New dammarane triterpenoid saponins from the leaves of Cyclocarya paliurus
Abstract Three new dammarane triterpenoid saponins, cyclocariosides O-Q (1–3), were isolated from the ethanolic extracts of the leaves of Cyclocarya paliurus. The structures of these compounds were elucidated by spectroscopic methods.
Triterpenoids from Cyclocarya paliurus that Enhance Glucose Uptake in 3T3-L1 Adipocytes
Four previously undescribed compounds, including three rarely occurring seco-dammarane triterpenoid glycosides and a pentacyclic triterpenic acid, were isolated from a 70% ethanol extract of the leaves of Cyclocarya paliurus (Juglandaceae), along with eleven known triterpenoids. Their structures were determined by spectroscopic techniques, including 2D NMR and HRESIMS, as well as chemical methods. Among them, several triterpenoids enhanced insulin stimulated glucose uptake in both 3T3-L1 adipocytes and C2C12 myotubes. Furthermore, compound 1 dose-dependently increased glucose uptake through activating AMP-activated protein kinase (AMPK)-p38 pathway. Collectively, triterpenoids from C. paliurus could be developed as insulin sensitizers, which might have therapeutic potential for insulin resistance and hyperglycemia.
Pharmacokinetics of Mivacurium Isomers and Their Metabolites in Healthy Volunteers after Intravenous Bolus Administration
Background Previous studies report the pharmacokinetics of mivacurium isomers after an infusion using venous blood sampling. Although the extent of the mivacurium arterial‐venous gradient is not known, the sampling site is likely to influence mivacurium pharmacokinetic parameters because the drug is rapidly metabolized as it traverses the circulation. The objectives of this study were (1) to determine the pharmacokinetics of mivacurium isomers in healthy persons after intravenous bolus administration using intensive arterial blood sampling, and (2) to characterize the formation and elimination of mivacurium metabolites in human plasma. Methods Eight persons classified as American Society of Anesthesiologists physical status 1 or 2 who were scheduled to undergo elective surgery under balanced anesthesia received 0.15 mg/kg mivacurium chloride as an intravenous bolus. Arterial blood samples were collected every 10 s during the first 2 min and at frequent intervals for 4 h thereafter. Plasma concentrations of mivacurium isomers and their metabolites were determined by two stereoselective high‐performance liquid chromatographic methods coupled with fluorometric detection and noncompartmental pharmacokinetic parameters. Results Mean elimination half‐lives of the trans‐trans, cis‐trans, and cis‐cis isomers were 2.4, 2, and 28.5 min, respectively, with corresponding mean plasma clearances of 29.2, 45.7, and 6.7 ml [center dot] min‐1 [center dot] kg‐1. The volumes of distribution at steady state of the trans‐trans, cis‐trans, and cis‐cis isomers were 0.047, 0.054, and 0.189 l/kg, respectively. Plasma concentrations of monoester and alcohol metabolites peaked 25 s (median) after mivacurium injection, with half‐lives in the range of 90 min, except for the cis alcohol metabolite, which was only negligibly and transiently formed. Conclusions Substantial hydrolysis of mivacurium isomers by cholinesterases was confirmed by the rapid appearance of mivacurium metabolites in plasma. The intensive arterial sampling proved to be critical for the trans‐trans and cis‐trans isomers because the area under the curve between 0 and 2 min accounted for 75% and 86% of the total, respectively.