Rotundic acid(RA),an ursane-type pentacyclic triterpene acid isolated from the dried barks of Ilex rotunda Thunb.(Aquifoliaceae),possesses diverse bioactivities.To further study its pharmacokinetics,a simple and sensi...Rotundic acid(RA),an ursane-type pentacyclic triterpene acid isolated from the dried barks of Ilex rotunda Thunb.(Aquifoliaceae),possesses diverse bioactivities.To further study its pharmacokinetics,a simple and sensitive liquid chromatography with triple quadrupole mass spectrometry(LC-QqQ-MS/MS)method was developed and validated to quantify RA concentration in rat plasma and tissue using etofesalamide as an internal standard(IS).Plasma and tissue samples were subjected to one-step protein precipitation.Chromatographic separation was achieved on a ZORBAX Eclipse XDB-C_(18) column(4.6mm×50mm,5μm)under gradient conditions with eluents of methanol:acetonitrile(1:1,V/V)and 5mM ammonium formate:methanol(9:1,V/V)at 0.5mL/min.Multiple reaction monitoring transitions were performed at m/z 487.30→437.30 for RA and m/z 256.10→227.10 for IS in the negative mode.The developed LC-QqQ-MS/MS method exhibited good linearity(2-500 ng/mL)and was fully validated in accordance with U.S.Food and Drug Administration bioanalytical guidelines.Dose proportionality and bioavailability in rats were determined by comparing pharmacokinetic data after single oral(10,20,and 40mg/kg)and intravenous(10mg/kg)administration of RA.Tissue distribution was studied following oral administration at 20mg/kg.The results showed that the absolute bioavailability of RA after administration at different doses ranged from 16.1%to 19.4%.RA showed good dose proportionality over a dose range of 10-40 mg/kg.RA was rapidly absorbed in a dose-dependent manner and highly distributed in the liver.In conclusion,this study is the first to systematically elucidate the absorption and distribution characteristics of RA in rats,which can provide additional information for further development and evaluation of RA in drug metabolism and pharmacokinetic studies.展开更多
Objective To study the chemical constituents from Millettia speciosa. Methods The compounds were isolated and purified by silica gel, Sephadex LH-20, ODS column chromatography, and recrystallization. The structures we...Objective To study the chemical constituents from Millettia speciosa. Methods The compounds were isolated and purified by silica gel, Sephadex LH-20, ODS column chromatography, and recrystallization. The structures were identified using physicochemical and spectral data. Results Thirteen compounds were isolated from M. speciosa and identified as docosanoic acid （1）, tetracosane （2）, octadecane （3）, hexacosanoic acid （4）, β-sitosteroi acetate （5）, β-sitosterol （6）, syringin （7）, maackiain （8）, formononetin （9）, ψ-baptigenin （10）, rotundic acid （11）, pedunculoside （12）, and daucosterol （13）. Conclusion Compounds 5, 7, and 10-12 are obtained from this plant for the first time.展开更多
基金supported by CAMS Innovation Fund for Medical Sciences(Grant No.:2019-I2M-5e020)the National Natural Science Foundation of China(Grant No.:81503154)the National Major Scientific and Technological Special Project for Significant New Drugs Development(Grant No.:2017ZX09101002-001-005).
文摘Rotundic acid(RA),an ursane-type pentacyclic triterpene acid isolated from the dried barks of Ilex rotunda Thunb.(Aquifoliaceae),possesses diverse bioactivities.To further study its pharmacokinetics,a simple and sensitive liquid chromatography with triple quadrupole mass spectrometry(LC-QqQ-MS/MS)method was developed and validated to quantify RA concentration in rat plasma and tissue using etofesalamide as an internal standard(IS).Plasma and tissue samples were subjected to one-step protein precipitation.Chromatographic separation was achieved on a ZORBAX Eclipse XDB-C_(18) column(4.6mm×50mm,5μm)under gradient conditions with eluents of methanol:acetonitrile(1:1,V/V)and 5mM ammonium formate:methanol(9:1,V/V)at 0.5mL/min.Multiple reaction monitoring transitions were performed at m/z 487.30→437.30 for RA and m/z 256.10→227.10 for IS in the negative mode.The developed LC-QqQ-MS/MS method exhibited good linearity(2-500 ng/mL)and was fully validated in accordance with U.S.Food and Drug Administration bioanalytical guidelines.Dose proportionality and bioavailability in rats were determined by comparing pharmacokinetic data after single oral(10,20,and 40mg/kg)and intravenous(10mg/kg)administration of RA.Tissue distribution was studied following oral administration at 20mg/kg.The results showed that the absolute bioavailability of RA after administration at different doses ranged from 16.1%to 19.4%.RA showed good dose proportionality over a dose range of 10-40 mg/kg.RA was rapidly absorbed in a dose-dependent manner and highly distributed in the liver.In conclusion,this study is the first to systematically elucidate the absorption and distribution characteristics of RA in rats,which can provide additional information for further development and evaluation of RA in drug metabolism and pharmacokinetic studies.
基金Natural Science Foundation of Guangdong Province (No.9151040701000037)
文摘Objective To study the chemical constituents from Millettia speciosa. Methods The compounds were isolated and purified by silica gel, Sephadex LH-20, ODS column chromatography, and recrystallization. The structures were identified using physicochemical and spectral data. Results Thirteen compounds were isolated from M. speciosa and identified as docosanoic acid （1）, tetracosane （2）, octadecane （3）, hexacosanoic acid （4）, β-sitosteroi acetate （5）, β-sitosterol （6）, syringin （7）, maackiain （8）, formononetin （9）, ψ-baptigenin （10）, rotundic acid （11）, pedunculoside （12）, and daucosterol （13）. Conclusion Compounds 5, 7, and 10-12 are obtained from this plant for the first time.
