ABSTRACT
Objective: To investigate the effect and the mechanism of Astragalus membranaceus (Huangqi in Chinese, HQ) extract on the intestinal absorption of six alkaloids of Aconitum carmichaelii (Fuzi in Chinese, FZ) in rats with spleen deficiency and provide novel insights into the application of HQ on modulating intestinal barrier. Methods: Four-week-old male Sprague-Dawley rats were fed with Xiaochengqi Decoction to induce the spleen deficiency model for 40 d. Single-pass intestinal perfusion model were used to study the effects of HQ extract on the absorption of alkaloids. Protein expression and mRNA levels of MRP2 and BCRP and tight junction proteins (TJ, including Claudin-1, Occludin and ZO-1) were measured using Western blot and real-time PCR, respectively. The location and expression of TJ protein was also investigated by the immunofluorescence method. Results: Compared with the normal group, the protein expression of MRP2, BCRP and TJ proteins in the model group were significantly down-regulated. After oral administration of HQ, the alkaloid absorption in intestinal villi was inhibited, MRP2, BCRP and TJ proteins were up-regulated, the green fluorescence staining of Claudin-1, Occludin, and ZO-1 was enhanced, and a thick layer of mucus was deposited on the surface of the epithelium of the intestinal cavity. Conclusion: HQ as an intestinal barrier modulator improves the physiological changes of the intestinal environment of spleen deficiency to reduce the absorption of toxic components, leading to a decrease in the absorption of drug-like molecules.
ABSTRACT
OBJECTIVE： To study the effects of Aconitum carmichaelii water extract on the expression of 3 kinds of efflux transporters and 3 kinds of tight junction proteins as well as their genes in duodenum tissues of rats. METHODS： Thirty-two SD male rats were randomly divided into normal group， A. carmichaelii water extract low-dose， medium-dose and high-dose groups [0.45， 0.9， 1.8 g/（kg·d）， by crude drug]， with 8 rats in each group. They were given water and relevant liquid 0.1 mL/kg intragastrically for consecutive 7 d. After last administration， the duodenal segments of rats were collected. Western blotting assay was used to detect the expression of efflux transporters as P-glycoprotein （P-gp）， breast cancer resistance protein （Bcrp）， multidrug resistance protein 2 （Mrp2） as well as tight junction proteins as Claudin-1， Occludin and ZO-1. mRNA expression of 6 kinds of proteins relevant gene were determined by qRT-PCR respectively. RESULTS： Compared with normal group， the protein expression of P-gp， Mrp2， Bcrp， Claudin-1， Occludin and ZO-1 in duodenum of rats were increased significantly in A. carmichaelii water extract groups （P＜0.01）. mRNA expression of P-gp in A. carmichaelii water extract groups， mRNA expression of Bcrp in A. carmichaelii water extract low-dose and high-dose groups as well as mRNA expression of Claudin-1 in A. carmichaelli water extract medium-dose and high-dose groups were increased significantly， with statistical significance （P＜0.05 or P＜0.01）. There was no statistical significance in mRNA expression of other genes （P＞0.05）. CONCLUSIONS： A. carmichaelii water extract can up-regulate the expression of 3 kinds of efflux transporters and 3 kinds of tight junction proteins at the level of mRNA and/or protein， thus may interact with other substrates of the aforementioned efflux transporters and drugs with cell bypass pathway as the main transport pathway. In clinical practice， adjustment of dosage may be considered in drug combination.
