Combination of ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry and network pharmacology to reveal the key effective compounds and mechanism of Shengxian decoction for ameliorating doxorubicin cardiotoxicity.

Shengxian decoction, a traditional Chinese medicinal prescription, has been shown to alleviate doxorubicin-induced chronic heart failure. This study established an ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry method to separate and characterize the complex chemical compositions of Shengxian decoction, and the absorbed compounds in the bio-samples of the cardiotoxicity rats with chronic heart failure after its oral delivery. Note that 116 chemical compounds were identified from Shengxian decoction in vitro, 81 more than previously detected. Based on the three-dimensional data of these compounds, 28 absorbed compounds were confirmed in vivo. Network pharmacology and molecular docking experiments indicated that timosaponin B-II, timosaponin A-III, gitogenin, and 7,8-didehydrocimigenol were recognized as the key effective compounds to exert effects against doxorubicin cardiotoxicity by acting on targets such as caspase 3, cyclin-dependent kinase 1, cyclin-dependent kinase 4, receptor tyrosine-protein kinase erbB-2, and mitogen-activated protein kinase 1 in p53 and phosphatidylinositol 3-kinase-Akt signaling pathways. This study developed the understanding of the composition of Shengxian decoction for the treatment of doxorubicin cardiotoxicity, as well as a feasible strategy to elucidate the effective constituents in traditional Chinese medicines.

Exploring the effective compounds and potential mechanisms of Shengxian Decoction against coronary heart disease by UPLC-Q-TOF/MS and network pharmacology analysis.

As a well-known classical Chinese medicine prescription, Shengxian Decoction (SXD) has been applied for a century to treat cardiovascular diseases, especially coronary heart disease (CHD), but the potentially effective compounds and underlying mechanisms remain unclear. With ultra-performance liquid chromatography-quadrupole-time of flight-mass spectrometry (UPLC-Q-TOF/MS) and network pharmacology analysis, the potential effective compounds of SXD and their pharmacological mechanisms against CHD were identified and revealed. 57 effective compounds with favorable pharmacokinetic characteristics and biological activities were screened through UPLC-Q-TOF/MS analysis, database and literature mining, interacting with 96 CHD-related targets to support potential synergistic therapeutic actions. Systematic analysis of the PPI network and microarray data further revealed six core targets, including TNF, IL-1ß, IL-6, TP53, VEGFA and PTGS2, which were mainly involved in fluid shear stress and atherosclerosis, lipid and atherosclerosis, PI3K-Akt signaling pathway et al. Moreover, the proposed contribution indexes of effective compounds indicated these compounds, including isoferulic acid, quercetin, calycosin, ferulic acid, kaempferol, calycosin 7-O-glycoside, formononetin, astragaloside IV and saikosaponin D, as the core compounds of SXD. The molecular docking results confirmed that those core compound-target pairs exhibited strong binding energy. Furthermore, we validated that SXD significantly alleviated myocardial tissue injury in CHD rats and reversed H/R-induced decreases in H9c2 cell viability by attenuating the production of TNF, IL-6 and IL-1ß, and reducing cardiomyocyte apoptosis via down-regulating the TP53, caspase3 and cytochrome C mRNA expression levels as well as caspase3, caspase9 and cytochrome C protein expression levels according to RT-qPCR and Western blot results. Our findings explained the pharmacological mechanisms underlying the effectiveness of SXD in the treatment of CHD, and laid a foundation for future basic and clinical research of SXD.

