Pharmacological effects and mechanisms of muscone.

Musk, the dried secretion from the preputial follicles of the male musk deer (genus Moschus), possesses various pharmacological activities and has been used extensively in traditional Chinese medicine for thousands of years. Muscone is the main active ingredient of musk and exerts pharmacological effects similar to those of musk. Although muscone was notably used to treat various disorders and diseases, such as neurological disorders, chronic inflammation and ischemia-reperfusion injury, most of the mechanisms of the pharmacological action of muscone remain unclear because of slow progress in research before the 21st century. In recent years, the pharmacological activities and mechanisms of muscone have been clarified. The present article summarizes the pharmacological and biological studies on cerebrovascular disease, cardiovascular disease, neurological effects, cancer and others and the associated mechanisms of the action of muscone to date.

Coupling electrokinetics with microbial biodegradation enhances the removal of cycloparaffinic hydrocarbons in soils.

An innovative approach that couples electrokinetics with microbial degradation to breakdown cycloparaffinic hydrocarbons in soils is described. Soils were spiked with cyclododecane, used as a model pollutant, at approximately 1000mgkg-1. A mixture of petroleum-utilizing bacteria was added to achieve about 106-107 CFUg-1. Then, three treatments were applied for 25 days: (1) no electric field, control; (2) a constant voltage gradient of 1.3Vcm-1 in one direction; and (3) the same electric field, but with periodical switching of polarity. The degradation pathway of cyclododecane was not changed by the electric field, but the dynamic processes were remarkably enhanced, especially when the electric field was periodically switched. After 25 days, 79.9% and 87.0% of the cyclododecane was degraded in tests 2 and 3, respectively; both much higher than the 61.5% degraded in test 1. Analysis of the intermediate products strongly indicated that the competitive advantage of the electric field was the increase in ring-breaking of cyclododecane, resulting in greater concentrations of linear substances that were more susceptible to microbial attack, that is, ß-oxidation. The conditions near the cathode were more favorable for the growth and metabolism of microorganisms, which also enhanced ß-oxidation of the linear alkanoic acids. Therefore, when the electric field polarity was periodically switched, the functions of both the anode and cathode electrodes were applied across the whole soil cell, further increasing the degradation efficiency.

Merocyclophanes A and B, antiproliferative cyclophanes from the cultured terrestrial Cyanobacterium Nostoc sp.

The cell extract of a cultured terrestrial Nostoc sp. (UIC 10062), obtained from a sample collected at Grand Mere State Park in Michigan, displayed antiproliferative activity against the HT-29 human colon cancer cell line. Bioactivity-guided fractionation of the cell extract, combined with LC-MS analysis, led to the isolation of two cyclophanes, named merocyclophanes A and B (1 and 2). Their structures were determined by various spectroscopic techniques including HRESIMS, and 1D and 2D NMR analyses. The stereoconfiguration was assigned on the basis of X-ray crystallographic and CD analyses. The structures of merocyclophanes A and B (1 and 2) established a hitherto unknown [7.7]paracyclophane skeleton in nature, as characterized by α-branched methyls at C-1/14. Merocyclophanes A and B (1 and 2) displayed antiproliferative activity against the HT-29 human colon cancer cell line with IC50 values of 3.3 and 1.7 µM, respectively.

A facile solvent free Claisen-Schmidt reaction: synthesis of α,α'-bis-(substituted-benzylidene)cycloalkanones and α,α'-bis-(substituted-alkylidene)cycloalkanones.

