Liaoning University of Traditional Chinese Medicine

About: Liaoning University of Traditional Chinese Medicine is a education organization based out in Shenyang, China. It is known for research contribution in the topics: Randomized controlled trial & Acupuncture. The organization has 2040 authors who have published 1326 publications receiving 14664 citations.

The impact of CYP2D6 polymorphisms on the pharmacokinetics of codeine and its metabolites in Mongolian Chinese subjects

Abstract: Codeine is an analgesic drug acting on μ-opioid receptors predominantly via its metabolite morphine formed almost exclusively by CYP2D6. Genetic polymorphisms in CYP2D6 are associated with diminished pain relief and/or severe opioid side effects. In Chinese individuals, CYP2D6*10 is the most common allele with reduced enzyme activity. In this study, we investigated the effect of this allele on the pharmacokinetics of codeine and its metabolites. A blood sample was collected from healthy Mongolian volunteers for CYP2D6 genotyping using a PCR-RFLP assay. A pharmacokinetic study was then carried out in three groups with CYP2D6*1/*1 (n = 10), CYP2D6*1/*10 (n = 10) and CYP2D6*10/*10 (n = 9) genotypes by collecting serial blood samples for determination of plasma levels of codeine and its metabolites, morphine, morphine 3-glucuronide (M3G) and morphine 6-glucuronide (M6G) before and after a single 30-mg oral dose of codeine phosphate. Codeine and its metabolites were measured by LC-MS/MS. No significant differences were observed in the pharmacokinetic parameters of codeine in the three genotype groups. However, the C max and AUC0-∞ of morphine, M3G and M6G were significantly different between the study groups (P < 0.05). Compared with the *1/*1 group, the AUC0-∞ for morphine in the *1/*10 and *10/*10 groups decreased by ratios (95 % CI) of 0.93 (0.26–1.59) and 0.494 (0.135–0.853) respectively. Corresponding ratios for M3G were 0.791 (0.294–1.288) and 0.615 (0.412–0.818) and for M6G were 0.643 (0.39–0.957) and 0.423 (0.267–0.579). This study demonstrates that the CYP2D6*10 allele plays an important role in the pharmacokinetics of the O-demethylated metabolites of codeine after oral administration.

The Coumarin Derivative Osthole Stimulates Adult Neural Stem Cells, Promotes Neurogenesis in the Hippocampus, and Ameliorates Cognitive Impairment in APP/PS1 Transgenic Mice.

Abstract: It is believed that neuronal death caused by abnormal deposition of amyloid-beta peptide is the major cause of the cognitive decline in Alzheimer's disease. Adult neurogenesis plays a key role in the rescue of impaired neurons and amelioration of cognitive impairment. In the present study, we demonstrated that osthole, a natural coumarin derivative, was capable of promoting neuronal stem cell (NSC) survival and inducing NSC proliferation in vitro. In osthole-treated APP/PS1 transgenic mice, a significant improvement in learning and memory function was seen, which was associated with a significant increase in the number of new neurons (Ki67(+)/NF-M(+)) and a decrease in apoptotic cells in the hippocampal region of the brain. These observations suggested that osthole promoted NSC proliferation, supported neurogenesis, and thus efficiently rescued impaired neurons in the hippocampus and ameliorated cognitive impairment. We also found that osthole treatment activated the Notch pathway and upregulated the expression of self-renewal genes Notch 1 and Hes 1 mRNA in NSCs. However, when Notch activity was blocked by the γ-secretase inhibitor DAPT, the augmentation of Notch 1 and Hes 1 protein was ameliorated, and the proliferation-inducing effect of osthole was abolished, suggesting that the effects of osthole are at least in part mediated by activation of the Notch pathway.

Development of functional docetaxel nanomicelles for treatment of brain glioma.

Abstract: The efficacy of anticancer drugs is rather limited in the treatment of brain glioma due to the hindrance of the blood-brain barrier (BBB). Herein, we reported an easy formulation of functional docetaxel nanomicelles for the treatment of brain glioma using a graft copolymer soluplus as basic material through dual-modifications with a glucose-lipid derivative and a dequalinium-lipid derivative. The studies were performed on brain glioma U87MG cells, in vitro BBB models and brain glioma-bearing nude mice. The functional docetaxel nanomicelles were approximately 100 nm. The results demonstrated that the functional docetaxel nanomicelles could transport across the BBB, enhance the cellular uptake, target to the mitochondria, induce the apoptosis, increase the cytotoxicity in the brain glioma cells, and extend survival span of the brain glioma-bearing mice. The action mechanisms were associated with dual-modifications by the glucose-lipid derivative and the dequalinium-lipid derivative, both of which are beneficial for the transport across the BBB. Furthermore, the modification with dequalinium-lipid derivative was able to target to the brain glioma cells and to the mitochondria. In conclusion, the functional docetaxel nanomicelles would be a promising formulation for the treatment of brain glioma, deserving further development for clinical trials.