Study on network pharmacology of Polygalae Radix- Acori Tatarinowii Rhizoma medicinal pair for depression and Alzheimer disease with the same treatment / 国际中医中药杂志

Objective:To explore the molecular mechanism of Polygalae Radix - Acori Tatarinowii Rhizoma medicinal pair for depression and Alzheimer disease (AD) with the same treatment through network pharmacology. Methods:Effective components of Polygalae Radix - Acori Tatarinowii Rhizoma medicinal pair were retrieved from TCMSP, TCMID and ETCM databases. The disease targets of depression and AD were retrieved from GeneCards, TTD and CTD databases. Targets of action of drugs on active components were predicted through SwissTargetPrediction, and then the intersection targets of medicinal pair and the diseases were taken. Cytoscape 3.6.1 was used to construct the interaction network of Polygalae Radix - Acori Tatarinowii Rhizoma medicinal pair on "component-common target-disease". The enrichment analysis of GO function and KEGG pathway was carried out with the help of Metascape platform, and molecular docking verification was carried out. Results:Through searching the databases and literature, 78 compounds in Polygalae Radix - Acori Tatarinowii Rhizoma medicinal pair were obtained, corresponding to 41 targets of different diseases with the same treatment. The GO function was mainly concentrated in response to lipopolysaccharide and cellular response to nitrogen compound. The KEGG pathway was mainly concentrated in lipid and atherosclerosis, calcium signaling pathway, serotonergic synapse, insulin resistance and so on. The core targets were PTGS2, ESR2, etc. Molecular docking showed that most of the core components could form stable conformation with the core targets. Conclusions:Polygalae Radix - Acori Tatarinowii Rhizoma medicinal pair has the characteristics of multi-component, multi-target and multi-pathway in the same treatment of depression and AD. Through their core components of senegenin, 1-carbobutoxy-β-carboline, 6-hydroxy-1,2,3,7-tetramethoxyxanthone, kaempferol and etc., the pair can act on PTGS2 and other targets, regulate lipid and atherosclerosis, calcium signaling pathway, serotonergic synapse, insulin resistance and so on, and play a therapeutic role in depression and Alzheimer's disease with the same treatment.

Antiepileptic Pharmacological Mechanism of Acori Tatarinowii Rhizoma： A Review / 中国实验方剂学杂志

Epilepsy is a recurrent neurological disease with synchronous abnormal high discharge of neurons in the brain. The pathogenesis of this disease is extremely complex， which is closely related to neurotransmitter regulation， oxidative stress response， inflammatory factors， neuroglial cell， and abnormal gene expression. Western medicine mainly uses phenobarbital， phenytoin sodium， carbamazepine， and other drugs， but long-term use also produces certain toxic and side effects. Traditional Chinese medicine （TCM） believes that the pathogenesis of epilepsy is related to wind， fire， phlegm， and blood stasis， which leads to dysfunction of viscera， disorder of Qi movement， and finally uncontrolled spirit. In recent years， TCM has achieved certain curative effects on the treatment of epilepsy. As a high-frequency antiepileptic drug， Acori Tatarinowii Rhizoma has the effects of opening orifices and eliminating phlegm， awakening spirit and benefiting intelligence， and removing dampness and opening stomach， which has been widely used in clinic. In this paper， the pathogenesis of epilepsy and the pharmacological mechanism of Acori Tatarinowii Rhizoma extract and chemical components in the treatment of epilepsy were expounded by referring to relevant pharmacological studies and animal experiments. It was found that Acori Tatarinowii Rhizoma played a role in regulating the neurotransmitter level， antioxidant stress response， scavenging oxygen free radicals， regulating the expression of c-fos gene， reducing the level of inflammatory mediators， resisting neuronal apoptosis， and regulating the neuroglial cells and the permeability of blood-brain barrier. This paper summarizes the positive effects of Acori Tatarinowii Rhizoma on the treatment of epilepsy， and provides a scientific basis for the popularization and application of Acori Tatarinowii Rhizoma in the prevention and treatment of epilepsy.

