分析药物学之父——詹姆斯·怀特·布莱克爵士

20世纪下半叶,人类平均寿命得到极大提高,这一方面得益于相对和平的环境减少了战争引起的巨大人员伤亡,另一方面则在于人类社会的全面进步,尤其是医学的快速、迅猛发展发挥了尤为重要的作用。药物学是医学中快速发展的学科之一。

小儿支气管肺炎的药物利用评价及药物学研究

目的:分析小儿支气管肺炎的药物应用情况。方法:将2015年7月~2016年6月在本院接受治疗的90例小儿支气管肺炎病例作为研究对象,采用回顾性分析方法。结果:病患在治疗期间共采用了32种抗菌药物,其中,包括10种抗感染类药物,占所用药物的39.75%;用药合理共60例(45.87%),基本合理共19例(34.75%),用药不合理的共11例(19.38%)。结论:就小儿支气管肺炎病患而言,能否及时、有效地得到用药治疗在改善其症状方面起着十分关键的作用。

Flow injection chemiluminescence determination of meloxicam using potassium permanganate and formaldehyde system

A simple, rapid and sensitive flow injection chemiluminescence （FI-CL） method has been developed for the determination of meloxicam. The method is based on the CL-emitting reaction between meloxicam and potassium permanganate in a hydrochloric acid medium, enhanced by formaldehyde （HCHO）. Under optimum conditions, calibration curve over the range of 1.0-20.0μg/mL was obtained. The proposed method was successfully applied to the determination of meloxicam in capsules with no evi- dence of interference from common excipients. The detection limit of this method was 25.6 ng/mL. The relative standard deviation was 2.1% for 10.0 μg/mL meloxicam. The sample throughput was found to be 120 samples/h.

The Alkaloids from Leaves of Croton hemiargyerius var. gymnodiscus

Aim Investigation of alkaloids from the leaves of Brazilian medicinal plantCroton hemiargyerius var. gymnodiscus. Methods Silica gel column chromatography was used repeatedlyfor the isolation and purification, and their structures were identified by extensive spectroscopyand comparison of the chemical and physical data with those of authentic samples reported inliterature. Results Twelve alkaloids were isolated and their structures were identified. ConclusionFour new alkaloids named hemiargines A (1), B (5), C (6) and D (7), together with eight knownalkaloids namely isoc-orydine (2), corydine (3), norcorydine (4), salutaridine (8), glaucine (9),tetrahydropalmatrubine (10), xylopinoine (11), and norlaudanosine (12) were isolated.

Preparation of low molecular weight Sargassum fusiforme polysaccharide and its anticoagulant activity

Heparin has been used as an anticoagulant drug for many years, but it has significant side ef fects. In the search for good substitutes, low molecular weight(MW) polysaccharides from S argassum fusiforme have been examined and confi rmed to possess biological activities. Here, S. fusiforme polysaccharides(SFP) were extracted and subjected to a hydrogen peroxide(H_2O_2) oxidation method for the preparation of low-MW SFP(LSFP). The effects of temperature, pH, and H_2O_2 concentration on the degradation process were also examined. Several LSFP of 36, 9, 5.7, and 2.7 kDa were obtained under different conditions, and their anticoagulant activities studied in vitro. The results showed that SFP and LSFP prolonged activated partial thromboplastin(APTT), prothrombin(PT) and thrombin times(TT) significantly, indicating that these low MW polysaccharides possessed anticoagulant activity in the intrinsic, extrinsic, and common coagulation pathways. As these ef fects were related to the MW of the polysaccharides in APTT and TT but not in PT, the contents of the monosaccharide fucose and sulfate and the polysaccharide MW could have exerted combined ef fects. The details of this mechanism require further verifi cation.

Chemical component analysis of volatile oil in drug pair Herba Ephedrae-Ramulus Cinnamomi by GC-MS and CRM

Active volatile components in drug pair(DP)Herba Ephedrae-Ramulus Cinnamomi(HE-RC),single drug HE and RC were analyzed by gas chromatography/mass spectrometry(GC/MS),chemometric resolution method(CRM)and overall volume integration.By means of CRM,the two-dimensional data obtained from GC-MS instruments were resolved into a pure chromatogram and a mass spectrum of each chemical compound.In total,97,62,and 78 volatile chemical components in volatile oil of HE,RC,and DP HE-RC,were respectively determined qualitatively and quantitatively,accounting for 90.08%,91.62%,and 89.76% total contents of volatile oil of HE,RC,and DP HE-RC respectively.It is further demonstrated that the numbers of volatile components of DP HE-RC are almost the sum of those of two single drugs,but some relative contents of them are changed.Some new components,such as 1,6-dimethylhepta-1,3,5-triene,tetracyclo[4.2.1.1(2,5).0(9,10)]deca-3,7-diene,globulol and(E,E)-6,10,14-trimethyl-5,9,13-pentadecatrien-2-one are found in DP HE-RC because of chemical reactions and physical changes during decoction.