Shengxian decoction improves lung function in rats with bleomycin-induced idiopathic pulmonary fibrosis through the inhibition of PANoptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Shengxian decoction (SXD) is a classic Chinese medicinal formula that can effectively improve clinical symptoms and quality of life and delay disease progression in idiopathic pulmonary fibrosis (IPF) patients; however, the underlying mechanisms remain unclear. AIM OF THE STUDY: This study aimed to observe PANoptosis in bleomycin-induced IPF and to assess the efficacy and mechanism of action of SXD in the treatment of IPF. MATERIALS AND METHODS: Fifty SD rats were randomly divided into the sham, IPF, IPF + pirfenidone (PFD), IPF + SXD-medium dose (SXD-M), and IPF + SXD-low dose (SXD-L) groups. Lung function analysis and microcomputed tomography imaging of the rats with IPF treated with oral pirfenidone or oral SXD for 28 days were performed. Hematoxylin and eosin (HE) staining and Masson's trichrome staining were used to observe pathological lung damage. Enzyme-linked immunosorbent assays (ELISAs) were used to determine the serum levels of IL-1ß, IL-18, TNF-α, and IFN-γ. Pyroptosis, apoptosis, and necroptosis were assessed using TUNEL, TUNEL/caspase-1, and PI fluorescence staining, respectively. GSDMD, caspase-3, and MLKL were examined by immunohistochemistry. The expression of fibrin-, ZBP1-, pyroptosis-, apoptosis-, and necroptosis-related proteins in the lung tissue was determined by western blotting. RESULTS: SXD normalized lung function in rats with bleomycin-induced IPF and reduced serum inflammatory factor levels and lung tissue fibrosis. The underlying mechanism of action involves the inhibition of pyroptosis pathway proteins, such as NLRP3, caspase-1, cleaved caspase-1, and GSDMD; apoptotic pathway proteins, such as Bax, Bcl-2, cleaved caspase-3, and caspase-3; and necroptosis pathway proteins, such as RIPK1, RIPK3, p-MLKL and MLKL. These pathways are modulated by the PANoptosis initiator ZBP1. Notably, the efficacy of SXD is concentration dependent, with a medium dose exhibiting superior effectiveness compared to a low dose. CONCLUSION: Bleomycin induced PANoptosis in the lung tissue of rats with IPF. Additionally, SXD effectively delayed or reversed the early pathological changes in bleomycin-induced pulmonary fibrosis by inhibiting PANoptosis.

[Retracted] Shengxian decoction decreases doxorubicin­induced cardiac apoptosis by regulating the TREM1/NF­κB signaling pathway.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the majority of the Histone H3 control western blotting data featured in Figs. 2D and 4C were strikingly similar to data appearing in different form in other articles written by different authors at different research institutes. Owing to the fact that the contentious data in the above article had already been published elsewhere prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 23: 219, 2021; DOI: 10.3892/mmr.2021.11858].

Exploration of the Mechanism of Shengxian Decoction Against Chronic Obstructive Pulmonary Disease Based on Network Pharmacology and Experimental Verification.

Shengxian decoction (SXT) is clinically used in chronic obstructive pulmonary disease (COPD) treatment. This study aimed to explore the mechanism and target genes of SXT acting on COPD. Differentially expressed genes (DEGs) between COPD and controls were identified and then performed enrichment analysis. The effective active compounds and corresponding target genes were obtained from the traditional Chinese medicine systems pharmacology database. We also compiled COPD related genes from the GeneCards database. Through the protein-protein interaction (PPI) network and least absolute shrinkage and selection operator (LASSO) regression was performed to identify key genes. Molecular docking was used for docking of key genes and compounds. The expression of key genes was detected by quantitative real-time PCR in COPD patients and bronchial epithelial cells stimulated with cigarette stroke extract (CSE). We identified 1,458 intersected DEGs from GSE47460 and GSE57148 datasets. Compared with intersected DEGs, we obtained 33 SXT target COPD-related genes. PI3K-Akt signaling pathway, MAPK signaling pathway, and focal adhesion were enriched by these 33 genes, as well as intersected DEGs. According to LASSO regression, there were 12 genes considered as signature genes. Then we constructed active compounds and corresponding six target genes. Finally, HIF1A and IL1B were selected as key genes by combining PPI network. HIF1A and IL1B were all upregulated expression in COPD and CSE stimulated cells and recovered in SXT treated CSE stimulated cells. This study provides a scientific basis for the identification of active compounds and target genes of SXT in the treatment of COPD.

