Mechanism of Danggui Sini Decoction in improving kidney injury caused by blood stasis syndrome based on metabolomics and network pharmacology / 中国中药杂志

This article analyzed the mechanism of Danggui Sini Decoction(DSD) in improving kidney injury caused by blood stasis syndrome(BSS) in rats. Firstly, 32 female SD rats were randomly divided into the following four groups: a normal group and a BSS group, both receiving an equal amount of distilled water by gavage; a normal+DSD group and a BSS+DSD group, both receiving 5.103 g·kg~(-1) DSD orally for a total of 14 days. Daily cold water bath was given to establish the BSS model, and on the 14th day, BSS rats were subcutaneously injected with 0.8 mg·kg~(-1) adrenaline. Normal rats were subjected to the water bath at 37 ℃ and injected with an equal volume of distilled water. After the experiment, 24-hour urine, serum, and kidney samples were collected for metabolomic analysis, biochemical measurements, and hematoxylin-eosin(HE) staining. The study then employed ~1H-NMR metabolomic technology to reveal the metabolic network regulated by DSD in improving BSS-induced kidney injury and used network pharmacology to preliminarily elucidate the key targets of the effectiveness of DSD. Pathological and biochemical analysis showed that DSD intervention significantly reduced inflammation and abnormal levels of blood creatinine, blood urea nitrogen, and urine protein in the kidneys. Metabolomic analysis indicated that DSD attenuated BSS-induced kidney injury primarily by regulating 10 differential metabolites and three major metabolic pathways(taurine and hypotaurine metabolism, citrate cycle, and acetaldehyde and dicarboxylic acid metabolism). Network pharmacology analysis suggested that the protective effect of DSD against BSS-induced kidney injury might be related to two key genes, ATP citrate lyase(ACLY) and nitric oxide synthase 2(NOS2), and two main metabolic pathways, i.e., arginine biosynthesis, and arginine and proline metabolism. This study, from the perspective of network regulation, provides initial insights and evidence into the mechanism of DSD in improving kidney injury induced by BSS, offering a basis for further investigation into the molecular mechanisms underlying its efficacy.

Mechanism of Danggui Sini Decoction in treatment of primary dysmenorrhea based on network pharmacology and molecular docking / 中国中药杂志

Network pharmacology, molecular docking and in vivo experiments were used to explore the pharmacodynamic basis and potential mechanism of Danggui Sini Decoction in the treatment of primary dysmenorrhea(PD). The chemical constituents of Danggui(Angelicae Sinensis Radix), Guizhi(Cinnamomi Ramulus), Tongcao(Tetrapanacis Medulla), Baishao(Paeoniae Radix Alba), Xixin(Asari Radix et Rhizoma), Gancao(Glycyrrhizae Radix et Rhizoma), and Dazao(Jujubae Fructus) from Danggui Sini Decoction were retrieved through TCMSP(Traditional Chinese Medicine Systems Pharmacology Database), and the action targets of Danggui Sini Decoction were collected through DrugBank. "Primary dysmenorrhea" and "dysmenorrhea" were used as the key words to search the corresponding targets in the GeneCards, OMIM and TTD databases, and then the intersection targets of Danggui Sini Decoction and the primary dysmenorrhea targets were taken for reverse screening to obtain the corresponding active ingredients. Cytoscape 3.6.1 software was used to construct a traditional Chinese medicine-compound-target-disease network; STRING database was used to build a protein-protein interaction(PPI) network; Gene ontology(GO) function enrichment analysis and Kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment analysis were conducted by using DAVID database. The action mechanism of the intersection targets were then predicted, and a histogram chart and bubble chart were drawn for visualization. Then the top five targets in the PPI network were used for docking with the most compounds. In animal experiments, Sprague Dawley(SD) female rats were used to establish a primary dysmenorrhea model by intraperitoneal injection of diethylstilbestrol once a day. A total of 60 SD female rats were randomly divided into 6 groups, namely control group, model group, Danggui Sini Decoction low(1.5 g·kg~(-1)), medium(3.0 g·kg~(-1)), high(6.0 g·kg~(-1)) dose groups, and ibuprofen(20 mg·kg~(-1)) positive control group, with 10 rats in each group. From day 4, except for the control group, rats in the other groups were given intragastric administration of corresponding drugs, and the control group received intragastric administration of normal saline for 7 consecutive days. The number of writhing before and after the administration, the ute-rine contraction inhibition rate and the uterine index after administration were observed, and ELISA assay was used to detect the levels of prostaglandin-endoperoxide synthase 2(PTGS2) and vascular endothelial growth factor A(VEGFA) in the tissues of each group as well as the levels of serum inflammatory factors interleukin 1(IL-1), interleukin 6(IL-6), and tumor necrosis factor-alpha(TNF-α). According to network analysis, 7 Chinese medicines contained 114 active ingredients, 149 targets, and 30 common target genes with PD were obtained. The key targets included VEGFA, IL6, PTGS2, TNF, etc.; GO function enrichment analysis showed a total of 399 terms(P<0.05) were obtained, 353 of which were biological process(BP) terms, 21 were cell composition(CC) terms, and 25 were molecular function(MF) terms. In KEGG pathway enrichment analysis, 14 signaling pathways were obtained, 3 of which were related to inflammation, namely arachidonic acid metabolism, MAPK signaling pathway and NOD-like receptor signaling pathway. The compounds in Danggui Sini Decoction can play a therapeutic role in the treatment of PD by acting on VEGFA, IL-6, PTGS2, TNF and other targets to regulate arachidonic acid and inflammatory signaling pathways.

