Mechanism of Danggui Sini Decoction(当归四逆汤)for Atherosclerosis Obliterans Based on Network Pharmacology and Molecular Docking

Objective:Based on network pharmacology and molecular docking,we want to explore the pharmacological effects and mechanism of Danggui Sini Decoction in the treatment of lower extremity arteriosclerosis obliterans.Methods:Using TCMSP database to search the main active components of Danggui Sini Decoction(当归四逆汤,DSD)and their related targets,Cytoscape3.8.1 software was used to construct a"component-disease-target"interaction network.Meanwhile,DAVID database was used to enrich the key target genes with GO and KEGG functions.And we used Auto Dock Tools 1.5.6 for molecular docking.Results:A total of 45 candidate active molecules and 250 potential target proteins related to ASO were screened.Key genes such as TNF,IL6,VEGFA,MMP9,IL1B,CCL2,CXCL8,ICAM1,VCAM1,and IL10 are mainly through TNF signaling pathway,HIF-1 signaling pathway,cytokine-cytokine receptor interaction,Toll-like receptor signaling pathway,NF-kappa B signaling pathway,MAPK signaling pathway and other biological pathways exert their effects.The results of molecular docking showed that 5UUI-sesamin,5UUI-paeoniflorin,4XCT-sesamin,and 4XCT-sesamin have extremely strong binding ability.Conclusion:Danggui Sini Decoction(当归四逆汤,DSD)can synergistically exert pharmacological effects through multiple components,multiple targets,and multiple pathways.On the basis of regulating immunity and inhibiting smooth muscle proliferation,it can prevent the occurrence and development of ASO.

Danggui Sini decoction treatment of refractory allergic cutaneous vasculitis:A case report

BACKGROUND Allergic cutaneous vasculitis(ACV)is a difficult disease to treat.At present,there is no effective treatment for this condition.Traditionally,immunosuppressants and hormones have been primarily used in its management,but the treatment effect is suboptimal,and it has several side effects.CASE SUMMARY We present the case of a 19-year-old woman who presented at our hospital with a four-year history of symmetric skin lesions mainly affecting her lower extremities.She had previously undergone treatment with prednisolone acetate,cetirizine hydrochloride,and loratadine tablets but had not experienced any relief in her condition.Thereafter,she was treated with oral traditional Chinese medicine.Her skin damage gradually improved within two months of treatment initiation.After six months,the skin ulcers had completely subsided.No evidence of skin ulcer recurrence was observed during the subsequent follow-up.This report presents the first case of a female patient who received oral Danggui Sini decoction for the treatment of ACV.CONCLUSION Danggui Sini decoction may be a promising oral treatment for ACV patients.

Effect of Sini Decoction plus Ginseng on COVID-19 based on network pharmacological analysis

Objective:To explore the effect of Sini Decoction plus Ginseng on COVID-19 based on network pharmacological analysis.Methods:TCMSP platform was used to search the compounds of Sini Decoction plus Ginseng with oral bioavailability(OB)≥30%and drug-likeness(DL)≥0.18,and the results were input into the UniProt database and converted into standard target names;Genecards and OMIM database were used to find COVID-19 target,and the intersection targets were obtained and Venn diagram was drawn.Cytoscape 3.7.2 was applied to make the network diagram of composition-disease-target;The interaction database platform-String was used to analyze the target protein interaction,and the data were input into the software of Cytoscape 3.7.2 to make the network diagram;David database was used to analyze the accumulation of Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathways of drug-disease intersection targets.The component target pathway network was constructed by using Cytoscape 3.7.2.Results:Altogether,112 active components of Sini Decoction plus Ginseng were screened,corresponding to 234 targets.Besides,261 COVID-19 targets were obtained after screening,and the Venn map showed that 50 targets were intersected.Quercetin,kaempferol,naringenin,andβ-sitosterol were found to have higher moderate values shown by the component-disease-target network.The target proteins with high PPI network analysis value were IL-6,MAPK8,MAPK3,MAPK1,TP53,TNF,and CASP3.GO enrichment function analysis showed that 341 biological processes,33 cell components,and 50 molecular functions were involved,which showed inflammatory reaction,cell response to lipopolysaccharide,exogenous apoptosis signal pathway,positive regulation of RNA polymeraseⅡpromoter transcription,cytokine activity,chemokine activity,heme binding,and other biological processes.KEGG signaling pathway enrichment function analysisshowed that there were 112 signaling pathways.It included TNF signaling pathway,tuberculosis,influenza A,PI3K Akt signaling pathway,HIF-1 signaling pathway,and Toll-like receptor signaling pathway.According to the component-target-pathway network diagram,quercetin,kaempferol,naringenin,andβ-sitosterol in Sini Decoction plus Ginseng may act on IL-6,MAPK8,MAPK3,MAPK1,TP53,TNF,CASP3,and other targets through TNF signaling pathway,MAPK signaling pathway,Tolllike receptor signaling pathway,PI3K-Akt signaling pathway,and HIF-1 signaling pathway.Conclusion:Sini Decoction plus Ginseng can affect COVID-19 through multiple active components,multiple targets,and multiple pathways.

