Inhibition of microglial activation by the herbal flavonoid baicalein attenuates inflammation-mediated degeneration of dopaminergic neurons.

Accumulating evidence has suggested that inflammation in the brain participates in the pathogenesis of Parkinson's disease (PD). Therefore, anti-inflammatory therapy has attracted much attention as novel interference to neurodegenerative diseases. Baicalein, a major flavonoid extracted from a traditional Chinese herb Scutellaria baicalensis Georgi (Huangqin), possesses potent anti-inflammatory and antioxidant properties. To test the potential neuroprotective effect of baicalein on dopaminergic neurons, primary midbrain neuron-glia cultures from E-14 rat embryos were used. Cultures were pretreated with baicalein for 30 min prior to stimulation with lipopolysaccharide (LPS, 10 ng/ml). LPS leads to massive activation of microglial cells revealed by OX-42 immunostaining, and produced excessive quantities of NO. Excessive elevation of superoxide level was also observed in enriched-microglia after stimulating with LPS. LPS-induced damage to dopaminergic neurons was evaluated by uptake capacity for [3H]dopamine and tyrosine hydroxylase (TH)-immunocytochemistry. Pretreatment with baicalein concentration-dependently attenuated LPS-induced decrease in [3H]dopamine uptake and loss of TH-immunoreactive (TH-ir) neurons, which the maximum protective effect was observed at the concentration of 5 microM. Post-treatment with baicalein (5 microM) was also shown to be effective even if baicalein administered up to 2 h later than LPS application. Morphological study shows that baicalein (5 microM) almost completely blocked LPS-induced activation of microglia. Excessive production of TNF(alpha) and free radicals such as NO and superoxide by LPS stimulation were also attenuated by baicalein at a concentration-dependent pattern. The present study indicates that baicalein exerts potent neuroprotective effect on LPS-induced injury of dopaminergic neurons. We hypothesize that the inhibition of LPS-induced production of NO and free radicals from microglia may underlie the mechanism of baicalein's neuroprotection.

[Tetrandrine loaded sustained-release microcapsules for lung targeting].

AIM: To prepare lung targeted tetrandrine (TET) loaded sustained-release drug delivery system by microencapsulation, decrease the toxicity and enhance the therapeutic function of anti-pulmonary hypertension of TET. METHODS: Albumin microcapsules were produced by spray drying-thermal denaturation, a new technique. Some characterization of the prepared microcapsules was evaluated. Distribution of the microcapsules and their anti-pulmonary hypertension effect in vivo were investigated. RESULTS: The spherical microcapsules showed a drug loading of 37.88%. Compared to the original drug, the rate of TET released from the positively charged microcapsules in vitro was significantly decreased and fitted well by Higuchi equation. The TET concentrations in mouse lungs of TET microcapsules were significantly higher than those of TET injection, and the mean retained time of TET in lungs was prolonged from 157.1 h to 223.6 h after microencapsulation. The in vitro--in vivo correlation was established and confirmed (P < 0.001). CONCLUSION: The new spray drying-thermal denaturation method allows the preparation of drug loaded albumin microcapsules with desired results. The prepared microcapsules were found to have the potential function of delivering TET to pulmonary artery via i.v., with low toxicity and high efficacy.

[Experimental chemotherapy of human gastric cancer cell lines in vitro and in nude mice].

Cytotoxic effects of allyl trisulfide (Alt, a synthetic chemical identical with one of the main active principles of garlic), 5 FU, MMC and DDP on SGC 7901 ( a moderately differentiated human gastric adenocarcinoma cell line) and MGC 803 (a poorly differentiated human gastric mucoadenocarcinoma cell line) had been reported before. In this paper, effects of repeated two doses of each drug and the combination of two drugs on these two cell lines were studied using relative clone-survival test. The inhibitory effects of Alt, MMC alone or combined on MGC tumor in nude mice were observed. No drug resistance was found when any one of the four agents at the same concentration were repeated twice separately at 60 hour interval in vitro. The cytotoxic effect of the repeated two doses was approximately equal to that of the single dose at double concentration. The in vitro test of combinations of two drugs showed that Alt plus MMC or 5 FU plus DDP had markedly synergistic effect on MGC cells; 5 FU plus DDP had markedly synergistic effect on SGC cells. The inhibition test on the growth of MGC tumor in nude mice indicated that the inhibition rates of Alt, MMC alone or combined were 58.3%, 86.3% and 84.3%. The systemic toxic effect of MMC alone was severe, whereas Alt alone or MMC plus Alt showed mild toxicity. For this reason, Alt plus MMC is recommended for clinical trials on poorly differentiated gastric cancer. In addition, for the comparison of in vitro test dose and clinical dose of each drug, the principle of clinical adult dose range (CADR) is proposed.