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Ephedrae Herba is a commonly used medicine for dispersing wind and cold， which has a long medicinal history. By referring to the herbal literature， medical books and prescription books， this paper intends to carry out herbal textual research on the name， origin， medicinal part， producing area， harvesting and processing methods of Ephedrae Herba in famous classical formulas， in order to provide the basis for the development of relevant famous classical formulas. According to textual research， the main base of ancient Ephedrae Herba was Ephedra sinica. The medicinal part is the herbaceous stems of Ephedrae Herba. Before the Northern and Southern dynasties， the origin of the records was Jindi and Hedong， which is now Shanxi province. In the Northern and Southern dynasties and later generations， the producing area expanded， and now it is mainly distributed in Hebei， Shanxi， Shaanxi， Inner Mongolia， Gansu， Liaoning and other places， among which Inner Mongolia is the main producing area. The harvesting and processing methods in the past dynasties are to harvest the stems in autumn， dry them in the shade or air to 70%-80% dry， and then dry them in the sun. The processing methods in the past dynasties mainly include removing the knots， wine-fried， honey-fried， processing with vinegar and so on， at present， only honey-fried is still in use. Based on the research results， it is suggested that Ephedrae Herba in famous classical formulas should be selected the dry herbaceous stems of E. sinica. If the processing requirements are not indicated， it is suggested to use raw products of Ephedrae Herba.
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OBJECTIVE：To provide reference for elucidating the anti-allergic asthma constituents in alkaloids-free part of Ephedrae Herba. METHODS ：Ephedrae Herba was extracted with 85％ ethanol and n-heptane，and then subjected to solid-phase extraction（filler AC 18）for pretreatment to enrich alkaloids-free part from the extract of Ephedrae Herba. HPLC method was adopted，and alkaloids-free fractions of Ephedrae Herba were performed on Unitary C 18 column and Eclipse XDB-C 18 column. Using high expression G protein coupled-receptor 35（GPR35 receptor）in HT- 29 cell as target ，GPR35 receptor agonist zaprinast （1 μmol/L）as positive control ，DMR response value as the detection index ，the agonistic and desensitizing activity of each fraction（100 μg/mL）on GPR 35 receptor was screened by label-free integrated pharmacological method ，so as to screen active anti-allergic asthma fraction. HPLC-Q-TOF-MS method was used to identify the chemical composition of the selected active fractions. RESULTS ：The alkaloids-free part of Ephedrae Herba was divided into two parts ，involving the precipitated part before solid phase extraction and the 95％ methanol elution part ；from them ，20 fractions were screened. Among them ，the precipitated fraction F 1.5-F1.10 and 95％ methanol eluted fraction F 2.5-F2.10 had a strong agonistic activity on GPR 35 receptor；at the same time，GPR35 receptor agonist zaprinast showed a relatively strong desensitization activity. The signal intensity of DMR induced by F1.5-F1.10 in the precipitated part of HT- 29 cells was even higher than that of reference drug zaprinast. By HPLC-Q-TOF-MS analysis，24 chemical components were identified from active fractions ，involving 14 flavonoids，2 volatile oils ，7 organic carboxylic acids ，1 anthraquinones. CONCLUSIONS ：The alkaloid-free part of Ephedrae Herba is mainly flavonoids and has anti-allergic asthma activity.
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Objective: To predict the active constituents and targets of Guizhi Shaoyao Zhimu Decoction (GSZD) in the treatment of rheumatoid arthritis by using molecular docking and network pharmacology, and to analyze the effect of multi component-multi target-multi pathway combined with the theory of compatibility of TCM prescriptions. Methods: The main chemical constituents of nine kinds of Chinese herbal medicines (Cinnamomi Ramulus, Paeoniae Radix Alba, Anemarrhenae Rhizoma, Glycyrrhizae Radix et Rhizoma, Ephedrae Herba, Zingiberis Rhizoma Recens, Atractylodis Macrocephalae Rhizoma, Saposhnikoviae Radix and Aconiti Lateralis Radix Praeparata) were collected from TCMSP, TCM-Datebas@Taiwan and PubChen Compound database. The protein targets to the treatment of rheumatoid arthritis are found through DrugBank and TTD databases and uploaded to the String online database to build the network relationship of protein interaction. Appropriate crystal structures of protein targets were downloaded from PDB database, and molecular docking between compounds and targets was performed by using Discovery studio 4.5.0 software. A drug-compound-target visualization network was constructed by using Cytoscape 3.6.1 software to elucidate the main mechanism of GSZD against rheumatoid arthritis. Results: The results of molecular docking showed that there were 316 potential anti-arthritis active components in GSZD, acting on 26 targets, among which MAPK1, ZADH2, P38, AKR1C2, DHODH, CA2, MMP3, MMP9, RANKL, and other proteins were the main targets. Biological function and pathway analysis indicated that the mechanism of GSZD mainly involved in bone absorption (28%), histone kinase activity (20%), peptide tyrosine phosphorylation (20%), prostaglandin metabolism (12%), and other biological processes. The main pathway was osteoclast differentiation (94.12%). Conclusion: In this study, molecular docking combined with network pharmacology was used to study the pharmacodynamic material basis and molecular mechanism of GSZD in the treatment of rheumatoid arthritis from the perspective of multi-target and multi-approach, providing reference and basis for better clinical use.