Research progress of Sini decoction in pharmacy, pharmacology and clinical application

Sini decoction originated from Zhang Zhongjing's Treatise on Cold Pathogenic and Miscellaneous Diseases(200-210 C.E.)in the Eastern Han Dynasty.It is a traditional and famous prescription in China.Its preparations mainly include Sini decoction,Sini decoction drop pills and Sini decoction suppositories.The main chemical components are diterpenoid alkaloids,gingerol,volatile oil,coumarin,polysaccharide,triterpene saponins,flavonoids,amino acids,and alkaloids.This product has a cardiovascular function,anti-shock,anti-diabetes complications,anti-tumor,anti-atherosclerosis,and effects on the nervous system.Modern clinical practice is widely used in cardiovascular,respiratory,digestive,neurological and gynecological diseases.This paper reviews the pharmaceutical research,pharmacological effects,safety evaluation and clinical application of Sini decoction,including the source and composition of Sini decoction,the origin and resource status of authentic medicinal materials of Sini decoction,the research on preparation form reform,chemical composition and quality control,to provide a reference for further research and clinical promotion of Sini decoction.

Network pharmacology and experimental validation to reveal the pharmacological mechanisms of Sini decoction(四逆汤)against renal fibrosis

OBJECTIVE:To investigate the mechanism by which Sini decoction(四逆汤,SND)improves renal fibrosis(Rf)in rats based on transforming growth factor β1/Smad(TGF-β1/Smad)signaling pathway.METHODS:Network pharmacology was applied to obtain potentially involved signaling pathways in SND's improving effects on Rf.The targets of SND drug components and the targets of Rf were obtained by searching databases,such as the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCSMP)and GeenCard.The intersection targets of two searches were obtained and underwent signaling pathway analysis using a Venn diagram.Then experimental pharmacology was utilized to prove and investigate the effects of SND on target proteins in the TGF-β1/Smad signaling pathway.The Rf rat model was established by unilateral ureteral occlusion(UUO).The expression levels of transforming growth factor,matrix metalloproteinase-9(MMP-9),matrix metal protease-2(MMP-2),connective tissue growth factor(CTGF),and tissue inhibitor of metalloproteinase-1(TIMP-1)were determined by Masson staining of rat renal tissue,and immunohistochemical methods.The expression levels of Smad3,Smad2,and Smad7 in renal tissue were determined by Western blotting(WB).The mechanism of the improving effects of SND on Rf was investigated based on TGF-β1/Smad signaling pathway.RESULTS:A total of 12 drug components of Fuzi(Radix Aconiti Lateralis Preparata),5 drug components of Ganjiang(Rhizoma Zingiber),and 9 drug components of Gancao(Radix Glycy et Rhizoma)were obtained from the database search,and 207 shared targets were found.A total of 1063 Rf targets were found in the database search.According to the Venn diagram,in total,96 intersection targets were found in two database searches.The metabolic pathways involved included TGF-β signaling pathway,phosphatidylinositol-3-kinase/serine-threonine protein kinase signaling(PI3K/Akt)pathway,and hypoxia-inducible factor-1(HIF-1)signaling pathway.Masson staining analysis showed that compared with the model group,the renal interstitial collagen deposition levels in the SSN and SND groups were significantly lower(P<0.05).Immunohistochemical analysis,compared with the control group,the positive cell area expression levels of MMP-9/TIMP-1 and MMP-2/TIMP-1 in the kidney tissue of the model group were significantly decreased(P<0.05,P<0.01),and the positive cell area expression levels of CTGF and TGF-β1 were significantly increased(P<0.01).Compared with the model group,the positive cell area expression levels of MMP-9/TIMP-1 and MMP-2/TIMP-1 in the kidney tissue of the SSN and SND groups were significantly increased(P<0.05,P<0.01),and the positive cell area expression levels of CTGF and TGF-β1 in the kidney tissue were significantly decreased(P<0.05,P<0.01).WB results showed that the SSN group and the SND group could reduce the expression of Smad2 and Smad3(P<0.05)and increase the expression of Smad7(P<0.05).

