Analysis on Quality Attribute of Substance Benchmarks of Shentong Zhuyutang Based on Supramolecular "Imprinting Template" Theory / 中国实验方剂学杂志

ObjectiveBased on the supramolecular "imprinting template" theory， the autonomous action law of the component groups of Shentong Zhuyutang in the preparation process of medicinal materials-decoction pieces-formulas was studied to clarify the quantitative transfer law of its quality attributes. MethodUltra performance liquid chromatography（UPLC） fingerprint of Shentong Zhuyutang was established with mobile phase of 0.4% phosphoric acid aqueous solution（A）-acetonitrile（B） for gradient elution（0-2.5 min， 100%A； 2.5-6 min， 100%-96%A； 6-15 min， 96%-92%A； 15-25 min， 92%-88%A； 25-35 min， 88%-75%A； 35-50 min， 75%-65%A； 50-60 min， 65%-50%A； 60-65 min， 50%-30%A； 65-70 min， 100%A） and detection wavelength of 235 nm， and the total statistical moments， information entropy and primary feeding amount of fingerprint of medicinal materials， decoction pieces and benchmark samples were calculated. Dry extract rate of the benchmark samples， the transfer rates and the addition parameters of medicinal materials-decoction pieces-formulas were calculated. ResultSimilarities of the total statistical moments of UPLC fingerprint of 15 batches of medicinal materials and decoction pieces were>0.89， the relative standard deviations（RSDs） of information entropy of UPLC fingerprint of 12 medicinal materials and decoction pieces were<10%. RSDs of total first-order moment（MCRTT） and information entropy of Shentong Zhuyutang（medicinal materials） were 5.5% and 2.3%， while the RSDs of MCRTT and information entropy of Shentong Zhuyutang（decoction pieces） were 4.8% and 2.6%， respectively. The dry extract rate of 45 batches of Shentong Zhuyutang was 17.2%-20.2%. The transfer rate of medicinal materials to decoction pieces was within the range of data fluctuation， which was 70%-130% of the average value. The overall transfer rates of medicinal materials to decoction pieces and decoction pieces to benchmark samples were 101.8% and 83.0%， respectively. ConclusionThe quality properties of Shentong Zhuyutang benchmark samples can be studied by total statistical moment analysis and primary feeding amount analysis， which can confirm the supramolecular "imprinting template" theory to a certain extent.

Mutual Information Entropy Analysis of Compatibility of Traditional Chinese Patent Medicines Against Liver Diseases in Chinese Pharmacopoeia（2020 Edition） / 中国实验方剂学杂志

ObjectiveTo investigate the compatibility rule of traditional Chinese patent medicines （TCPMs） against liver diseases through network analysis. MethodWith “liver” as the search term， TCPMs against liver diseases were retrieved from volume Ⅰ of Chinese Pharmacopoeia （2020 edition）， and the basic information of them was collected. TCPMs with same Chinese medicinal materials （CMMs）， usage， and indications， but different dosage forms， were unified as one formula. Mutual information entropy （MIE） of CMM couples was calculated to quantify the relationship between them， and the top 25% CMM pairs in MIE were used to construct the compatibility network， with CMM as node and the relationship between CMM pairs as the edge. Key CMM and frequently used CMM combinations were identified based on node centrality and cluster analysis， respectively. The indications of TCPMs related to the CMMs in clusters were recorded. Cytoscape 3.6.1 was employed for visualization and topology analysis of the compatibility network. ResultA total of 179 TCPMs， involving 428 CMMs， were retrieved. Angelicae Sinensis Radix， Paeoniae Radix Alba， and Glycyrrhizae Radix et Rhizoma were identified as key CMMs with high frequency， and Cuscutae Semen-Lycii Fructus， Citri Reticulatae Pericarpium-Cyperi Rhizoma， and Ecliptae Herba-Ligustri Lucidi Fructus combinations had high MIE. Furthermore， the CMMs were clustered into ten groups corresponding to different diseases which， however， all belonged to digestive diseases. ConclusionThis study unveils potential CMM pairs and common CMM combinations against liver diseases， which can serve as a reference for revealing compatibility rules of CMMs and research and development of Chinese medicine.