Solvent-free Claisen-Schmidt reactions of cycloalkanones with various substituted benzaldehydes (aryl aldehydes) using solid NaOH (20 mol%) and applying a grinding technique were studied. Quantitative yields (96-98%) of α,α'-bis-(substituted-benzylidene)cycloalkanones were obtained. Aliphatic aldehydes also provided α,α'-bis-(substituted-alkylidene)cycloalkanones in very good yields with minor amounts of a-(substituted-alkylidene)cycloalkanones. The catalytic performance of solid NaOH was examined. The molar ratio of NaOH was optimized. The catalytic effect of solid NaOH was also evaluated by comparing it with KOH, NaOAc, and NH(4)OAc and it turns out that 20 mol% of solid NaOH was good enough to catalyze the Claisen-Schmidt reactions of cycloalkanones with various substituted benzaldehydes. Additionally, the regioselectivity of the Claisen-Schmidt reaction of acetone with benzaldehyde was examined. Using the same method, we could synthesize the corresponding bis-benzylidene- and mono-benzylideneacetone separately in 98% and 96% yields, respectively.

Irresolvable complex mixture of hydrocarbons in soybean oil deodorizer distillate.

Aliphatic hydrocarbons (HCs) can be used as a fingerprint of a given seed oil. Only by characterization of aliphatic HCs could contamination by mineral oil in that seed oil be confirmed. During the isolation of squalene from soybean oil deodorizer distillate, a significant amount of unknown HCs, ca. 44 wt%, was obtained. These seemingly-easy-to-identify HCs turned out to be much more difficult to elucidate due to the presence of an irresolvable complex mixture (ICM). The objective of this study was to purify and identify the unknown ICM of aliphatic HCs from soybean oil deodorizer distillate. Purification of the ICM was successfully achieved by using modified Soxhlet extraction, followed by modified preparative column chromatography, and finally by classical preparative column chromatography. FT-IR, TLC, elemental analysis, GC/FID, NMR and GC-MS analyses were then performed on the purified HCs. The GC chromatogram detected the presence of ICM peaks comprising two major peaks and a number of minor peaks. Validation methods such as IR and NMR justified that the unknowns are saturated HCs. This work succeeded in tentatively identifying the two major peaks in the ICM as cycloalkane derivatives.

Identification and field evaluation of attractants for the cranberry weevil, Anthonomus musculus Say.

Studies were conducted to develop an attractant for the cranberry weevil, Anthonomus musculus, a pest of blueberry and cranberry flower buds and flowers in the northeastern United States. In previous studies, we showed that cinnamyl alcohol, the most abundant blueberry floral volatile, and the green leaf volatiles (Z)-3-hexenyl acetate and hexyl acetate, emitted from both flowers and flower buds, elicit strong antennal responses from A. musculus. Here, we found that cinnamyl alcohol did not increase capture of A. musculus adults on yellow sticky traps compared with unbaited controls; however, weevils were highly attracted to traps baited with the Anthonomus eugenii Cano aggregation pheromone, indicating that these congeners share common pheromone components. To identify the A. musculus aggregation pheromone, headspace volatiles were collected from adults feeding on blueberry or cranberry flower buds and analyzed by gas chromatography-mass spectrometry. Three male-specific compounds were identified: (Z)-2-(3,3-dimethyl-cyclohexylidene) ethanol (Z grandlure II); (Z)-(3,3-dimethylcyclohexylidene) acetaldehyde (grandlure III); and (E)-(3,3- dimethylcyclohexylidene) acetaldehyde (grandlure IV). A fourth component, (E)-3,7-dimethyl-2,6-octadien-1-ol (geraniol), was emitted in similar quantities by males and females. The emission rates of these volatiles were about 2.8, 1.8, 1.3, and 0.9 ng/adult/d, respectively. Field experiments in highbush blueberry (New Jersey) and cranberry (Massachusetts) examined the attraction of A. musculus to traps baited with the male-produced compounds and geraniol presented alone and combined with (Z)-3-hexenyl acetate and hexyl acetate, and to traps baited with the pheromones of A. eugenii and A. grandis. In both states and crops, traps baited with the A. musculus male-produced compounds attracted the highest number of adults. Addition of the green leaf volatiles did not affect A. musculus attraction to its pheromone but skewed the sex ratio of the captured adults towards females. Although the role of plant volatiles in host-plant location by A. musculus is still unclear, our studies provide the first identification of the primary A. musculus aggregation pheromone components that can be used to monitor this pest in blueberry and cranberry pest management programs.