Shengxian decoction protects against chronic heart failure in a rat model via energy regulation mechanisms.

BACKGROUND: Chronic heart failure (CHF) is actually a disease caused by an imbalanced energy metabolism between myocardial energy demand and supply, ultimately resulting in abnormal myocardial cell structure and function. Energy metabolism imbalance plays an important role in the pathological process of chronic heart failure (CHF). Improving myocardial energy metabolism is a new strategy for the treatment of CHF. Shengxian decoction (SXT), a well-known traditional Chinese medicine (TCM) formula, has good therapeutic effects on the cardiovascular system. However, the effects of SXT on the energy metabolism of CHF is unclear. In this study, we probed the regulating effects of SXT on energy metabolism in CHF rats using various research methods. METHODS: High-performance liquid chromatography (HPLC) analysis was used to perform quality control of SXT preparations. Then, SD rats were randomly assigned into 6 groups: sham, model, positive control (trimetazidine) and high-, middle-, and low-dose SXT groups. Specific reagent kits were used to detect the expression levels of ALT and AST in rats' serum. Echocardiography was used to evaluate cardiac function. H&E, Masson and TUNEL staining were performed to examine myocardial structure and myocardial apoptosis. Colorimetry was used to determine myocardial ATP levels in experimental rats. Transmission electron microscopy was used to observe the ultrastructure of myocardial mitochondria. ELISA was used to estimate CK, cTnI, and NT-proBNP levels, and LA、FFA、MDA、SOD levels. Finally, Western blotting was used to examine the protein expression of CPT-1, GLUT4, AMPK, p-AMPK, PGC-1α, NRF1, mtTFA and ATP5D in the myocardium. RESULTS: HPLC showed that our SXT preparation method was feasible. The results of ALT and AST tests indicate that SXT has no side effect on the liver function of rats. Treatment with SXT improved cardiac function and ventricular remodelling and inhibited cardiomyocyte apoptosis and oxidative stress levels induced by CHF. Moreover, CHF caused decrease ATP synthesis, which was accompanied by a reduction in ATP 5D protein levels, damage to mitochondrial structure, abnormal glucose and lipid metabolism, and changes in the expression of PGC-1α related signal pathway proteins, all of which were significantly alleviated by treatment with SXT. CONCLUSION: SXT reverses CHF-induced cardiac dysfunction and maintains the integrity of myocardial structure by regulating energy metabolism. The beneficial effect of SXT on energy metabolism may be related to regulating the expression of the PGC-1α signalling pathway.

Bioactive components and the molecular mechanism of Shengxian Decoction against lung adenocarcinoma based on network pharmacology and molecular docking.

OBJECTIVE: The aim of this study was to identify the active components of Shengxian Decoction (SXT) and to elucidate the multi-component, multi-target, and multi-pathway regulatory mechanisms underlying the efficacy of SXT in treating lung adenocarcinoma (LUAD). METHODS: The effects of SXT extract on proliferation, migration, and invasion capabilities of human LUAD cells were determined through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), wound healing, and Transwell assays. High-Performance Liquid Chromatography (HPLC) was employed to pinpoint the primary active constituents of SXT. The SXT-active component-target-pathway network and protein-protein interaction (PPI) network were constructed based on network pharmacology. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed using DAVID. The clinical significance of key targets was assessed using several external databases, and molecular docking confirmed the binding affinities between key targets and SXT active components. RESULTS: SXT significantly inhibited the proliferation, migration and invasion of human LUAD cells. HPLC identified and quantified seven active SXT components. Network pharmacology yielded 197 targets, 128 signaling pathways, and 448 GO terms. The PPI network and external validation underscored 13 key targets significantly associated with the influence of SXT on LUAD progression. Molecular docking demonstrated strong interactions between SXT active components and key targets. CONCLUSION: SXT treats LUAD through a multifaceted approach involving various components, targets, and pathways. This research offers novel insights into the constituents and molecular mechanisms of SXT in LUAD therapy.