Comparative analysis and research on composition of mulberry-sourced medicinal materials by fingerprint division total statistical moment method and information entropy / 中国中药杂志

The present work is to analyze the HPLC fingerprints of mulberry-sourced materials(Mori Ramulus, Mori Folium, Muri Cortex, Mori Fructus) using the fingerprint division total statistical moment method and information entropy, and to study the diffe-rences of the chemical components and the overall characteristics of the imprinting template in different parts of mulberry-sourced medicinal materials, so as to provide the basis for finding the effective substances in response to "homologous and different effect" of mulberry(Morus alba). The fingerprints of 24 batches of mulberry-related materials, such as Mori Ramulus, Mori Folium, Muri Cortex, Mori Fructus, were established, and the similarities and differences of the fingerprints were analyzed by calculating the division total statistical moment parameters and information entropy. The AUC_T, MCRT_T, VCRT_T and H values of 24 batches of mulberry-sourced materials were less than 0.05, with significant difference. Among them, all samples showed absorption peaks within 3-11, and 20-24 min, indicating that the four types had the identical or similar chemical composition in the same time period. After 34 min, none of the four types showed absorption peaks. Greater VCRT_T value of the fingerprints of the four kinds was observed at the retention time ranges of 3-4, 16-18, 25-27, and 31-32 min, indicating that the components of the four kinds were significantly different in these time periods; and VCRT_T value of the mulberry was significantly higher than that of the other three kinds of medicinal materials at the retention time windows of 3-4 and 15-17 min; the VCRT_T value of the mulberry white skin was significantly higher at the time windows of 8-10 and 28-30 min; the VCRT_T value of all four kinds was significantly higher within 21-23 min, indicating that the four herbs contain the same or similar components in the chromatogram during this period, but there may be significant differences between the content and the proportion. In addition, the information entropy of mulberry branches is the largest at 7-12, 23-27 min, and that of mulberry fruits is the largest at 2-8 min, which indicates that the components of mulberry branches and mulberry fruits respond greatly in the corresponding period of time, which is also the main peak period of their chemical components. For the chemical components and corresponding efficacy here. The results showed that there are significant differences in the components and contents of mulberry-sourced medicinal materials. The division total statistical moment and information entropy of the total amount of segments can be used to analyze the differences in the components of "homology and different effects", which could provide a more comprehensive analysis method for the determination of quality markers.

Quality evaluation of Saposhnikoviae Radix based on QAMS combined with information entropy-response surface method / 中国中药杂志

This research was used with high performance liquid chromatography(HPLC), combined with information entropy-response surface method(RSM) to investigate the ethanol concentration, extraction time, liquid-to-material ratio. Taking the content of four chromogens as evaluation indexes, the weight coefficients of each index were given, and the comprehensive score was calculated to optimize the extraction process. Then, prim-O-glucosylcimifugin was used as the reference, the relative calibration factors(RCFs) of cimifugin, 4'-O-β-D-glucosyl-5-O-methylvisamminol and sec-O-glucosylhamaudo to prim-O-glucosylcimifugin were calculated respectively. The contents of four components in Saposhnikoviae Radix were determined by both external standard method(ESM)and quantitative analysis of multi-components by single marker(QAMS) method, and the results were compared. At last, combined with principal component analysis(PCA) and orthogonal partial least squares discriminant analysis(OPLS-DA) to evaluate the quality of the Saposhnikoviae Radix in different production areas. The optimal extraction process parameter of the Saposhnikoviae Radix was as follows: liquid-to-material ratio is 60∶1(mL·g~(-1)), extraction time is 35 min, and ethanol concentration is 70%. The repeatability of the RCFs was perfect, and the results calculated by the QAMS were consistent with the results from the ESM. The stoichiometric results indicate that there are obvious differences in the distribution of Saposhnikoviae Radix in different production areas, and cimifugin and prim-O-glucosylcimifugin are the characteristic compounds that cause this difference. In this study, the optimal extraction process is stable and feasible, and the method of QAMS is accurate and reliable. From the perspective of four chromogens, there are differences in the quality of the Saposhnikoviae Radix in different production areas. Therefore, the established extraction process combined with the method of QAMS can be used to evaluate the quality of Saposhnikoviae Radix and provide a scientific basis for the quality control of Saposhnikoviae Radix.