Antiepileptic Pharmacological Mechanism of Acori Tatarinowii Rhizoma： A Review / 中国实验方剂学杂志

Epilepsy is a recurrent neurological disease with synchronous abnormal high discharge of neurons in the brain. The pathogenesis of this disease is extremely complex， which is closely related to neurotransmitter regulation， oxidative stress response， inflammatory factors， neuroglial cell， and abnormal gene expression. Western medicine mainly uses phenobarbital， phenytoin sodium， carbamazepine， and other drugs， but long-term use also produces certain toxic and side effects. Traditional Chinese medicine （TCM） believes that the pathogenesis of epilepsy is related to wind， fire， phlegm， and blood stasis， which leads to dysfunction of viscera， disorder of Qi movement， and finally uncontrolled spirit. In recent years， TCM has achieved certain curative effects on the treatment of epilepsy. As a high-frequency antiepileptic drug， Acori Tatarinowii Rhizoma has the effects of opening orifices and eliminating phlegm， awakening spirit and benefiting intelligence， and removing dampness and opening stomach， which has been widely used in clinic. In this paper， the pathogenesis of epilepsy and the pharmacological mechanism of Acori Tatarinowii Rhizoma extract and chemical components in the treatment of epilepsy were expounded by referring to relevant pharmacological studies and animal experiments. It was found that Acori Tatarinowii Rhizoma played a role in regulating the neurotransmitter level， antioxidant stress response， scavenging oxygen free radicals， regulating the expression of c-fos gene， reducing the level of inflammatory mediators， resisting neuronal apoptosis， and regulating the neuroglial cells and the permeability of blood-brain barrier. This paper summarizes the positive effects of Acori Tatarinowii Rhizoma on the treatment of epilepsy， and provides a scientific basis for the popularization and application of Acori Tatarinowii Rhizoma in the prevention and treatment of epilepsy.

Data mining-based analysis of formulation rules for prescriptions containing herbal pair Acori Tatarinowii Rhizoma-Polygalae Radix / 中国中药杂志

By the in-depth excavation of prescriptions containing herbal pair Acori Tatarinowii Rhizoma-Polygalae Radix in the Dictionary of Traditional Chinese Medicine Prescriptions, this study analyzed their formulation rules, so as to provide reference for their clinical application and new drug development. First, the prescriptions containing Acori Tatarinowii Rhizoma-Polygalae Radix were collected from the Dictionary of Traditional Chinese Medicine Prescriptions, and their indications, herbal compatibility, and dosage forms were analyzed statistically using the Traditional Chinese Medicine Inheritance Support System(TCMISS). Meanwhile, the formulation rules and common dosage forms for the top four indications(amnesia, palpitation, mania, and epilepsy) sorted by frequency were analyzed with Apriori algorithm. A total of 507 prescriptions containing Acori Tatarinowii Rhizoma-Polygalae Radix were screened out, involving 15 indications(frequency>10) like amnesia, palpitation, mania, and epilepsy. There were 30 commonly used Chinese herbs(frequency≥60), with the Qi-tonifying herbs(Ginseng Radix et Rhizoma and Glycyrrhizae Radix et Rhizome), mind-tranquilizing herbs(Poria and Poria cum Radix Pini), and Yin-nourishing herbs(Angelicae Sinensis Radix and Ophiopogonis Radix) being the core ones. The commonly used dosage forms were honey pill, paste pill, decoction, and powder. These have indicated that the herbal pair Acori Tatarinowii Rhizoma-Polygalae Radix is often combined with Qi-tonifying, Yin-nourishing, and mind-tranquilizing herbs for the treatment of "heart or brain diseases" caused by phlegm production due to spleen deficiency, Qi and blood deficiency, and phlegm-turbidity blocking orifice. In the treatment of amnesia, supplementing essence and replenishing marrow are considered on the basis of tonifying Qi, nourishing Yin, and tranquilizing mind. In the treatment of palpitation and mania, tranquilizing mind is emphasized. In the treatment of epilepsy, the emphasis is placed on resolving phlegm, extinguishing wind, and stopping convulsion.

