80.0%(χ2 =4.402,P<0.05);before and after treat-ment,TCMsyndrome scores were significantly decreased in the two groups (t=21.40,25.40,all P<0.01)and treatment group decreased more significantly(t=4.30,P<0.01 ).Before and after treatment,TSH,FT3,FT4 in the two groups were significantly improved (control group:t=5.31,1.14,4.13,treatment group:t=6.27,1.85,6.08,all P<0.01),and the degree of improvement in treatment group was more obvious compared with the control group (t=1.33,0.67,278,all P<0.05).Conclusion Sijunzi decoction and shenqi pills can significantly improve the clinical symptoms of primary hypothyroidism of spleen-kidney yang deficiency type in addition to thyroid function and blood lipid,indicating that this method is capable of achieving satisfactory clinical effects in treating primary hypothyroidism of spleen-kidney yang deficiency type.