Effect of Angelica sinensis polysaccharide fraction AP-3 on IL-2 and IFN-gamma induction / 药学学报

<p><b>AIM</b>To investigate the effects of Angelica sinensis polysaccharide fraction AP-3 on IL-2 and IFN-gamma induction and its further immunomodulatory feature.</p><p><b>METHODS</b>The percentage of CD4+ lymphocyte was detected by flow cytometric method, the production of IL-2 and IFN-gamma in cell culture supernatant were determined by ELISA, mRNA expressions of IL-2 and IFN-gamma cytokines were detected by RT-PCR.</p><p><b>RESULTS</b>At the range of 0. 6 - 2 micromol x L(-1), AP-3 significantly enhanced the percentage of CD4+ lymphocytes in total splenocytes. At the range of 2 - 6 micromol x L(-1), the treatment of AP-3 augmented both productions of IL-2 in cell culture supernatant and cell IL-2 mRNA transcription level in a time and dose dependent manner. While in the case of IFN-gamma, AP-3 stimulated at early time after exposure but down-regulated thereafter.</p><p><b>CONCLUSION</b>Angelica sinensis polysaccharide could regulate the immune response through upregulating IL-2, IFN-gamma expression and activating Th1 cell.</p>

Metabolic kinetics of MN9202 in Beagle dog liver microsomes / 药学学报

<p><b>AIM</b>To study the metabolic kinetics of MN9202 in Beagle dog liver microsome.</p><p><b>METHODS</b>Beagle dog liver microsomes were prepared by using ultracentrifuge method. After incubating 0.4 micromol x L(-1) MN9202 with 1 g x L(-1) microsomes for 30 min at 37 degrees C, the reaction was terminated by adding 0.5 mL alkalization. The RP-HPLC was used to determine the drug in the incubation mixture. The Michaelis-Menten parameters Km, and Vmax in Beagle dog liver microsomes were initially estimated by analyzing Lineweave-Brurk plot. Various selective CYP inhibitors were used to investigate their inhibitory effect on the metabolism of MN9202.</p><p><b>RESULTS</b>The Km, Vmax and CLint of MN9202 were (22.6 +/- 8.0) micromol x L(-1), (0.54 +/- 0.17) micromol x g(-1) x min(-1) and (0.0242 +/- 0.0009) L x g(-1) x min(-1), respectively. The metabolism of MN9202 was significantly inhibited by ketoconazole (Ket) and troleandomycin (Tro) in Beagle dog liver microsomes. Tranylcypromine (Tra) could inhibit the metabolism of drug as well. While other inhibitors showed little inhibitory effect on the metabolism of MN9202.</p><p><b>CONCLUSION</b>It was shown that CYP3A and CYP2C19 were involved in MN9202 metabolism. The inhibitors of human CYP3A and CYP2C19 may have potential interaction with MN9202, and this can reduce the metabolism rate and increase the toxicity of MN9202.</p>

Pharmacokinetics of m-nifedipine in Beagle dogs / 药学学报

<p><b>AIM</b>To study the pharmacokinetics of m-nifedipine (m-Nif) in Beagle dogs.</p><p><b>METHODS</b>The Beagle dogs were divided into two groups. m-Nif was intravenously administered to the Beagle dogs in group 1 at the dose of 0. 288 mg x kg(-1), and it was orally administered to the Beagle dogs in group 2, 3 and 4 at the dose of 1.152, 3.456 and 10.370 mg x kg(-1), respectively. m-Nif in plasma was detected by reversed phase high performance liquid chromatography. The pharmacokinetic parameters were calculated by 3P97 software.</p><p><b>RESULTS</b>When m-Nif was intravenously administered, the plasma concentration-time curve was fit to a two-compartment model and T1/2beta was 117 min. When m-Nif was orally administered, the plasma concentration-time curve was fit to a one-compartment model. T1/2 (Ke) and Cmax were 147 min and 20 microg x L(-1); at the low dose of 1.152 mg x kg(-1). T1/2 (Ke) was 122 min and Cmax was 36 microg x L(-1) at the middle dose of 3.456 mg x kg(-1). T1/2 (Ke) was 144 min and Cmax was 69 microg x L(-1) at the high dose of 10.37 mg x kg(-1), respectively.</p><p><b>CONCLUSION</b>It was showed that the speed of elimination of m-Nif was high in Beagle dogs. The absolute bioavailability of m-Nif given orally was very low.</p>