Optimization of ethanol reflux extraction process of Ziziphi Spinosae Semen- Schisandrae Sphenantherae Fructus based on network pharmacology combined with response surface methodology / 中国中药杂志

The present study optimized the ethanol extraction process of Ziziphi Spinosae Semen-Schisandrae Sphenantherae Fructus drug pair by network pharmacology and Box-Behnken method. Network pharmacology and molecular docking were used to screen out and verify the potential active components of Ziziphi Spinosae Semen-Schisandrae Sphenantherae Fructus, and the process evaluation indexes were determined in light of the components of the content determination under Ziziphi Spinosae Semen and Schisandrae Sphenantherae Fructus in the Chinese Pharmacopoeia(2020 edition). The analytic hierarchy process(AHP) was used to determine the weight coefficient of each component, and the comprehensive score was calculated as the process evaluation index. The ethanol extraction process of Ziziphi Spinosae Semen-Schisandrae Sphenantherae Fructus was optimized by the Box-Behnken method. The core components of the Ziziphi Spinosae Semen-Schisandrae Sphenantherae Fructus drug pair were screened out as spinosin, jujuboside A, jujuboside B, schisandrin, schisandrol, schisandrin A, and schisandrin B. The optimal extraction conditions obtained by using the Box-Behnken method were listed below: extraction time of 90 min, ethanol volume fraction of 85%, and two times of extraction. Through network pharmacology and molecular docking, the process evaluation indexes were determined, and the optimized process was stable, which could provide an experimental basis for the production of preparations containing Ziziphi Spinosae Semen-Schisandrae Sphenantherae Fructus.

Quality evaluation of Aralia taibaiensis based on spectrum-activity relationship / 中国中药杂志

A spectrum-activity relationship is established with high performance liquid chromatography(HPLC) fingerprints and the in vitro antioxidant activity to improve the quality evaluation system of Aralia taibaiensis. The HPLC profiles of 12 batches of samples were collected, and the similarity evaluation, heat map analysis and principal component analysis were conducted for the chemometric study of the fingerprint data. Combined with grey correlation analysis, the contributions of the common peaks in the fingerprints to the antioxidant activity were clarified, and the important peaks reflecting the efficacy were identified. The results showed that 17 common peaks were found in 12 batches of A. taibaiensis samples, and 6 of them were identified as saponins. Similarity evaluation, heat map analysis and principal component analysis roughly classified the A. taibaiensis herbs into two categories, i.e.,(1) S1-S10, S12 and(2) S11. Twelve batches of samples showed different antioxidant activities in a dose-dependent manner. In particular, S9 had the strongest antioxidant activity, while S11 was the weakest in antioxidant capacity, which was basically consistent with the overall score results. The results of grey correlation analysis demonstrated that the 17 common peaks scavenged DPPH radicals in the following order: X_3>X_(17)>X_4>X_8>X_7>X_(13)>X_2>X_6>X_(11)>X_(10)>X_(16)>X_(12)>X_9>X_5>X_(14)>X_1>X_(15), and scavenged ABTS radicals in the order of X_4>X_3>X_7>X_8>X_2>X_(17)>X_(13)>X_6>X_(16)>X_(11)>X_5>X_(12)>X_(10)>X_9>X_(14)>X_1>X_(15). Among them, X_3, X_4, X_7(araloside C), X_8 and X_(17) were the important peaks reflecting the efficacy of A. taibaiensis, which were basically consistent with those contained in the principal component 1. In this study, the correlation between the HPLC fingerprints of 12 batches of A. taibaiensis and its antioxidant activity provides a reference for the Q-marker screening and quality control of A. taibaiensis.

Powder modificationfor improving content uniformity of Ziyin Yiwei Capsules / 中国中药杂志

