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Danggui Sinitang is first recorded in the Treatise on Cold Damage written by ZHANG Zhongjing in the Han dynasty. It is composed of Angelicae Sinensis Radix， Cinnamomi Ramulus， Paeoniae Radix Alba， Asari Radix et Rhizoma， Glycyrrhizae Radix et Rhizoma， Tetrapanacis Medulla， and Jujubae Fructus and serves as a classic formula for treating the syndrome of blood deficiency and cold reversal. This study systematically reviews the records of Danggui Sinitang in ancient Chinese medicine books of various dynasties and the modern clinical applications to probe into the composition， plant species， processing， dosage， decocting method， and indications of Danggui Sinitang， aiming to provide a reference for the development and clinical application of this classic formula. The review of the records showed that there were a variety of records of Danggui Sinitang with different composition， and the composition of this formula listed in the Treatise on Cold Damage has a significant impact on later generations and has been used by medical practitioners throughout history. Although the dosage of some drugs decreased during the Ming and Qing dynasties， the medical practitioners continued to use the original formula. In terms of processing， although there were slight changes in the processing of Angelicae Sinensis Radix， Paeoniae Radix Alba， Glycyrrhizae Radix et Rhizoma， and Tetrapanacis Medulla， the original processing method was inherited. In terms of indications， Danggui Sinitang was designed to treat cold reversal due to blood deficiency and dysentery. Furthermore， it was used to treat headache， convulsive disease， infantile convulsion， and private part adduction in the Ming and Qing dynasties. Nowadays， this formula is mostly used to treat diabetes peripheral neuropathy， rheumatoid arthritis， dysmenorrhea， Raynaud's disease and other diseases. In terms of precautions， ancient physicians believed that Danggui Sinitang should not be taken by pregnant women and should only be used for limb chills caused by blood deficiency and cold coagulation. For limb chills caused by other reasons， this formula should not be used indiscriminately. Modern research has not reported any serious adverse reactions related to this formula. Danggui Sinitang has a definite therapeutic effect. In subsequent research and development， quality control standards of Danggui Sinitang should be established while its safety is ensured， and the related preparations should be developed and applied.
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ObjectiveTo study the mechanism of Danggui Sinitang in mitigating gouty arthritis （GA） in rats by regulating autophagy via the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR） signaling pathway. MethodSixty male SD rats were randomly assigned into normal， model， colchicine （0.3 mg·kg-1）， and low-， medium-， and high-dose Danggui Sinitang （6.54， 13.08， and 26.16 g·kg-1） groups （n=10） and administrated with corresponding drugs by gavage. The rats in the normal group and model group were administrated with equal volume of normal saline by gavage for 7 days. One hour after administration on day 5， the GA model was established by injecting sodium urate suspension （50 g·L-1） into the right ankle joint of rats in other groups except the normal group， and the rats in the normal group were injected with sterile normal saline of the same volume. The swelling and pathological changes of the ankle joint were observed. The serum levels of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and IL-1β were determined. Western blot was employed to determine the protein levels of PI3K， phosphorylated PI3K （p-PI3K）， protein kinase B （Akt）， phosphorylated Akt （p-Akt）， mTOR， phosphorylated mTOR （p-mTOR）， microtubule-associated protein 1 light chain 3 Ⅱ/Ⅰ （LC3Ⅱ/Ⅰ）， autophagy effector Beclin-1， and ubiquitin-binding protein p62 in the synovial tissue. Real-time fluorescent quantitative PCR （Real-time PCR） was employed to determine the mRNA levels of PI3K， Akt， mTOR， LC3， Beclin-1 and p62. ResultCompared with the normal control， the model group showed increased joint swelling index （P<0.01）， elevated serum levels of TNF-α， IL-6， and IL-1β， inflammatory cell infiltration， and fibrous tissue hyperplasia. In addition， the model group showed up-regulated protein levels of PI3K， p-PI3K， Akt， p-Akt， mTOR， p-mTOR， and p62 and mRNA levels of PI3K， Akt， mTOR， and p62 in the synovial tissue， while it showed down-regulated protein levels of LC3Ⅱ/Ⅰ and Beclin-1 and mRNA levels of LC3 and Beclin-1 （P<0.01）. Compared with the model group， medium- and high-dose Danggui Sinitang alleviated the joint swelling （P<0.01）， lowered the serum levels of TNF-α， IL-6， and IL-1β （P<0.05）， and relieved the inflammatory cell infiltration in the synovial tissue of the ankle joint and the fibrous tissue hyperplasia. Moreover， they down-regulated the protein levels of PI3K， p-PI3K， Akt， p-Akt， mTOR， p-mTOR， and p62 and the mRNA levels of PI3K， Akt， mTOR， and p62 in the synovial tissue （P<0.05）， while they up-regulated the protein levels of LC3Ⅱ/Ⅰ and Beclin-1 and the mRNA levels of LC3 and Beclin-1 （P<0.05）. ConclusionDanggui Sinitang， especially at a high dose， can inhibit PI3K/Akt/mTOR signaling pathway to improve autophagy in the synovial tissue， thereby mitigating GA.