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Objective: To study the effective substance foundation of Ephedrae Herba and explore its mechanism, in order to further enrich the theory of drug resistance of Ephedrae Herba.Method: In this experiment, a compound model was used to establish rat model of Harmful Fluid Retention in upper Jiao. The Rats were randomly divided into model group, captopril group (4.38 mg·kg-1), Ephedrae Herba decoction group(468 mg·kg-1), polysaccharide group (265.36 mg·kg-1), volatile oil group (2.34 mg·kg-1), alkaloid group(40.71 mg·kg-1) and phenolic acid group (210.60 mg·kg-1), and normal group (10 mL·kg-1). The normal group and the model group were given the same volume of normal saline for four weeks. The 24 h urine volume of rats was collected by metabolic cage method. The changes of heart and lung tissue morphology were observed under light microscope. The heart index, lung index, left ventricular ejection fraction(LVEF), left ventricular short axis shortening rate(LVFS) and pulmonary permeability index, number(LPI), lung dry-wet ratio(W/D), creatine kinase isoenzyme(CK-MB), angiotensin Ⅱ(Ang Ⅱ), aldosterone(ALD), cardiac aquaporin 1(AQP1), lung AQP1, aquaporin-3(AQP3) and kidney AQP1, aquaporin-2(AQP2), interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) change were detected.Result: Compared with the normal group, heart and lungs of the model group were significantly damaged. The amount of 24 h urine, LVEF, LVFS of model rats were significantly reduced(Pα were significantly increased(PPα were significantly increased (PPα were significantly reduced (PPConclusion: Alkaloid components "Wen" and "Xin" are the effective substance basis of its action. The mechanism may be related to the inhibition of renin angiotensin aldosterone system (RAAS) and the anti-inflammatory effect.
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To reveal the medication patterns of Chinese patent medicine in the treatment of cough based on the analysis of the patent status of Chinese materia medica (CMM) in the field of cough control in nearly 20 years. Patents of Chinese patent medicine in the treatment of cough were systematically searched in SIPO Platform and CNKI, association analysis and network analysis of high-frequency medicines were used to reveal the medication patterns of Chinese patent medicine in the treatment of cough with software Clementine 12.0. The results showed that Chinese medicine with highest frequency in 316 formulas was Glycyrrhizae Radix et Rhizoma, the other Chinese herbs with higher frequency were Platycodonis Radix, Ephedrae Herba, Citri Reticulatae Pericarpium, Pinelliae Rhizoma, etc. The main categories were the medicines used to treat cough and asthma, as well as to reduce phlegm. The commonly used herbal pairs were Glycyrrhizae Radix et Rhizoma-Platycodonis Radix, Glycyrrhizae Radix et Rhizoma-Citri Reticulatae Pericarpium, Pinelliae Rhizoma-Glycyrrhizae Radix et Rhizoma, Ephedrae Herba-Glycyrrhizae Radix et Rhizoma, etc. It was concluded that the medication patterns of Chinese patent medicine in the treatment of cough can be revealed based on the analysis of the herbal frequency, herbal pairs, association rules, and the network of high-frequency medicines and the theory of traditional Chinese medicine, so as to provide reference evidences for clinical medication.
