Exploring the mechanism of Guizhi decoction’s“Jun-Chen-Zuo-Shi”in treating plant nervous disorders based on weighted network pharmacology and molecular docking techniques

Objective:To explore the mechanism of Guizhi decoction’s“Jun-Chen-Zuo-Shi”in treating plant nervous disorders based on network pharmacology and molecular docking methods.Methods:The main active ingredients of Guizhi decoction were screened from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),and plant nervous disorder-related targets were screened from the Gene Cards database,OMIM database,and PharmGKB database.The intersection of the two was obtained.The intersection targets were used to draw a protein interaction network and a“Traditional Chinese Medicine-active ingredient-target”network using the STRING database and Cytoscape 3.9.1.The nodes in the“Traditional Chinese Medicine-active ingredient-target”network were weighted according to the“Jun-Chen-Zuo-Shi”principle.Kyoto Encyclopedia of Genes and Genomes,and gene ontology enrichment analysis were performed on the intersection targets.Molecular docking was used to verify the affinity between core targets and key ingredients.Results:A total of 225 effective components of Guizhi decoction were screened,among which 127 components could bind to 160 common targets and play a therapeutic role.The common targets were mainly enriched in 2785 gene ontology entries and 189 Kyoto Encyclopedia of Genes and Genomes pathways.Molecular docking confirmed that core targets could spontaneously bind to key ingredients.Conclusion:The key targets for the treatment of plant nervous disorders by Guizhi decoction are MAPK1,TP53,RB1,STAT3,MAPK3,MAPK14,etc.,which reflect the characteristics of the synergistic mechanism of traditional Chinese medicine with multiple components,targets,and pathways through the regulation of inflammatory signal pathways and oxidative stress processes.

Guizhi Decoction(桂枝汤) Inhibits Cholinergic Transdifferentiation by Regulating Imbalance of NGF and LIF in Salt-Sensitive Hypertensive Heart Failure Rats

Objective: To observe the imbalance of anatomical and functional innervation factors of sympathetic nerves, nerve growth factor(NGF) and leukemia inhibitory factor(LIF), in salt-sensitive hypertensive heart failure rats and to explore the effects of treatment with Guizhi Decoction(桂枝汤) on sympathetic remodeling by inhibiting cholinergic transdifferentiation. Methods: SS-13 BN and Dahl salt-sensitive(DS) rats were divided into 3 groups: SS-13 BN group(control group, n=9), DS group(model group, n=9) and GS group(Guizhi Decoction, n=9). After 10 weeks of a high-salt diet, the GS group rats were given Guizhi Decoction and other two groups were given saline at an equal volume as a vehicle. After 4 weeks’ intragastric administration, rats were executed to detect the relevant indicators. Echocardiography and plasma n-terminal pro-B type natriuretic peptide(NT-proBNP) levels were used to assess cardiac function. Noradrenaline(NA) levels in the plasma and myocardium were detected to evaluate the sympathetic function. NGF and LIF expression were detected in the myocardium by Western blot or quantitative real-time PCR. Double immunofluorescence or Western blot was used to detect tyrosine hydroxylase(TH), choline acetyltransferase(CHAT) and growth associated protein 43(GAP43) in order to reflect anatomical and functional changes of sympathetic nerves. Results: DS group had anatomical and functional deterioration of sympathetic nerves in the decompensation period of heart failure compared with SS-13 BN group. Compared with the DS group, Guizhi Decoction significantly decreased the expression of LIF mRNA/protein(P<0.01), increased the expression of NGF(P<0.05 or P<0.01), enhanced the levels of TH^+/GAP43^+ and TH^+/CHAT^+ positive nerve fibers(P<0.01), and improved the protein expression of TH and GAP43 in left ventricle, but had no effect on CHAT(P>0.05). Guizhi Decoction inhibited inflammatory infiltration and collagen deposition of myocardial injury, increased the content of myocardial NA(P<0.05), reduced the plasma NA level(P<0.01), improved cardiac function(P<0.01), and improved weight and blood pressure to some extent(P<0.05), compared with DS group. Conclusions: Guizhi Decoction could inhibit cholinergic transdifferentiation of sympathetic nerves, improve the anatomical and functional denervation of sympathetic nerves, and delay the progression of decompensated heart failure. The mechanism may be associated with the correction of the imbalance of NGF and LIF.