A New Cyclic Bisdesmoside from Tubers of Bolbostemma paniculatum

The structure of tubeimoside V (1), a new cyclic bisdesmoside, isolated from tubers of Bolbostemma paniculatum (Tu Bei Mu), was established by means of 2D NMR spectral and chemical methods. Compound 1 has inter-saccharide chain bridging by a dicrotalic acid to form a unique macrocyclic structure.

Network Pharmacology-based Analysis on the Molecular Biological Mechanisms of Xin Hui Tong Formula in Coronary Heart Disease Treatment

Objective To investigate the potential molecular mechanism of Xin Hui Tong Formula (XHTF) in the treatment of coronary heart disease (CHD) by using network pharmacology and bioinformatics. Methods The targets network of CHD was constructed through Therapeutic Targets Database (TTD) and Drugbank database;The XHTF pharmacodynamic molecule-targets network and the XHTF pharmacodynamic molecule-CHD targets network were explored by the traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP). And the multi-targets mechanism and molecular regulation network of XHTF in the treatment of CHD were explored from multiple perspectives by Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) database pathway enrichment analysis. Results A total of 88 CHD targets were screened out through the Therapeutic Targets and the Drugbank database. 393 compounds and corresponding 205 drug targets of XHTF were retrieved from TCMSP. A total of 13 known targets directly related to the development of CHD were retrieved from the disease-related databases: TP53, MAPK14, NFKB1, HSPA5, PLG, PTGS2, ADRB1, NOS2, CYP3A4, GRIA2, CYP2A6, GRIA1, PTGS1. XHTF also contained 118 drug targets that directly interact with CHD targets. GO enrichment analysis showed that the biological processes of 13 direct targets proteins were found to be mainly enriched in response to drug, cellular response to biotic stimulus, long-chain fatty acid metabolic process, fatty acid metabolic process and regulation of blood pressure. KEGG pathway enrichment analysis found that XHTF participated in the CHD pathological process mainly through retrograde endocannabinoid signaling, regulation of lipolysis in adipocytes, cAMP signaling pathway, chemical carcinogenesis and other pathways. Conclusions XHTF plays a role in the treatment of CHD through multiple targets and multiple pathways, and provides a scientific basis for the theory of "virtual standard" in the treatment of CHD.

Investigation of the Mutagenic Potential of Immunomodulator Arglabin Native in Tablets in the Ames Test

The mandatory preclinical safety evaluation is an essential prerequisite to obtain the qualitative and effective medicines. Due to the fact that drugs may reveal genotoxic properties, the investigation of their mutagenic activity is an obligatory part of the preclinical drug safety program. The aim of the research is to study mutagenic properties of a new original immunomodulator Arglabin native in tablets in the induced test of gene mutations （the Ames test） on Salmonella typhimurium strains. Materials and methods： Four strains of S. typhimurium TA98, TA100, TA1535, and TA1537 were used to assess the mutagenicity in the Ames test. Results and conclusions： No statistically reliable dose-dependent increase in the number of revertant colonies of Salmonella typhimurium has been observed in the presence of the given drug within the investigated dose ranges from 5.0 to 100.0 μg/mL for strains TA100 and TA1535, and from 5.0 to 250 μg/mL for strains TA98 and TA1537 against the baseline of spantaneous mutations. Arglabin native in tablets does not reveal a mutagenic activity within the studied dose ranges on Salmonella typhimurium strains TA98, TA100, TA1535, TA1537.

Development and Validation of Proximal Chemistry Analytical Procedure in Semi-automated Equipment

The proximal chemical analysis （AQP） includes 5 fundamental tests, which are： determination of crude protein, determination of crude fiber, determination of humidity, determination of ashes and determination of fat. This last determination can be made in two different ways, which will depend on the type of sample being treated, as well as the amount of fat expected to be obtained in the food to be analyzed. For foods with low amounts of fat the hydrolysis technique is used, which is divided into 3 phases. All the methods before being taken to the daily practice in a laboratory of food analysis either internal control, verification or third authorized must be validated, in order to obtain consistent, robust and reliable results. In those cases in which the method that will be tested differs with the method that is reported in the literature, a comparison of both methods should be made in order to ensure that both are compatible and the results will be equally reliable. In the validation, the acceptance parameters will be established for each one of the tests that are carried out in it, while at the end of it the acceptance criteria for the general method will be established. The objective of this work was to carry out the development of analytical methodology that was validatable in order to reduce analysis time by using semi-automated equipment. In the case of semi-automated equipment, this comparison of methods is carried out, as it was the case of the analysis of fat with hydrolysis, which used a hydrolysis unit and the extraction equipment using samples of finished food for animal consumption. The results obtained in the validation using the traditional method correspond to a CV less than 2%, while the results obtained using semi-automated equipment correspond to a CV less than 2% for the case of fat determination with hydrolysis.

