ABSTRACT
Therapeutic drug monitoring(TDM)has played an important role in clinical medicine for precise dosing.Currently,chromatographic technology and immunoassay detection are widely used in TDM and have met most of the needs of clinical drug therapy.However,some problems still exist in practical appli-cations,such as complicated operation and the influence of endogenous substances.Surface plasmon resonance(SPR)has been applied to detect the concentrations of small molecules,including pesticide residues in crops and antibiotics in milk,which indicates its potential for in vivo drug detection.In this study,a new SPR-based biosensor for detecting chloramphenicol(CAP)in blood samples was developed and validated using methodological verification,including precision,accuracy,matrix effect,and extraction recovery rate,and compared with the classic ultra-performance liquid chromatography-ultraviolet(UPLC-UV)method.The detection range of SPR was 0.1-50 ng/mL and the limit of detec-tion was 0.099±0.023 ng/mL,which was lower than that of UPLC-UV.The intra-day and inter-day ac-curacies of SPR were 98％-114％and 110％-122％,which met the analysis requirement.The results show that the SPR biosensor is identical to UPLC-UV in the detection of CAP in rat blood samples;moreover,the SPR biosensor has better sensitivity.Therefore,the present study shows that SPR technology can be used for the detection of small molecules in the blood samples and has the potential to become a method for therapeutic drug monitoring.
ABSTRACT
Astragali Radix(AR)is a clinically used herbal medicine with multiple immunomodulatory activities that can strengthen the activity and cytotoxicity of natural killer(NK)cells.However,owing to the complexity of its composition,the specific active ingredients in AR that act on NK cells are not clear yet.Cell membrane chromatography(CMC)is mainly used to screen the active ingredients in a complex system of herbal medicines.In this study,a new comprehensive two-dimensional(2D)NK-92MI CMC/C18 column/time-of-flight mass spectrometry(TOFMS)system was established to screen for potential NK cell acti-vators.To obtain a higher column efficiency,3-mercaptopropyltrimethoxysilane-modified silica was synthesized to prepare the NK-92MI CMC column.In total,nine components in AR were screened from this system,which could be washed out from the NK-92MI/CMC column after 10 min,and they showed good affinity for NK-92MI/CMC column.Two representative active compounds of AR,isoastragaloside Ⅰ and astragaloside Ⅳ,promoted the killing effect of NK cells on K562 cells in a dose-dependent manner.It can thus suggest that isoastragaloside Ⅰ and astragaloside Ⅳ are the main immunomodulatory compo-nents of AR.This comprehensive 2D NK-92MI CMC analytical system is a practical method for screening immune cell activators from other herbal medicines with immunomodulatory effects.
ABSTRACT
P-glycoprotein (P-gp) highly expressed in cancer cells can lead to multidrug resistance (MDR) and the combination of anti-cancer drugs with P-gp inhibitor has been a promising strategy to reverse MDR in cancer treatment. In this study, we established a label-free and detergent-free system combining surface plasmon resonance (SPR) biosensor with styrene maleic acid (SMA) polymer membrane proteins (MPs) stabilization technology to screen potential P-gp inhibitors. First, P-gp was extracted from MCF-7/ADR cells using SMA polymer to form SMA liposomes (SMALPs). Following that, SMALPs were immobilized on an SPR biosensor chip to establish a P-gp inhibitor screening system, and the affinity between P-gp and small molecule ligand was determined. The methodological investigation proved that the screening system had good specificity and stability. Nine P-gp ligands were screened out from 50 natural products, and their affinity constants with P-gp were also determined. The in vitro cell verification experiments demonstrated that tetrandrine, fangchinoline, praeruptorin B, neobaicalein, and icariin could significantly increase the sensitivity of MCF-7/ADR cells to Adriamycin (Adr). Moreover, tetrandrine, praeruptorin B, and neobaicalein could reverse MDR in MCF-7/ADR cells by inhibiting the function of P-gp. This is the first time that SMALPs-based stabilization strategy was applied to SPR analysis system. SMA polymer can retain P-gp in the environment of natural lipid bilayer and thus maintain the correct conformation and physiological functions of P-gp. The developed system can quickly and accurately screen small molecule ligands of complex MPs and obtain affinity between complex MPs and small molecule ligands without protein purification.
ABSTRACT
Biochromatography is a new chromatographic technology with great development potential. It has been widely used in drug screening and biomolecular interaction analysis. The core of this technology is the chromatographic stationary phase of biomolecules. Nowadays, it mainly develops cell membrane chromatography, artificial biomimetic membrane chromatography and the various immobilization strategies to directly immobilizes proteins on the stationary phase carrier. This paper reviews the research progress of new biochromatographic stationary phase and the application of biochromatographic analysis based on new stationary phase. And, the applications of biochromatographic stationary phase and micro biochromatographic analysis system based on monolithic column are prospected.
