[Effects of Realgar and prescription containing Realgar on stress response proteins, inflammatory mediators and complements in fever rat models].

OBJECTIVE: To explore the pharmacological mechanism of Realgar by the way of studying the effects of Realgar and the prescription containing Realgar named Niuhuang Jiedu Tablet on stress response proteins (heat shock protein 70, HSP70 and heme oxygenase-1, HO-1), inflammatory cytokines (IL-1beta, IL-6 and TNF-alpha), activities of nitric oxide synthetase (NOS) and its isoenzyme (inducible nitric oxide synthetase, iNOS), and complements C3, CA under pathologic status (fever model). METHODS: SD rats were randomly divided into four groups, 15 rats in each: untreated normal group, fever model group, Realgar (90 mg/kg) group and Niuhuang Jiedu Tablet (NJT, 1.404 g/kg) group. Each group was divided into three subgroups (5 rats/subgroup). Blood samples of the rats in subgroups were collected at 1 h, 2 h and 4 h after administration, respectively. ELISA method was used to determine HSP70, IL-1beta, IL-6, and TNF-alpha levels in serum. Dual wavelength spectrophotometry was used to determine activity of HO-1 in serum. Spectrophotometry was used to test activities of nitric oxide synthetase (NOS) and its isoenzyme (inducible nitric oxide synthetase, iNOS) in serum. Immunonephelometery method was used to test complements C3, C4 in serum. RESULTS: Realgar and NJT significantly increased the level of HSP70 in rat serum as compared with the fever model group. Realgar and NJT significantly enhanced the activity of HO-1 in rat serum as compared with the fever model group. The increase ranges of HO-1 activities at different time post administration changed with the arsenic concentration in rat serum. Realgar and NJT significantly decreased the level of IL-1beta in rat serum as compared with fever model group, and the level of IL-lbeta recovered normaly at 4 h after administration. NJT significantly inhibited activities of NOS and iNOS in rat serum as compared with the fever model group at 2 h after administration. CONCLUSION: Realgar as contained in certain prescriptions, at certain specific levels, assists in removal of internal toxins by inducing stress protein (HSP70, HO-1) to improve the positive stress level in the body and inhibiting some over-releasing inflammatory mediators (IL-1beta) to reduce the inflammatory reactions under pathologic status.

[Pharmacokinetics of Chuanxinlian tablet in healthy Chinese volunteers].

OBJECTIVE: To study pharmacokinetics of debydroandrographolide, that is a main active component in Chuanxinlian tablet, in healthy Chinese volunteers. METHODS: Eight volunteers were chosen for a single dose of two Chuanxinlian tablet drug concentrations in plasma were measured by HPLC-MS method and the pharmacokinetic parameters were calculated by PK Solution 2.0 software. RESULTS: t(1/2) ka, t(1/2) alpha, t/(1/2) beta, Cmax, tmax and AUCO-t were (0.51 +/- 0.28) h, (0.60 +/- 0.33) h, (3.62 +/- 1.16) h, (147.30 +/- 53.29) microg x L(-1), (1.50 +/- 0.21) h, and (256.63 +/- 64.18) microg x h x L(-1), respectively. CONCLUSION: Dehydroandrographolide has rapid absorption and long elimination rate after oral administration. The results can provide an evidence for the safety and efficiency of Chuanxinlian tablet in clinical application.

[Effects of cinnabar and realgar in angong niuhuang powder on lactate dehydrogenase and its isoenzymes in rats with infectious cerebral edema].

OBJECTIVE: To explore the pharmacologic mechanism of cinnabar (CA) and realgar (RG) in Angong Niuhuang powder (ANP) by way of studying the characteristics of their effects on organism under physiologic and pathologic states. METHODS: SD rats were randomly divided into six groups, 8-10 rats in each group. Group A: untreated normal rats; Group B: normal rats administered by ANP (drug I) 278 mg/kg; Group C: normal rats administered by ANP subtracted CA and RG (drug II) 222.7 mg/kg; Group D: brain edema model rats established by unilateral common carotid artery injection of Bacillus pertussis 250 million/kg; Group E: model rats administered by ANP 278 mg/kg 1 hr before modeling; Group F: model rats administered by drug II 222.7 mg 1 hr before modeling. Blood sample and brain tissue in Group D were obtained 4 hrs after modeling and those in other groups obtained 5 hrs after drug administration. The total activity of lactate dehydrogenase (LDH) in serum and brain tissue was determined by colorimetry and that of serum LDH isoenzymes (LDH(1-5)) were determined by gel electrophoresis. RESULTS: As compared with Group A, LDH, LDH1 and LDH2 activities increased in Group D (P < 0.01), and increased also in Group B and C (P < 0.05), while LDH4 and LDH5 decreased obviously in Group B and C. But except that of LDH5, no significant difference of LDH(1-4) in brain tissue and serum was shown in comparison of Group B and C. As compared with Group D, LDH was lower (P < 0.01) and LDH5 was higher (P < 0.01) in Group E and F without significant difference, LDH2, LDH3 were lower in Group E (P < 0.01) but unchanged in Group F, LDH1 and LDH4 were not changed in Group E but significantly lowered in Group F (P < 0.05 and P < 0.01). CONCLUSION: Administration of ANP in normal physiologic condition would cause damage on myocardium and kidney to certain extent, administration of ANP and drug II in pathologic (infectious brain edema) would suppress the hyper-activated LDH, with no significant difference between the effects of drug II and ANP. However, CA and RA in ANP are proven to have influence on the serum LDH isoenzymes, indicating that the two ingredients may have some potential pharmacological effects.

Pharmacokinetics of dihydroartemisinin in Artekin tablets for single and repeated dosing in Chinese healthy volunteers.

Aim. To study the pharmacokinetics of dihydroartemisinin (DHA) in Artekin (compound dihydroartemisinin) tablets in Chinese healthy volunteers. Methods. Eighteen healthy volunteers (9 males, 9 females) received Artekin tablets for oral administration. The plasma samples of DHA were analysed by liquid-liquid extraction and determined by HPLC/ESI/MS. Results. The plasma DHA concentration-time curves of single dose and repeated doses of DHA were fitted to a two-compartment open model. The mean pharmacokinetic parameters of DHA in a single dose were: t(1/2(beta))=1.245 +/- 0.495 h, C(max)=243.6 +/- 56.15 microg/l, AUC(0 --> infinity)=450 +/- 69 h x microg/l, V(d)=5.75 +/- 2.2 l/kg and Cl=3.245 +/- 0.38 l/h/kg, while in repeated doses they were: t(1/2(beta))=1.085 +/- 0.298 h, AUC(0 --> infinity)=444.35 +/- 80.43 h x ng/ml, V(d)=4.62 +/- 1.128 ml/kg, Cl=3.0125 +/- 0.875 ml/h/kg, respectively. Conclusion. The study showed that DHA in Artekin was rapidly absorbed, distributed and eliminated in the healthy subjects. The pharmacokinetic properties of DHA in Artekin were not affected by gender in a single dose. While in repeated doses accumulation of DHA did not appear after repeated doses.