Chemical shift assignments of two oleanane triterpenes from Euonymus hederaceus

1H-NMR and 13C-NMR assignments of 12-oleanene-3,11-dione (compound 1) were completely described for the first time through conventional 1D NMR and 2D shift-correlated NMR experiments using 1H-1HCOSY, HMQC, HMBC techniques. Based on its NMR data, the assignments of 28-hydroxyolean-12-ene-3,11-dione (compound 2) were partially revised.

Fluid-Solid Interaction Analysis of Drug Delivery Mechanism to Damaged Cancer Cellules in the Shape of Single-Walled Carbon Nanocone by Molecular Mechanics Approach

Drug delivery systems able to deliver the required dose of the drug to the target level use active or passive nano metric designed systems. In the earlier researches, carbon nanocones are used for transferring the serum to damaged proteins and damaged cancer cellules. In this lecture, stability analysis of drug delivery to damaged cancer cellutes is studied in the shape of single-walled carbon nanocone. In this method, each atom is considered as node and interactions between them are supposed as 3D-beam elements. By supposing that potential energy in macro relations is equal to the nano relations, nano-drug characteristics can be calculated. Then shape functions can be extracted to use in blood＇s FEM model and using reduced-order method, divergence velocities of carbon nanocone can be found. In this lecture, carbon nanocones are modeled with different dimensions and boundary conditions and stability of them in blood flow is studied and optimized carbon nanocone is selected in blood flow. Results show that conical nano-drug structures have more efficiency in blood flow rather than tube nano-drug structures and by increasing length of carbon nanocones, dimensionless stability parameter decreased and by increasing declination angle of carbon nanocones, dimensionless stability parameter increased.

Tailoring active compounds across biological membranes by cubosomal technology: an updated review

It is challenging for many drugs to be transported across various biological membranes. Furthermore, development of many drugs gets thwarted owing to their hydrophilic nature. The bioavailability of such drugs, which is the function of their ability to cross the membrane, tends to be low and exhibit high intra and inter subject variability. At present, formulation scientists are pursuing many projects for transdermal, nasal, target delivery of many active compounds, and it is prudent to explore alternative possibilities. Cubosomes offer transportation and tailoring of active compounds intended for both systemic and dermal delivery. Cubosomes are dispersed, self-assembled nanoparticles of bicontinuous cubic liquid crystalline phase formed from lipid and surfactant systems. Monoolein, poloxamer 407 and polyvinyl alcohol are the mostly used ingredients in the formulation of cubosomes. The adjustment in lipid composition can control the internal and structural changes of cubosomes. Based on the nodal surfaces, three structures of cubosomes proposed are Pn3m, Ia3d and Im3m. Top-down and bottom-up techniques are widely considered in the formulation process of extreme viscous bulk phase and aggregate from a precursor respectively. This article gives a bird's eye view about the engineering, characterization and evaluation of cubosomes, covering researches and applications of cubosomes done till date.

Characterization and evaluation in vivo of baicalin-nanocrystals prepared by an ultrasonic-homogenization-fluid bed drying method

AIM： To improve the absorption and bioavailability of baicalin using a nanocrystal （or nanosuspension） drug delivery system. METHODS： A tandem, ultrasonic-homogenization-fluid bed drying technology was applied to prepare baicalin-nanocrystal dried powders, and the physicochemical properties of baicalin-nanocrystals were characterized by scanning electron microscopy, photon correlation spectroscopy, powder X-ray diffraction, physical stability, and solubility experiments. Furthermore, in situ intestine single-pass perfusion experiments and pharmacokinetics in rats were performed to make a comparison between the microcrystals of baicalin and pure baicalin in their absorption properties and bioavailability in vivo. RESULTS： The mean particle size of baicalin-nanocrystals was 236 nm, with a polydispersity index of 0.173, and a zeta potential value of-34.8 mV, which provided a guarantee for the stability of the reconstituted nanosuspension. X-Ray diffraction results indicated that the crystallinity of baicalin was decreased through the ultrasonic-homogenization process. Physical stability experiments showed that the prepared baicalin-nanocrystals were sufficiently stable. It was shown that the solubility of baicalin in the form of nanocrystals, at 495 ug·mL-1, was much higher than the baicalin-microcrystals and the physical mixture （135 and 86.4 ug·mL- 1, respectively）. In situ intestine perfusion experiments demonstrated a clear advantage in the dissolution and absorption characteristics for baicalin-nanocrystals compared to the other formulations. In addition, after oral administration to rats, the particle size decrease from the micron to nanometer range exhibited much higher in vivo bioavailability （with the AUC（0-t） value of 206.96 ± 21.23 and 127.95 ± 14.41 mg·L-1·h-1, respectively）. CONCLUSION： The nanocrystal drug delivery system using an ultrasonic-homogenization-fluid bed drying process is able to improve the absorption and in vivo bioavailability of baicalin, compared with pure baicalin coarse powder and micronized baicalin.