GC-MS analysis of extraction kinetics of volatile oil from Acori Tatarinowii Rhizoma by steam distillation / 中草药

Objective: The experiment was designed to reveal the extraction, distribution and influencing factors of volatile components in the extraction process of volatile oil from Acori Tatarinowii Rhizoma (ATR). Methods: Volatile oil of ATR was extracted by steam distillation and the extract was collected every 30 min to separate the aromatic water and volatile oil. Results: A total of 56 volatile compounds were determined, of which β-asarone, methyleugenol, cis-methylisoeugenol and γ-asarone were the main characteristic constituents. There were 41 kinds of components distributed only in water, four components only in oil and 11 kinds in both oil and water. Correlation analysis showed that the specific components in water were positively correlated with the dissolution/diffusion of the main components in water, but negatively correlated with the main components in volatile oil. The water solubility of the unique components in water was the highest. The results of radar and PCA showed that the water solubility and boiling point of the specific components in water were very high, the vapor pressure of the common components of oil and water was the highest, and the polar surface areas of the special components in oil were high. Conclusion: Affected by the physical and chemical properties of volatile component, some components specifically distributed in water increased the content of main components in the aromatic water, may resulting in volatile oil extraction process easy to "emulsification", in turn, leading to an important reason for the declining quality of volatile oil.

Research on network pharmacology of Acori Tatarinowii Rhizoma combined with Curcumae Radix in treating epilepsy / 中国中药杂志

The chemical constituents and action targets of Acori Tatarinowii Rhizoma and Curcumae Radix were screened by network pharmacological method,and the mechanism of the combination of Acori Tatarinowii Rhizoma and Curcumae Radix in the treatment of epilepsy was analyzed. All chemical constituents of Acori Tatarinowii Rhizoma and Curcumae Radix were retrieved by TCMSP,and their action targets were screened. Component target PPI network was constructed. Epilepsy-related genes were retrieved from PharmGkb database,and PPI networks of disease targets were drawn by Cytoscape software. Cytoscape software was used to merge the network,screen the core network,and further analyze the gene GO function and KEGG pathway enrichment,which was verified by experimental research. One hundred and five chemical constituents of Acori Tatarinowii Rhizoma and 222 chemical constituents of Curcumae Radix were retrieved. Nineteen compounds were selected as candidate compounds according to OB and DL values. Among them,4 chemical constituents of Acori Tatarinowii Rhizoma and 15 chemical constituents of Curcumae Radix were found. A total of 88 target proteins were retrieved by retrieving TCMSP data,and PPI network was constructed. Through PharmGkb database,29 epilepsy-related genes were retrieved and disease target network was established. Cytoscape software and plug-ins were used for network merging and core network screening,and 69 genes were screened out. Through GO function analysis and KEGG pathway analysis,the mechanism of anti-epilepsy is related to prolactin signaling pathway,HTLV-Ⅰ infection signaling pathway,MAPK signaling pathway and herpes simplex infection signaling pathway. Further experimental verification showed that the serum prolactin level in epileptic rats was significantly increased. The neurons in hippocampal CA1 area degenerated,necrotized and lost 24 hours after epileptic seizure,and some neuron interstitial edema occurred. The possible mechanism of compatibility of Acori Tatarinowii Rhizoma and Curcumae Radix is related to serum prolactin level,MAPK signaling pathway,HTLV-Ⅰ infection and herpes simplex infection. The analysis may be related to viral encephalitis caused by HTLV-Ⅰ virus and herpes simplex infection,which damages nerve cells and causes seizures.