A multidimensional strategy to rapidly identify the chemical constituents in Shengxian Decoction by using ultra-performance liquid chromatography coupled with ion mobility spectrometry quadrupole time-of-flight mass spectrometry.

As a well-known traditional Chinese medicine formula, the chemical constituents of Shengxian Decoction still remain unclear due to its complexity. In this study, a multidimensional strategy based on ultra-performance liquid chromatography coupled with ion mobility spectrometry quadrupole time-of-flight mass spectrometry and informatics UNIFI platform was applied to achieve rapid and comprehensive identification of the complex composition of Shengxian Decoction. Data-independent acquisition, fast data-directed analysis, and high-definition MSE were used to obtain more and cleaner mass spectrum information. As a result, a total of 120 compounds including 74 saponins, 17 flavonoids, 7 cinnamic acid derivatives, 8 triterpenoids, and 14 others were identified or tentatively characterized by high-resolution molecular mass, fragment ions, and collision cross-section values. Furthermore, high-definition MSE was used to identify six pairs of co-eluting isomers that could not be detected from conventional data-independent acquisition and fast data-directed analysis. This research strategy has a certain potential for the analysis of other compound formulae and lays the foundation for the study of traditional Chinese medicine efficacy.

Chemical and Biological Evidence of the Efficacy of Shengxian Decoction for Treating Human Lung Adenocarcinoma.

Shengxian Decoction (SXT) is a traditional Chinese medicine prescription comprising several anti-cancer medicinal herbs. However, the anti-cancer effect of SXT has rarely been reported. Herein, we explored the therapeutic potential of SXT for the treatment of lung adenocarcinoma (LUAD). High-performance liquid chromatography analysis of crude SXT extract revealed the abundance of mangiferin, an established anti-cancer compound. The serum pharmacological evaluation revealed that serum SXT suppressed A549 lung cancer cell proliferation in vitro. The tumor-inhibitory activity of SXT was confirmed in vivo via tumor formation assays in nude mice. We applied biochemical, histopathological and imaging approaches to investigate the cellular targets of SXT. The results indicated that the treatment with SXT induced tumor necrosis, and downregulated hypoxia-inducible factor 1 alpha in the serum. In vivo biosafety assessment of SXT revealed low levels of toxicity in mouse models. Our study provides the first scientific evidence that SXT effectively represses cancer cell growth and, thus, may serve as a safe anti-cancer agent for LUAD treatment.

Evaluation of the effect of Shengxian Decoction on doxorubicin-induced chronic heart failure model rats and a multicomponent comparative pharmacokinetic study after oral administration in normal and model rats.

Shengxian Decotion (SXT), a well-known Traditional Chinese Medicine (TCM) formula composed of Astragali Radix, Bupleuri Radix, Cimicifugae Rhizoma, Anemarrhenae Rhizoma and Platycodonis Radix, is clinically considered as an effective formula against cardiovascular diseases. However, the exact effective substance of SXT in treating chronic heart failure (CHF) still remains unclear. In the current study, we investigated the benefit of SXT in doxorubicin (DOX)-induced CHF rats and established a UHPLC-MS/MS method to simultaneously determine 18 key compounds in a subsequent comparative pharmacokinetic study in normal and CHF rats. Histopathological studies, transmission electron microscopy, and echocardiography were applied to assess the therapeutic effect of SXT on DOX-induced CHF rats, which indicated that SXT significantly ameliorated DOX-induced CHF, similar to enalapril. In addition, we successfully established a UHPLC-MS/MS method to determine the pharmacokinetics of the components in rat plasma, which was validated with good linearity, inter-day and intra-day precisions and accuracies, matrix effects, extraction recovery, and stability values. Our results showed that only astragaloside IV showed increased plasma exposure in the CHF rats, while saikosaponin A, quercetin, timosaponin B-II, ferulic acid, isoferulic acid and formononetin decreased compared to their pharmacokinetic characteristics in the normal and CHF rats. This study demonstrates that SXT enjoys obvious therapeutic effect on DOX-induced CHF rats, and the altered metabolism of some compounds in SXT is affected by the pathological state of CHF rats. Our findings provide a better understanding of the in vivo exposure to complex compounds of SXT, supporting effective substance screening and further investigation of the therapeutic mechanism.

