Effect of Drynaria total flavonoids on the expression of NMDAR1,GluR2 and CaMKⅡin the brain of hydrocortisone model mice

Objective:To study the effect of total flavonoids of Rhizoma Drynariae on the expression of NMDAR1,GluR2 and CAMKⅡprotein in model mice of kidney deficiency induced by exogenous glucocorticoid hydrocortisone and its mechanism.Methods:Kunming(KM)mice were randomly divided into the blank group,the hydrocortisone model group,the anti-brain failure capsule group,the Drynaria total flavonoids group,the Drynaria total flavonoids+ER blocker group,with 15 animals in each group.Except for the blank group,all groups were injected intramuscularly with hydrocortisone(25 mg·kg^(-1)·d^(-1))to create models.The water maze experiment,new object recognition experiment and platform jump experiment were used to conduct behavioral investigations.HE staining was used to observe the pathological changes of mouse hippocampus,and Western blotting detected the expressions of NMDR1,GluR2 and CAMKⅡproteins in the hippocampus of mice in each group.Results:The experimental results showed that compared with the model group,the learning and memory ability of the mice in the Drynaria fortunei total flavonoids group was significantly improved,and the difference was statistically significant(P<0.01),the expression of NMDR1 and GluR2 proteins in the hippocampus of the mice was significantly increased(P<0.01),and the level of CAMKⅡprotein significantly decreased(P<0.01).Conclusion:The total flavonoids of Rhizoma Drynariae may enhance the expression of NMDAR1 and GluR2 protein in the brain of hydrocortisone model mice through ER,reduce the expression of CAMKⅡprotein,and alleviate the damage to the brain tissue of the model mice and play a neuroprotective effect.

Population Pharmacokinetics of Naringin in Total Flavonoids of Drynaria Fortunei(Kunze) J.Sm.in Chinese Women with Primary Osteoporosis

Objective： To evaluate the effect of covariates on the pharmacokinetic profiles of naringin in the total flavonoids of Drynaria fortunei （Kunze） J. Sin. in the Qianggu Capsule （强骨胶囊） by evaluating Chinese women with primary osteoporosis. Methods： A total of 98 female patients from the communities of Jingshan, Beixinqiao, Jiaodaokou, Chaoyangmen, and Donghuamen in Beijing, China, aged 40 to 80 years, were included in this study. Blood samples were collected before and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 h after a single oral dose of Qianggu Capsule. The concentration in blood samples from 32 patients before and 0.5, 1, 2, 3, and 4 h after drug administration were determined by liquid chromatography-tandem mass spectrometry （LC-MS/MS） method, and full set of pharmacokinetic data was analyzed with nonlinear mixed-effect modeling （NONMEM） software. The mean of population parameters clearance （C1）, central distribution volume （V）, absorption rate constant （Kal）, inter-compartmental clearance （C2）, peripheral distribution volume （V2） were set as parameters and estimated through base model, covariate model, and final model. Age, height, weight, blood urea nitrogen （BUN）, serum creatinine （Scr）, alanine transaminase （ALT）, aspartate transaminase （AST）, hyperlipidemia, Liver （Gan） Kidney （Shen） yin insufficiency （GSYI）, Kidney （Shen） yang insufficiency （SYI） were set as covariates. Results： The relationships between these parameters and covariates were analyzed. The results showed that C1 was the main parameter influenced by the selected covariates among the population parameters, and the relationships between the covariates and C1 were analyzed, among the selected covariates hyperlipidemia was identified as significant covariate of C1. Conclusion： The pharmacokinetic behaviors of naringin are altered with hyperlipidemia in Chinese women with primary osteoporosis.

Effect of naringenin in Qianggu capsule on population pharmacokinetics in Chinese women with primary osteoporosis

OBJECTIVE:To characterize naringenin(NAR) population pharmacokinetics(PPK) in Chinese women with primary osteoporosis.METHODS:Ninety-eight female patients with primary osteoporosis from the Jingshan,Beixinqiao,Jiaodaokou,Chaoyangmen,and Donghuamen communities in Beijing,China,aged 40 to 80 years,received oral Qianggu capsules(250 mg).Blood samples were collected before and at 0.5,1,2,3,4,6,8,10,12,and 24 h after administration.The concentration of NAR in the blood samples was measured using high performance liquid chromatography-tandem mass spectrometry.PPK analyses were performed with nonlinear mixed-effect modeling software(version 7.1.2,PsN3.2.12).The clearance(C1),central distribution volume(V),absorption rate constant(Ka1),peripheral distribution volume(VII),and inter-compartmental clearance(CLII) were set as parameters and estimated by the base model,covariate model,and final model.Kidney-Yang deficiency[Shenyangxu(SYAX)]and liver-kidney-Yin deficiency(Ganshenyinxu) are patterns of symptoms in Traditional Chinese Medicine that were set as covariates,along with age,height,blood urea nitrogen,serum creatinine,alanine transaminase,aspartate transaminase,and hyperlipidemia.Both stepwise forward and backward procedures were accomplished to build models.The final model was evaluated by internal and external validation,visual predictive check,bootstrap,and leverage analysis.RESULTS:A one compartment open model with first order degradation was the best fitted to the concentration-time profiles following oral administration of NAR.The mean of population parameters of the final model,C1,SYAX on C1,V,Ka1,CLII,and VII,were measured to be 37.6 L/h,0.427 L,123 L/h,0.12/h,0.3056,and 1.446,respectively.Inter-individual variability was estimated and SYAX was identified as a significant covariate.CONCLUSION:The population pharmacokinetic model described in this study could effectively characterize the pharmacokinetic profile of NAR following administration of a single dose of oral Qianggu capsules in Chinese women with primary osteoporosis.Among the tested covariates,only SYAX was a significant factor.