ABSTRACT
OBJECTIVE： To provide reference for the clinical use and dosage form development of Strychnos nuxvomica. METHODS： The prescriptions containing S. nuxvomica were collected and sorted from the Dictionary of Traditional Chinese Medicine Prescription， and then formula name， prescription source， name of treatment disease， composition， usage and dosage， medication route were input into Access 2010 and database was established. According to the usage， these prescriptions were divided into internal use and external use， and the frequencies of diseases treated by internal/external use prescriptions were counted respectively. Apriori algorithm of SPSS Modeler 18.0 software was used to analyze the drug combination rule of compound prescription containing S. nuxvomica. RESULTS： A total of 78 prescriptions were included， of which 42 were oral prescriptions， 33 were external prescriptions and 3 were both oral and external prescriptions. Internal prescriptions were used to treat diseases such as atrophy-flaccidity disease， arthralgia， hemorrhoids， anal fistula， bones and muscles pain. The external prescriptions were mainly used to treat skin diseases， tumors， lump. Internal and external prescriptions could treat sore， injuries and fractures. In internal prescriptions， S. nuxvomica was often compatible with Boswellia carterii， myrrha， Daemonorops draco， Manis pentadactyla， pyritum， Angelica sinensis， Ephedra sinica， Aconitum kusnezoffii. In external prescriptions， S. nuxvomica was often compatible with Radix Paeoniae， Rehmannia glutinosa， Phellodendron chinense， Coptis chinensis， Scutellaria baicalensis， Angelica sinensis， Angelica dahurica， Buthus martensii. Most of S. nuxvomica were used after processing， and mainly took sesame oil as an auxiliary material （77.97％）. CONCLUSIONS： Diseases treated with the prescriptions containing S. nuxvomica can be classified into three types of diseases， i.e. polymyalgia rheumatica and paralysis， bruise and bone fracture， carbuncle and stubbornness tinea. In external prescriptions， S. nuxvomica is often compatible with drug for clearing heat and drying dampness， cooling blood and activating blood， and relieving pain. In internal prescriptions， S. nuxvomica is often compatible with the agents for blood-activating and stasis-resolving medicinal. In addition， the processing of S. nuxvomica with sesame oil is an important measure to ensure its safety.
ABSTRACT
<p><b>OBJECTIVE</b>To study the effect of extractive Angelica dahutica on intestinal absorption of puerarin, the mechanism of the absorption enhancement of A. dahutica was investigated, providing a new thread of combinations of the Chinese herbal drugs.</p><p><b>METHOD</b>Everted intestinal sac and in situ single pass perfusion were used to study the effect of gut absorption of puerarin solution containing the extractive A. dahurica as well as the influence of P-gp on the absorption of puerarin, and explore weather the extractive A. dahutica can enhance the absorption of puerarin and the mechanism of absorption of puerarin.</p><p><b>RESULT</b>The puerarin could be absorbed at all of four intestinal segments with increaing absorption amount perunit as follows: ileum > colon > jejunum > duodenum. The absorption of puerarin in jejunum was significantly increased with the extractive A. dahutica in situ single pass perfusion of jejunum. The apparent permeability coefficient (Papp) and absorption rate constant (Ka) of puerarin in the jejunum were descreased gradually with higher concentrations, and the Papp with the Ka of jejunum solution containing the P-gp inhibitor of verapamil were increasing respectively 2.49, 2.60 (P < 0.001) than only the jejunum solution in absorption. The absorption of jejunum in pH 5.0, 6.8 were better than it in pH 7.4.</p><p><b>CONCLUSION</b>The mechanism of absorption of jejunum was active absorption and was effected by P-gp. The extrative A. dahurica can enhance the absorption of the jejunum.</p>
Subject(s)
Animals , Male , Rats , Angelica , Hydrogen-Ion Concentration , Intestinal Absorption , Isoflavones , Pharmacokinetics , Jejunum , Metabolism , Plant Extracts , Pharmacology , Pueraria , Chemistry , Rats, Sprague-DawleyABSTRACT
This study is to investigate the effect of ferulic acid on learning and memory impairments of vascular dementia (VD) rats and its mechanism of action. VD rats model was replicated by permanent bilateral common carotid artery occlusion (2VO). The learning and memory capability of VD rats was evaluated by Morris water maze. The activity of acetylcholinesterase (AChE) and superoxide dismutase (SOD) and the content of glutamic acid (Glu) and malondialdehyde (MDA) in hippocampus of VD rats' brain were determined, separately. The results showed that ferulic acid could alleviate learning and memory deficits of VD rats significantly. Ferulic acid was found to inhibit the activity of AChE and increased the activity of SOD in rat hippocampus. In addition, ferulic acid could also decrease the content of Glu and MDA in rat hippocampus. These results suggested that ferulic acid could alleviate VD rats' learning and memory deficits, which might be due to antioxidation, the improvement of cholinergic system in brain, or the inhibitory of nerve injury by excitatory amino acids.