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Objective To establish a method for detecting the chemical compositions of “decocted first and defoamed” of Ephedra Herba by UPLC-DAD-TOF/MS coupled with HPLC-UV, so as to clarify the difference of chemical constituents among them. Methods The analysis was performed on an ACQUITY UPLC® BEH C18 column (50 mm × 2.1 mm, 1.7 μm ) by UPLC-DAD-TOF/MS with gradient elution. The mobile phase consists of methanol and 0.1% formic acid-water at a flow rate of 0.3 mL/min. The column temperature was 40 ℃. The information of compounds was acquired on positive and negative mode. Similarly, HPLC-UV was applied for measuring the content of alkaloids respectively. The C18 column was used, the mobile phase was acetonitrile-0.1% phosphoric acid (containing 0.05% triethylamine) (99 : 1) at the flow rate of 1 mL/min, the detective wavelength was set up at 210 nm, and the column temperature was 30 ℃. Results There were less content in the upper foam, and the chemical components in the lower liquid and the whole liquid were basically same. Five alkaloids and one carboxylic acid (4-hydroxy-7-methoxyl-2-quinoline carboxylic acid) was identified from all kinds of liquids. However, the content of alkaloids in the upper foam was very low, and the content of three alkaloids in the whole solution was slightly higher than that in the lower liquid. Conclusion The defoamed method may not be related to the chemical compositions of alkaloids, but it still needs further research and verification.
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Objective To determine equilibrium solubility and apparent oil/water partition coefficient of ephedra alkaloid in the compatibility Ephedrae Herba-Aconiti Lateralis Radix Praeparata; To provide a basis for transdermal delivery.Methods The extract was prepared by 70% ethyl alcohol and D101 macroporous absorbent resins. Dissolvability of its main effective components (ephedrine and pseudoephedrine) in the compatibility Ephedrae Herba-Aconiti Lateralis Radix Praeparata was determined by precipitation method and HPLC method; the oil/water partition coefficient of ephedrine and pseudoephedrine in n-octanol-water buffer solution system were determined by shaking flask method.Results The extract had optimum solubility in methyl alcohol and acetonitrile, and ephedrine and pseudoephedrine had optimum solubility in buffered solution of pH 7.4. Oil/water partition coefficient of ephedrine and pseudoephedrine in n-octanol-water system was 0.101 with lgP=-0.99 and 0.076 with lgP=-1.12. Oil-water partition coefficients of ephedrine and pseudoephedrine in the extract were affected by pH.Conclusion The extract has optimum solubility in high polar solvents. Ephedrine and pseudoephedrine have certain fatsoluble and water-soluble in suitable pH, which was beneficial for transdermal absorption.
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Objective: Through the accelerated experiment and long-term experiment, the main contents of ephedrine and white peony root in Chinese materia medica (CMM) lotion were taken as the main indexes, and the stability of the medicine lotion of infants with bronchitis was investigated. Methods: According to the quality standard of CMM lotion for infant bronchitis, the existence of Ephedrae Herba, Poria, Paeoniae Radix Alba, Aurantii Fructus and Epimedii Folium in the sample was identified by thin layer chromatography. The contents of Ephedrae Herba (ephedra hydrochloride and pseudoephedrine hydrochloride) and Paeoniae Radix Alba (paeoniflorin) were determined by HPLC, and the stability of CMM lotion samples was evaluated by plate method. Results: The contents of Ephedrae Herba, Poria, Paeoniae Radix Alba, Aurantii Fructus, and Epimedii Folium were measured. The contents of Ephedrae Herba and Paeoniae Radix Alba were higher than 0.18 mg and 0.72 mg; The total contents of aerobic bacteria and mycorrhizal yeasts were not more than 100 cfu/mL, and Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus were not detected, in line with quality standards. Conclusion: The three batches of CMM lotion prepared by the First People’s Hospital of Guangxi have good stability and long-term stability, for the goods packaging, transportation, and storage conditions to provide the necessary information.
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To establish the quality control methods for the standard decoction of Ephedrae Herba, and provide the reference for quality evaluation method of all Chinese herbal medicine decoction.Standard decoction of Ephedrae Herba was prepared, and UPLC-UV fingerprint was established to determine the total contents of ephedrine and pseudoephedrine. Then UPLC-QTOF/MS was used to confirm the major common peaks in the fingerprint to clarify the main chemical constituents in the decoction. In addition, the stability of the process was evaluated by calculating the parameters such as the extraction ratio, transfer rate of the index components and the pH values.In the decoction of Ephedrae Herba, the total average concentration of ephedrine and pseudoephedrine was (2.11±0.70) g•L⁻¹; the similarities of all the fingerprints were more than 0.85; there were 10 major common peaks in the fingerprint, including alkaloids, flavonoids and organic acids; the extraction ratio was (17±3.2)%, and the overall transfer rate of ephedrine and pseudoephedrine was (32.4±8.1)%.The method for evaluating the quality of standard decoction of Ephedrae Herba was established in this article, providing reference for the quality control of products which were stemmed from the water extract of Ephedrae Herba.