Q-marker prediction analysis of Cinnamomi Ramulus in Danggui Sini Decoction based on fingerprint and network pharmacology / 中草药

Objective: To analyze and predict the Q-marker of Cinnamomi Ramulus in Danggui Sini Decoction based on fingerprint and network pharmacology. Methods: The fingerprints of Cinnamomi Ramulus Decoction and Danggui Sini Decoction were established, and analyzed by using the similarity evaluation system software for chromatographic fingerprint of traditional Chinese medicine (2012 edition); The network pharmacology was used to screen and analyze the function target and pathway of related components of Cinnamomi Ramulus, and the "component-target-pathway" network was constructed to predict the potential Q-marker of Cinnamomi Ramulus in Danggui Sini Decoction. Results: The fingerprints of 15 batches of Cinnamomi Ramulus Decotion and 15 batches of Danggui Sini Decoction were established. The similarity of fingerprints was more than 0.96, and seven common components were identified, including protocatechuic acid, coumarin, cinnamic acid, cinnamaldehyde, cinnamyl alcohol, 2-methoxy cinnamic acid, and 2-methoxy cinnamaldehyde. A total of five active components, seven core target sites and 15 key pathways of Cinnamomi Ramulus were screened out through network pharmacology system, and based on the "Five Principles" of quality markers, 2-methoxy cinnamaldehyde, cinnamaldehyde, and cinnamic acid were predicted as potential quality markers. Conclusion: In this study, the quality markers of Cinnamomi Ramulus in Danggui Sini Decoction are analyzed by fingerprint and network pharmacology, which provides a basis for comprehensive control of the quality of Danggui Sini Decoction, reference for further study on the mechanism of Danggui Sini Decoction, and demonstration for the correlation study of quality markers of compound and single medicine in the classic prescription.

Q-marker prediction analysis of Paeoniae Radix Alba based on fingerprint and network pharmacology / 中草药

Objective: To explore the potential Q-marker of Paeoniae Radix Alba in Danggui Sini Decoction based on fingerprint and network pharmacology. Methods: The fingerprints of Paeoniae Radix Alba decoction and Danggui Sini Decoction were established, and the law of components transfer was also defined. The "compounds-targets-pathways" network was then established to predict the potential Q-marker of Paeoniae Radix Alba through the network pharmacology. Results: The fingerprints of 15 batches of Paeoniae Radix Alba decoction and 15 batches of Danggui Sini Decoction were established, and the five chromatographic peaks were identified, they were gallic acid, albiflorin, paeoniflorin, 1,2,3,4,6-O-pentagalloylglucose, and benzoyl paeoniflorin. Through the network pharmacology analysis, the potential two active components, eight core targets and 13 key pathways were screened out, which indicated that paeoniflorin and albiflorin were preliminarily predicted to the potential Q-marker of Paeoniae Radix Alba. Conclusion: The analysis and prediction of the Q-marker in this study can provide a reference for the whole control of the Paeoniae Radix Alba quality, which can also provide the basis for the further research on the efficacy-related substance and mechanism of Paeoniae Radix Alba.