ABSTRACT
Objective To qualitatively analyze the main chemical components in compound Jinqiancao granules by ultra high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF/MS). Methods XBridge BEH C18 column (2.1 mm×100 mm, 2.5 µm) was used for chromatographic separation. The mobile phase was composed of 0.1% formic acid water and 0.1% formic acid-acetonitrile, gradient elution, and the flow rate was 0.4 ml/min. Mass spectrometry was characterized by Quadrupole time-of-flight mass spectrometry (Q-TOF/MS) and positive ion mode scanning. Results Under the optimized LC/MS condition, 47 components in compound Jinqiancao granules were identified. The isomers were distinguished by software calculation. The source of medicinal materials was assigned. Conclusion A rapid and efficient analytical method was established for the identification of chemical components in compound Jinqiancao granules by UHPLC-Q-TOF/MS.
ABSTRACT
Lianhuaqingwen (LHQW) capsule, a herb medicine product, has been clinically proved to be effective in coronavirus disease 2019 (COVID-19) pneumonia treatment. However, human exposure to LHQW components and their pharmacological effects remain largely unknown. Hence, this study aimed to determine human exposure to LHQW components and their anti-COVID-19 pharmacological activities. Analysis of LHQW component profiles in human plasma and urine after repeated therapeutic dosing was conducted using a combination of HRMS and an untargeted data-mining approach, leading to detection of 132 LHQW prototype and metabolite components, which were absorbed
ABSTRACT
Objective To discuss the system and classification of military pharmacy disciplines. Methods Based on the analysis and induction of the military pharmacy subject positioning, classification status, classification ideas and classification methods, the military pharmacy subject system is described with system analysis and system structured approach. Results The military pharmacy disciplinary system may be divided into four major categories: military pharmacy science, military pharmacy technology, military pharmacy engineering, and military pharmacy management, and several sub-categories. Conclusion Strengthening the research of military pharmacy disciplinary system will improve the disciplinary system classification, which will help improve the overall cognitive level of military pharmacy discipline and accelerate the development of military pharmacy disciplinary system.
ABSTRACT
Objective To optimize the extraction process of the compound herba lysimachiae by orthogonal experiment and response surface method. Methods The sum of the peak areas of multiple representative components in the compound herba lysimachiae was used as the evaluation index. The ultrasonic extraction time, ultrasonic temperature and ethanol ratio were analyzed to optimize the extraction process conditions by orthogonal experiment and Box-Behnken response surface analysis method. Results Ultrasonic extraction time and ethanol ratio are important factors in the extraction process of the compound herba lysimachiae. The effect of ultrasonic temperature in the extraction process is not significant. The optimal extraction condition for compound herba lysimachiaeare is 10 min ultrasonic extraction time at 55 ℃ with 55% ethanol. Conclusion The optimal extraction process parameters obtained by combining orthogonal experiment and Box-Behnken response surface method can be used for the extraction of representative components from the compound herba lysimachiae and pharmaceutical research in the future.
ABSTRACT
Apoptosis has been considered as the only form of regulated cell death for a long time. However, a novel form of programmed cell death called necroptosis was recently reported. The process of necroptosis is regulated and plays a critical role in the occurrence and development of multiple human diseases. Thus, the study on the molecular mechanism of necroptosis and its effective inhibitors has been an attractive field for researchers. Herein, we introduce the molecular mechanism of necroptosis and focus on the literature about necroptosis drug screening in recent years. In addition, the identification of the critical drug targets of the necroptosis is also discussed.
ABSTRACT
Network pharmacology is the basis of system biology,systematically expounded the interaction of the princi-ple and regulation between body and the drug,representing the idea of the modern biomedical philosophy and researching mod-el.It could be more easily understand the mechanism of action of Traditional Chinese Medicine treatment of diseases by the net-work pharmacology-related technical means.Network pharmacology is widely used in Traditional Chinese Medicine research in the current.The application and development of network pharmacology in the field of Traditional Chinese Medicine research in recent years were introduced in this paper from the aspects of Traditional Chinese Medicine concept,network pharmacology and network pharmacology application.
ABSTRACT
In recent years ,pharmacokinetics of traditional Chinese medicine has become essential for the modernization of traditional Chinese medicine .Pharmacokinetics is an important means for connecting traditional Chinese medicine with west-ern medicine .Medications exert efficacy only when there is sufficient concentration at the target sites .The drug concentration is not only related to the dosage ,but is also closely correlated to the metabolic processes in human body .Most pharmacokinetic studies of traditional Chinese medicine are based on healthy animals ,which ignore significant changes of pharmacokinetic pa-rameters in the diseased state .In this paper ,the comparative pharmacokinetics of the traditional Chinese medicine based on ani-mal models in their diseased states was reviewed .Developmental trends of pharmacokinetics of traditional Chinese medicine with different animal models were also discussed .