Preventive effect of different compatibilities of Ramulus Cinnamomai and Radix Paeomiae alba in Guizhi decoction on cardiac sympathetic denervation induced by 6-OHDA

Objective To observe the preventive effect of different compatibilities of Ramulus Cinnamomi(RC)and Radix Paeomiae alba(RPA)in Guizhi Decoction(GZD)on neurotransmitters and their rate-limiting enzymes,and neurotrophic factors of cardiac sympathetic denervation model rats induced by 6-hydroxydopamine(6-OHDA).Methods Totally 54 male Wistar rats were randomly divided into 6 groups,i.e.,the blank control group。

Effects of Guizhi Shaoyao Zhimu Decoction on Laboratory Indicators and Immune Functions of Patients with Rheumatoid Arthritis

[Objectives]To explore the effects of Guizhi Shaoyao Zhimu Decoction on laboratory indicators and immune functions of patients with rheumatoid arthritis.[Methods]A total of 110 patients with rheumatoid arthritis admitted to the Second Department of Orthopedics,the Affiliated Chinese and Western Medicine Hospital of Nanjing,Nanjing University of Chinese Medicine from December 2014 to December 2016 were selected as the research objects and divided into a control group and an observation group using the random number table method,with 55 cases in each group.The control group was treated with conventional western medicine,and the observation group was treated with Guizhi Shaoyao Zhimu Decoction on the basis of the control group.Both groups were treated for one month.The clinical effects,improvement of clinical symptoms,laboratory indicators and immune function indicator levels between the two groups were compared;the incidence of adverse reactions in the two groups was counted.[Results]The total effective rate of the observation group was 92.73%,higher than that of the control group(78.18%)(P<0.05).Compared with that before treatment,after one month of treatment,the grip strength of the two groups increased,and the observation group was greater than the control group(P<0.05);the morning stiffness time and 20 m walking time of both groups were shortened,and the observation group was shorter than the control group(P<0.05);the number of joint tenderness,joint swelling,ESR,MPV,PDW,serum CRP,plasma IgA,IgG,IgM,RF levels in both groups decreased,and the observation group was lower than the control group(P<0.05);the serum C3 levels in both groups increased,and the observation group was higher than the control group(P<0.05).During the treatment,the incidence of adverse reactions in the observation group was 0.00%,which was lower than that in the control group(10.91%,P<0.05).[Conclusions]Using Guizhi Shaoyao Zhimu Decoction to treat rheumatoid arthritis can improve the laboratory indicators of patients,and enhance their immune functions,improve the curative effect,and the safety is high.

Potential Mechanism of Huangqi Guizhi Wuwu Decoction for Cervical Spondylosis treatment based on Network Pharmacology

Objective:To study the potential mechanism of Huangqi Guizhi Wuwu Decoction in the treatment of cervical spondylosis based on the network pharmacological method,and to provide a basis for clinical application and pharmacological research.Methods:TCMSP search was used to screen the main active compounds and related action targets of Huangqi Guizhi Wuwu Decoction,the standard names of action targets were obtained through the Uniprot database,and the"drug-target"interaction network was constructed by using Cytoscape3.6.1 software.The related targets of cervical spondylosis were obtained by searching GeneCards,OMIM,DisGeNET,and CTD databases,and the disease targets and drug targets were mapped by the Venny platform,and the intersection genes of them were the potential targets for drug treatment of this disease.Then,the intersection genes were input into the STRING database and Cytoscape 3.6.1 software,and the protein-protein interactions(PPI)network of"drug-disease intersection targets"was constructed,and we screened the core targets.Finally,GO biological function analysis and KEGG signaling pathway analysis of core targets were carried out through the DAVID database.Results:According to the screening conditions,74 effective compounds and 138 drug action targets of Huangqi Guizhi Wuwu Decoction were obtained,12179 genes related to cervical spondylosis were obtained,and the Venny platform analysis obtained 105 intersecting targets.With visual network processing by Cytoscape software,33 core targets were obtained by analyzing and calculating the core target degree values,which were JUN,PTGS2,NR3C1,TNF,IL6,TP53,EGFR,VEGFA,NOS3,IL1B,and so on.GO analysis showed that there were 133 items(P<0.05),involving adrenergic receptor activation,neurotransmitter receptor activation,nuclear receptor activation,catecholamine binding,etc.KEGG analysis obtained a total of 139 pathways(P<0.05),involving IL-17 signaling pathway,and tumor necrosis factor signaling pathway,relaxin signaling pathway,AGE-RAGE signaling pathway of diabetic complications,fluid shear stress,and atherosclerosis.Conclusion:the active components in Huangqi Guizhi Wuwu decoction may act on the core targets such as JUN,PTGS2,NR3C1,TNF,IL6,TP53,VEGFA through IL-17 signal pathway,tumor necrosis factor signal pathway,and AGE-RAGE signal pathway of diabetic complications,and exert their therapeutic effects.The research results can provide a basis for future basic and clinical research.