Sini Decoction combined with spectinomycin B1 induced dissociation of PTEN and SUMO1 to treat lung cancer / 中草药

Objective To analyze the mechanism of the inhibition of proliferation, metastasis and the promotion of apoptosis of lung cancer cells by Sini Decoction combined with spectinomycin B1 from the perspective of protein SUMOylation modification. Methods The experiment was divided into control group, spectinomycin B1 group, Sini Decoction group, and combined treatment group. Human non-small cell lung cancer cell line A549 was treated for 48 h and Western blotting was used to detect the protein expression of small ubiquitin-related modified protein-1 (SUMO1), gene of phosphate and tension homology deleted on chromsome ten (PTEN), and phosphorylated Akt (p-Akt) and Caspase-9. Cell proliferation curves were drawn by MTT assay, and cell apoptosis was detected by flow cytometry; Cell migration and cell invasion were detected by cell scratch and Transwell assay. Results Both spectinomycin B1 and Sini Decoction an reduce the levels of covalent SUMO1 and p-Akt, increase the protein levels of PTEN and activate Caspase-9, inhibit cell proliferation, migration and invasion, and promote cell apoptosis. Combined treatment group can further enhance the above changes. Conclusion Sini Decoction can synergize with spectinomycin B1 to induce the dissociation of PTEN and SUMO1, thereby inhibiting the proliferation, metastasis and promoting apoptosis of lung cancer cells.

Clinical Study on the Sini-Moxibustion Therapy in the Treatment of Gastrointestinal Cancer Yang-Deficiency Patients with Fatigue Caused by Cancer / 世界科学技术-中医药现代化

Objective: To study the clinical efficacy of Sini-Moxibustion in the treatment of cancer-induced fatigue in patients with yang- deficiency gastrointestinal cancer. Methods: A total of 120 patients with gastrointestinal cancer treated in our department from January 2017 to January 2018 were randomly divided into 2 groups: the fire moxibustion group and the conventional group. The conventional group and the fire therapy group were treated with basic treatments such as anti-cancer and nutritional support. The conventional group added Sini-Moxibustion to the basic treatment, and the fire therapy group added"Sini-Moxibustion"therapy for a period of 1 month. Tthe indicators of the 2 groups of patients with Piper fatigue scale and grade, quality of life, symptoms of yang deficiency symptoms, clinical efficacy and blood tests of patients with chemotherapy were evaluated. Results: After the treatment, the degrees of fatigue in the fire moxibustion group was lower than that in the conventional group with statistically significant difference ( χ2 =4.24, P =0.037 ＜ 0.05). The scores of improvement in the quality of life scale and five subscales in the fire moxibustion were higher than those in the conventional group with statistically significant difference (P ＜ 0.01), and the improvement score of the body yang deficiency in the fire moxibustion group was greater than that of the conventional group (P ＜ 0.01). The scores of fatigue, nausea and vomiting, insomnia, anorexia, and diarrhea in the fire moxibustion group were higher than those in the conventional group with statistically significant difference (P ＜ 0.05 or P ＜ 0.01). After treatment, the total effective rate was 76.67％ in the fire moxibustion treatment group, which was higher than the conventional group 91.53％ with statistically significant difference ( χ2 =5.64, P =0.012 ＜ 0.01). Hemoglobin improvement value of 3.92 ± 1.18 in the fire moxibustion group was higher than that of the conventional group 1.02 ± 0.52 with statistically significant difference (t =7.212, P =0.003 ＜ 0.01). Conclusion: Sini-moxibustion can improve the CRF of patients with yangdeficiency gastrointestinal cancer, reduce the symptoms of yang deficiency, improve the quality of life, and increase the hemoglobin content in patients with chemotherapy.

Sini Decoction improves rat myocardial fibrosis by inhibiting RhoA/ROCK signaling pathway / 中成药

AIM To explore the effects of Sini Decoction (Aconiti lateralis Radix Praeparata,Zingiberis Rhizoma,Glycyrrhizae Radix et Rhizoma) on rat myocardial fibrosis induced by isoproterenol.METHODS Forty SD rats were randomly divided into blank,model,captopril [100 mg/(kg · d)] and Sini Decoction [3.8 g/(kg · d)] groups,with ten rats in each group.Except for the blank group,the rest rats were given subcutaneous injection of isoproterenol [5 rg/(kg · d)] to prepare myocardial fibrosis model,and successive administration lasted for four weeks.At 20 h after the last administration,hemodynamics changes of heart were detected;heart weight indexes were calculated;the changes of myocardial pathological morphology were observed by HE and Masson staining;NO level in serum was measured by nitrale reduetase;SOD activity in serum was measured by xanthinoxidase method;MDA level in serum was measured by thiobarbituric acid method;the protein expressions of RhoA,ROCK1 and eNOS in myocardial tissue were detected by Western blot method.RESULTS Compared with the model group,the cardiac function of rats was significantly improved;the myocardial collagen content was significantly decreased;the MDA level in serum was obviously decreased;the NO level and SOD activity were significantly increased;the protein expressions of RhoA and ROCK1 in myocardium tissue were significantly reduced,and the protein expression of eNOS was markedly increased in the Sini Decoction group.CONCLUSION Sini Decoction can improve the isoproterenol-induced myocardial fibrosis in rats,and its mechanism may be related to inhibiting the RhoA/ ROCK signaling pathway,in turn,raising the expression of eNOS,which leads to reduced oxidative stress.

