ABSTRACT
Objective: To prepare and evaluate bionic enzymatic Epimedium flavonoids-loaded enteric-coated capsules, composed of Epimedium flavonoids as drug, snail enzyme as hydrolase and common formulation accessories, which is in favor of in vivo real-time enzymolysis and real-time absorption of Epimedium flavonoids. Methods: The UV method and single factor experiment were applied to investigating the effects of key factors such as filling agents species and dosage, disintegrating agents species and dosage, wetting agents species and drying temperature on the cumulative release degree of Epimedium flavonoids. Response surface method was used to optimize the prescription for bionic enzymatic Epimedium flavonoids-loaded enteric-coated capsules, and the enzymatic process of the four Epimedium flavonoids (icariin and epimendin A, B, C) was also evaluated by HPLC. Results: The optimal formulation for the bionic enzymatic Epimedium flavonoids-loaded enteric-coated capsules was composed of 100 mg Epimedium flavonoids extract, 68 mg snail enzyme, 65 mg α-lactose, and 11.7 mg low-substituted hydroxypropyl cellulose. This enteric-coated capsules showed a cumulative Epimedium flavonoids release rate of 85.43% within 45 min in simulated intestinal fluid and a complete enzymolysis within the intestine emptying time (3-6 h). Conclusion: The bionic enzymatic Epimedium flavonoids-loaded enteric-coated capsules show an advantage in improving hydrolysis and anti-osteoporosis efficacy of Epimedium flavonoids, providing some research ideas for improving the oral bioavailability of other flavonoids.
ABSTRACT
To study pharmacokinetic characteristics of epimedin A, B, C and icariin after intermuscular administration of Chuankezhi injection to rat. The established RRLC-MS/MS method was applied for simultaneous determination of four analytes in rat plasma and calculating their pharmacokinetic parameters. As a result, each analyte showed a good linear relationship in the concentration range of 1-1 000 μg•L⁻¹.The intra-day precise was 96.9%-107.5% with RSD<5.99%, inter-day precise was 92.3%-105.0% with RSD<10.16%. The relative recovery of four analytes was 88.1%-101.1% with RSD<7.9% and their absolute recovery was 72.0%-86.6% with RSD<6.3%. After intermuscular administration of Chuankezhi injection, the plasma concentration of four flavonoid glycosides rapidly arose to peaks at about 10 min, and then quickly declined in rat. Tmax of epimedin A, B, C and icariin was 0.21, 0.19, 0.16 and 0.49 h, respectively, and their mean elimination half-life(t1/2z) was 0.60, 0.62, 0.47 and 0.49 h. The established method was validated to be sensitive, rapid and specific for determination of the four analytes. Serum concentration of 4 species of epimedium flavonoids in Chuankezhi injection was low, and their absorption and elimination seem quickly, displaying similar pharmacokinetic characteristics in this study.
ABSTRACT
The fried method with suet oil, which can strengthen the effect of Epimedii Folium in warming kidney and enhancing yang, has been widely used in the processing of Epimedii Folium in traditional Chinese medicine. In this paper, we adopted hydrocortisone-induced kidney-yang deficiency rat models, and took physical signs, serum testosterone, corticosterone levels and histopathological examination of rats as indictors to systematically study the synergistic effect of suet oil in warming kidney and enhancing yang of fried Epimedii Folium in the dosage form of self-assembled micelles. Drugs were given orally, and compared with model group, indicating normal physical signs and biochemical indicators, and significant alleviation in disorder of hypothalamic-pituitary-adrenal-thymus (HPAT) axis suppression. All these experimental results indicated that both Epimedium flavonoids and its self-assembled micelles, especially the processed self-assembled micelles of Epimedii Folium, showed the significant effects in warming kidney and enhancing yang, which might be correlated with the regulation of the disorder of HPAT axis suppression and the improvement of major pathological conditions of testicular gonadal tissues. This discovery can further reveal the synergistic effect and mechanism of processing material suet oil on Epimedii Folium.
ABSTRACT
Objective:To uncover the molecules and signal transduction underlying apoptosis in lymphocytes in old rats.Methods:The rats were grouped into three of old rats control,young rats control,EF-treated group,and studied the gene expression in genome-wide scale with genechip.Results:Compared to young rats control,pro-apoptotic genes were up-regulated and anti-apoptotic genes were down-regulated in old rats.And pro-proliferation genes were down-regulated,the anti-proliferation genes were regulated reversely.Furthermore,a number of genes involved in signal transduction in immune activation and immune response showed lower expression level.But in EF-treated group,pro-apoptotic genes such as Caspase1、Caspase2、Caspase3、Caspase6、CalpainⅡ、Cathepsin S、Dnase ?、PKCdelta,and anti-proliferation genes including Rb were predominantly down-regulated.Anti-apoptotic genes such as Cathepsin B、Mtal、NF-kappa B、Notch,and pro-proliferation genes including c-Fos、c-Myc、c-Jun、PCNA、A-raf;CyclinG-associated kinase were regulated reversely.Especially many genes mediating apoptosis signal including CD2、CD3、CD5、TCR、IL-2、IL-2R(CD25)、CD28、CTLA4 were up-regulated.Conclusion:By a novel mean including up-regulation of anti-apoptotic and down-regulation of pro-apoptotic gene expression,up-regulation of pro-proliration and down-regulation of anti-proliferation gene expression,the normal lymphocyte function in old rats was reconstructed.Additionally EF can coordinate TCR/CD3、CD28、CTLA4、TGF?、IL-2R-mediated signal to reach its anti-apoptotic effects on lyphocytes in old rats. [