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To analyze the study advance of Strychni Semen, a kind of traditional Chinese medicine, this study systematically retrieved the related Chinese literatures about Strychni Semen from CNKI database platforms and the core database of Web of Science, and used bibliometrics and CiteSpace 5.6.R5 software to visually display the authors, research institutions, keywords and other contents. A total of 1 895 Chinese literatures and 1 599 English literatures were included in the study. The analysis of Chinese and English literature authors showed that CAI Bao-chang and CHEN Jun had the most publications on Strychni Semen, and CAI Bao-chang's team was the core research team. According to the analysis of publishing institutions, Nanjing University of Traditional Chinese Medicine and Chinese Academy of Science were the research institutions with the largest number of Chinese and English literatures, respectively. But there was less cooperation between Chinese and English study institutions. The analysis of keywords in Chinese and English literatures showed that the research contents of Strychni Semen mainly focused on component analysis, research methods, receptor targets, clinical application, synergistic and attenuation measures. Break analysis showed that the apoptosis induced by Strychni Semen was a hot research topic, and research on components, toxicity and pharmacokinetics will be the research hotspot in future. The research on Strychni Semen is still in the developing period. This study has provided reference for the rapid grasp of the research contents and the judgment of research hotspots.
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Bibliometrics , Databases, Factual , Medicine, Chinese Traditional , Research Design , SemenABSTRACT
Objective: To study the pharmacokinetics and tissue distribution of procesed Strychni Semen in rats after multiple administration at clinical dose. Methods: The rats were given procesed Strychni Semen by intragastric administration for single and several times. The plasma concentrations of brucine and strychnine in plasma and tissues of rats were determined by UPLC-Q-Orbitrap HRMS method, and the organizational distribution differences were compared to explore whether there was accumulation in the body. Results: After single intragastric administration of procesed Strychni Semen, the main pharmacokinetic parameters of brucine and strychnine were as follow: t1/2 was 10.59 and 8.39 h, tmax was 0.77 and 0.64 h, t1/2Ka was 5.38 and 2.63 h, Cmax was 2.97 and 10.83 ng/L, AUC0-t was 87.36 and 172.24 ng∙h/L, CL/F was 40 637.08 and 38 370.26 L/(h∙kg); Brucine and strychnine in processed Strychni Semen reached a steady state after 3 d of administration in rats. After the last administration, the main pharmacokinetic parameters of brucine and strychnine in rats were as follow: t1/2 was 7.07 and 4.75 h, tmax was 0.48 and 0.46 h, t1/2Ka was 3.23 and 1.09 h, Cmax is 5.77 and 34.83 ng/L, AUC0-t was 32.80 and 107.86 ng∙h/L, and CL/F was 75 920.52 and 43 871.54 L/(h∙kg). Compared with the single administration, the content of brucine and strychnine in the liver and kidney tissues was significantly reduced after multiple administrations, and there was no significant change in other tissues. Conclusion: The pharmacokinetics of brucine and strychnine in healthy rats is consistent with one-compartment model. Both of them have the pharmacokinetic characteristics of fast absorption in rats. After 3 d of administration, the serum concentrations of brucine and strychnine reached steady state, and the blood concentration was increased continuously with the increase of administration times. The content of each tissue did not increase after single and multiple administrations. It is suggested that long-term administration of brucine and strychnine will not cause the superposition of the concentration of brucine and strychnine in the blood of rats, which may lead to the occurrence of poisoning.
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Objective:To research the best processing method for Strychni Semen with children's urine by orthogonal test. Methods:L9(34) orthogonal test was used with the types of children's urine, dosage of children's urine, soaking time and drying temperature as the influencing factors,HPLC was applied to determine the contents of brucine and strychnine as the indices to obtain the comprehensive weighted score. ANOVA was used to optimize the processing technology of Strychni Semen with children's urine. Results:The soaking time showed significant effect on the content of brucine and strychnine, while the other three factors had no significant effect. The best processing technology was A1B1C3D3. Conclusion:The optimum processing of Strychni Semen with children's urine is as follows:3-year-old children's urine with 3-fold amount is used to soak for 10 d,and the drying temperature is 90 ℃. The method is stable and reliable, which can be used for the new processing technology of Strychni Semen.