Comparing the mechanism of four classic Gualou-Xiebai prescriptions for cardiovascular diseases with phlegm and blood stasis syndrome based on molecular network modeling

Background:Four classical Traditional Chinese Medicine prescriptions,namely Gualou Xiebai Baijiu decoction,Gualou Xiebai Banxia decoction(GLXBBX),Zhishi Xiebai Guizhi decoction(ZSXBGZ)and Danlou prescription(DL),have been frequently used for treatment of phlegm and blood stasis syndrome(PBSS)-related cardiovascular diseases.However,its therapeutic mechanism has not been clearly elucidated.This study aimed to explore PBSS and its molecular mechanism,clarify and compare the mechanisms of four prescriptions in treating PBSS-related diseases.Method:In this study,we collected four prescriptions’compounds,predicted therapeutic targets,and enriched pathways which were based on network pharmacology.Then,we analysed the commen and different mechanisms by combing the network of components,targets and pathways.Finally,molecular docking was engaged to assess the binding potential of key compounds and hub targets.Results:We showed that four prescriptions’intersection genes(VEGFA,SRC,EGFR,etc.)were commonly enriched in PI3K-AKT signaling pathway,HIF-1 signaling pathway,etc.In addition,platelet activation and cAMP signaling pathway were singly enriched from the GLXBBX through unique compounds 12,13-epoxy-9-hydroxynonadeca-7,10-dienoic acid and Cyclo(L-tyrosyl-L-phenylalanyl).These bioactive compounds may exert GLXBBX’s unique pharmacological pathways via involving in mediating PPARA,PTGER3,etc.Sphingolipid signaling pathway was singly enriched from the ZSXBGZ through unique compounds tetramethoxyluteolin,ergosterol peroxide,etc.These bioactive compounds could mediate ADORA1,ADORA3 and TNFRSF1A to regulate ZSXBGZ’s unique pharmacological pathways.AMPK signaling pathway was singly enriched from the DL through unique compounds kaempferol,evofolinb,ethyl acid and aureusidin.These bioactive compounds were involved in mediating the main targets of AMPK signaling pathway,such as TNF,TNFRSF1A,etc.Conclusions:Our research demonstrated that GLXB-prescriptions involved in almost all pathological stages of PBSS-related cardiovascular diseases by modulating high-frequency shared pathways and targets mainly through key compounds(quercetin,mandenol,sitosteryl acetate and luteolin,etc.),for example,participate in the process of atherosclerosis,lipid metabolism,inflammation,immune response,thrombosis,inhibit inflammatory factors and platelet aggregation,regulate immune function,vascular function,oxidative stress.In addition to common pharmacological efficacies,there could also be specificities among GLXB prescriptions due to different compounds.For example,GLXBBX tends to regulate the function of vascular and endothelial barrier,prevent thrombosis.ZSXBGZ tends to regulate lipid metabolism and protect the heart from lipid accumulation.DL tends to maintain energy homeostasis and improve inflammation.