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AIM To investigate the effects of the compatibility of Ephedrae Herba (Mahuang) and Glycyrrhizae Radix et Rhizoma (Gancao) on pharmacokinetic changes of the plasma levels of glycyrrhizic acid,glycyrrhetinic acid and liquiritin by UPLC-MS/MS.METHODS Twelve SD rats were randomly divided into two groups and orally administered with Glycyrrhizae Radix et Rhizoma and Ephedrae Herba-Glycyrrhizae Radix et Rhizoma (2 ∶ 1) Decoction.Blood samples were collected at different time points,and the main pharmacokinetic parameters were calculated by DAS3.2.2 software.RESULTS Compared with Glycyrrhizae Radix et Rhizoma group,the AUC0-t and Cmax were decreased,the MRT0-t and t1/2z were extended,the Vz/F was increased for glycyrrhizic acid,glycyrrhetinic acid and liquiritin;the CLz/F was increased for glycyrrhizic acid and liquiritin;the Tmax of glycyrrhizic acid was shortened and the Tmax of glycyrrhetinic acid was extended.CONCLUSION After combining Glycyrrhizae Radix et Rhizoma and Ephedrae Herba,the bioavailability of glycyrrhizic acid,glycyrrhetinic acid and liquiritin are reduced,the elimination of them delays,and the distribution volume increases.
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AIM To investigate the effects of the compatibility of Ephedrae Herba (Mahuang) and Glycyrrhizae Radix et Rhizoma (Gancao) on pharmacokinetic changes of the plasma levels of glycyrrhizic acid,glycyrrhetinic acid and liquiritin by UPLC-MS/MS.METHODS Twelve SD rats were randomly divided into two groups and orally administered with Glycyrrhizae Radix et Rhizoma and Ephedrae Herba-Glycyrrhizae Radix et Rhizoma (2 ∶ 1) Decoction.Blood samples were collected at different time points,and the main pharmacokinetic parameters were calculated by DAS3.2.2 software.RESULTS Compared with Glycyrrhizae Radix et Rhizoma group,the AUC0-t and Cmax were decreased,the MRT0-t and t1/2z were extended,the Vz/F was increased for glycyrrhizic acid,glycyrrhetinic acid and liquiritin;the CLz/F was increased for glycyrrhizic acid and liquiritin;the Tmax of glycyrrhizic acid was shortened and the Tmax of glycyrrhetinic acid was extended.CONCLUSION After combining Glycyrrhizae Radix et Rhizoma and Ephedrae Herba,the bioavailability of glycyrrhizic acid,glycyrrhetinic acid and liquiritin are reduced,the elimination of them delays,and the distribution volume increases.
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Objective: To optimize the extraction technology of Saposhnikoviae Radix, Perillae Folium, Magnoliae Flos, Armeniacae Amarum Semen, and honey-fried Ephedrae Herba in Xiaochuan Decoction by information entropy theory. Methods: With the contents of prem-O-glucosylcimifugin, 4'-O-beta-glucopyranosyl-5-O-methylvisamminol, amygdalin, and the yield of extract as comprehensive evaluation indexes in order to optimize the extraction process parameters of orthogonal test, the weight coefficient of each index was determined by the information entropy weight method. Results: Optimum extraction technology was as follows: reflux extraction for 3 times with 10 fold water, for 1.5 h each time. Conclusion: The optimized method is stable and reliable, and can provide the reference for further development and utilization of the formula.
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Objective: To establish an HPLC fingerprint method of Jizhi Syrup and determine the contents of its main components. Methods: The Waters XTerra RP-18 (250 mm × 4.6 mm, 5 μm) column was used with a mobile phase of 0.8% acetic acid (containning 0.2% triethylamine) and acetonitrile gradient elution, the flow rate was 1.0 mL/min, the column temperature was 35℃, and the detection wavelength was 280 nm. The Similarity Evaluation System for Chromatographic Fingerprint of TCM (2012 edition) was used to establish the fingerprint spectra and analyze the similarity degree. The common peaks were identified by reference compounds and negative controls, and the content was detected. Results: The fingerprint chromatography included 17 mutual peaks. Peak 2 and peak 8 were from Houttuyniae Herba, peak 4 and peak 10 were from Fagopyri Dibotryis Rhizoma, peaks 7, 12, and 15 were from Ilicis Chinensis Folium, peaks 1 and 13 were from Ephedrae Herba, peaks 16 and 17 were from Aurantii Fructus, and peaks 3 and 6 were from Houttuyniae Herba, Fagopyri Dibotryis Rhizoma, and Ilicis Chinensis Folium. The similarity among the batches was more than 0.98. Based on the retention time of master compounds, six components [protocatechuic acid (peak 3), protocatechualdehyde (peak 6), ferulic acid (peak 7), chlorogenic acid (peak 10), ephedrine hydrochloride (peak 13), and naringin (peak 16)] were identified and quantified. The contents of protocatechuic acid, protocatechualdehyde, ferulic acid, chlorogenic acid, ephedrine hydrochloride, and naringin in 10 batches of Jizhi Syrup were 3.122 1-3.270 0, 5.108 6-5.224 9, 8.893 2-9.120 8, 6.792 1-6.931 0, 2.154 4-2.236 2, and 4.125 8-4.183 3 mg/mL, respectively. Conclusion: The established method has high sensitivity, fast, precise and specificity, and can be used for the quality control of Jizhi Syrup.