Preparation and quality evaluation of Acori Tatarinowii Rhizoma-volatile oil microemulsion / 中草药

Objective: Taking the volatile oil of Acori Tatarinowii Rhizoma with the effect of anti-senile dementia as model drug to prepare Acori Tatarinowii Rhizoma-volatile oil microemulsion (AO-ME). Methods: The composition of microemulsion was preliminarily determined according to the solubility of volatile oil from Acori Tatarinowii Rhizoma in various solvents. By drawing pseudo-ternary phase diagram, the optimal microemulsion formulation was selected according to the size of particles and microemulsion region, stability of preparations and drug loading. Results: The optimal microemulsion formulation was that volatile oil of Acori Tatarinowii Rhizoma-Cremophor EL-glycerol-water was 6.25:20.83:10.42:62.5. The average particle size of AO-ME was (30.5 ± 0.2) nm with a polydispersity index of 0.150 ± 0.002. The viscosity value of AO-ME was (2.80 ± 0.21) mPa∙s. In vitro transdermal rate of AO-ME was (1 288.76 ± 16.20) μg/(cm2∙h), measured in β-asarone. Compared with ordinary emulsion, the transdermal rate of AO-ME was increased 14 times. The ciliary toxicity test of toad showed that the preparation had no significant toxicity. Conclusion: The preparation of AO-ME was prepared with stable physicochemical properties, good transdermal properties, and low toxicity to nasal mucosa cilia.

Screening of anti-depressant active ingredients in Acori Tatarinowii Rhizoma based on molecular docking technique / 中草药

Objective: To screen the anti-depressant active ingredients in Acori Tatarinowii Rhizoma by molecular docking technique. Methods: All the chemical constituents of Acori Tatarinowii Rhizoma were obtained by Traditional Chinese Medicine Pharmacology Database (TCMSP). Combined with oral bioavailability, 65 candidate compounds were obtained. The studied anti-depressant targets included monoamine oxidase A, dopamine transporter, serotonin transporter, and histamine H1 receptor. AutoDock Vina was used to explore the affinity and binding modes of the candidate compounds with the above targets. Results: There were 18 compounds from Acori Tatarinowii Rhizoma that could bind to the above four targets. Among them, four compounds could bind to four targets, three compounds could bind to two targets, and the other 11 compounds could interact with one target. Conclusion: Molecular docking technology can be used to investigate the molecular mechanism of Acori Tatarinowii Rhizoma and determine the active ingredients, which provides an alternative method for the discovery of novel anti-depressants and lead compounds from Chinese herbal medicines.

Memory-improving Substances Basis and Mechanism of Polygalae Radix, Acori Tatarinowii Rhizoma and Its Couplet Medicines / 中国实验方剂学杂志

Polygalae Radix and Acori Tatarinowii Rhizoma were first recorded in Shennong's Herbal Classic. Both of them can "improve people's memory". Long-term administration can make body light and macrobian. They have often been used as couplet medicines and the core combination of nootropic and memory improvement prescriptions. At present, traditional Chinese medicine clinicians believes that the principle of Polygalae Radix and Acori Tatarinowii Rhizoma in improving memory or intelligence is to supplement the deficiency, remove phlegm and unblock nine orifices, with sufficient evidences for the traditional theory. However, its material basis and mechanism for improving memory have not been fully elucidated. In this paper, we searched the literatures about pharmacological and pharmacodynamics mechanism of Polygalae Radix,Acori Tatarinowii Rhizoma and their chemical components on nervous system in recent ten years from Pubmed database and CNKI. The main material basis for improving memory of Polygalae Radix-saponins, oligosaccharides and alone, the main material basis for improving memory of Acori Tatarinowii Rhizoma-α-asarone,β-asarone and eugenol, the changes of the quality and quantity of the active substances after combination, and the mechanism of improving memory of the single drugs and their couplet medicines, such as scavenging free radicals, regulating cholinergic system, clearing β-amyloid protein(Aβ), decreasing the level of phosphorylation of Tau protein, improving the rate of apoptosis and regulating synaptic plasticity, were systematically collected, analyzed and summarized. In view of the current research situation, this paper points out the possible shortcomings, with the aim to further explore the mechanism of Polygalae Radix combined with Acori Tatarinowii Rhizoma with the mechanism of "1+1>2".