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Objective To prepare a new kind of preparation formulation of the total alkaloids from seed of Strychni Semen (TASS), by which could improve their drug loading content and the transdermal function. Methods TASS-LLCN were prepared by hot solvent and high pressure homogeneous method. Using encapsulation efficiency (EE) measured by ultrafiltration as index, the prescription of TASS-LLCN was optimized by response surface methodology with central composite design, and the basic properties of the optimized TASS-LLCN was evaluated. The Franz diffuser method was used to compare the transdermal capacity of both LLCN gel and ordinary gel of TASS. Results The best prescription of TASS-LLCN was as follow: the content of glycerin monooleate (GMO) was 1 403.19 mg/mL, the ratio between GMO and F127 was 7.25:1, the drug loading content was 9.48% and the predicted encapsulation efficiency was 64.01%. The evaluation of basic properties of the optimized TASS-LLCN showed that the average grain diameter was about 186 nm, zeta potential was -33.1 mV, pH was 6.83, the stability was good. The transdermal experiment in vitro showed that the cumulate osmotic quantities in 24 h and the permeation rate of TASS-LLCN gel were both better than ordinary gel of TASS, which had obvious discrepancy (P < 0.05) and showed that LLCN could promote the absorption of active components; the skin retention volume of LLCN gel was still bigger than ordinary gel, which showed that LLCN gel of TASS could store in the skin and release the drug sustainedly. Conclusion TASS-LLCN could obviously enhance the drug loading content and the transdermal function. It is a potential new kind of preparation formulation which have the sustainable effect.
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Objective To evaluate the applicability of small molecular markers of nephrotoxicity that in prediction of drug toxicity.Method Extracts of five kinds of traditional Chinese medicines (Tripterygium wilfordii,Strychni semen,Aristolochiafangchi,Rhei Radix et Rhizoma,and Xanthium sibiricum) that had known as nephrotoxicity were ig given to rats to establish renal injury models,and the blood samples were collected after administration for 1 and 7 d.Then blood samples were analyzed by UPLC/Q-TOF-MS for five kinds of small molecule biomarkers-thymidine,lyso-phosphatidylcholine (LPC 16:1),LPC (18:4),LPC (20:5),and LPC (22:5).The support vector machine (SVM) prediction model was established to determine the toxicity.The levels of Cr and BUN in serum were determined by automatic biochemical analyzer.The rats in each group were sacrificed after blood collection,and the kidneys were taken for HE staining.Result No toxicity was observed in the control group,and the biochemical test results showed no renal injury after mentioned five kinds Chinese herbs were given for 1 d,while SVM model of nephrotoxicity had been found abnormal.After administration for 7 d,the results of SVM model show renal toxicity,which were consistent with biochemical and pathological examination.Conclusion Metabonomics combined with the earlier established SVM model enabled prediction of drug nephrotoxicity more sensitively,quickly and \ccurately,and it is of great significance for the discovery of drug toxicity as well as the prevention and treatment of drug-induced renal injuries in clinic.
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AIM To investigate the equilibrium solubilities,oil-water partition coefficients and in vitro skin permeation features of brucine and strychnine in total alkaloids from Strychni Semen.METHODS Saturated dissolution method was applied to determining the equilibrium solubilities of two constituents in ethanol (10％,20％,30％,60％,90％,anhydrous ethanol),trichloromethane,n-octanol and surfactants (0.5％ tween,0.5％ sodium deoxycholate,0.5％ oleic acid).Shake-flask method was adopted in detecting their oil-water partition coefficients in PBS (pH 2.5,4.0,5.0,5.8,6.8,7.0,7.4,9.0).Modified Franz diffusion cell method was used for evaluating their in vitro skin permeation features in PBS,20％ ethanol and anhydrous ethanol.RESULTS Both brucine and strychnine showed the highest equilibrium solubilities in trichloromethane and the lowest equilibrium solubilities in surfactants.The equilibrium solubility of strychnine was higher than that of brucine in ethanol (＞ 20％) or PBS (pH ＜ 8.0),which reached the highest in 60％ ethanol and pH 2.5 PBS,respectively.The similar oil-water partition coefficients of two constituents,proportional to pH value,reached the highest at pH9.0.And they exhibited the highest accumulated transdermal absorptivities in anhydrous ethanol and pH 9.0 PBS,respectively.CONCLUSION Solvent type has obvious effects on the equilibrium solubilities,oil-water partition coefficients and in vitro skin permeation features of both brucine and strychnine.This study can provide a reference for the bioavailability improvement of transdermal drug delivery and development of related preparations.