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Objective: To observe the effect of Cinnamomi Ramulus on the distribution kinetics of ephedrine (E) and pseudoephedrine (PE) from Ephedrae Herba in brain tissues of mice. Methods: Mice were ig adminstered by Cinnamomi Ramulus and codecoction of Cinnamomi Ramulus combined with Ephedrae Herba. Brain tissues of mice were collected at different time after drug administration. The variation of E and PE with time was determined by GC-MS method. The non compartmental kinetic was fitted and the parameters were calculated by Kinetica 5.0.11 software, so as to evaluate the effect of Cinnamomi Ramulus on the distribution kinetics of E and PE from Ephedrae Herba in brain tissues of mice. Results: Compared with the Ephedrae Herba group, in the group with the codecoction of Cinnamomi Ramulus combined with Ephedrae Herba, the tmax of E and PE distributed in the brain tissues of mice was delayed, the AUC0-∞ of E and PE in the brain tissues of mice under the drug concentration curve was smaller and the MRT0-∞ of E was reduced. Conclusion: Cinnamomi Ramulus combined with Ephedrae Herba has the propertis of delaying the distribution process of E and PE, reducing the cumulative distribution volume, and accelerating the elimination of E and PE in the brain tissues of mice. Above all, Cinnamomi Ramulus can relieve the neurotoxicity of Ephedrae Herba, and there is the combination function of mutual restraint and mutual supression between the two drugs.
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Objective To establish the method for determining ephedrine hydochloride and pseudoephedrine hydrochloride in Keke Tablets by HPLC. Methods The samples were analyzed by a phemomenex Synergi Polar-RP column (4.6 mm×250 mm, 4 μm), with mobile phase methanol∶0.092%phosphoric acid (0.04%triethylamine and 0.02%second butylamine)=1.5∶98.5 at flow rate of 1.0 mL/min and detection at UV wavelength of 210 nm. The column temperature was 30 ℃. Results The linear ranges of ephedrine hydrochloride and pseudoephedrine hydrochloride were 6.51×10-3-0.651 μg (r=0.999 9) and 6.27×10-3-0.627 μg (r=1), respectively. The average recoveries (n=6) of ephedrine hydrochloride and pseudoephedrine hydrochloride were 102.26%and 103.71%, with RSD of 0.34%and 0.22%, respectively. Conclusion This method is simple, accurate, reproducible, highly specific and reliable results, and has the ability to effectively control the quality of alkaloids in Keke Tablets.
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Decoctions of Ephedrae Herba were prepared using tap water sampled in Changping District, Beijing City(China), tap water sampled in Niigata City (Japan) and some mineral water samples sold in markets. Various dissimilarities were found between drug extracts prepared using tap water in Japan and China, and the extraction efficiency of the alkaloids with Beijing tap water was approximately 80% of that with Niigata tap water. It is suggested that these dissimilarities result from concentrations of temporally hard components, such as calcium and magnesium bicarbonate salts, in the water. In addition, when Zizyphi Fructus and Ephedrae Herba were decocted together in hard water, the state of the decoction, ephedra-alkaloid content included, was found to come close to that of single Ephedrae Herba decoctions prepared using soft water. It was suggested that Ziziphi Fructus might possibly play roles as a softening agent in decoctions prepared using hard water.
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It is well known that there exist inter-individual variations in the pharmacokinetics of pharmaceutical components in Kampo prescriptions. In the area of Kampo medicine, however, there have so far been no reports on the analysis by introducing these variations.<br>In this paper, from the perspective of population pharmacokinetics, we analyze the data of plasma concentration of ephedrine obtained from 8 healthy male volunteers after single oral administration of Sho-seiryu-to (extract) by introducing the inter-individual variations.<br>On the results, we simulate the plasma concentration in multiple oral administrations.