[Studies on quality standard of PsL 5F injections].

OBJECTIVE: To establish the quality standard of PsL injections containing mainly 5F (ent-11alpha-hydroxy-15-oxo-kaur-16-en-19-oic-acid). METHOD: The identification of PsL was performed by thin-layer chromatography, and the content was determined by HPLC. The column was Hypersil C18 (4.6 mm x 250 mm, 5 microm), the mobile phase was the mixture of methane-water-acitic acid (55:45: 0.045) with a flow rate of 1.0 mL x min(-1), the detective wavelength was 254 nm, and the column temperature was maintained at 35 degrees C. The pH value and K+ content of the three batchs injection were determined with pH meter and flame photometric meter, and the contents of tannin, protein, oxalic acid salt and heavy metals were detected by deferent methods. RESULT: The TLC method was suitable for the identification of PsL5F. The linearity for 5F was obtained over the range of 30-240 microg x mL(-1) (r = 0.999 8), the average recovery of 5F was 99.8%. The injections were of pH value range from 7.80 to 8.20, K+ contents less than 10 mmol x L(-1), and the contents of tannin, protein, oxalic acid salt and heavy metals were qualified with the Chinese pharmacopoeia, respectively. CONCLUSION: It's sensitive and reliable that can be used as quality control methods of PsL5F injections.

Cell death induced by ent-11alpha-hydroxy-15-oxo-kaur-16-en-19-oic-acid in anaplastic thyroid carcinoma cells is via a mitochondrial-mediated pathway.

The chemical compound ent-11alpha-hydroxy-15-oxo-kaur-16-en-19-oic-acid (5F), isolated from the Chinese herbal medicine plant Pteris semipinnata L, has been known to exert antitumor activity. However, the molecular mechanism of the action is not understood. In this study we demonstrated that apoptotic cell death induced by 5F in FRO cells was concentration- and time-dependent. The rapid increase in intracellular reactive oxygen species (ROS) levels was involved in the mechanism of cell death. c-Jun N-terminal kinase (JNK) activation and G2 block were related to cell death induced by 5F. Extracellular signal-related kinase (ERK) and p38 were also activated, but as survival signals in response to 5F treatment to counteract the induction of cell death. In the process of the induction of apoptotic cell death, Bax translocated into mitochondria, a reduction in Delta psi(m) was observed and a release of cytochrome c and apoptosis inducing factor (AIF) from mitochondria into the cytosol occurred, indicating that cell death induced by 5F was through a mitochondrial-mediated pathway.

Pharmacokinetics of Astragaloside IV in rats by liquid chromatography coupled with tandem mass spectrometry.

Pharmacokinetics of Astragaloside IV (AGS-IV) in rats was studied by high performance liquid chromatography coupled with tandem mass spectrometry. The concentration in plasma was determined after i.v. administration of 1, 2, 4 mg/kg and p.o. administration of 20 mg/kg of AGS-IV. The AUC were linearly correlated to doses. Recoveries of AGS-IV in bile, urine and feces were also analyzed following i.v. dose of 2 mg/kg. Cumulative recovery of AGS-IV in bile reached 30.8% in 24h. Cumulative recovery of AGS-IV in urine and feces was 52.14%, which indicates that about 50% of AGS-IV was metabolized in vivo. The bioavailability of AGS-IV after p.o. administration was found to be 3.66%. These findings provide useful information for the research and development of AGS-IV and other potential agents.

Over-expression of Bcl-2 against Pteris semipinnata L-induced apoptosis of human colon cancer cells via a NF-kappa B-related pathway.

Ent-11 alpha-hydroxy-15-oxo-kaur-16-en-19-oic-acid (5F), an antitumor component, is a chemical compound isolated from Pteris semipinnata L (PsL), a Chinese traditional herb. We examined whether 5F could affect apoptosis in human colon cancer HT-29 cells, and test whether and how the over-expression of Bcl-2 and Bcl-xL could offset the effect of 5F on cell growth. The result demonstrated that 5F significantly induced apoptosis of HT-29, as shown by MTT assay and DNA fragmentation measurement. Treatment of HT-29 with 5F increased both p38 and iNOS levels, suggesting these two molecules may contribute to the apoptotic effect of 5F. Over-expression of Bcl-2 or Bcl-xL attenuated the increase of p38 and iNOS induced by 5F. The cells with Bcl-2 or Bcl-xL over-expression showed an elevation of nuclear factor kappa B (NF-kappa B) activity, accompanying a significant reduction of 5F-induced apoptosis. Furthermore, inhibition of NF-kappa B by I k B alpha SR, which is a powerful inhibitor of NF-kappa B, restored the ability of 5F to induce apoptosis in the cells transfected with Bcl-2. These data strongly indicated that the apoptotic effect of 5F on HT-29 was closely associated with the activity of NF-kappa B, which was up-regulated by Bcl-2 and Bcl-xL. In conclusion, 5F induced apoptosis in HT-29 cells and this apoptotic effect was associated with the high level of p38 and iNOS expression. The apoptotic effect of 5F could be significantly offset by over-expression of either Bcl-2 or Bcl-xL. Bcl-2, and to the less extent, Bcl-xL, were able to increase the activity of NF-kappa B, which was a known anti-apoptotic molecule in human colon cancer cells.

Current and future treatments for cognitive deficits in dementia.

In this article, we primarily focus on the treatment approaches currently marketed and in advanced stages of development for Alzheimer's disease (AD). Amyloid plaques and neurofibrillary tangles remain the pathologic hallmarks of AD, and much progress has been made in unraveling the molecular biology of these changes. In addition, there is also intense research into inflammatory and oxidative mechanisms as well as vascular and neurochemical alterations in AD. Therapies targeted at these mechanisms are discussed.

A prosencephalic neuronal circuit possibly involved in modulation of pain.

Both anatomical and physiological studies in cats substantiated the existence of a thalamus-cortex-thalamus neuronal circuit in which neurons in the centre median send fibers to wide areas of the cerebral cortex and the cerebral cortex, the motor cortex in particular, may send the fibers back to the parafascicular nucleus. The cortical neurons concerned tend to discharge spontaneously and constantly. These spontaneous discharges can be readily inhibited by the corticopetal impulses from the centre median, which itself can be activated by general afferent impulses. On the basis of this observation it is assumed that constantly discharging corticothalamic neurons may exert a tonic excitatory influence on the pain-receiving center, parafascicular nucleus, so as to keep it in a state of constant alertness to the tissue-damaging danger signals and that the inhibitory action of the ascending fibers from centre median would serve to suspend the excitatory action of the cortex on the parafascicular nucleus, resulting in relief of pain. The corticofugal fibers in this forebrain circuit terminating in the centromedian nucleus may reinforce the inhibitory action of the centromedian neurons so as to inhibit the spontaneous discharges of the cortical neurons . A self-regulating mechanism is thus formed by which a stabilized state of brain excitability can be maintained.