[Effective components of Shengxian Decoction and its mechanism of action in treating chronic heart failure based on UHPLC-Q-TOF-MS integrated with network pharmacology].

This study aimed to elucidate the effective components of Shengxian Decoction and its mechanism of action in treating chronic heart failure. Firstly, UHPLC-Q-TOF-MS was established to identify the main chemical constituents in the rat serum after intragastric administration with Shengxian Decoction. Secondly, the absorbed components in serum were then used for the network pharmacology analysis to infer the mechanism and effective components. Targets for constituents in serum were predicted at TCMSP and Swiss-TargetPrediction database. An association network map was drawn by network visualization software Cytoscape 3.6.1. Finally, GO enrichment analysis and KEGG pathway enrichment analysis were carried out for the core target genes. By UHPLC-Q-TOF-MS, 18 prototype compounds were definitely identified, including five compounds from Astragali Radix, four compounds from Anemarrhenae Rhizoma, four compounds from Bupleuri Radix, four compounds from Cimicifugae Rhizoma, and one compound from Platycodonis Radix. Those components of Shengxian Decoction were closely associated with 13 key protein targets, including inflammatory factors, like IL6, IL1 B, TNF, PTGS2, IL10; redox enzymes CAT, HMOX1, and MPO; cardiovascular targets, like VEGFA, NOS3, and NOS2; and transmememial proteins CAV1 and INS. Network pharmacology analysis showed that the 18 compounds could be responsible for the treatment of chronic heart failure by regulating HIF-1 signaling pathways, PI3 K-Akt signaling pathways, cGMP-PKG signaling pathways, cAMP signaling pathways and TNF signaling pathways. This study provided a scientific basis for mechanism and effective ingredients of Shengxian Decoction.

Shengxian decoction decreases doxorubicin­induced cardiac apoptosis by regulating the TREM1/NF­κB signaling pathway.

Shengxian decoction (SXT) is a traditional Chinese medicine that is clinically used for treating cardiovascular diseases. It is known for its beneficial effect on cardiomyocyte injuries, some of which can be induced by anticancer agents including doxorubicin (DOX). To determine the molecular mechanisms involved in the cardioprotective effects of SXT, DOX­induced H9c2 cells were analyzed for apoptosis and expression levels of apoptosis biomarkers. Cell viability and apoptosis were measured by CCK­8 and flow cytometry. Triggering receptors expressed on myeloid cells 1 (TREM1), cleaved caspase­3, survivin and NF­κBp65 expression levels were measured by reverse transcription­quantitative PCR and/or western blotting. A total of 30 adult male Sprague­Dawley rats were randomly allocated into five groups (n=6 each); control group receiving 0.9% saline, 1 DOX group receiving 2.5 mg/kg of DOX and 3 DOX + SXT groups, receiving a DOX dose equivalent to the DOX­only group and either 0.4, 0.8 or 1.6 g/kg of SXT. It was found that DOX increased apoptosis and NF­κB activation of H9c2 cells by increasing TREM1 expression and that SXT inhibited apoptosis and NF­κB activation of H9c2 cells induced by DOX or Trem1 overexpression. SXT also significantly reversed DOX­induced cardiotoxicity in rats. The results suggested that the protective effects of SXT against DOX­induced apoptosis may be attributed to its downregulation of TREM1.