Structural characterization and identification of major constituents in Radix Scrophulariae by HPLC coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry

AIM: To analyze the major constituents in Radix Scrophulariae(Scrophularia ningpoensis). METHOD: Radix Scrophulariae was analyzed by HPLC coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry(ESI-Q-TOF MS/MS). Compounds were separated by HPLC using a C18 column and gradient elution of acetonitrile and 0.1 %(V/V) acetic acid-water. Negative ion mode was employed. RESULTS: A total of thirty-six compounds, including fourteen iridoid glycosides, nineteen phenylpropanoid glycosides, and three organic acids, were identified from Radix Scrophulariae based on the accurate mass measurement of precursor and product ions. Twenty-one of the constituents were identified by comparing their retention times(tR) and ESI-MS/MS data with those of reference standards and/or previous publications, while another fifteen compounds were tentatively identified or deduced according to their Q-TOF MS/MS data which afforded sufficient structural information. CONCLUSION: It is believed that this study is useful for the identification of constituents in Radix Scrophulariae, as well as related plants and complex prescriptions.

Chemical profiles and anticancer effects of saponin fractions of different polarity from the leaves of Panax notoginseng

AIM： To evaluate the chemical profiles and cytotoxic effects among the total saponin fraction （TSF）, 25% ethanol fraction （25EF）, 50% ethanol fraction （50EF）, and 85% ethanol fraction （85EF） prepared by macroporous resin from the leaves of Panax notoginseng. METHOD： The simultaneous determination of thirteen main saponins, as well as the chemical profiles of saponin fractions of different polarity, was made by HPLC-DAD and LC-ESI-MSn analysis. The cytotoxic effects were determined against KP4 cells （human pancreatic cancer）, NCI-H727 ceils （human lung cancer）, HepG2 cells （human hepatocellular cancer）, and SGC-7901 cells （human gastric adenocarcinoma）. RESULTS： Chemical analysis indicated that 85EF possessed the most abundant cytotoxic protopanaxadiol saponins, including the marker saponins F2, 20（R）-Rg3, 20（S）-Rg3, and Rh2. The MTT assay showed that 85EF also had the strongest cytotoxic effects among the four fractions. 25EF showed no anti-proliferative effects, while 50EF and TSF exhibited weak anti-proliferative activity. CONCLUSION： From the aspect of comprehensive utilization of resources, 85EF, enriched with low polarity PPD group saponins, is a new alternative source of anticancer saponins, and a promising botanical preparation for further anticancer studies.

Chemical constituents of Euphorbia tibetica and their biological activities

AIM: To investigate the chemical constituents and their biological activities of the aerial parts of Euphorbia tibetica. METHOD: Compounds were isolated and purified by various chromatographic methods, and their structures were elucidated through the use of extensive spectroscopic techniques including 2D-NMR, the structures of compounds 5 and 6 were confirmed by single-crystal X-ray crystallography. Bioactivities of all the isolated compounds were evaluated by the MTT method on A549 and anti-angiogenesis assay. RESULTS: One new compound, methyl 4-epi-shikimate-3-O-gallate(1), together with twenty-three known constituents(2–24) were isolated from the aerial parts of E. tibetica. CONCLUSION: Compound 1 is new, and the other compounds were isolated from this plant for the first time. Compounds 5–7, 9, 11, 17, 18 and 20 exhibited inhibitory effects on the growth of human lung cancer cell A549 and compounds 5, 7, 12, 13, 17 and 19 showed anti-angiogenic effects in a zebrafish model.