Clinical Observation of Gegen Decoction Plus Sini Powder for Treatment of Polycystic Ovarian Syndrome Women with Acne / 广州中医药大学学报

Objective To observe the therapeutic effect of Gegen Decoction plus Sini Powder for polycystic ovarian syndrome(PCOS) women with acne and to explore its possible therapeutic mechanism.Methods Seventy cases of PCOS women with acne aged 18-45 years were randomized into treatment group and control group,35 cases in each group.The treatment group was given Gegen Decoction plus Sini Powder orally and the control group was given Diane-35 orally.The treatment lasted for 12 weeks.After treatment,the skin lesions and symptom scores were observed.The body mass index (BMI),serum dihydrotestosterone (DHT),interleukin-6 (IL-6) and interleukin-8 (IL-8) were detected before and after treatment.Results (1) The markedly effective rate of the treatment group was 80.00％ and that of the control group was 57.14％,the difference being significant between the two groups(P ＜ 0.05).(2) After treatment,the total scores of the symptoms and the scores of each symptom such as sweating,sleeping and physical strength in both groups were decreased(P ＜ 0.01),and the decrease in the treatment group was superior to that in the control group(P ＜ 0.05).(3) The BMI and serum levels of DHT,IL-6 and IL-8 in both groups were significantly decreased after treatment (P ＜ 0.01),and the decrease in the treatment group was superior to that in the control group(P ＜ 0.05).Conclusion Gegen Decoction plus Sini Powder is effective for the treatment of PCOS women with acne,and the mechanism is probably related with the decrease of BMI and serum DHT,IL-6 and IL-8 levels.

Clinical efficacy of Sini decoction adjustment combined rabeprazole enteric capsules in gastroesophageal reflux cough and its effect on IL-8, SP, MCT levels / 中国生化药物杂志

Objective To research the clinical efficacy of Sini decoction adjustment combined rabeprazole enteric capsules in treatment of gastroesophageal reflux cough and its effect on interleukin 8 (IL-8) and substance P (SP), the mast cell tryptase (MCT) levels.Methods 92 cases of gastroesophageal reflux cough were divided into control group and experimental group by drawing method , each had 46 cases.Control group were treated by rabeprazole enteric capsules, experimental group were treated with rabeprazole enteric capsules based on the control group.The curative effect, cough symptoms integral, IL-8, SP, MCT, gastric dynamic element (MOT) and the gastrin-releasing (GAS), pulmonary function and safety were compared between two groups.Results The total effective rate of experimental group(93.47%) was higher than the control group(76.08%), the difference was statistically significant (P<0.05).After treatment, the symptoms of experimental group(1.53 ±0.19) points was higher than the control groupthe difference was statistically significant(1.96 ±0.24)points,P<0.05.The IL-8, SP, MCT levels of experimental group were all lower than the control group ( P<0.05 ) .The MOT, GAS, and lung function of experimental group improved more significantly than the control group ( P <0.05 ) .The security between two groups has no significant difference .Conclusion The curative effect of Sini decoction adjustment combined Rabeprazole enteric capsules in treatment gastroesophageal reflux cough is obvious, can decrease IL-8, SP, MCT levels.

An experimental study on brain protective effect of Sini decoction on post-resuscitation syndrome / 中国中西医结合急救杂志