Protective effect of Shengxian decoction and the decoction of single herb component against myocardial injury induced by hypoxia/reoxygenation / 药学实践杂志

Objective To study the protective effect of Shengxian decoction and the single herb decoction against myocardial injury induced by hypoxia/reoxygenation. Methods The H9c2 cells were cultured to establish hypoxia/reoxygenation model. Rats were divided into 8 groups: normal control group, hypoxia/reoxygenation group (model group) and treated groups (Shengxian decoction and the single herb decoction). The apoptotic rate of cardiomyocytes, the activity of reactive oxygen species (ROS) and intracellular calcium concentration (Ca2+) were measured. Results Compared with hypoxia/reoxygenation group, the apoptosis rate, ROS activity and intracellular Ca2+ concentration were significantly lower in all treated groups (P<0.05). The ROS activity and intracellular Ca2+ concentration was decreased by 41.37% and 15.20% in Shengxian decoction group compared to the model group. Conclusion Shengxian decoction and the single herb decoction had protective effect on myocardial injury induced by hypoxia/reoxygenation.

Effective components of Shengxian Decoction and its mechanism of action in treating chronic heart failure based on UHPLC-Q-TOF-MS integrated with network pharmacology / 中国中药杂志

This study aimed to elucidate the effective components of Shengxian Decoction and its mechanism of action in treating chronic heart failure. Firstly, UHPLC-Q-TOF-MS was established to identify the main chemical constituents in the rat serum after intragastric administration with Shengxian Decoction. Secondly, the absorbed components in serum were then used for the network pharmacology analysis to infer the mechanism and effective components. Targets for constituents in serum were predicted at TCMSP and Swiss-TargetPrediction database. An association network map was drawn by network visualization software Cytoscape 3.6.1. Finally, GO enrichment analysis and KEGG pathway enrichment analysis were carried out for the core target genes. By UHPLC-Q-TOF-MS, 18 prototype compounds were definitely identified, including five compounds from Astragali Radix, four compounds from Anemarrhenae Rhizoma, four compounds from Bupleuri Radix, four compounds from Cimicifugae Rhizoma, and one compound from Platycodonis Radix. Those components of Shengxian Decoction were closely associated with 13 key protein targets, including inflammatory factors, like IL6, IL1 B, TNF, PTGS2, IL10; redox enzymes CAT, HMOX1, and MPO; cardiovascular targets, like VEGFA, NOS3, and NOS2; and transmememial proteins CAV1 and INS. Network pharmacology analysis showed that the 18 compounds could be responsible for the treatment of chronic heart failure by regulating HIF-1 signaling pathways, PI3 K-Akt signaling pathways, cGMP-PKG signaling pathways, cAMP signaling pathways and TNF signaling pathways. This study provided a scientific basis for mechanism and effective ingredients of Shengxian Decoction.

Experience of GU Wei-chao in Treating Heart and Lung Diseases Through Application of Modified Shengxian Decoction / 中国中医药信息杂志

Professor GU Wei-chao is with great academic and clinical experience. He has thoughts in ZHANG Xi-chun's academic thoughts, especially his application of Zhang's theory. He added Rhodiolae Crenulatae Radix et Rhizoma, Agrimoniae Herba, Taxilli Herba, Nardostachyos Radix et Rhizoma, Corni Fructus, and Glycyrrhizae Radix et Rhizoma Praeparata cum Melle to Shengxian Decoction to make modified Shengxian Decoction to strengthen the efficacy of invigorating qi and ascending qi collapse, reinforcing heart and astringing qi, cultivating the essence and notifying kidney, and inducing resuscitation and allaying tiredness, with a purpose to treat sinking qi syndrome of heart and lung diseases and expand the application areas of Zhang's Shengxian Decoction. This article introduced experience of GU Wei-chao in treating heart and lung diseases by using modified Shengxian Decoction through three clinical cases of effusion after lung surgery, chest and heart pain and difficulties in breathing.