Optimization of the Extraction Technology of Senecio scandens by Orthogonal Design Combined with Informa- tion Entropy Weighting Method / 中国药房

OBJECTIVE：To optimize the extraction technology of Senecio scandens ，and to provide reference for the further development and utilization of the medicinal material. METHODS ：The method of reflux extraction with 80 ℃ water bath was used to extract S. scandens . HPLC method was adopted to determine the contents of chlorogenic acid and hyperoside. The determination was performed on Diamonsil C 18 with mobile phase consisted of 0.2％ glacial acetic acid water solution-methanol （82∶18，V/V）at the flow rate of 1.0 mL/min；the column temperature was set at 35 ℃；the detection wavelength was 327 nm，and the sample size was 5 μL. UV-Vis spectrophotometry was used to determine the contents of total flavonoids（by rutin ）and total alkaloids （by matrine）and the detection wavelengths were set at 509 nm and 208 nm，respectively. Based on single factor tests ，using ethanol volume fraction （A，％），solvent folds （B，mL/g），extraction time （C，h），extraction times （D，times）as factors ，using the contents of chlorogenic acid ，hyperoside，total flavonoids and total alkaloids as indexes ，and t he weight coefficients of above indicator components were calculated based on information entropy weighting method so as to calculate their comprehensive scores ， then L 9（34）orthogonal design was used to further optimize the extraction technology. The validation tests were also performed. RESULTS：The optimal extraction technology of S. scandens included that 8-fold 50％ ethanol，extracting for 3 times，lasting for 1.5 h each time. Results of 3 times of validation tests showed that RSDs of the contents of chlorogenic acid ，hyperoside，total flavonoids and total alkaloids were all lower than 1.5％（n＝3）. CONCLUSIONS ：The optimized technology is reproducible ， stable and feasible ，and can be used for the extraction of S. scandens .

Study on optimization of UPLC fingerprint of classic prescription of Shentong Zhuyu Decoction based on principle of information entropy maximization / 中草药

Objective: To optimize the condition of the fingerprint of the classic prescription Shentong Zhuyu Decoction (SZD) by the principle of information entropy maximization. Methods: The chromatographic fingerprint was obtained with Acquity UPLC HSS T3 column (100 mm × 2.1 mm, 1.8 μm) and gradient eluted with acetonitrile and 0.4% phosphoric acid aqueous solution; The flow rate was 0.6 mL/min, and the column temperature was maintained at 40 ℃; The detection wavelengths were set at 190-400 nm, and the injection volume was 1 μL, and calculate the information entropy to optimize the wavelength of maximizing the information entropy of the fingerprint of SZD, under the optimal wavelength, investigate the mobile phase, column temperature, flow rate, sample volume, select the optimal conditions based on the principle of maximizing the information entropy, and carry out the fingerprint study of 15 batches of SZD under the optimal conditions. Results : Under the principle of information entropy maximization, the optimal conditions of the fingerprint of SZD were as follows: the detection wavelength was 235 nm, and gradient eluted with acetonitrile and 0.4% phosphoric acid aqueous solution; The flow rate was 0.4 mL/min, and the column temperature was maintained at 40 ℃, the injection volume was 3 μL; The absolute and relative entropy was the largest. The total statistical moment similarity of 15 batches of SZD fingerprints ranged from 0.882 8 to 0.995 3. The RSD values of the total first-order moment and information entropy of the total amount were 5.40% and 2.25% respectively, all of which were less than 10%, indicating that the imprinting effect of the overall chemical structure of the multi-component system of traditional Chinese medicine was stable. Conclusion: When the number and area of chromatographic peaks reach the best characterization, the information entropy is the largest. At this time, the number of peaks is high, the shape of peaks is better, the resolution is good, the number of theoretical plates is higher, and the best condition of fingerprint can be determined. The principle of information entropy maximization can provide scientific basis for fingerprint optimization of traditional Chinese medicine and its compound prescription, and lay a foundation for quality control of classical formulas.