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ObjectiveTo predict the mechanism of Sinitang in treating myocardial ischemia-reperfusion injury （MI/RI） based on network pharmacology and verify the prediction results by cellular experiments. MethodThe traditional Chinese medicine system pharmacology database and analysis platform （TCMSP） was employed for retrieval of the main components and potential targets of Sinitang. Online Mendelian Inheritance in Man （OMIM） and GeneCards were employed to obtain the targets of Sinitang in treating MI/RI. STRING was employed to construct the protein-protein interaction （PPI） network， and DAVID to perform gene ontology （GO） annotation and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment. Finally， cellular experiments were carried out to verify the predicted anti-MI/RI mechanism of Sinitang. ResultA total of 105 active ingredients and 234 targets of Sinitang were screened out， among which 116 targets were predicted to be involved in the treatment of MI/RI. The GO annotation gave 587 entries， including 417 biological process entries， 101 cell component entries， and 69 molecular function entries. The KEGG analysis enriched 125 signaling pathways， involving vascular endothelial growth factor （VEGF）， phosphoinositide 3-kinase/protein kinase B （PI3K/Akt）， forkhead box transcription factor O （FoxO）， hypoxia-inducible factor-1 （HIF-1） apoptosis and other signaling pathways. The results of cell viability assay showed that Sinitang increased the survival rate of H9C2 cells damaged by hypoxia/reoxygenation （H/R）. Sinitang decreased the levels of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and creatine kinase-MB （CK-MB） in H9C2 cells damaged by H/R. The results of flow cytometry demonstrated that Sinitang decreased the apoptosis rate of H9C2 cells damaged by H/R. Western blot showed that Sinitang down-regulated the expression of Bcl-2 related X protein （Bax） and up-regulated that of B-cell lymphoma-2 （Bcl-2） in H/R-injured H9C2 cells. ConclusionSinitang treats MI/RI in a multi-target and multi-pathway manner， which involves the signaling pathways associated with apoptosis.
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Objective:To evaluate the clinical efficacy of Sanjiao Cidi therapy on acute cerebral infarction and its effect on levels of S100-β protein （S100-β）， tumor necrosis factor-α （TNF-α）， hypersensitive C-reactive protein （hs-CRP） and neuropeptide （NPY）. Method:One hundred and eighty patients were randomly divided into control group （90 cases） and observation group （90 cases） by random number table. Patients in control group got aspirin enteric-coated tablets， 100 mg/time， 1 time/day， edaravone injection （injected within 30 minutes） for 14 days， 30 mg/time， 2 times/day， simvastatin tablets， 20 mg/time， 1 time/day. In addition to the basic therapy of meloxicam tablets， patients in observation group were also treated with Sanjiao Cidi therapy. In the first step， patients got Guizhi therapy to dredge Zhongjiao and Shangjiao， 1 dose/day， for 8 days. In the second step， patients got Sini therapy to dredge Zhongjiao and Xiajiao， 1 dose/day， for 10 days. In the third step， patients got Tianjing Gubentherapy， 1 dose/day， for 10 days. The course of treatment was 4 weeks. Before the treatment， and at the first， second， third and fourth weeks after treatment， National Institutes of Health Stroke Scale （NIHSS） was scored. And before and after treatment， function scale of fuglmeyer （FMA）， ability of daily life activities （ADL）， mini-mental state examination （MMSE） and main symptoms of traditional Chinese medicine were scored. Comprehensive assessment of patient report outcome （PRO） was made. And levels of S100-β， hs-CRP， TNF-α and NPY were detected. And the incidence rate of pulmonary infection， urinary infection， skeletal myalgia， shoulder hand syndrome and shoulder subluxation of patients were recorded during hospitalization. Result:The clinical efficacy in observation group was better than that in control group （Z=2.141， P<0.05）. Scores of NIHSS in observation group were lower than those in control group at the first， second， third and fourth weeks after treatment （P<0.01）. Scores of upper limb， legs and the total scores from FMA were higher than those in control group （P<0.01）. Scores of the main symptoms of traditional Chinese medicine， symptoms， psychological and social scores， total scores of PRO， S100-β， hs-CRP， TNF-α and NPY were lower than those in the observation group （P<0.01）. And scores of ADL and MMSE were higher than those in control group （P<0.01）. Total incidence of complications in observation group was 27.27%（21/77）， which was lower than 46.15%（36/78） in control group （χ2=5.941， P<0.05）. Conclusion:In addition to conventional western medicine treatment， Sanjiao Cidi therapy can treat the patients with acute cerebral infarction， alleviate the degree of neurological deficit， improve the cognitive function， motor function of limbs and the ability of daily life， reduce the main symptoms of traditional Chinese medicine， the incidence of complications and the inflammatory response， protect the nerve cells， with a better clinical efficacy and comprehensive effect in patients than pure Western medicine.