Analytic Report of Treatment Experience of GU Wei-chao in Theory of Sinking Qi for Cases ;of Chronic Diseases / 中国中医药信息杂志

GU Wei-chao has been a TCM doctor for over 50 years, with enriched learning and practicing experience. He has experience in ZHANG Xi-chun's academic thoughts, especially used Zhang’s theory of sinking qi in his medical practice. He added Rhodiolae Crenulatae Radix et Rhizoma, Agrimoniae Herba, Taxilli Herba, Nardostachyos Radix et Rhizoma, Corni Fructus, and Glycyrrhizae Radix et Rhizoma Praeparata cum Melle to Shengxian Decoction to make modified Shengxian Decoction, in order to strengthen the efficacy of invigorating qi and ascending qi collapse, cultivating the essence and notifying kidney, reinforcing heart and astringing qi, and inducing resuscitation and allaying tiredness. This article introduced GU Wei-chao using Zhang’s theory of sinking qi to strengthen the efficacy of modified Shengxian Decoction for chronic diseases by combining two medical cases of unexplained diabetes and myasthenia gravis. Therefore, this article believed that invigorating qi and ascending qi collapse method has advantages in treating chronic diseases, with worth of clinical promotion and application.

Research on immune mechanism of Shengxian decoction in experimental autoimmune myasthenia gravis rats / 中国免疫学杂志

Objective:To investigate the immune mechanism of Shengxian decoction in experimental autoimmune myasthenia gravis(EAMG) rats. Methods:Lewis rats were immunized with the rat sequence 97-116 of the AChRαsubunit(Rα97-116) in CFA, 25 of which were successful. They were randomly divided into 5 groups:EAMG model group,prednisone group(5. 4 mg/kg),Shengxian decoction low, medium, high dose groups ( dosage 2. 6 g/kg, 5. 2 g/kg, 10. 4 g/kg ) . Clinical symptoms, weight, and the decrement percentage of RNS(5 Hz) were evaluated,and ELISA were adopted to determine the titers of AChR Ab,TGF-β,IFN-γ,IL-2,IL-4 and IL-17 in serum. Results:After molding,the percentage of decrement of RNS in each group noticeably increased by more than 10% in comparison with that in the CFA control group ( P<0. 01 or P<0. 05 ) . At the same time, they were also subjected to progressive decreasing weight and typical myasthenia symptoms,showing the successful molding. With medication,the decrement percentage of RNS of rats in the groups with low,medium and high dose of Shengxian decoction were all on obvious decline with alleviated weight decrease (P<0. 01),testifying to the symptom improvement. Compared with the CFA control group,the groups with low,medium and high dose of Shengxian decoction were coupled with decreasing AChR Ab content(P<0. 05),rising TGF-βlevel and reducing IFN-γ,IL-2,IL-4 and IL-17 level(P<0. 01 or P<0. 05). Conclusion: Shengxian decoction can turn the decrement percentage of RNS around,improve the progressive weight decrease in EAMG rats and increase the weight gains. By up-regulating the TGF-βlevel,lowering IFN-γ,IL-2,IL-4 and IL-17 level,preventing B cells from producing AChR Ab and reducing the content of AChR Ab in serum,it will soothe the damage of NMJ to AChR and cure EAMG.

Chemical profile- and pharmacokinetics-based investigation of the synergistic property of platycodonis radix in traditional Chinese medicine formula Shengxian decoction.