Optimization of Water Extraction Technology of Taohe Chengqi Decoction by Response Surface Methodology Combined with Information Entropy Theory / 中国药房

OBJECTIVE： To optimize the water extraction technology of classic formula Taohe chengqi decoction. METHODS： Based on single factor test， combined with response surface methodology and information entropy theory， the soaking time， solid-liquid ratio and extraction time were investigated. Using the contents of rhein， amygdalin， cinnamaldehyde and glycyrrhizic acid in Taohe chengqi decoction as indexes， information entropy theory was used to assign weight coefficients to each evaluation index and calculate the comprehensive score. Through Design-Expert 10 software， the interactions of each factor were analyzed. Water extraction technology was optimized， and validation test was also performed. RESULTS： According to information entropy theory， the weight coefficients of rhein， amygdalin， glycyrrhizic acid and cinnamaldehyde were located at 0.097 6， 0.363 2， 0.173 5 and 0.365 7. The results of interaction analysis showed that the material-liquid ratio had a greater impact on the comprehensive score. The optimal water extraction technology of Taohe chengqi decoction were determined as that soaking time was 60 min； the ratio of material to liquid was 1 ∶ 10 （g/mL）； total extraction time was 130 min （extracting for 3 times， lasting for 65， 33， 32 min each time）. The results of verification test showed that RSD of content of each index component and the comprehensive score was less than 3％. CONCLUSIONS： The optimal water extraction technology is proved to be stable and feasible， which can provide the basis for the further development and utilization of Taohe chengqi decoction.

Comparison of Improvement Effects and Its Mechanism of Different Doses of Total Alkaloids from Aconitum racemulosum on CIA Model Rats Based on Information Entropy Theory / 中国药房

OBJECTIVE： To investigate the effects of different doses of total alkaloids from Aconitum racemulosum （ARTA） on serum inflammation factors and FOS protein expression in synovial tissue of joint in collagen-induced arthritis （CIA） model rats， and to investigate its potential mechanism of anti-rheumatoid arthritis （RA）. METHODS： Male SD rats were randomly divided into blank group， model group， positive group （Compound dexamethasone acetate ointment， 0.2 g/kg）， ARTA low-dose， medium-dose and high-dose groups （56.26， 112.50， 225.00 mg/kg， by the weight of ARTA in the extract）， with 10 rats in each group. Except for blank group， other groups were given subcutaneous injection of Bovine collagen Ⅱ emulsified with incomplete Freund’s adjuvant into the left foot to establish CIA model； the left foot were smeared with relevant medicine from the day of modeling. Blank group and model group were smeared with constant volume of 65％ ethanol， 3 times a day， for consecutive 28 days. On the 7th， 14th， 21st and 28th day of administration， the thickness of left hind toe was measured with vernier caliper， and the degree of foot swelling was calculated. The serum contents of IL-1β， IL-6 and TNF-α in rats were measured by ELISA after last administration. The expression of FOS protein in synovial tissue was determined by immunohistochemical method [expressed by HIS]. The comprehensive score was conculated by entropy weight method. Effects of each dosage on above indexes of CIA model rats were evaluated with the comprehensive score. RESULTS： Compared with blank group， the degree of foot swelling， serum content of inflammatory factors and HIS value were increased significantly in model group （P＜0.05）. Compared with model group， the degree of foot swelling in each administration group， serum contents of IL-1β， IL-6 and TNF-α， HIS in positive group and ARTA high-dose group， serum contents of IL-6 and TNF-α in ARTA medium-dose group as well as serum content of TNF-α in ARTA low-dose group were decreased significantly（P＜0.05）. Comprehensive score of above indicators were 0.37（positive group）， 0.31（ARTA high-dose group）， 0.23（ARTA medium-dose group） and 0.09（ARTA low-dose group）. CONCLUSIONS： ARTA can improve CIA model rats， and the effect tends to increase with the increase of dose. Above effect may be associated with reducing serum content of inflammatory factors and inhibiting the expression of FOS protein in synovial tissue.