Objective To approach the brain protective effect and mechanism of Sini decoction on rats with cardiopulmonary resuscitation (CPR) syndrome.Methods Fifty Sprague-Dawley (SD) rats were divided into sham operation group (n = 10), CPR model group (n = 20) and Sini decoction treatment group (n = 20) by random number table. The rat models were established by trachea clipping to induce cardiac arrest, and after heart beat stopped for 5 minutes, CPR was carried out. In the Sini decoction group, Sini decoction 5 g/kg was given through a stomach tube, once per 24 hours, while in the sham and CPR model groups, the same amount of normal saline was given by the same method at the same time. Venous blood was collected before CPR and 6, 12, 24, 48 and 72 hours after CPR, and the levels of serum interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) were determined by enzyme linked immunosorbent test (ELISA); after CPR for 72 hours, the rat brain tissue was obtained from all the groups, the content of caspase-3 in brain tissue was detected by immunohistochemistry method, and its protein expression caspase-3 was detected by Western Blot; the apoptosis situation of brain tissue was detected by terminal deoxynucleotidyl transferase-mediated duTP nick end labeling (TUNEL).Results With the prolongation of time, the levels of IL-6 and TNF-α in CPR model and Sini decoction groups showed a tendency firstly increased and then decreased, IL-6 reached its peak value after resuscitation for 24 hours, while TNF-α reached its peak value after resuscitation for 48 hours, and both IL-6 and TNF-α were decreased after resuscitation for 72 hours ; beginning from 6 hours after resuscitation, the levels of serum IL-6 (ng/L: 61.79±1.31, 62.49±1.42 vs. 21.48±0.79) and TNF-α (ng/L: 48.32±1.98, 25.32±1.96 vs. 18.34±2.45) in CPR model and Sini decoction treatment groups were all significantly higher than those in sham group, since 12 hours after resuscitation, the level of IL-6 was significantly lower in Sini decoction than that in CPR model group (ng/L: 70.41±2.21 vs. 88.32±1.59), and since 6 hours after resuscitation, TNF-α was obviously lower in Sini decoction group than that in CPR model group (ng/L: 25.32±1.96 vs. 48.32±1.98, allP < 0.05), both IL-6, TNF-α persisting to 72 hours after resuscitation, and their levels did not return to normal at the end of experiment in the two groups. After the end of resuscitation, the content and protein expression of caspase-3 and rate of cell apoptosis in the brain tissue in CPR model group were significantly higher than those in the sham group [caspase-3 content (A value,×103): 2.59±0.26 vs. 1.57±0.06, caspase-3 protein (gray value): 0.80±0.08 vs. 0.43±0.04, apoptosis rate: (2.01±0.08)% vs. (0.26±0.02)%, allP < 0.05], above indexes in the Sini decoction treatment group were significantly lower than those in the CPR model group [caspase-3 content (A value,×103): 1.89±0.08 vs. 2.59±0.26, caspase-3 protein (gray value): 0.57±0.02 vs. 0.80±0.08, apoptosis rate: (1.03±0.05)% vs. (2.01±0.08)%, allP < 0.05).Conclusion The Sini decoction has a protective effect on rats with post-resuscitation syndrome, and its mechanism is possibly realized by the inhibition of inflammatory factors and reduction of cell apoptosis.

Comparative Study on the HPLC Fingerprint of Sini Decoction Prepared by Traditional Decoction and Mod-ern Machine Decoction / 中国药房

OBJECTIVE:To establish the HPLC fingerprints for Sini decoction and compare the differences of compositions of Sini decoction prepared by traditional decoction and modern machine decoction. METHODS:HPLC was performed on the column of Kromasil C18 with mobile phase of acetonitrile-0.1% phosphoric acid(gradient elution)at a flow rate of 1.0 ml/min,the detec-tion wavelength was 235 nm,column temperature was 30 ℃,and injection volume was 10 μl. The HPLC fingerprints of 10 batch-es of Sini decoction were determined with reference peak of liquiritin peaks,and common peak identification and similarity evalua-tion were conducted by using Chromatographic Fingerprint Similarity Evaluation System(2004 A edition). RESULTS:There were 18 common peaks and the similarity was no less than 0.982. According to the verification,the fingerprint of 10 batches of Sini de-coction showed good similarity with reference fingerprint,and the similarity of 10 batches of Sini decoction was high,which was prepared by the 2 methods. CONCLUSIONS:The established fingerprint is specific and stable,and can provide reference for quali-ty evaluation and control for Sini decoction;and there are no obvious differences in the main chemical compositions of Sini decoc-tion prepared by traditional decoction and modern machine decoction.

Scientific principle analysis on prescription of Sini Decoction / 中草药

To analyze the background of Sini Decoction prescription, taking the clinical emergency treatment of shock syndrome by Sini Decoction as the main line, to explore the following three problems on rescuing shock syndrome faced by Zhang Zhong-jing: The first is how to use Aconiti Lateralis Radix Preparata (fuzi) to restore yang for saving from collapse, in the case that the blood capacity can not be quickly supplied; The second is how the active constituents in fuzi could be quickly absorbed, in the pathological state of the shock with severe gastrointestinal disturbance; The third is how to relieve the toxicity of fuzi, in the condition that the active components are not affected; The aim of the study is to reveal the scientificality and rationality in the theory of traditional Chinese medicine, which could provide the guidance for the application of classical prescription in modern clinic or the development of new Chinese materia medica.

