Tissue distribution of TPGS modified artesunate liposome and its metabolites in rats / 中国中药杂志

Artesunate, which is a widely used anti-malaria medicine, can be made into liposome to overcome its poor bioactivity. Its tissue distribution in rats may change with different dosage forms, which therefore shall be studied after ARS-TPGS-Lipo was injected. Based on this experiment, ARS-TPGS-Lipo and ARS-Lipo were prepared by thin-film hydration method. LC-MS/MS method was used to simultaneously determine ARS and DHA in rat tissues at different time points. The results showed that this method was suitable for the content analysis of ARS and DHA in biological samples. The distribution of ARS and DHA in ARS-TPGS-Lipo, ARS-Lipo and ARS groups were quite different. The content of ARS-TPGS-Lipo in liver was the highest, with significant differences.ARS and DHA contents in ARS group eliminated rapidly. ARS and DHA contents in ARS-Lipo group were higher in liver and spleen, while those in ARS-TPGS-Lipo group significantly increased only in liver (<0.05).

Simultaneous determination of eleven constituents in Huxin Oral Liquid by LC-MS/MS / 中成药

AIM To establish a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the simultaneous content determination of matrine,oxymatrine,salvia acid B,tanshinol,protocatechualdehyde,liquiritin,astragaloside,cinnamaldehyde,tanshinone Ⅱ A,ophiopogonin D and ruscogenin in Huxin Oral Liquid (Glycyrrhizae Radix et Rhizoma,Astragali Radix,Ophiopogonis Radix,etc.).METHODS The analysis of methanol extract of this drug was performed on a 25 ℃ thermostatic Ultimate XB-C18 column (4.6 mm × 100 mm,3 μm),with the mobile phase comprising of water-methanol (containing 0.05％ formic acid) flowing at 0.4 mL/min in a gradient elution manner.RESULTS Eleven constituents showed good linear relationships with-in their own ranges (r ＞0.999 0),whose average recoveries were 96.66％-103.2％ with the RSDs of 1.4％-3.4％.CONCLUSION This sensitive,reliable and accurate method can be used for the quality control of Huxin Oral Liquid.

Effect of Gegen Qinlian decoction on hepatic cytochrome CYP450 isozymes in rats by HPLC-MS/MS / 中国中药杂志

To study the effect of Gegen Qinlian decoction and its major effective components on five hepatic microsomal CYP450 isozymes in rats. The in vitro hepatic microsomal incubation technique was used to co-culture Gegen Qinlian decoction and its major effective components together with each probe substrate. HPLC-MS/MS was used to establish the analytical method for metabolites of the five isoform probe substrates of CYP450 isozymes, detect the linearity among micoromal protein concentration, incubation time and metabolite formation amount. And HPLC-MS/MS was applied to determine the formation rate (V) of corresponding metabolites (acetaminophen, 4-OH-chlorzoxazone, dextrophan, 6-OH-chlorzoxazone and 6β-hydroxytestosterone) specific probe substrates of the five isoform probe substrates of CYP450 isozymes (phenacetin, polbutamide, dextromethorphan, chlorzoxazone, testosterone), in order to determine the activity of each isozyme. The result showed good linearity among acetaminophen, 4-OH-tolbutamide, dextrophan, 6-OH-chlorzoxazone and 6β-hydroxytestosterone, satisfactory precision, stability and average recovery, suggesting the method was feasible. The optimized in vitro microsomal incubation conditions conformed to the requirements in the guideline of drug-drug interaction. Gegen Qinlian decoction showed different degrees of inhibitor effect on 5 CYP450 isoforms (CYP1A2, CYP2C11, CYP2D2, CYP2E1, CYP3A1/2). Its major effective component berberine could inhibit each CYP450 isoform at high concentrations (except for CYP1A2, CYP3A1/2).

Improvement of kidney yang syndrome by icariin through regulating hypothalamus-pituitary-adrenal axis / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate whether Epimedium brevicornu Maxim (EB) and icariin could exert their protective effects on hydrocortisone induced (HCI) rats by regulating the hypothalamus-pituitary-adrenal (HPA) axis and endocrine system and the possible mechanism.</p><p><b>METHODS</b>Male 10-week-old Sprague Dawley (SD) rats were allotted to 6 groups (A-F) with 12 each, group A was injected normal saline (NS) 3 mL/kg day intraperitoneally, group A and B were given NS 6 mL/kg day by gastrogavage, group B-F were injected hydrocortisone 15 mg/kg intraperitoneally, group C and D were given EB 8 or 5 g/(kg day) by gastrogavage, group E and F were given icariin 25 or 50 mg/(kg day) by gastrogavage. Gene expressions of hypothalamus corticotropin releasing hormone (CRH) and pituitary proopiomelanocortin (POMC) were detected by reverse transcription-polymerase chain reaction (RT-PCR), and protein of pituitary POMC by Western-blot.</p><p><b>RESULTS</b>The serum T4, testosterone, cortisol and POMC mRNA expression were increased after treatment with EB or icariin in HCI rats, the serum CRH and the hypothalamus CRH mRNA expression released from hypothalamus corticotropin decreased compared with group B (P<0.05).The treatment with only icariin increased serum adrenocorticotropic hormone (ACTH) compared with group B (P<0.05).</p><p><b>CONCLUSION</b>EB and icariin might be therapeutically beneficial in the treatment of HCI rats through attuning the HPA axis and endocrine system which was involved in the release of CRH in hypothalamic, and the production of POMC-derived peptide ACTH in anterior pituitary, the secretion of corticosteroids in adrenal cortex.</p>