ABSTRACT
According to the Chinese Pharmacopoeia 2015, only processed Aconitum tubers can be clinically applied, and the effect of processing is unclear. This research aimed to explore the effect of processing on cardiac efficacy of alkaloids in Aconitum tubers. First, the chemical ingredients in unprocessed and processed Aconitum tubers were identified and compared by using high performance liquid chromatography time-of-flight mass spectrometry (HPLC-TOF/MS) and multivariate pattern recognition methods. Then the representative alkaloids in Aconitum tubers, aconitine, benzoylaconine, and aconine, which belong to diester-diterpenoid alkaloids, monoester-diterpenoid alkaloids, and amine-diterpenoid alkaloids, respectively, were selected for further validation of attenuated mechanism. Subsequent pharmacological experiments with aconitine, benzoylaconine, and aconine in SD rats were used to validate the effect of processing on cardiac functions. After processing the Aconitum tubers, it was found that the contents of diester-diterpenoid alkaloids were reduced, and those of monoester-diterpenoid alkaloids and amine-diterpenoid alkaloids were increased, suggesting that diesterditerpenoid alkaloids were transformed into monoester-diterpenoid alkaloids and amine-diterpenoid alkaloids. Through further decocting the aconitine in boiling water, it was confirmed that the three alkaloids could be progressively transformed. Pharmacological experiments with aconitine, benzoylaconine, and aconine in SD rats showed that aconitine at a dose of 0.01 mg/kg and aconine at a dose of 10 mg/kg enhanced the cardiac function, while benzoylaconine at a dose of 2 mg/kg weakened the cardiac function. The effect of processing is attributed to the transformation of the most toxic diester-diterpenoid alkaloids into less toxic monoesterditerpenoid alkaloids and amine-diterpenoid alkaloids.
ABSTRACT
Objective Experimental study on effects of Yangxinshi tablets in the prevention and treatment of chronic is-chemic heart failure and acute myocardial ischemia reperfusion injury in order to provide a theoretical basis for its clinical appli-cation .Method Rat model of chronic ischemic heart failure and acute ischemia reperfusion mouse model of myocardial infarc-tion were constructed through coronary artery ligation .Those animals were randomized to sham operation group ,model group , positive drug group ,high Yangxinshi tablet dose group ,middle Yangxinshi tablet dose group ,low Yangxinshi tablet dose group .Rat electrocardiogram ,ultrasound ,ACE ,ACD ,TNF-a ,mouse myocardial infarction area ,CK ,LDH ,SOD and relat-ed factors were recorded during pre-dosing and post-dosing after modeling .Morphological changes were observed with cardiac pathological section .Results The biochemical indicators in model group were significantly different from sham operation group with statistical significance (P<0 .001) .Compared to the model group ,positive drug group and high Yangxinshi tablet dose group exhibited biochemical differences with statistical significance (P<0 .001 ,P<0 .01 ,P<0 .05) ,significant myocardial in-farction area reduction (P<0 .01 ,P<0 .05) ,improvement in myocardial cells and reduction in the cell infiltration .Conclusion Yangxinshi tablets have preventive and therapeutic effects on chronic ischemic heart failure and acute ischemia reperfusion in-jury .
ABSTRACT
Objective To explore and analyze the current status of the postgraduate education of clinical pharmacy in China for improving its level and quality .Methods Comprehensive analysis and evaluation were applied for the education mod-els and trends of clinical pharmacy in China through the internet and related databases .Results 136 articles were analyzed ,of which 70 articles (51 .47% ) involved status analysis ,education pattern discussion ,in China and international comparison and curriculum optimization .The analysis result indicates that there are two main cultivation models for postgraduate education of clinical pharmacy :professional degree and scientific degree .The educational model is still immature in curriculum and teaching methods .The main problems are:curriculum unreasonable ,lack of clinical practice hours ,and disconnection of teaching con-tents and clinical needs .Conclusion The current postgraduate education of clinical pharmacy in China cannot achieve the goal of postgraduate education ,it is hard to meet the needs of clinical pharmacy postgraduate talents .We recommended that clinical pharmacy postgraduate training process should focus on linking theory with practice ,outstanding mastery medicine as well as clinical pharmacy ,optimizing teaching content and methods ,and regulating the quality of teaching standards .