Comparative study of effects of Sini Decoction before and after compatibilities on experimental myocardial ischemia in rats / 中草药

Objective: To study the effects of Sini Decoction before and after compatibilities on acute myocardial ischemia rats. Methods: The model of myocardial ischemia in rats was established by ig Pit. The effects of Sini Decoction, Aconiti Lateralis Radix Praeparata (ALRP)-Glycyrrhizae Radix et Rhizoma (GRR) decoction, ALRP-Zingiberis Rhizoma (ZR) decoction, ZR-GRR decoction, single ALRP decoction, single ZR decoction and single GRR decoction on the extension of myocardial infarction, lactic dehydrogenase (LDH), creatine kinase (CK), aspartate aminotransferase (AST), superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), and lactic acid in rats were evaluated. Results: Sini Decoction, ALRP-GRR decoction, ALRP-ZR decoction, and single ALRP decoction obviously decreased the extension of myocardial infarction (P ALRP-ZR decoction > ALRP-GRR decoction > single ALRP decoction. It reveals the scientific connotation of the compatibilities of Sini Decoction and accurate action about drug using of Sini Decoction from the perspective of efficacy.

Screening and Validation of Active Ingredients in Sini Decoction by Combination Method of Pharmacophore Modeling and Molecular Docking / 中草药·英文版

Objective: To screen the active compounds in Sini Decoction showing the potential to inhibit tumor necrosis factor α (TNFα) to alleviate Doxorubicin (DOX)-induced heart failure. Methods: A chemical database of Sini Decoction was constructed from literature research. The generated pharmacophore models based on TNF-α used to screen active ingredients of Sini Decoction in the database by Discovery Studio 2.5. Molecular docking by Autodock 4.2 was adopted to demonstrate the hit compounds' affinities with TNFα. Furthermore, DOX-induced heart failure model on H9c2 cell line was constructed and cell viability was detected by CCK-8 to validate the therapeutic effect of potential active compounds. Results: The higenamine showed potential cardiovascular protective effect through virtual screening. And the activity was identified in vitro. Conclusion: In this study, we found that higenamine may inhibit TNF-α through virtual docking and validated that higenamine may have the potential of treatment for heart failure in the model of doxorubicin-induced myocardial toxicity to H9c2 cells.

Study on Sini decoction in treatment of hypothyroidism by metabonomic method / 药学实践杂志

Objective To evaluate therapeutic effects of Sini decoction (SND) on hypothyroidism based on serum meta-bonomics method .Methods Twenty-four rats were randomly divided into three groups including sham group ,surgery-induced hypothyroid model group and SND-treated group .The SND-treated group was given SND for 4 weeks .After 4 weeks ,the ser-um samples of each rat were collected and analyzed by UHPLC-Q-TOFMS ,pattern recognition analysis of metabolomics differ-ences among the groups and therapeutic effects of SND were evaluated .Results Total of 9 metabolites were identified through serum metabonomics analysis .It was showed that there was a possible mechanism that hypothyroidism was mainly involved in citrate cycle ,phenylalanine metabolism ,sphingolipid metabolism and phospholipid metabolism and the damage of hypothyroid-ism was reversed by SND .Conclusion SND administration could provide satisfactory effects on hypothyroidism through par-tially regulating the perturbed citrate cycle ,phenylalanine metabolism and phospholipid metabolism .

A clinical observation on Danggui Sini decoction for treatment of patients with chronic non-atrophic gastritis and spleen-stomach vacuity cold syndrome / 中国中西医结合急救杂志

