Pharmacokinetics of acteoside following single dose intragastric and intravenous administrations in dogs / 中国天然药物

Acteoside (verbascoside), a phenylethanoid glycoside widely distributed in various plants, has been shown to have potential activity against Alzheimer's disease, attracting great attentions recently. The present study was designed to develop a selective and sensitive LC-MS/MS method for the determination of acteoside in biological samples and carry our a pharmacokinetic (PK) study in beagle dogs. The PK parameters were calculated using non-compartmental models. Following a single-dose oral administration, acteoside was rapidly absorbed and eliminated, with Tmax being between 30 to 45 min and terminal half-life being about 90 min. The areas under the time-concentration curve (AUC) were 47.28 ± 8.74, 87.86 ± 13.33, and 183.14 ± 28.69 mg · min · L(-1) for oral administration of 10, 20, and 40 mg · kg(-1), respectively, demonstrating that the exposure of acteoside proportionally increased with the dose level. The absolute bioavailability of acteoside was around 4%. For all the PK parameters, there were large variations between individual dogs. In conclusion, the pharmacokinetic characteristics observed in the present study can be of great value to help better understand the pharmacological properties of acteoside and to improve the outcome of its clinical use.

Study on protective effect of acteoside on cellular model of Alzheimer's disease induced by okadaic acid / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the effect of acteoside on SK-N-SH nerve cell injury induced by okadaic acid (OA).</p><p><b>METHOD</b>SK-N-SH nerve cells were processed with 20 nmol * L OA to establish the Alzheimer's disease (AD) cellular model, and 5, 10, 20 mg . L-1 acteoside was used to antagonize against its effect. Cell morphology was observed under inverted microscope. The cell survival rate was detected with MTT, and the LDH release rate was measured by enzyme label kit. Western blot was applied to determine the expression of phosphorylation tau proteins in nerve cells.</p><p><b>RESULT</b>The acteoside could significantly improve SK-N-SH cell morphology, enhance the cell survival rate, decrease the cell LDH release rate and the expression of phosphorylated tau proteins at p-Ser 199/202 and p-Ser 404 sites, up-regulated the expression of at non-phosphorylated tau proteins at Ser 202 site and Ser 404 sites.</p><p><b>CONCLUSION</b>Acteoside has significant protective effect on nerve cell injury induced by OA.</p>

Spectrum-effect relasionship of extract from rhizome of Alpinia officinarum on promotion of melanogenesis / 中草药

Objective: To establish the fingerprint of the extract from the rhizome of Alpinia officinarum, to investigate the effects on the proliferation, tyrosinase activity, and melanogenesis in melanoma B16 cells, and to analyze the spectrum-effect relasionship. Methods: The fingerprint of alcohol extract from the rhizome of A. officinarum (G1), water sediments of G1 (G2), macroporous resin purified extract of G2 (G3), and refined polyamide extract of G3 (G4) were established by HPLC, and the proliferation of each extract on B16 cells was measured by MTT. The tyrosinase activity and melanin content were measured by colorimetry assay. The spectrum-effect relasionship was analyzed by grey relation analysis. Results: Compared with the control group, the proliferation of B16 cells was promoted significantly after treatment with 1.00-5.00, 0.50-5.00, 0.25-5.00, and 0.25-10.00 μmol/L of G1, G2, G3, and G4, respectively. The tyrosinase activity was promoted by G1 and G2 with 0.50 μmol/L, and G3 and G4 with 0.50-1.00 μmol/L (P < 0.05, 0.01); The synthesis of melanin was promoted after the treatment with 0.5 and 5.00 μmol/L of G1, 0.50-5.00 μmol/L of G2 and G4, and 0.25-5.00 μmol/L of G3 (P < 0.01); At the same concentration, G4 had the strongest effect to promote the cell proliferation and to increase the tyrosinase activity. The galangin (peak 7) had the highest correlation with pharmacodynamics, and the contents of galangin in G1, G2, G3, and G4 were 27.61, 88.72, 348.53, and 693.35 mg/g, respectively. The proliferation, tyrosinase activity, and galangin content were promoted significantly after the treatment with galangin (0.25-10.00 μmol/L) by the verification experiment. Conclusion: The effect of the extract from the rhizome of A. officinarum on the proliferation, tyrosinase activity, and melanogenesis of B16 melanoma cells could be enhanced with the increased content of galangin, which demonstrates that the galangin is one of the efficient substances in the rhizome of A. officinarum for the treatment of vitiligo.

Pharmacokinetic study on acetoside in rats / 中国中药杂志

<p><b>OBJECTIVE</b>To establish a HPLC method for determining acetoside in rat plasma and to investigate the pharmacokinetic characteristics of acetoside in rats.</p><p><b>METHOD</b>Six rats were orally administered with 150 mg x kg(-1) acetoside and their blood samples were collected at different time points. The plasma concentration of acetoside was determined by reserved HPLC, and the pharmacokinetic parameters were calculated by DAS 2.0 software.</p><p><b>RESULT</b>The regression equation of acetoside in rats plasma was Y = 3.509 8X-0.096 8 (r = 0.996 8), which showed a good linear relation at 0.125-2.5 mg x L(-1). The method showed a recovery of more than 85%, and both inter-day and intra-day RSDs were less than 15%. After the oral administration of 150 mg x kg(-1) acetoside, the concentration-time curves of acetoside were expressed in a open two-compartment model. The main pharmacokinetics parameters of T(max), C(max), t(1/2alpha), t(1/2beta), AUC(0-t), AUC(0-infinity), CL/F, V/F and K(a) were respectively 0.36 h, 1.126 mg x L(-1), 0.759, 4.842 h, 3.134, 3.766 mg x h x L(-), 87.089 L x h(t) x kg(-1), 207.704 L x kg(-1) and 6.345 h(-1) respectively.</p><p><b>CONCLUSION</b>It is first time to establish such a HPLC method to determine the concentration of acetoside in plasma. The method is so highly specified and sensitive that it can ble used in quantitative analysis in vivo on acetoside.</p>

Effect of acteoside on learning and memory impairment induced by scopolamine in mice / 中国中药杂志

<p><b>OBJECTIVE</b>To study on the effect of acteoside on learning and memory of dementia mice.</p><p><b>METHOD</b>Mice were orally administered with acteoside for 10 days. Scopolamine was used to establish the acquired learning disability in mice. Their learning and memory were detected with a behavioral experiment (step-down test). After the behavior test, corticocerebral and hippocampus tissues of mice were detected with biochemical indexes, including GSH-Px, T-SOD, MDA, TChE and contents of protein in brain tissues.</p><p><b>RESULT</b>Mice were administered with acteoside for 10 d in advance to alleviate the acquired learning disability induced by scopolamine. Compared with the model group, acteoside increased the latency period in the step-down test and reduced error times. Besides, acteoside increased the activity of GSH-Px, T-SOD, TChE and protein content in their brain tissues, but decreased MDA content.</p><p><b>CONCLUSION</b>Acteoside can significantly alleviate the acquired learning disability in mice induced by scopolamine. Its mechanism may be related with its effect of inhibiting the generation of free radicals in mice and improving the function of the central cholinergic system.</p>