ETHNOPHARMACOLOGICAL RELEVANCE: To investigate the synergistic property of Platycodonis radix (PG) in a classic traditional Chinese medicine (TCM) prescription Shengxian decoction (SXT) by combining chemical profile with pharmacokinetic analysis strategy. The synergized prescription consisted of Astragali radix, Anemarrhenae rhizoma, Bupleuri radix, and Cimicifuage rhizoma. MATERIALS AND METHODS: Ultra-performance liquid chromatography/quadruple time-of-flight mass spectrometry (UPLC-Q-TOF/MS) was employed to investigate the chemical fingerprints of SXT and decreased SXT (SXT that removed Platycodonis radix, SXT-PG). A reliable LC-MS/MS method was developed to examine the pharmacokinetics of 9 marker compounds (including formononetin, calycosin-7-O-ß-d-glucoside, ononin, caffeic acid, isoferulic acid, mangiferin, timosaponin E1, timosaponin B-II and timosaponin B) following oral administration of SXT and SXT-PG in rats. Both in vitro chemical profiles and in vivo pharmacokinetic parameters differences between SXT and SXT-PG were conducted. RESULTS: By using UPLC-Q-TOF/MS method, a total of 25 compounds identified from SXT, including 13 triterpenoids, 5 caffeinic derivatives, 4 isoflavonoids and 3 xanthone glycosides. Comparing the chemical fingerprints between SXT and decreased SXT did not reveal significant difference in the chemical profile of other four TCMs. The improved pharmacokinetic profiles of mangiferin, timosaponin E1, timosaponin B-II and timosaponin B were found in SXT group, suggesting the quicker distribution and more effective absorption, when compared with those in the SXT-PG group. CONCLUSIONS: These results indicated that PG did not increase the dissolution of synergized prescription when co-decocting, but guided the synergized prescription to target location, reflecting the courier role of PG, which was in line with the clinical principle of TCM. It also established a useful method for TCM synergistic property research.

Clinical observation on 32 cases of hypothyroidism of thyroid cancer after operation treated with Shengxian decoction combined with levothyroxine sodium tablets / 国际中医中药杂志

Objective To observe the clinical effects of modified Shengxian decoction in the treatment of thyroid cancer postoperative hypothyroidism patients.Methods 60 patients of thyroid cancer postoperative hypothyroidism due to deficiency of spleen and kidney were randomly divided into a control group and a treatment group.The control group (28 cases) was by levothyroxine sodium tablets conventional treatment,while the treatment group (32 cases) was treated with Shengxian decoction based on thecontrol group.The changes of the symptom integral and HAMD-17 were observed between two groups before and after treatment.Results After treatment,the total effective rate was 87.5％ in the treatment group and 64.3％ in the control group,the clinical effect of treatment group was significantly better than the control group (x2=4.499,P＜ 0.05).After treatment,the total score of HAMD-17 was 6.8±2.3 in the treatment group and 15.8±2.1 in the control group,both significantly improved than that before the treatment (which were 19.4±1.45 and 18.9± 1.32 respectively).Compared with the control group,the treatment group improved significantly (P＜ 0.01).Conclusion Shengxian decoction plus western medicine has remarkable curative effect in the treatment of thyroid cancer postoperative hypothyroidism,it can improve the depressive state of patients and improve the quality of life.

A Clinic Observation on 38 Patients with Obstructive Sleep Apnea Hypopnea Syndrome Treated by Shengxian Decoction in Combination with Duxil / 中医杂志

Objective To observe the effect of Shengxian Decoction (Decoction for lifting the depressed organs) in the treatment of 38 patients with obstructive sleep apnea hypopnea syndrome (OSAHS) in the TCM syndrome of qi deficiency of the lung and spleen. Methods Totally 68 patients were randomized into a control group (30 cases) treated by Duxil for oral taking and a treatment group (38 cases) treated by Duxil and Shengxian Decoction for 10 days. The changes in the symptom scores of both groups after treatment were observed. The polysomnogram (PSG) was applied before and after treatment to record the total sleep time,hypopnea total time,and average heart rate to calculate the times when oxygen saturation was less than 90% in each hour sleep time,the total continuous time when oxygen saturation was less than 90% in the whole night,apnea-hypopnea index (AHI),and hypopnea index (HI). Results After treatment,the main symptoms in the treatment group were significantly improved (P