Objective To observe the clinical effect of Danggui Sini decoction for treatment of patients with chronic non-atrophic gastritis and spleen-stomach deficiency cold syndrome.Methods A prospective randomized control trial was conducted, including 126 in- and out-patients with chronic non-atrophic gastritis diagnosed by gastroscopy and spleen-stomach deficiency cold syndrome differentiated by traditional Chinese medicine (TCM) method admitted to Chinese Medicine Hospital of Haikou City. They were randomly assigned to an observation group (65 cases) and a control group (61 cases). The patients in observation group were given Danggui Sini decoction with addition or/with subtraction of ingredients according to individual situation (ingredients: angelica 15 g, ramulus cinnamomi 15 g, paeonia 15 g, asari 5 g, glycyrrhizae 10 g, Chinese jujube 12, medulla tetrapanacis 10 g ). The warm 200 mL (one dose) decoction was divided into two parts, one part was taken orally before a meal, twice daily, the therapeutic course was 4 weeks and in one week only 6 doses were applied; while the patients in control group, omeprazole capsules (dissolved in intestine), each time 20 mg, once a day combined with domperidone (bite phenanthroline) 10 mg each time, 3 times a day were given. After 4 weeks of treatment, the clinical efficacy, the total integral of symptoms, the therapeutic effect of TCM symptoms score, the improvement of the therapeutic effect of mucosal histological and changes of the number of patients with the patholoyical changes of mucosa under gastroscopy were observed.Results The total effective rate in the observation group was significantly higher than that in the control group [96.9% (63/65) vs. 86.9% (53/61),P < 0.05]. After treatment, the total integral of symptoms and the integrals of main TCM symptoms after treatment were lower than those before treatment, the degree of decrease in the observation group being more marked (the total integral of symptoms score: 12.36±2.11 vs. 15.94±2.37, epigastric distention integral score: 1.23±0.72 vs. 2.12±0.78, epigastric pain score: 1.18±0.67 vs. 2.25±0.94, thermophilic and like pressure integral score: 1.03±0.46 vs. 1.62±0.79, anorexia: 1.06±0.57 vs. 1.43±0.53, integral of loose stools score: 1.36±0.43 vs. 1.67±0.58, lassitude integral score: 1.24±0.32 vs. 1.65±0.42, allP < 0.05). Under gastroscope, the efficacy of mucosal histological change was significantly higher in observation group than that in control group [90.77% (59/65) vs. 81.97% (50/61),P < 0.05]. After treatment, the numbers of patients with chronic inflammatory cell infiltration (47 cases vs. 54 cases), erythema exudation (28 cases vs. 30 cases), flat erosion (8 cases vs. 15 cases), swelling erosion (5 cases vs. 6 cases), bile reflux (2 cases vs. 3 cases) and positive pylorus spirobacteria (20 cases vs. 29 cases) were significantly lower in the observation group than those in the control group (allP < 0.05).Conclusion The therapeutic effects of Danggui Sini decoction for treatment of patients with chronic non-atrophic gastritis and TCM syndrome of spleen-stomach deficiency-cold are remarkable.

Discuss Asthenia or Sthenia Cold of True Cold and False Heat / 浙江中医药大学学报

Objective] Differentiate and analyse the asthenia or sthenia attribute about the cold attribute of true cold and pseudo hot syndrome, further to simply make a summary.[Method] In order to compare with other doctor’s viewpoint and prove the opinion from the etiology and pathogenesis, clinical symptoms, clinical application and so on, by researching the related literature and theoretical works.[Result]Pathological condition of inner true cold and outer false heat appears because Yang deficiency of spleen and kidney is so long that yin exopathogen is in stasis and yang fails to transport and transform ying, further to repel yang outside in the etiology and pathogenesis. Clinical symptoms show that the red zygomas looking like being made up, low spirit, coldblooded and huddling up body, chilly limbs, drinking much and hot, diarrhea with undigested food in the stool and extreme weak pulse and even no feelings. In clinical application, the prescription is sini tang and the main medicines are fuzi and ganjiang which restore yang and get rid of cold. [Conclusion]True cold and pseudo hot syndrome belongs to asthenia-cold. And no matter in disease diagnosis even in clinical treatment, it has an important theoretical and practical significance to distinguish and clear the asthenia or sthenia attribute.

Research on preparation technology for Sini Boiling Powder / 中草药

Objective: To optimize the extracting process for Sini Boiling Powder at the condition of optimum particle size. Methods: The optimum size of particle was prepared, HPLC method was used for the determination of the content of ammonium glycyrrhetate and UV spectrophotometry was used for the determination of the content of total alkaloids. The decoction process was optimized by single factor test with boiling time, amount of water, and boiling times as factors. Then compared with traditional decoction, we can have a basis on clinic. Results: The optimal conditions of decoction process were soaking 20 min,14-fold water, boiling 30 min, once. The results showed that both the yield of dry extract and the content of active ingredient at different time points from the boiling powder granule were greatly more then its traditional one during the whole decoction process, and it suggested that Sini Boiling Powder is more safe then Sini traditional decoction. Conclusion: The advantage of high decoction rate and short preparing time on boiling powder can solve the problems that the traditional Chinese medicine is currently facing and should not be ignored.

