Comparative pharmacokinetics of baicalin and geniposide in juvenile and adult rats after oral administration of Qingkailing Granules

Objective:To explore the effect of age on Qingkailing Granules disposition by comparing the pharmacoknetics of geniposide and baicalin in juvenile and adult rats.Methods:A simple and rapid LC-MS/MS method was developed and validated to simultaneously determine geniposide and baicalin in rat plasma after a simple protein precipitation.The analytes were separated on an Agilent ZORBAX Extend-C18 column.The mobile phase consisted of acetonitrile and water with 0.1%(volume percent)formic acid at a flow rate of 0.6 mL/min.The ionization was conducted using an ESI source in negative ion mode.Multiple reaction monitoring was used for quantification at transitions of m/z 445.0→m/z 268.9 for baicalin,m/z 433.2→m/z 225.0 for geniposide,m/z 431.0→m/z341.0 for vitexin(IS).Juvenile and adult rats were administrated Qingkailing Granules(3 g/kg)orally.Plasma concentrations of baicalin and geniposide were determined by LC-MS/MS.Results:The linear ranges of the analytes were 1-1000 ng/mL for baicalin and 2-2000 ng/mL for geniposide.The method was successfully applied to compare the pharmacokinetics of the analytes between juvenile and adult rats after oral administration of Qingkailing Granules.AUC was bigger in adult rats,while t1/2 was longer in juvenile rats.Conclusion:These results suggested that the absorption and elimination of baicalin and geniposide in juvenile rats was lower than that in adult rats.Additional attention should be paid to the pharmacokinetic difference when Qingkailing Granules were used in children.

Association of the retinol to all-trans retinoic acid pathway with autism spectrum disorder

Background Autism spectrum disorder(ASD)is a complex group of neurodevelopmental disorders.Research has highlighted a close association between the retinoic acid(RA)signaling pathway and ASD.This study investigates alterations in the vitamin A(VA,retinol)to RA metabolic pathway in children with ASD and speculates on the underlying reasons for these changes.We propose a subtype characterized by downregulated RA signaling in ASD,laying the groundwork for precise diagnosis and treatment research.Methods We included 489 children with ASD and 280 typically developing(TD)children.Those with ASD underwent evaluations of core symptoms and neuro-developmental levels,which were conducted by professional developmental behavior physicians using assessment scales.Serum VA and all-trans RA(atRA)levels were determined by high-performance liquid chromatography and ultra-high-performance liquid chromatography–tandem mass spectrometry.The expression levels and concentrations of enzyme molecules such as retinol dehydrogenase 10 were assessed using quantitative polymerase chain reaction and enzyme-linked immunosorbent assay.Results Children with ASD exhibited reduced serum atRA,accompanied by a downregulation of atRA synthesis enzymes.The reduction in serum atRA levels was linked not only to VA levels but also to the aberrant expression of metabolic enzymes responsible for atRA.Furthermore,the serum atRA levels in children with ASD were more strongly correlated with core symptoms and neurodevelopmental levels than VA levels.Conclusion Children with ASD exhibited a dual regulation of reduced serum atRA levels,influenced by both VA levels and abnormal expression of atRA metabolic enzymes.