Effect of Acori Tatarinowii Rhizoma on Intestinal Absorption of Ginsenosides in Dingzhi Xiaowan / 中国实验方剂学杂志

Objective: To explore the effect of Acori Tatarinowii Rhizoma on intestinal absorption of ginsenosides in Dingzhi Xiaowan,and reveal the mechanism of Acori Tatarinowii Rhizoma acting as " adjuvant drug" in this formula. Method: The contents of ginsenoside Rg1,Re and Rb1 were measured by UPLC-MS/MS and the absorption of three ginsenosides in different intestine segments was investigated by rat single pass intestinal perfusion in situ,including absorption rate constant(Ka) and apparent permeability coefficient(Papp).Everted intestinal sac model was used to investigate the absorption dosage of three ginsenosides affected by volatile oil from Acori Tatarinowii Rhizoma and verapamil[Ver,a P-glycoprotein(P-gp) inhibitor]. Result:Papp values of three ginsenosides were ≤ 0.191×10-3 cm·min-1 in Dingzhi Xiaowan when lack of Acori Tatarinowii Rhizoma.Compared with lack of Acori Tatarinowii Rhizoma in Dingzhi Xiaowan group,the Ka and Papp values of lack of volatile oil from Acori Tatarinowii Rhizoma in Dingzhi Xiaowan group slightly increased without significant difference in the four intestinal segments,but when the prescription had Acori Tatarinowii Rhizoma,the Ka increased by 3.97-8.35 fold and the Papp increased by 3.99-8.49 fold.The results of everted intestinal sac test showed that volatile oil of Acori Tatarinowii Rhizoma could significantly promote the intestinal absorption of ginsenoside Rg1,Re and Rb1,but there was no dose-dependent. Conclusion:Volatile oil of Acori Tatarinowii Rhizoma can promote the intestinal absorption of three ginsenosides in Dingzhi Xiaowan,and the mechanism may be related to the inhibiting function on P-gp.

Preparation and quality evaluation of volatile oil from Acori Tatarinowii Rhizoma self-nanoemulsion / 中国中药杂志

In order to increase the solubility of volatile oil from Acori Tatarinowii Rhizoma, this study was to prepare self-nanoemulsion of volatile oil from Acori Tatarinowii Rhizoma . The prescriptions were preliminarily screened by miscibility studies, excipient compatibility tests, and pseudo-ternary phase diagrams, and then the optimal formulation was obtained by using the Box-Behnken response surface method, with particle size and drug-loading rate as the indicators. The self-nanoemulsion prepared by optimal prescription was characterized and evaluated for dissolution. The results showed that the optimal prescription for this volatile oil self-nanoemulsion was as follows: 41.7% volatile oil, 46.8% Tween-80, and 11.5% PEG-400. The prepared self-nanoemulsion was clear and transparent, with drug-loading of (192.77±1.64) mg·g⁻¹, particle diameter of (53.20±0.94) nm, polydispersity index of 0.230± 0.013, and Zeta potential of (-12.2±0.7) mV. The dissolution of self-nanoemulsion was higher than that of volatile oil. In this research, volatile oil served as the oil phase in self-nanoemulsion, so the prescription was simpler and the drug loading rate was higher. The prepared self-nanoemulsion complied with the relevant quality requirements, providing a reference for the preparation of volatile oil formulations.