Sini decoction as an adjuvant therapy for angina pectoris:a systematic review of randomized controlled trials

OBJECTIVE: To systematically assess the effects and safety of Sini decoction as an adjuvant therapy for patients with angina pectoris.METHODS: We searched Pub Med, Excerpt Medica Database, the Cochrane library, Wanfang Database,China National Knowledge Infrastructure Database,China Science and Technology Journal Database from the date of its inception until August 1, in2014. Available literatures were selected according to the inclusion criteria. Two reviewers finished data extraction, checked the data and assessed the methodological quality of studies, independently.The Review Manage Software 5.1.0 was used for data analysis.RESULTS: Six trials involving 453 participants were eligible. None of the trials reported the mortality due to angina pectoris. The secondary outcomes showed that Sini decoction, together with nitroglycerin when necessary, may have some effects on reducing the number of angina attacks and the amount of nitroglycerin. But in terms of reducing the duration of angina and improvement of electrocardiogram, there were no statistical differences between Sini decoction group and isosorbide dinitrate group. Only one reported that no adverse events were found.CONCLUSION: Based on this systematic review, Sini decoction can reduce the dosage of nitroglycerin, when compared with isosorbide dinitrate group.And there were no enough evidence in the papers to draw any conclusions for the safety of Sini decoction.

Analysis on Chemical Constituents of Chinese Materia Medica Formulation Sini Decoction by HPLC-DAD-MS/MS

Objectives 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. Conclusion The phytochemical compositon of Sini prescription is tentatively characterized by HPLC-DAD-ESI-IT-MS.. 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.

Screening and Validation of Active Ingredients in Sini Decoction by Combination Method of Pharmacophore Modeling and Molecular Docking

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-ɑ 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.

Clinical Study on The rapeutic Mechanism of Sini Decoction (四逆汤) in Treating Post-Percutane ous Transluminal Coronary Angioplasty Ische mia-Reperfusion In jury in Terms of Syndrome Typing of TCM

Objective: To study the mechanism of Sini Decoction (SND) in prevention and treatment of post-percutaneous transluminal coronary angioplasty (PTCA) ischemia-reperfusion injury with different Syndrome typing of TCM.Methods: Forty patients who received PTCA were randomly divided equally into the SND group and the control group, there were 10 of Excess Syndrome (ES) and 10 of Deficiency Syndrome (DS)in each group.25 ml SND was gi ven daily to the SND group from 3 days before operation to the third day after operation. The blood superoxide dismutase (SOD) activity, malondialdehyde (MDA) and nitric oxide (NO) content of patients were determined before PTCA, and 1 hr, 12 hrs, 24 hrs, 48 hrs and 72 hrs after PTCA. Results: Before PTCA, the cases with DS were characterized by low SOD activity and high MDA content, as compared with the patients with ES, P<0.05. SND could relieve the post-PTCA deprivation of SOD activity and NO content and the elevation of MDA level in both ES and DS patients, the amplitude of elevation of SOD activity in DS patients was higher than that in ES patients (P<0.05). Conclusion: SND has antagonizing effect on post-PTCA ischemia-reperfusion injury, which is more effective in treating patients with DS.

Study on Influence of Sini Decoction (四逆汤) on Quality of Life of Patients after Percutane ous Transluminal Coronary Angioplasty

Objective: To determine the influence of Sini Decoction (SND) on quality of life(QOL) of patients after percutaneous transluminal coronary angioplasty (PTCA). Methods: Randomized case-control clinical trial was conducted to evaluate QOL of 40 post-PTCA patients before and after SND treatment by scoring. Results: The scores in physical symptoms, sense of well-being, degree of depression, index of satisfaction of life and work capacity of the patients after PTCA were improved significantly as compared with before PTCA, P<0.01. Scores of patients who received SND treatment were higher than those untreated with SND in the first three criteria, P<0.05, particularly in relieving palpitation and dyspnea. Conclusion: SND is helpful in improving QOL of patients after PTCA.