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Objective::This paper aims to explore the potential anti-neoplasm targets and mechanism of Danggui Sinitang on hepatocellular carcinoma by analyzing the prescription of Danggui Sinitang with the method of network pharmacology, in order to provide targeted guidance for further studies. Method::The Traditional Chinese Medicine System Platform (TCMSP) and SwissTargetPrediction database were adopted to establish the database of Danggui Sinitang' s effective ingredients and targets. The Comparative Toxicogenomics Database (CTD), Therapeutic Target Database (TTD), and Human Phenotype Ontology (HPO) were used to build the hepatocellular carcinoma target database, which was then matched with Danggui Sinitang' s target database. Based on the matching results, STRING database was applied to analyze the interactions between the targets and the Database for Annotation, Visualization and Integrated Discovery (DAVID) was utilized for the enrichment analysis on gene ontology (GO) biological process and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. Then Cytoscape 3.6.0 software was used for networks analysis. Result::A total of 56 significant targets of Danggui Sinitang were found for treatment of hepatocellular carcinoma. The 106 cellular biological processes were obtained through GO biological process enrichment analysis and 23 related pathways were obtained by KEGG enrichment analysis, mainly including TNF signaling pathway, FoxO signaling pathway, Toll-like receptor signaling pathway, p53 signaling pathway, phosphatidylinositol-3-kinases(PI3K)/protein kinase B(Akt) signaling pathway, AMP activated protein kinase(AMPK) signaling pathway, Janus kinase(JAK)/signal transducer and activator of transcription(STAT) signaling pathway, et al. Conclusion::The therapeutic effect of Danggui Sinitang on hepatocellular carcinoma may be multi-target, multi-channel and multi-level. It can be inferred that quercetin and kaempferol may be two important active components, and PI3K/Akt signaling pathway and MAPK signaling pathway may be two important signaling pathways. This study not only makes a contribution to a better understanding of the anti-hepatocellular carcinoma mechanism of Danggui Sinitang, but also proposes a strategy to develop new TCM candidates at a network pharmacology level.
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Objective: To explore the protective effect and mechanisms of Renshen Sinitang and its active ingredients on cardiomyocyte injury induced by pentobarbital sodium. Method: H9C2 cells were sub-cultured with ginsenoside Rb2 0.01, 0.1, 1 μmol ·L-1, Re 0.01, 0.1, 1 μmol·L-1, isoliquiritigenin 20, 40, 80 μmol·L-1, glycyrrhetinic acid 10, 20, 40 μmol·L-1, Renshen Sinitang, 10, 100, 400 mg·L-1, for 4 h. After treatment with 0.1% of sodium pentobarbital for 30 min, cell viability, lactate dehydrogenase (LDH), lipid peroxide malondialdehyde (MDA), Na+-K+-adenosine triphosphate(ATP) ase, Ca2+-ATPase activity, and real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) were used to detect the expressions of peroxisome proliferative activated receptor-1α (PGC-1α), B-cell lymphoma-2 associated X protein(Bax) and cysteine aspartate-specific protease-3(Caspase-3) mRNA. Result: Renshen Sinitang and its active ingredients have a protective effect on heart failure cell model. Compared with the normal group, the cell survival rate of the model group decreased significantly, while the LDH and MDA contents increased significantly, and the Na+-K+-ATPase activity increased. Ca2+-ATPase activity was significantly decreased, PGC-1α mRNA expression was down-regulated, Bax and Caspase-3 mRNA expressions indicates the modeling(P+-K+-ATPase activity, increased Ca2+-ATPase activity, up-regulated PGC-1α mRNA expression, and inhibited Bax and Caspase-3 mRNA expression (PPConclusion: Renshen Sinitang and its active ingredients have a significant protective effect on heart failure cell model, and its mechanisms of action are related to anti-oxidation, improvement of mitochondrial energy metabolism and inhibition of mitochondrial apoptosis pathway.
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Objective To investigate the effect of a Chinese herbs mixture(Monkshood,ginger and licorice)on blood pressure(BP)and its possible mechanism in renovascular hypertensive rats.Methods 2K1C hypertensive rats received placebo(n=8)or Sinitung(n=8)by gavage for 2 weeks.BP was measured by tail-cuff.Plasma angiotensin Ⅱ(Ang Ⅱ)and calcium gene related peptide(CGRP)were examined by histochemical assay.Results Sinitang treatment significantly decreased BP(116.2?8.3 mm Hg vs placebo:131.6?14.2 mm Hg,P