Analysis on Chemical Constituents of Chinese Materia Medica Formulation Sini Decoction by HPLC-DAD-MS/MS / 中草药·英文版

Objective: To develop a high-performance liquid chromatography (HPLC) tandem mass spectrometry method for screening and identifying the multiple constituents in the complex Chinese materia medica (CMM) formulation Sini Decoction. Methods: The chemical constituents in Sini prescription as an entirety were isolated and analyzed by HPLC coupled with electrospray ionization ion-trap mass spectrometry (ESI-IT-MS) in order to clarify the chemical components of Sini Decoction and explore the chemical methods of studying CMM prescriptions. Results: Twenty-five compounds were isolated from the water extract of this decoction. Through chemical and spectral analyses, the structures of 20 compounds were elucidated, including 15 flavonoids, one triterpene, two coumarins, and two other types of compounds. By using HPLC-DAD-MSn technique, the MSn cleavage behaviors of the flavonoids have been summarized as well as the origin of the isolated compounds was assigned. Conclusions: The phytochemical compositon of Sini prescription is tentatively characterized by HPLC-DAD-ESI-IT-MSn. The results of the experiments demonstrate that the combination of HPLC and ESI-MSn is a sensitive and effective tool for rapidly investigating the complex CMM formulations.

Experimental study of the influence of Sini decoction on the inflammatory response and the immune function in septic rats / 中华危重病急救医学

Objective To observe the effect of Sini decoction on inflammatory response and immune function in septic rats and to discuss its possible mechanism.Methods 66 Sprague-Dawley (SD) rats were randomly divided into normal control group (n=6),model group (n=30),and Sini decoction group (n=30).Septic model was reproduced by intraperitoneal injection of lipopolysaccharide (LPS,5 mg/kg).After the reproduction of sepsis,rats in Sini decoction group received Sini decoction (5 g/kg) by gavage,while those in model group were given equal dose of normal saline in the same way.Rats in normal control group did not receive any treatment.Blood was collected via eye sockets at 2,12,24,48,72 hours after LPS administration,then the rats were sacrificed.The concentrations of inflammatory mediators,such as interleukin (IL-1,IL-6,IL-10),tumor necrosis factor-α (TNF-α),and the expression level of monocyte human leukocyte antigen-DR (HLA-DR) were determined with enzyme linked immunosorbent assay (ELISA),and the pathological changes in intestinal mucosa were observed under electron microscope.Results The concentration of IL-1 (ng/L) at 2 hours in model group was gradually increased and peaked at 48 hours (4.07 ± 0.10),and then gradually decreased,while the IL-1 level in Sini decoction group peaked at 12 hours (2.98 ± 0.12) followed by a gradual decrease.IL-6 (ng/L) in model and Sini decoction groups peaked twice at 12 hours (91.39 ± 1.55,73.00 ± 2.38) and 48 hours (82.51 ± 1.49,64.68 ± 1.68) respectively.IL-10 (ng/L) in model group gradually decreased after peaking at 2 hours (86.66 ± 6.12),and that in Sini decoction decreased at 12 hours (71.61 ± 2.35) followed by an increasing tendency,and approached normal level at 48 hours (109.09 ±4.77 vs.124.01 ± 7.89,P＞0.05).TNF-α (ng/L) in model group was gradually increased and peaked at 48 hours (83.37 ±3.79),and that in Sini decoction peaked at 12 hours (48.52 ± 1.21),and decreased to normal level at 72 hours (18.59 ± 1.97 vs.15.50 ± 2.68,P＞0.05).During the course of the experiment,as compared with those of the model group,level of IL-1,IL-6,and TNF-α were significantly lower at all time points in Sini decoction group,and IL-10was significantly higher.The expression level of HLA-DR (μg/L) in model and Sini decoction groups peaked at 2 hours (4.86 ± 0.15,4.85 ± 0.17),and then gradually lowered.HLA-DR expression μg/L) at 48 hours and 72 hours in Sini decoction group was significantly lower than that in model group (48 hours:4.21 ± 0.12 vs.2.74 ± 0.16,72 hours:3.80 ± 0.09 vs.2.27 ± 0.12,both P＜0.01).Pathological study of intestinal mucosa showed that the intestinal mucosa were infiltrated significandy by inflammatory cells,and villi were damaged severely in both model group and Sini decoction group at 2 hours after LPS challenge.Infiltration of inflammatory cells in Sini decoction group was less intense after 12 hours,and the intestine villi repair was more obvious compared with model group.Conclusion Sini decoction could regulate systemic inflammatory response,and promote the repair of intestinal mucosa,the intestinal function and the immune status of septic rats.