Based on the defects in powder properties of the contents of Ziyin Yiwei Capsules, this study screened out the main medicinal slice powders causing the poor powdery properties, and introduced the powder modification process to improve the powdery properties of these slice powders, the pharmaceutical properties of the capsule contents, and the content uniformity of Ziyin Yiwei Capsules, so as to provide a demonstration for the application of powder modification technology to the preparation of Chinese medicinal solid preparations. Through the investigation on the powder properties of the contents of Ziyin Yiwei Capsules, it was clarified that the pulverized particle size of the capsule contents had a good correlation with the pulverization time. According to the measurement results of the powder fluidity and wettability, the quality defects of the capsule contents were caused by the fine powders of Taraxaci Herba and Lungwortlike Herba. "Core-shell" composite particles were prepared from medicinal excipients magnesium stearate and fine powders of Taraxaci Herba and Lungwortlike Herba slices after ultra-fine pulverization to improve the powder properties of the problematic fine powders. Powder characterization data including fluidity and wettability were measured, followed by scanning electron microscopy(SEM) and infrared ray(IR) detection. It was determined that the optimal dosage of magnesium stearate was 2%, and the compositing time was 3 min. The composite particles were then used as content components of the Ziyin Yiwei Capsules. The powder characteristics between the original capsule and the modified composite capsule including the particle size, fluidity, wettability, uniformity of bulk density, and uniformity of chromatism as well as the content uniformity and in vitro dissolution were compared. The results showed that the powder characteristics and content uniformity of the prepared composite capsule were significantly improved, while the material basis of the preparation was not changed before and after modification. The preparation process was proved to be stable and feasible. The powder modification technology solved the pharmaceutical defects that were easy to appear in the preparation of traditional capsules, which has provided experimental evidence for the use of powder modification technology for improving the quality of Chinese medicinal solid preparations and promoting the secondary development and upgrading of traditional Chinese medicinal dosage forms such as capsules.

Particle design for improving content uniformity of Hewei Jiangni Capsules / 中国中药杂志

Targeting the poor powder characteristics of the contents in Hewei Jiangni Capsules, this study characterized the powder properties of the contents and employed particle design technique for improving the content quality. The content composite particles of Hewei Jiangni Capsules prepared by the particle design technique were evaluated by scanning electron microscopy(SEM), followed by infrared ray(IR), content uniformity, and in vitro dissolution detection. It was found that there was a good correlation between the crushed particle size of slices and the crushing time, and the calcined Haematitum was responsible for the poor content uniformity. After the fine powder of calcined Haematitum was super-finely ground for 8.5 min and those of the other contents in the capsule for 1 min, they were prepared into the composite particles, whose property characterizations were compared with those of the physical mixtures. The content uniformity of the prepared composite particles was significantly improved, and the preparation process was stable and reliable. The adoption of particle design technology to correct the poor uniformity of the physical mixture, solve the pharmaceutical defects of Hewei Jiangni Capsules, and improve the quality of prescriptions has provided important reference for the clinical application and development of Chinese medicinal preparations.

Application of particle design technology in field of traditional Chinese medicine powder / 中国中药杂志

Solid preparations account for more than 50% of traditional Chinese medicines(TCM). TCM powder is an important raw material for solid preparations of TCM. Its powder properties directly affect the quality of solid preparations, and even clinical safety and effectiveness. Particle design technology based on the characteristics of powder in TCM is an important means to improve and enhance the quality of solid preparations. This study summarized the relevant principles, methods, characteristics, classification, equipment, and other elements of particle design technology in recent years, analyzed the difficulties in its application in the field of TCM powder, and proposed the strategies in conjunction with the development of computer data mining. The present study is expected to provide a reference for the suitability of particle design in the field of TCM powder.

Study on Stability of Volatile Oil in Foeniculi Fructus and Screening Its Antioxidants in Accelerated Oxidation Environment / 中国实验方剂学杂志

Objective: To screen the accelerated oxidation environment with the most drastic changes in the volatile oil composition of Foeniculi Fructus, and to optimize the type and concentration of antioxidants. Method: The volatile oil of Foeniculi Fructus was extracted by steam distillation. Taking thiobarbituric acid reactive substances (TBARS) value and peroxide value (POV) as evaluation indexes, response surface method was used to investigate the effects of temperature, concentrations of ferrous ion (Fe2+) and azoamidine initiator V50 (AAPH) on volatile oil components of Foeniculi Fructus and its oxidation products. TBARS and POV were detected by ultraviolet chromatography. The oxidative environment with the most drastic changes of volatile oil composition of Foeniculi Fructus was screened. The type and concentration of antioxidants were selected by single factor experiments. The change discipline of volatile oil in Foeniculi Fructus after added different concentrations of antioxidants were analyzed by GC-MS. Result: The worst oxidizing environment for volatile oil of Foeniculi Fructus was as follows:temperature at 42.5℃,AAPH concentration of 1 g·L-1,Fe2+ concentration of 20.85 mg·L-1. Ascorbyl palmitate with concentrations of 0.2 mol·L-1 and 0.8 mol·L-1 could effectively improve the stability of volatile oil from Foeniculi Fructus. Conclusion: Under the accelerated oxidation environment, the terpenes in volatile oil from Foeniculi Fructus are significantly changed, but its stability can be improved by ascorbyl palmitate.