Optimization of the Extraction Technology of Volatile Oil from Schizonepeta tenuifolia and Forsythia suspensa / 中国药房

OBJECTIVE： To establish the method for content determination of volatile oil of Schizonepeta tenuifolia and Forsythia suspensa， and to optimize the extraction technology of the volatile oil. METHODS： The contents of β-pinene and pulegone were determined by GC method. The determination was performed on Hp-5 capillary column. The detector was hydrogen flame ion detector with programmed temperature. The sample size was 0.5 μL， the split ratio was 70 ∶ 1， the carrier gas was nitrogen， the inlet temperature was 250 ℃， the detector temperature was 280 ℃， the air flow rate was 390 mL/min， the hydrogen flow rate was 36 mL/min， the tail flow rate was 15 mL/min， and the nitrogen flow rate was 1 mL/min. Based on single factor test， orthogonal test combined with information entropy method were used to optimize the extraction technology of S. tenuifolia and F. suspensa using soaking time， extraction time， material-liquid ratio and forsythia grain size as factors， with the extraction amount of volatile oil， the content of β-pinene and pulegone and their comprehensive score as indexes.  RESULTS： The linear range of β-pinene and pulegone 1.575-7.875（r＝0.999 9） and 1.892-9.46 μg（r＝0.999 7）， respectively. The limits of quantitation were 0.10 and 0.25 μg； the limits of detection were 0.03 and 0.08 μg； RSDs of precision， stability and reproducibility tests were less than 2％ （n＝6）； the recoveries were 97.77％-100.01％ （RSD＝0.93％，n＝9） and 96.47％-99.00％（RSD＝0.89％， n＝9）. The optimal extraction technology was soaking 2 h， extracting for 6 h， 10-fold water （mL/g）， half a clove of granularity. Under this condition， the extraction amount of volatile oil， the contents of β-pinene and pulegone were 3.6 mL， 1 450.4 mg， 127.6 mg， respectively. RSD were 1.62％， 0.20％， 1.42％. CONCLUSIONS： Established method is simple， accurate and reproducible， and the optimal extraction technology is stable and feasible.

Study on the Optimization of Extraction Technology of Qiwei Chanshen Formula by Orthogonal Test Based on Information Entropy Theory / 中国药房

OBJECTIVE： To optimize the water extraction technology of Qiwei chanshen formula. METHODS： The content of polysaccharides from Gekko japonicus and Panax quinquefolium was determined by UV spectrophotometry， the contents of camptothecin from Camptotheca acuminata and ginsenoside Rb1 from P. quinquefolium were determined by HPLC. The extraction rate of above three components， dry extractum yield and HPLC fingerprint similarity were used as evaluation indicators； information entropy theory was used to determine the weight of each indicator so as to calculate comprehensive score. L9（34） orthogonal test was used to screen the optimal extraction technology of Qiwei chanshen formula with decoction time， water volume and decoction times as factors. Validation test was also performed. RESULTS： The optimal extraction technology included 10-fold water， decocting for 3 times， 1.0 h each time. The results of validation test showed that the average extraction rate of polysaccharide， camptothecin and ginsenoside Rb1 were 74.306％， 13.860％ and 52.958％， respectively. The average dry extractum yield was 16.150％， the average value of fingerprint similarity was 0.991 （all RSDs＜3.0％， n＝3）. CONCLUSIONS： The optimized extraction technology is reproducible， stable and feasible， providing reference for the subsequent development and industrial production of the formula.