Fractionation by liquid chromatography combined with comprehensive two-dimensional gas chromatography-mass spectrometry for analysis of cyclics in oligomerisation products of Fischer-Tropsch derived light alkenes.

In oligomerisation products of High Temperature Fischer-Tropsch (HTFT) derived light alkenes using a solid phosphoric acid (SPA) catalyst, the presence of cyclics was presumed although their occurrence could not be explained by the generally accepted oligomerisation mechanism. Notwithstanding the use of GC×GC-TOFMS, the cyclic alkanes could not be differentiated from the alkenes. On the one hand, compounds co-eluted in GC×GC and, on the other hand, MS cannot distinguish between these classes because of identical molecular masses and very similar mass fragmentation patterns. An LC pre-fractionation procedure utilising a silver-modified column was developed to separate the saturates from the unsaturates. Using this approach we were able, for the first time, to confirm the presence of cyclics, probably resulting from secondary reactions, in HTFT oligomerisation products. The occurrence of cyclics can be an indication of the beginning of carbonaceous deposit formation that could eventually lead to catalyst deactivation.

Cooliatin, an unprecedented natural dioxocyclononane from dinoflagellate Coolia monotis from South China Sea.

Cooliatin, an unprecedented dioxocyclononane, was isolated from the dinoflagellate Coolia monotis from South China Sea. Its structure was identified on the basis of spectroscopic evidence.

Characterization of sorbent properties of soil organic matter and carbonaceous geosorbents using n-alkanes and cycloalkanes as molecular probes.

Nonspecific interactions and modes (i.e., adsorption vs absorption) of sorption by noncondensed, amorphous organic phases (here termed organic matter; OM) in soils and by rigid, aromatic, and condensed phases (termed carbonaceous geosorbents; CGs) were investigated using n-alkanes and cycloalkanes as molecular probes. Sorption isotherms of n- and cyclooctane from water for seven CGs (charcoal, lignite coke, activated carbon, graphite, partially oxidized graphite, diesel soot, bituminous coal), four sorbents with a predominance of OM (lignite, peat, two sapric soils), and two soils containing OM and high amounts of CGs were measured in batch systems. The peat and the sapric soils showed extensively linear sorption, while the CGs exhibited highly nonlinear (Freundlich exponents 0.2-0.7) and strong (Koc values being up to 10(5) times those for the OM-rich materials at low concentrations) sorption for the alkanes studied, showing that enhanced sorption by CGs can occur to completely apolar sorbates that do not undergo any specific interaction. Sorption by CGs was generally stronger and more nonlinear for n-octane than for cyclooctane, which suggests a strong dependence of sorption on the 3-D structure of sorbate molecules. The n-octane-to-cyclooctane sorption coefficient ratios (Kn/Kc) for adsorption to CGs were > or = 1, being distinctly different from those for absorption to the OM-rich materials (Kn/Kc < 1). The measured sorption isotherms and the CG compositions in the soils determined by quantitative petrography analysis suggest, however, that CGs occurring in soils may be far less effective sorbents than the reference CGs used in the sorption experiments at least for nonspecifically interacting sorbates, probably because of competitive sorption and/or pore blocking by natural OM. The presented approaches and results offer a basis for interpreting sorption data for other organic compounds, as nonspecific interactions and sorption modes are relevant for any compound.

[Effects of series of Muskone on heart hemodynamics and myocardial consumption of oxygen in experimental dogs].

