Metabolism and pharmacokinetic study of ardipusilloside I in rats.

Ardipusilloside I, extracted from ARDISIA PUSILLA A.DC, effectively inhibits the progression of several cancers in animal models and is a potential anti-cancer drug candidate. However, the metabolism and pharmacokinetic characteristics of ardipusilloside I remain unknown. In this study, we developed a highly sensitive liquid chromatography-tandem MS method to determine the ardipusilloside I concentration in rat plasma using ginsenoside Re (whose structure is similar to ardipusilloside I) as the internal standard. After oral administration of ardipusilloside I, its four possible metabolites (M1, M2, M3, and M4, whose structures were determined by MS) were detected in the content from rat small intestine. In rat plasma, however, only M3 and M4 were detected after oral administration of ardipusilloside I. None of the metabolites were detected in plasma samples after intravenous administration of ardipusilloside I to rats. These results indicated that the metabolites, but not the drug itself, were absorbed into plasma after oral administration of ardipusilloside I to rats and that M3 and M4 may be responsible for the antitumor activity of orally administered ardipusilloside I in rat models of cancer.

Achyranthes bidentata root extract prevent OVX-induced osteoporosis in rats.

AIM: The objective of the present study was to systematically investigate the effects of Achyranthes bidentata root extract (ABRE) on postmenopausal osteoporosis. MATERIALS AND METHODS: Eighty 3-month-old female Sprague-Dawley rats were used and randomly assigned into sham-operated group (SHAM) and five ovariectomy (OVX) subgroups, i.e. OVX with vehicle (OVX); OVX with 17 ß-ethinylestradiol (E(2), 25 µg/kg/day); OVX with ABRE of graded doses (100, 300, or 500 mg/kg/day). Daily oral administration of ABRE or E(2) started on week 4 after OVX for 16 weeks. Bone mass, bone turnover and strength were analyzed by dual-energy X-ray absorptiometry (DEXA), biochemical markers and three-point bending test. The trabecular bone microarchitecture was evaluated by microcomputed tomography (µCT). RESULTS: 16 weeks treatment of ABRE slowed down the body weight gain and prevented the loss of bone mass induced by the OVX. The prevention effect on bone loss was due to altering the rate of bone remodeling, which could be inferred from the decreased level of bone turnover markers, such as serum alkaline phosphatase (ALP), osteocalcin (OC) and urinary deoxypyridinoline (DPD). The changes of urinary calcium and phosphorus excretion provided the same evidence. The treatment could also enhance the bone strength and prevent the deterioration of trabecular microarchitecture. CONCLUSIONS: We conclude that 16 weeks of ABRE treatment improve bone biomechanical quality through modifications of bone mineral density (BMD), and trabecular microarchitecture without hyperplastic effect on uterus, and it might be a potential alternative medicine for treatment of postmenopausal osteoporosis.

Determination of free and glucuronidated kaempferol in rat plasma by LC-MS/MS: application to pharmacokinetic study.

Flavanoid kaempferol is mainly present as glucuronides and sulfates in rat plasma, and small amounts of the intact aglycone are also detected. In the this study, a rapid, specific and sensitive liquid chromatography-electrospray ionization-tandem mass spectrometry method (HPLC-MS/MS) was developed and validated for determination of kaempferol and its major metabolite glucuronidated kaempferol in rat plasma. A liquid-liquid extraction with acetic ether was involved for the extraction of kaempferol and internal standard. Analytes were separated on a C18 column (150 mm x 2.1 mm, 4.5 microm, Waters Corp.) with isocratic elution at a flow-rate of 0.3 ml min(-1). The mobile phase was consisted of 0.5% formic acid and acetonitrile (50:50, v/v). The Quattro Premier HPLC-MS/MS was operated under the multiple reaction-monitoring mode (MRM) using the electrospray ionization technique. The method was validated according to the FDA guidelines for validation of bioanalytical method. The validated method was successfully applied to the study of the pharmacokinetics in rats after oral administration of kaempferol with different doses.

Study on the effect of Jia-Wei-Xiao-Yao-San decoction on patients with functional dyspepsia.

The effect of Jia-Wei-Xiao-Yao-San (JWXYS) decoction on patients with functional dyspepsia was studied by means of electrogastrography (EGG) and symptoms of dyspepsia were assessed. Twenty patients with functional dyspepsia were selected; before and after internal treatment with JWXYS, the integrated symptoms of the patients were down-regulated from 18.55 +/- 3.24 (before treatment) to 11.65 +/- 2.37 (after treatment) (p < 0.01); electrogastrography showed that all the EGG parameters of the patients were outside the normal range. After treatment with JWXYS, all these indices improved before and after dinner. The results showed that the JWXYS decoction could not only improve the symptoms, but also adjust the abnormal gastric motility and gastric myoelectrical activity of patients with functional dyspepsia.

[Biliary excretion of genistein and its metabolite at different doses in rats].

AIM: To study the biliary excretion of genistein and its metabolite at different doses in rats. METHODS: Suspended in 0.5% CMC-Na solution, genistein was orally administered to rats at the dose of 6.25, 12.5 and 50 mg x kg(-1), separately. At various time intervals, the bile was collected. The bile was treated with beta-glucuronidase. The genistein in bile was extracted twice by vortexing with 2.0 mL mixture of methyl tert-tubtyl ether and pentane (8:2). The organic phase was removed into the tubes and then evaporated in ventilation cabinet. The residue was dissolved in 50 microL of methanol. Twenty microL solution was drawn and detected by high-performance liquid chromatography. RESULTS: The accumulative biliary excretion of genistein was (42.56 +/- 6.54) , (75.17 +/- 18.87) and (126.60 +/- 34.78) microg at the dose of 6.25, 12.5 and 50 mg x kg(-1), respectively. The total drug (genistein plus glucuronidated genistein) excreted from bile was (108.46 +/- 35.23), (423.46 +/- 158.31) and ( 853.74 +/- 320. 84) microg, and the ratio of glucuronidated genistein was 60.76% , 82.25% and 85.17% at the dose of 6.25, 12.5 and 50 mg x kg(-1), respectively. CONCLUSION: The genistein was excreted mainly in the form of glucuronidated genistein in rat bile. The genistein and glucuronidated genistein were excreted in a nonlinear dose-dependent manner.

[Effect of oral administration of guanxin II decoction on coronary blood flow and cardiac systolic/diastolic function in healthy males].

OBJECTIVE: To observe the effects of oral administration of guanxin II decoction (GX II) on cardiovascular function, especially on the dynamics of coronary blood flow in healthy males. METHODS: Changes of heart rate, diastolic pressure, systolic pressure, left ventricular ejection fraction (LVEF), E peak, A peak, E/A value of mitral flow, diastolic peak velocity (Vmax) and diastolic flow velocity time integrals (VTI) of left anterior descending coronary artery (LAD) in 11 healthy male subjects were measured before and after oral administration of GX II, using non-invasive echocardiogram. RESULTS: Compared with those before GX II administration, the changes after administration in heart rate, systolic pressure, diastolic pressure, LVEF, E peak, A peak and E/A value, were insignificantly different (P>0.05), but the Vmax and VTI significantly increased at 30 min, 60 min, 90 min and 120 min after GX II administration (P<0.05). CONCLUSION: To increase the coronary blood flow is possibly one of the mechanisms of GX II in treating coronary heart disease and angina pectoris.