[Absorption mechanism of dragon's blood phenolic extracts in Caco-2 cells].

The purpose of this study was to study the absorption characteristics of eight main components from dragon's blood phenolic extracts in Caco-2 cells based on the humancolon cancer cell Caco-2 model, and to clarify the oral absorption mechanism of such phenolic extracts. UPLC-MS/MS was used in this study to determine the content of 8 active ingredients including thevetiaflavone, 7,4'-dihydroxyflavone, 7,4'-dihydroxy-5-methoxyhomoisoflavanone, 7,4'-dihydroxyhomoisoflavanone, loureirin C, loureirin A, loureirin B and pterostilbene from dragon's blood phenolic extracts, and Caco-2 cells were used to investigate the effects of incubation time, concentration, temperature, P-gp inhibitor, MRP inhibitor, OCTN1 inhibitor and OCTN2 inhibitor on the absorption of each component. In addition, the transport experiment was conducted to measure the apparent permeability coefficient P_(app) and transport rate of the eight main components to predict the oral absorption mechanism of dragon's blood phenolic extracts. The experimental results showed that the cell uptake of the eight main components in dragon's blood phenolic extracts was time-dependent and concentration dependent, and the uptake of each component did not need to consume energy, which was consistent with the passive diffusion process. P-gp inhibitor, MRP inhibitor and OCTN1 inhibitor had no effect on the cell uptake of each component, only the addition of OCTN2 inhibitor significantly reduced the uptake of pterostilbene(P<0.05). In the transport results, the ER values of the outflow rates of the eight components were all less than 1.5. The above results show that the absorption mechanism of the eight components in Draconis resina phenolic extract may be passive diffusion, and pterostilbene may be the substrate of OCTN2.

[An updated phytochemical and pharmacological progress on Syringa pinnatifolia].

Syringa pinnatifolia is an endemic species of Syringa in Oleaceae family in China, mainly distributed in Helan Mountain, which is located between Inner Mongolia and Ningxia. Its peeled roots, stems and thick twigs have been used as Mongolian folk medicine, called "Shan-chen-xiang" in Chinese, for the treatment of coronary heart diseases, angina pectoris and other cardiopulmonary diseases. Modern researches showed that S. pinnatifolia mainly contains lignans, sesquiterpenoids, and volatile oils, and displays anti-myocardial ischemia, sedation, analgesia, antibacterial and other effects. In the past five years, many groups have made new progress on the study of chemical constituents and pharmacological activities of S. pinnatifolia. On the basis of the previous review by our group, this paper summarizes the advances which is beneficial to the development, research and clinical application of S. pinnatifolia, particularly Shan-chen-xiang.

GSK3 beta mediates suppression of cyclin D2 expression by tumor suppressor PTEN.

PTEN, encoding a lipid phosphatase, is a tumor suppressor gene and is mutated in various types of cancers. It is reported to regulate G1 to S phase transition of the cell cycle by influencing the expression, protein stability and subcellular location of cyclin D1. Here, we provide evidence that PTEN modulates the transcription and protein stability of cyclin D2. Targeted deletion of Pten in mouse embryonic fibroblasts (MEFs) endowed cells with greater potential to overcome G1 arrest than wild-type MEFs and led to the elevated expression of cyclin D2, which was suppressed by the introduction of PTEN. We further defined a pathway involving GSK3beta and beta-catenin/TCF in PTEN-mediated suppression of cyclin D2 transcription. LiCl, an inhibitor of GSK3beta, abolished inhibitory effect of PTEN on cyclin D2 expression, and TCF members could directly bind to the promoter of cyclin D2 and regulate its transcription in a CREB-dependent manner. Our results indicate that the downregulation of cyclin D2 expression by PTEN is mediated by the GSK3beta/beta-catenin/TCF pathway in cooperation with CREB, and suggest a convergence from the PI-3 kinase/PTEN pathway and the Wnt pathway in modulation of cyclin D2 expression.

Conversion of angiotensin I to angiotensin II in sheep.

1. The methodology for measurement of angiotensin I in whole blood is described. 2. Angiotensin I was measured in arterial and venous blood samples from sodium-loaded, sodium-replete and sodium-depleted sheep. Venous blood concentrations were higher than arterial angiotensin I concentrations. Arterial angiotensin I concentrations increased with increasing sodium deficiency. 3. Angiotensin II was infused into six sodium-replete sheep, the blood concentrations of angiotensin II measured and the metabolic clearance rates calculated. The average value was 121 +/- 21 1/h. 4. Angiotensin I was then infused into these sheep and arterial and venous blood concentrations of angiotensins I and II determined. From this data and the metabolic clearance rate of angiotensin II, the degree of conversion of angiotensin I to II was calculated. The values varied in different sheep from 54 +/- 2% to 105 +/- 6% (n = 6).