OBJECTIVE: To observe the effects of series of Muskone (the muskone includes Slender Dutchmanspipe Root, Inula Root and neither kind of Common Aucklandia Root) on the heart hemodynamics and myocardial consumption of oxygen in experimental dogs, and to explain its pharmacological action on cardiovascular system. METHOD: Arterial blood pressure, coronary blood flow, resistance in coronary artery, total peripheral resistance, work of left artrium and oxygen consumption index of the cardiac muscles were observed in anaesthetic dogs. RESULT: The series of Muskone decreased arterial blood pressure significantly, dilated coronary artery and peripheral arteries significantly, increased coronary blood flow, decreased resistance in coronary artery, improved the work of left artrium, the oxygen availability of cardiac muscles and the complaisance of arteries in cardiac muscles.

[Review on investigations related to chemical constituents and biological activities of Periplaneta americana].

With the fast development of medicinal animals as new drugs, research on Periplaneta americana become hot recently. Several drugs which mainly consisted of P. americana were approved for clinical applications. The chemical constituents and pharmacological bioactivities of this insect were summarized herein, which provides informativon for further researches on this medicinal animal.

[Study on comparative pharmacology of series of Muskone].

OBJECTIVE: To study the therapeutic effects of the series of Muskone (the Muskone includes Slender Dutchmanspipe Root, Tumuxiang, and not Slender Dutchmanspipe Root) on experimental myocardial infarct and pain in rats. METHOD: Coronary artery ligation was applied for the model of myocardial infarct. Therapeutic effects were evaluated by measuring parameters of histomorphometry, blood plasm of ET, 6- keto-PGF1alpha and TXB2. Intraperitoneal injection acetic was applied for the model of ache, the frequency and eclipse period of writhing were evaluated its effect of resisting pain. RESULT: The Muskone including Radix Aristolociae, the Muskone including Radix Inulae and the Muskone without Radix Aucklandiae all can decrease the area of myocardial infarction in rats, the level of TXB2, ET, and the frequency of writhing significantly. Also it can increase the level 6-keto-PGF1alpha, the ratio of 6-keto-PGF1alpha and TXB2. Single Radix Aristolociae or Radix Inulae only relieved pain. CONCLUSION: The Muskone including Radix Aristolociae, the Muskone including Radix Inulae and the Muskone without Radix Aucklandiae all have significant therapeutic effect on both myocardial infarction and pain, while single Radix Aristolociae or Radix Inulae only can relieve pain.

Structural determination of cyclitol derivatives by fast-atom bombardment tandem mass spectrometry.

Three cyclitol derivatives were isolated from the marine sponge Sarcotragus sp. by reversed-phase high-performance liquid chromatography and analyzed by fast-atom bombardment mass spectrometry (FAB-MS). Their structural elucidation was carried out with FAB tandem mass spectrometry (FAB-MS/MS). FAB-MS spectra produced a significant abundance of the sodium adducts [M+Na]+ and [M+2Na-H]+ from a mixture of m-NBA and NaI. In addition, trifluoroacetylation of the cyclitol derivatives was used for confirmation of the presence of the cyclitol ring. High abundance [M-5H+5CF3CO+Na]+ ions were observed in the FAB-MS spectra of the trifluoroacetyl-cyclitol derivatives. Collision-induced dissociation (CID) of the [M+Na]+ ions produced diverse product ions via a series of dissociative processes. Charge-remote fragmentation (CRF) patterns of [M+Na]+ ions were very useful for the identification of product ions which are characteristic for the cyclitol ring and long hydrocarbon chains substituted at the glycerol backbone. Moreover, the CID-MS/MS spectra of the [M+Na]+ ions yielded characteristic product ions at m/z 53, 83, 113, 155 and 171 for the cyclitol moiety, and at m/z 213, 229 and 245 for the glycerol backbone attached to the cyclitol ring.

Normal-phase chiral liquid chromatography-mass spectrometry of non-UV-active compounds: applications for pharmaceutically relevant racemates.