Ursolic acid induces U937 cells differentiation by PI3K/Akt pathway activation

AIM: Ursolic acid(UA), a pentacyclic triterpenoid, is used as an anti-inflammatory and anti-cancer agent. There were few studies on the effects of UA on differentiation, and this is the first time to elucidate the potential effect and molecular mechanism of UA on inducing differentiation in the human leukemia cell line U937. METHODS: Wright-Giemsa staining, nitroblue tetrazolium reduction assay and flow cytometric analysis were utilized to demonstrate the differentiation of U937 cells induced by UA. Western blotting and immunofluorescence assay were used to investigate the possible mechanism. RESULTS: It was found that UA could induce the differentiation of U937cells and Akt-activity was significantly increased during differentiation. Additionally, LY294002, a PI3K-Akt inhibitor, could block the differentiation of U937 cells induced by UA. CONCLUSION: UA could induce the differentiation of U937 cells by activating the PI3K/Akt pathway, and it could be a potential candidate as a differentiation-inducing agent for the therapy of leukemia.

DT-13, a saponin of dwarf lilyturf tuber, exhibits anti-cancer activity by down-regulating C-C chemokine receptor type 5 and vascular endothelial growth factor in MDA-MB-435 cells

AIM： To investigate the anticancer activity of DT-13 under normoxia and determine the underlying mechanisms of action. METHODS： MDA-MB-435 cell proliferation, migration, and adhesion were performed to assess the anticancer activity of DT-13, a saponin from Ophiopogonjaponicus, in vitro. In addition, the effects of DT-13 on tumor growth and metastasis in vivo were evaluated by orthotopic implantation of MDA-MB-435 cells into nude mice; mRNA levels of vascular endothelial growth factor （VEGF）, C-C chemokine receptor type 5 （CCR5） and hypoxia-inducible factor 1a （HIF-1a） were evaluated by real-time quantitative PCR; and CCR5 protein levels were detected by Western blot assay. RESULTS： At 0.01 to 1 umol·L -1, DT-13 inhibited MDA-MB-435 cell proliferation, migration, and adhesion significantly in vitro. DT-13 reduced VEGF and CCR5 mRNAs, and decreased CCR5 protein expression by down-regulating HIF-1 a. In addition, DT-13 inhibited MDA-MB-435 cell lung metastasis, and restricted tumor growth slightly in vivo. CONCLUSION： DT-13 inhibited MDA-MB-435 cell proliferation, adhesion, and migration in vitro, and lung metastasis in vivo by reducing VEGF, CCR5, and HIF-la expression.

Pyrolysis characteristics of Radix Rhizoma Rhei, Cortex Moudan Radicis, and Radix Sanguisorbae and correlations with the carbonizing process of Chinese herbs

AIM： The aim of the work is to study the pyrolysis characteristics of Radix Rhizoma Rhei, Cortex Moudan Radicis, and Radix Sanguisorbae in an inert atmosphere of argon （Ar）, and to investigate the mechanism of the carbonizing process of the three traditional Chinese herbs. METHODS： The pyrolysis characteristics of the crude materials and their extracts were studied by thermogravimetry-mass spectrometry （TG-MS） in a carrier gas of argon, coupled with Fourier transform infrared spectrometry （FTIR） and scanning electron microscopy （SEM） methods. Correlation of the pyrolysis behaviors with the carbonizing process by stir-frying of traditional Chinese medicines was made. RESULTS： Within the temperature range of 200-300 ℃, which is the testing range for the study of the carbonizing process of Chinese herbs, the temperatures indicated by the maximum weight loss rate peak of the above three extracts were taken as the upper-limit temperatures of the carbonizing process of the herbs, and which were 200, 240 and 247 ℃ for Radix Rhizoma Rhei, Cortex Moudan Radicis, and Radix Sanguisorbae, respectively. The ion monitoring signal peaks detected by the TG-MS method corresponded with reports that the level of chemical components of traditional Chinese medicinal materials would decrease after the carbonizing process. It was confirmed by Fourier transform infrared spectrometry （FTIR） and scanning electron microscopy （SEM） methods that better results of ＂medicinal property preservation＂ could be obtained by heating at 200 ℃ for Radix Rhizoma Rhei, at about 250 ℃ for Cortex Moudan Radicis, and Radix Sanguisorbae, as the relative intensity values of the common peaks were among the middle of their three carbonized samples by programmed heating. CONCLUSION： The upper-limit temperatures of the carbonizing process for Radix Rhizoma Rhei, Cortex Moudan Radicis and Radix Sanguisorbae were 200, 240 and 247 ℃ respectively. It is feasible to research the mechanism and technology of the carbonizing process of traditional Chinese medicinal materials using thermogravimetry, Fourier transform infrared spectrometry, and scanning electron microscopy methods.