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AIM To investigate the equilibrium solubilities,oil-water partition coefficients and in vitro skin permeation features of brucine and strychnine in total alkaloids from Strychni Semen.METHODS Saturated dissolution method was applied to determining the equilibrium solubilities of two constituents in ethanol (10％,20％,30％,60％,90％,anhydrous ethanol),trichloromethane,n-octanol and surfactants (0.5％ tween,0.5％ sodium deoxycholate,0.5％ oleic acid).Shake-flask method was adopted in detecting their oil-water partition coefficients in PBS (pH 2.5,4.0,5.0,5.8,6.8,7.0,7.4,9.0).Modified Franz diffusion cell method was used for evaluating their in vitro skin permeation features in PBS,20％ ethanol and anhydrous ethanol.RESULTS Both brucine and strychnine showed the highest equilibrium solubilities in trichloromethane and the lowest equilibrium solubilities in surfactants.The equilibrium solubility of strychnine was higher than that of brucine in ethanol (＞ 20％) or PBS (pH ＜ 8.0),which reached the highest in 60％ ethanol and pH 2.5 PBS,respectively.The similar oil-water partition coefficients of two constituents,proportional to pH value,reached the highest at pH9.0.And they exhibited the highest accumulated transdermal absorptivities in anhydrous ethanol and pH 9.0 PBS,respectively.CONCLUSION Solvent type has obvious effects on the equilibrium solubilities,oil-water partition coefficients and in vitro skin permeation features of both brucine and strychnine.This study can provide a reference for the bioavailability improvement of transdermal drug delivery and development of related preparations.
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OBJECTIVE: To establish a high performance liquid chromatography coupled with tandem mass spectrometry and ultraviolet detector (HPLC-UV-MS) method for determination of the mixture of Glycyrrhiza Radix extract at detoxification dosage and Semen Strychni extract at poisonous dosage, which will be applied to the characteristic ingredients profiling in rat plasma. METHODS: Sino Chrome ODS-BP column (4.6 mm×250 mm, 5 μm) was employed, which was maintained at 40℃, and the mobile phase was composed of water (0.1% formic acid) (A) and acetonitrile (B). The gradient elution program was as follows: 0.01 min 8% B, 2 min 8% B, 30 min 25% B, 32 min 30% B, 50 min 45% B, 53 min 85% B, 60 min 85% B, 61 min 8% B, and terminated at 77 min, eluted at a flow rate of 0.3 mL·min-1. A UV detector was equipped and the detection wavelength was 254 nm. ESI+ mode was selected for strychnos alkaloids with cone voltage of 30 V and capillary voltage of 2.5 V, while ESI- mode for glycyrrhiza with cone voltage of 25 V and capillary voltage of 3.5 V. Acetonitrile was used as protein precipitation agent to determine the characteristic ingredients in rat plasma. RESULTS: An HPLC-UV-MS method for simultaneous determination of liquorice and Semen Strychni extract was established and applied to measure the components absorbed into blood. The material changes of liquorice and Semen Strychni in vivo and vitro were also compared. CONCLUSION: A simple, repeatable HPLC-UV-MS method for analysis of Glycyrrhiza Radix and Semen Strychni in vivo and vitro was established. The related components are speculates, which provided the experimental basis to research the detoxification mechanism of Glycyrrhiza Radix against strychninization.
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OBJECTIVE: To prepare the total alkaloids of Strychni Semen(TASS)-total glucosides of Paeony(TGP) gel and study its in vitro transdermal absorption of two alkaloids(strychnine and brucine) after the combination of TASS and TGP. METHODS: The excised abdominal skin of mice was used as the permeation model. Utilizing the modified Franz diffusion cell, the suitable receiving solution was elected to test the content of two alkaloids by HPLC, and thus the percutaneous rates and permeability coefficients were obtained. RESULTS: 20% Ethanol-normal saline was taken as receiving solution. With combination use of TASS and TGP, the penetration quantities of strychnine and brucine in different (1:1, 1:3, 1:6) gels were felled by 22.7%, 48.4%, 69.1% and 5.93%, 23.8%, 80.7% after 24 h. And with the increase of compatibility proportion, infiltration rate and skin retention rate also gradually reduced. CONCLUSION: The compatibility of TASS and TGP drug delivery can reduce the toxic ingredients through capacity, there is a"attenuated"effect, the best ratio is 1:6.
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Objective: To evaluate the in vivo pharmacokinetics of strychnos alkaloids [brucine, total alkaloids in Strychni Semen (TASS), and optimal total alkaloids in Strychni Semen (OTASS)] by ig administration to rats. Methods: The rats were ig administered with strychnos alkaloids and their blood samples were taken. Huperzine A was used as an internal standard. The brucine in plasma of rats was detected by HPLC method. The compartment model was fitted and the pharmacokinetic parameters were calculated by DAS1.0 program. Results: The pharmacokinetic analysis showed that brucine behaved as a two-compartment model in the three solutions after ig administration in rats. Compared with brucine monomer administration, the solution of TASS and OTASS could obviously increase the absorption of brucine in vivo, but other pharmacokinetic parameters had no significant difference. Conclusion: After ig administration with strychnos alkaloids, the other alkaloids in Strychni Semen could promote the absorption of brucine.