Mixtures of hexane-like ethoxynonafluorobutane with alcohols were used as MS-friendly mobile phases for separation and efficient detection of non-UV-active enantiomers and diastereomers using normal-phase HPLC-APCI-MS. Racemic muscone, camphorsulfonamide, camphorsultam, BOC-protected 1-(3-aminopropyl)-2-pipecoline and diastereomeric 2-methylhexanoyl camphorsultams were resolved on Chiralpak AS and AD and achiral Luna CN columns. The responses of UV and APCI-MS detectors were compared under separation conditions studied, with MS detection achieving lowest detectable quantity in the range of 0.5-2 ng per chromatographic peak. The absolute configuration of crystalline derivatives of racemic 2-methylhexanoic acid with (S)-(-)-2,10-camphorsultam was determined by X-ray analysis after their automatic purification by preparative LC-MS. The technique described can be used to purify and determine the absolute stereochemistry of compounds of unknown structure which contain free carboxy group and lack sufficient UV absorbance.

[Study on therapeutic effects of series of muskone on myocardial infarction canines].

OBJECTIVE: To observe the effects of the series of Muskone (the Muskone includes Slender Dutchmanspipe Root, Tumuxiang, and not Slender Dutchmanspipe Root) on myocardial ischemia, myocardial infarction and hematological index in experimental canines, and to explain the pharmacological action and characteristic of its therapeutic effect on ischemic heart disease. METHOD: The range and degree of myocardial ischemia was evaluated by epicardial electrogram mapping, and the range extent of myocardial infarction was determined by quantitate histology (N-BT staining method). Meanwhile, the changes of ET, TXB2, 6-Keto-PGF1alpha were determined to study the effects of the series of Muskone on myocardial ischemia, myocardial infarction and hematological index in experimental canines. RESULT: The series of Muskone can improve myocardial ischemia and infarction in experimental canines, and relieve significantly the degree of myocardial ischemia (Sigma-ST) determined by epicardial electrogram mapping, decrease the range of myocardial ischemia (N-ST) determined by epicardial electrogram mapping and decrease infarction zone determined by N-BT staining method. And it has a significant inhibition on activity of ET induced by myocardial ischemia and infarction, and increases 6-Keto-PGF1alpha and 6-Keto-PGF1alpha/TXB2 induced by myocardial ischemia. CONCLUSION: The series of Muskone has significant therapeutic effect on myocardial infarction.

Kedarcidin, a new chromoprotein antitumor antibiotic. II. Isolation, purification and physico-chemical properties.

Kedarcidin, a new chromoprotein antitumor antibiotic, was isolated from the culture broth of a novel actinomycete strain L585-6 (ATCC 53650). The antibiotic was recovered from the culture filtrate by adsorption to QAE ion exchanger and purified by successive application of gel filtration and ion exchange chromatography with Sephadex G-50 and DEAE-Sephadex, respectively. Kedarcidin is an acidic complex (pI 3.65) with an apparent molecular weight of 12,400. The complex consists of a highly unstable, solvent extractable chromophore and a water soluble peptide. The apoprotein is a single chain polypeptide of 114 residues.

[Method of isolating, identifying and quantitatively determining alkanes, cycloalkanes, monocyclic arenes and squalene in animal organs and tissues]. / Metod vydeleniia, identifikatsii i kolichestvennogo opredeleniia alkanov, tsikloalkanov, monotsiklicheskikh arenov i skvalena v organakh i tkaniakh zhivotnykh.

A method for analyzing hydrocarbons in animal organs and tissues has been developed. This is made up of the following stages: decomposition of the biological material through alkaline hydrolysis; extraction of non-saponifiable lipids fraction; separation by using preparative thin-layer chromatography of the alkanes and cycloalkanes, monocylic arenes and squalene from the non-saponifiable lipids fractions; determining the content of the alkanes and cycloakanes fraction and also ascertaining the alkanes of normal and isoprenoid structure, by means of gas-liquid chromatography, and, finally, quantification of monocyclic arenes, based on the UV spectra findings. The statistical characteristics obtained through a mathematical processing of the analyses results bear evidence to a sufficient accuracy and good reproducibility of the method stages.