Pharmacokinetic Study of Araloside A in Rats Based on LC-MS/MS Techniques / 中国药学杂志

OBJECTIVE: To develop a highly sensitive and specific LC-MS/MS method to explore the pharmacokinetic properties of araloside A. METHODS: Araloside A was administered in a dose of 50 mg•kg-1 via gastric in fusion and 5 mg•kg-1 by intravenous injection in rats. Araloside A was analyzed by a validated LC-MS /MS method in plasma after intravenous and intragastric administration. The pharmacokinetic parameters were evaluated by software DAS 3.0. RESULTS: The results of pharmacokinetic study showed that the linear range of araloside A was good in 1.0 - 10 000.0 μg•L-1 (r > 0.994 8). The specificity, precision and accuracy, matrix effect and extraction recovery rate and stability all meet the requirements. The main pharmacokinetic parameters for intragastric administration with araloside A 50 mg•kg-1 and intravenous injection of araloside A 5 mg•kg-1 were as follows: t1/2 was (8.65 ± 3.22 ) and (2.00 ± 0.21) h, AUC0-t was (277.14 ± 101.00) and (21 194.59 ± 4 385.13) ng•h•L-1, MRT0-t was (7.88 ± 0.64) and (1.21 ± 0.11) h, Vd/F was (2 229.99 ± 1 013.97) and (0.71 ± 0.20) L•kg-1, CL/F was (149.11 ± 62.28) and (0.24 ± 0.05) L•h-1•kg-1, respectively; ρmax was (32.68 ± 10.74) μg•L-1 for intragastric administration and tmax reached(1.21 ± 0.70) h, oral bioavailability of araloside A was about 0.14%. CONCLUSION: The LC-MS/MS method established is specific and sensitive, and can be successfully applied in basic pharmacokinetic study of araloside A in rat plasma.

Tissue distribution of araloside A in rats / 中国中药杂志

Araloside A is one of the main active ingredients of Aralia taibaiensis. In this study, HPLC-MS/MS analysis method of araloside A in the main organs of SD rats was established. At the same time, the content of araloside A in the main organs (heart, liver, spleen, lung, kidney, brain) after oral administration with araloside A (50 mg•kg⁻¹) were determined to explore the tissue distribution characteristics of araloside A in vivo. The results showed that the methodological study of araloside A in the main organs of SD rats met the requirements, araloside A distributed in heart, liver, spleen, lung, kidney and brain tissues reached peak at 1 h or 2 h after oral administration with 50 mg•kg-1.The distributions of araloside A at different time points after administration were distinct as follows： the content of araloside A at 20 min：liver>heart>spleen>lung>kidney>brain; the content of araloside A at 1 h： liver>spleen>kidney>lung>heart>brain; the content of araloside A at 2 h： liver>kidney>heart>spleen>lung>brain; the content of araloside A at 4 h： kidney>liver>spleen>heart>lung>brain; the content of araloside A at 8 h： spleen>heart>liver>kidney>lung>brain. Therefore, araloside A was mainly distributed in liver tissue, which had a certain correlation with the common use of Aralia taibaiensis in the treatment of hepatic disease. In addition, araloside A shows a low content but an obvious distribution in brain tissues, which indicates that the drug can pass through blood-brain barrier, and provides the basis for the study of araloside A in brain tissue.

In vivo intestinal absorption characteristics of phloridzin in rats / 中国中药杂志

To study the in vivo intestinal absorption kinetics of phloridzin in rats. The absorption of phloridzin in the small intestines and colon of rats was investigated using an in vivo single-pass perfusion method and the drug concentration was measured by HPLC. The effects on intestinal absorption of different drug concentration and P-glycoprotein (P-gp) inhibitor were conducted. The results showed that the phloridzin could be absorbed in whole intestine, but more fully in the jejunum and colon segment,poorly absorbed in the duodenum and ileum. The absorption rate constant (Ka) and the apparent absorption coefficient（Papp）of phloridzin decreased following the sequence of jejunum> colon > duodenum > ileum. Absorption parameters of phloridzin had no significant difference at different concentration (5.14, 10.28, 20.56 mg•L⁻¹) . The saturate phenomena was not observed under the test range of drug concentration, and the absorption mechanism may be the passive diffusion transport.There had a significant difference in Ka and Papp values between P-gp inhibitor and no P-gp inhibitor groups. Phloridzin may be the substrate of P-gp.