ABSTRACT
Objective To explore specific variables related to cisplatin induced acute kidney injury ,serum metabonomics techniques were applied and simultaneously the value of intervention effects of L-carnitine were appraised .Methods 19 mice were divided into the normal control group ,model group ,and intervention group ,After a three day accommodation period ,the intervention group was given L-carnitine (400 mg/kg ,ip) .Two days later ,cisplatin (20 mg/kg ,ip) was given to the model and intervention groups .The body weight of every mouse in each group was measured daily .Two days after the serum sample of each mice was collected and analyzed by LC-MS ,pattern recognition analysis of metabolomics differences among the groups , and the effectiveness of L-carnitine intervention were evaluated .Results A total of 28 metabolites were identified through ser-um metabolomics analysis .Our data shows that there is a possible mechanism that cisplatin induced AKI was mainly involved in changing phospholipids ,amino acid and fatty acid metabolic pathways and L-carnitine mitigates the damage of acute kidney in-jury induced by cisplatin .Conclusion L-carnitinecan alleviates cisplatin induced acute kidney injury by regulating tryptophan metabolism ,glutamate metabolism ,and energy metabolism .
ABSTRACT
The research progress on new technologies for high throughput screening of effective traditional Chinese med-icine (TCM) components was summarized based on the recent documents at home and abroad ,among which bio-chromatogra-phy ,chip-technology and computer-aided virtual screen technology were widely used .Compared with traditional screening technology ,those new ones had shown advantages in efficiency ,automation and high-throughput ,providing new ways to screen effective components of TCM with high throughput .
ABSTRACT
Objective To screen potential active anti-cancer components of Brucea javanica.Methods This research has em-ployed comprehensive two dimensional chromatographic technology and cell membrane chromatographic technology simultaneously with mass spectrometry as detector .Results Adenosine and Bruceine B were found to be potentially anti-cancer active .Conclusion This study has combined the advantages of online , high speed and high throughput for the screen of potential active components of traditional Chinese medicine .
ABSTRACT
ObjectiveTo investigate the clinical efficacy of coiling-dragon warm needling atHuatuo jiaji points plus Chinese herbal fumigation in treating ankylosing spondylitis (AS).MethodEighty AS patients were randomly allocated to treatment and control groups, 40 cases each. The treatment group received coiling-dragon warm needling at Huatuo jiaji points plus Chinese herbal fumigation and the control group, oral administration of salicylazosulfapyridine (SASP). An investigation was made of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the patients’ overall assessment, the Bath Ankylosing Spondylitis Functional Index (BASFI), the total number of swollen joints, the Bath Ankylosing Spondylitis Measurement Index (BASMI) and laboratory inflammatory indices: erythrocyte sedimentation rate (ESR), platelet (PLT) and C reactive protein (CRP).ResultThere was a statistically significant difference in the marked efficacy rate between the two groups (P<0.05). Clinical indices: disease activity index and functional index and laboratory indices: ESR, PLT and CRP improved somewhat inboth groups of patients after treatment (P<0.05). After two courses of treatment, the therapeutic effect was better in the treatment group and there was a statistically significant difference compared with the control group (P<0.05).ConclusionCoiling-dragon warm needling at Huatuo jiaji points plus Chinese herbal fumigation can effectively relieve the clinical symptoms and reduce inflammatory reactions in the active stage in AS patients. It is an effective way to treat AS.
ABSTRACT
A comparison of the volatile compounds in Rhizomes Curcumae （Ezhu） and Radix Curcumae （Yujin） was undertaken using gas chromatography mass spectrometi-y （GC-MS）. Ultrasonic extraction and GC-MS methods were developed for the simultaneous determination of five sesquiterpenes, namely, α-pinene, β-elemene, curcumol, germacrone and curdione, in Ezhu and Yunjin. Good linearity （r〉0.999） and high inter-day precision were observed over the investigated concentration ranges. The validated method was successfully used for the simultaneous determination of five sesquiterpenes in Ezhu and Yujin. The quantitative method can be effectively used to evaluate and monitor the quality of Chinese curcuma in clinical use.
ABSTRACT
An offline two-dimensional system combining a rat cardiac muscle cell membrane chromatography time-of-flight mass spectrometry (CMC-TOF/MS) with a high performance liquid chromatography time-of-flight mass spectrometry (HPLC-TOF/MS) was established for investigating the parent components and metabolites in rat urine samples after administration of the roots of Aconitum carmichaeli.On the basis of the analysis of the first dimension,retention components of the mine sample were collected into 30 fractions (one fraction per minute).Then offline analysis of the second dimension was carried out.34 compounds including 24 parent alkaloids and 10 potential metabolites were identified from the dosed rat urine,and then binding affinities of different compounds on cell membranes were compared and influences of some functional groups on activity were estimated with the semi-quantification and curve fitting method.As a result,binding affinities decreased along with the process of deacylation,debenzoylation and demethylation,which may be related to the alleviation of toxicity in the procedure of herb processing or metabolism.Moreover,some minor components in rat urine (Songorine,14-benzoylneoline,Deoxyaconitine,etc.) exerted relatively strong affinity on cell membranes are worth exploring.The results delivered by the system suggest that the CMC can be applied to in vivo study.