Optimization of extraction process of Xiaoruzeng Capsules based on orthogonal design in information entropy theory / 中草药

Objective: To optimize the extraction process parameters of seven herbs in Xiaoruzeng Capsules (XC). Methods: The content of paeoniflorin, ferulic acid, hesperidin, imperatorin and ligustilide was determined by HPLC. The extraction rate of five kinds of index components, the dry extract yield of extracted herbs and the fingerprint similarity of extracts were comprehensively evaluated. The orthogonal experiment was carried out to investigate the effects of ethanol concentration, extraction solvent, extraction time and extraction times on the extraction process. The information entropy weighting method was used to determine the objective weight of each index, and the extraction process parameters of seven herbs in XC were optimized. Results: According to the comprehensive scoring results, it was determined that the best extraction process of the preparation was to add six times the amount of 50% ethanol, and decocted two times for 2 h each time. The average score of the three batches of verification scores was 99.72, and the RSD was 0.24%. Conclusion: The preferred process has high extraction rate, with good stability and repeatability, which is suitable for mass production of the preparation.

Optimization of extraction of total flavonoids from leaves of Psidium guajava by orthogonal test based on information entropy weighting / 中草药

Objective: To optimize the extraction of total flavonoids from leaves of Psidium guajava. Methods: L9(34) orthogonal test was used to screen the optimal extraction technology of total flavonoids from leaves of P. guajava with ethanol concentration, solid-liquid ratio, extraction time, and extraction times as factors. The weight coefficient of the four evaluation indicators, including the yield of total flavonoids, hyperoside, quercetin-3-O-β-D-pyranarabinoside, and quercetin-3-O-α-L-furanarabinoside was calculated by information entropy weighting so as to calculate comprehensive score. We obtained the optimal technology by orthogonal analysis based on the comprehensive score. Results: The optimal extraction technology was that using 8-fold 70% ethanol water to extract 2 h for three times. The mean comprehensive score of the three batches was 0.142 1 and the RSD was 2.37%. Conclusion: The optimal extraction technology of total flavonoids from leaves of P. guajava was stable and feasible with high yield.

Optimization of dry granulation prescription and technology of Xiaochuan Granules based on physical characteristics of raw materials in preparations / 中草药

Objective: To utilize powder physical characteristics, optimize prescription of dry granulation process of Xiaochuan Granules (XG). Methods: Filtering of granulation prescription was guided by investigating of powder material physical characteristics such as angle repose, compression degree, water content, etc; With one time forming rate, friability and quality score of granulation process as indexes, L9(34) orthogonal test which based on the evaluation method of information entropy was used to optimize the process parameters in XG dry granulation. Results: The optimum accessory is CD, optimum dry granulation technology parameters was as follows: roll wheel pressure of 7 MPa, roll wheel speed of 10 r/min, and feed speed of 18 r/min. Conclusion: Study of physical property of preparation materials could guide filtering prescription of dry granulation preparation; The prepared granules have high forming rate with moderate hardness and good flowability, and this optimized dry granulation technology is stable and reasonable.

Optimization of extraction technology for Xiaochuan Decoction based on information entropy theory / 中草药

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.

Application of information entropy theory in optimization of extraction technology for Lonicerae Flos and Gardeniae Fructus in Reduning Oral Preparation / 中草药

To optimize the extraction technology for Lonicerae Flos and Gardeniae Fructus in Reduning Oral Preparation by information entropy theory. With the contents of chlorogenic acid, gardenoside, luteoloside, and the yield of extract as comprehensive evaluation indexes, the extraction time, dosage of water, and extraction times were selected as factors, the weight of them was determined by information entropy theory, and the extraction technology was optimized by orthogonal test. Optimum extraction technology was: Reflux extraction for 3 times with 12 folds water, 1 h each time. The information entropy theory could be used in optimizing the extraction technology for Reduning Oral Preparation.