Mechanism of Acori Tatarinowii Rhizoma-Curcumae Radix treating depression based on network pharmacology / 中国中药杂志

To screen the target for the treatment of depression of Acori Tatarinowii Rhizoma and Curcumae Radix using the pharmacological method of network pharmacology, in order to define the mechanism of antidepressant effect. Pharmacological data (TCMSP) of forall of chemical constituents of Acori Tatarinowii Rhizoma and Curcumae Radix through traditional Chinese medicine system (TCMSP) was retrieved to screen the target sites, and construct the component target PPI network. PharmGkb database was retrieved for the genes associated with depression, and the disease target was mapped using the Cytoscape software. The Cytoscape software was used to merge the network and filter the core network, and further analyze the gene GO function and the KEGG pathway enrichment. There were 62 nodes and 87 connections on the target PPI network. The PPI network had 1 289 nodes and 17 714 connections. After the network merged, the component-target-disease network had 1 337 nodes and 17 801 connections. Through screening the core network, there were 63 nodes and 935 connections, which represented the complex interaction between the components and the target. Gene GO functional analysis suggested that biological processes, molecular functions and cell components were involved. Gene KEGG pathway enrichment analysis showed associations with misfolded protein, secretory hormone secretion, and apoptosis of hippocampal neurons. The possible mechanism for treating depression is the adjustment of wrong folding protein, sex hormone secretion and apoptosis of hippocampal neurons.

Optimization of solvent-free microwave extraction for Acori Tatarinowii Rhizoma and analysis on volatile components by GC-MS / 中草药

Objective: To study the solvent-free microwave extraction for oils of Acori Tatarinowii Rhizoma and analyze the volatile components. Methods: The paper selected the best technological conditions by L9(34) orthogonal test, with the index of α-asarone, volume of volatile oils, and sum of the percentage, The essential oils in Acori Tatarinowii Rhizoma were analyzed with GC-MS. Results: The percentage of volatile oils was calculated according to peak area normalization method. The results showed similar amount of volatile oil components by two methods, and the extraction rates of α-asarone, β-asarone, and γ-asarone accounted for 4.12%, 55.11%, and 10.54% on the method of solvent-free microwave extraction, while the steam distillation was 5.39%, 47.03%, and 9.15%. To compare with two methods, solvent-free microwave extraction extracted volatile oil 0.235 mL and α-asarone 31.99 mg for 5 min, while steam distillation extracted volatile oil 0.175 mL and α-asarone 29.09 mg for 1 h. The method of solvent-free microwave extraction had the advantage of short reaction time and high yields. Conclusion: Solvent-free microwave extraction is a new method with shorter extracting time and better extracting efficiency.

Intestinal absorption of Ginseng Radix et Rhizoma extract combined with Acori Tatarinowii Rhizoma in rats / 中国中药杂志

To investigate the changes in intestinal absorption of ginsenosides Rg₁, ginsenosides Re and ginsenosides Rd after combined administration of Ginseng Radix et Rhizoma extract and Acori Tatarinowii Rhizoma, in order to confirm whether the combined administration is scientific and rational, and provide experimental basis for pharmaceutical studies of the formula. An in vivo single-pass perfusion method was performed to study the effect of various concentrations of ginsenosides Rg₁, ginsenosides Re, ginsenosides Rd on the intestinal absorption at duodenum, jejunum, ileum and colon. The concentrations of ginsenosides Rg₁, ginsenosides Re, ginsenosides Rd were determined by RP-HPLC.The absorption rate constant (Ka) and the apparent absorption coefficient(Papp) of ginsenosides Rg₁, ginsenosides Re, ginsenosides Rd were calculated.The result showed that ginsenosides Rg₁, ginsenosides Re, ginsenosides Rd had a high absorption rate on upper portion of the small intestine. The drug concentration had not significantly impact on the absorption rate, suggesting that ginsenosides Rg₁, ginsenosides Re, ginsenosides Rd were absorbed via passive diffusion.Volatile oil of Acori Tatarinowii Rhizoma had obvious effect in enhancing intestinal absorption of ginsenosides Rg₁, ginsenosides Re, ginsenosides Rd, indicating that the combined administration of Ginseng extract and Acorus tatarinowii Schott is scientific and rational.