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

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.     

Mixed nanomicelles loaded with thymopeptides-sodium deoxycholate/phospholipid improveDrugabsorption简

AIM： To improve the absorption of thymopeptides （TH） by preparing sodium deoxycholate/phospholipid-mixed nanomicelles （SDC/PL-MMs）. METHODS： TH-SDC/PL-MMs were prepared by a film dispersion method, and then evaluated using photon correlation spectroscopy （PCS）, zeta potential measurement, as well as their physical stability after storage for several days. Further- more, in situ intestinal single-pass perfusion experiments and pharmacodynamics in immunodeficient mice were performed to make a comparison with TH powders and the control drug in absorption properties. RESULTS： A narrow size distribution of nanomicelles, with a mean particle size of （149 ± 8.32） nm and a zeta potential of （-31.05 ± 2.52） mV, was obtained. The in situ intestine perfusion experiments demonstrated a significant advantage in absorption characteristics for TH compared to the other formulations, and oral administration of TH-SDC/PL-MMs potentiated an equivalent effect with i.h. TH in pharmacodynamic studies in immunodeficient mice. CONCLUSIONS： TH-SDC/PL-MMs prepared by a film dispersion method are able to improve the absorption of TH. SDC/PL-MMs might be a good approach for the more effective delivery of drugs like TH.     

Crebanine inhibits voltage-dependent Na+current in guinea-pig ventricular myocytes简

AIM： To study the effects of crebanine on voltage-gated Na＋ channels in cardiac tissues. METHODS： Single ventricular myocytes were enzymatically dissociated from adult guinea-pig heart. Voltage-dependent Na＋ current was recorded using the whole cell voltage-clamp technique. RESULTS： Crebanine reversibly inhibited Na＋ current with an IC50 value of 0.283 mmol.L-1 （95% confidence range： 0.248-0.318 mmol.L-1）. Crebanine at 0.262 mmol.L-1 caused a negative shift （about 12 mV） in the voltage-dependence of steady-state inactivation of Na＋ current, and retarded its recovery from inactivation, but did not affect its activation curve. CONCLUSION： In addition to blocking other voltage-gated ion channels, crebanine blocked Na＋ channels in guinea-pig ventricular myocytes. Crebanine acted as an inactivation stabilizer of Na＋ channels in cardiac tissues.     

Ethnopharmacology,phytochemistry and pharmacology of Tephrosia purpurea简

Tephrosiapurpurea （L.） Pers. is popularly known as ＇Sarapunkha＂ in classical Ayurvedic texts. It is a perennial plant belonging to the family Fabaceae, and occurs throughout the Indian subcontinent. T. purpurea is traditionally used to treat spleenomegaly, cirrhosis, cough and cold, abdominal swelling and as an antidote in the Ayurvedic system of medicine. Phytochemical investigations indicate the presence of semiglabrin, pongamole, lanceolatins A and B, rutin, lupeol, and β-sitosterol. Flavonoids including （＋）-tephrorin A and B, （＋）-tephrosone, an isoflavone, 7, 4＇-dihydroxy-3＇, 5＇-dimethoxyisoflavone and a chalcone, （＋）-tephropurpurin were isolated from the whole plant. Pharmacological activities of different parts of the plant reported include anti-inflammatory, antiulcer, antimicrobial, antioxidant, antiallergic, antidiabetic, hepatoprotective, antitumor and insect repellent activity. In the present review, the literature on the phytochemical and pharmacological investigations of Tephrosia purpurea （L.） Pers. are summarized to August, 2012.     

Chemical constituents of Euphorbia tibetica and their biological activities简

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 ofE. 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.     

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

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.     

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

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.