ABSTRACT
A mathematical model of microwave drying kinetics based on Fick's second diffusion law was established and and the influence of microwave drying on ferulic acid (FA) and hydrosafflower yellow A (HSYA) in Shuxiong prescription was studied. The proposed model has been verified by using experimental data from microwave drying of Shuxiong prescription. By increasing the microwave output power (500-650 W) and the sample amount (15-60 g), the diversion rate of FA and HSYA changed. In order to determine the kinetic parameters, the drying data were fifed to various models based on the ratios of differences between the initial and final moisture contents and equilibrium moisture content versus drying time. The activation energy was calculated using an exponential expression based on Arrhenius equation. The relationship between the drying rate constant and effective moisture diffusivity was also estimated, and it showed linear.
Subject(s)
Coumaric Acids , Metabolism , Desiccation , Methods , Diffusion , Drugs, Chinese Herbal , Chemistry , Metabolism , Kinetics , Microwaves , Models, Theoretical , Pharmaceutical Preparations , Chemistry , MetabolismABSTRACT
To explore the mechanism of the absorption enhancement of Angelica dahurica extract (Ade), the absorption mechanism of baicalin in the Scutcllaria water extraction as well as the effect of Angelica dahurica extract on absorption of baicalin were investigated. In order to determine the main absorption site, everted intestinal sac model was used to study the effect of Angelica dahurica extract on the absorption of baicalin at duodenum, jejunum, ileum and colon. In situ single pass intestinal perfusion model was performed to study the absorption of various concentrations of baicalin and the effect of Angelica dahurica extract on the absorption of baicalin at the main absorption site. To authenticate the consequence of perfusion by getting the blood from the hepatic portal vein and determine the concentration of the baicalin in the blood. The result showed that baicalin could be absorbed at all of the four intestinal segments with increasing absorption amount per unit as follows: ileum > colon > jejunum > duodenum. The absorption ofbaicalin in the duodenum significantly increased with Angelica dahurica extract, thus, duodenum was chosen to be the studying site. Apparent permeability values (Papp) and absorption rate constant (Ka) of baicalin in the duodenum increased gradually with higher concentrations. When the concentration of baicalin rises to a certain degree, the absorption increase had a saturable process, the absorption of baicalin may be an active transportation. Baicalin may be not a substrate of P-gp as verapamil which had not significantly affected the Papp and Ka of baicalin. The absorption of baicalin in the duodenum significantly increased (P < 0.01) in the two models with Angelica dahurica extract and the concentration of baicalin in the blood from the hepatic portal vein showed that the Angelica dahurica extract can increase the absorption of baicalin.
ABSTRACT
Objective To set up the preparing technology of paeonol-?-cyclodextrin (?-CD) inclusion compound. Methods The inclusion conditions were optimized by using the orthogonal test for the compound formation of paeonol-?-CD, taking the rate of recovery and inclusion as the criteria. Three different including methods or equipments were adopted and compared with the documentary method. The effect of pH and HPMC on the inclusion of paeonol with ?-CD was investigated. Results The inclusion rate and recovery rate were more than 80% and 75%, respectively following the optimized saturated solution method, i.e. resolving 1 part of paeonol in 6 parts of absolute alcohol, then slowly adding the solution into the saturated solution containing 10 parts of ?-CD in 1/30 V/h at 45 ℃, keeping stirring until the inclusion compound formation. An A_L-type phase solubility curve was obtained. The difference of apparent stability constant is significant under different pH values and different HPMC contents. Conclusion The technology and procedure are relative simple and high efficient, which are applied for the industrialization. HPMC (0.05%) in pH 2.5 is shown to increase the inclusion of paeonol with ?-CD.