Amelioration of Cognitive Dysfunction in Diabetic Rats by Jianpi Qinghua Prescription / 中国实验方剂学杂志

ObjectiveTo explore the amelioration of cognitive dysfunction in diabetes mellitus （DM） by Jianpi Qinghua prescription （JPQH） based on type 2 diabetes （T2DM） model rats. MethodFifty healthy male Wistar rats of SPF grade were randomly divided into control group （n=10） and experimental group （n=40）. The rats in the control group were fed conventionally， while those in the experimental group were fed on a high-sugar， high-fat diet for six weeks and administered with streptozotocin （STZ） for the induction of the DM model. The model rats were randomly divided into model group， sitagliptin group （1.2 g·L-1）， pioglitazone group （0.8 g·L-1）， and JPQH group （1.3 g·mL-1）， with 10 rats in each group. After six weeks of drug intervention， the changes in body weight， blood glucose， and other related indexes of each group were recorded. Enzyme-linked immunosorbent assay （ELISA） was performed to detect the levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6） in the peripheral blood and brain. The Morris water maze test was used to evaluate the cognitive function in rats. Hematoxylin-eosin （HE） staining was used to observe the pathological morphology of the hippocampal CA region. The amyloid β-protein 40 （Aβ40） level was detected by immunohistochemistry. The protein expression of t-tau and p-tau in hippocampal neurons of rats was detected by Western blot. ResultCompared with blank group， the body weight of model group was significantly decreased （P<0.05）， blood glucose level was significantly increased （P<0.01）， inflammatory cytokines TNF-α and IL-1β were increased （P<0.05）， learning and spatial ability were significantly decreased （P<0.01）， the arrangement of hippocampal cells was loose and disordered， and the intercellular space was significantly increased. The number of cells decreased significantly， and the expression of Aβ40 increased significantly. and increased t-tau and p-tau protein content in the hippocampus （P<0.01）. Compared with model group， the JPQH group showed reduced blood glucose （P<0.01）， decreased TNF-α and IL-1β levels in the peripheral blood and cerebrospinal fluid （P<0.05）， a downward trend of IL-6 without a statistical difference， improved learning and spatial memory ability （P<0.01）， densely arranged cells in the hippocampal CA1 area， increased cell number， reduced Aβ40 expression， and decreased p-tau protein expression （P<0.05）. ConclusionJPQH can prevent cognitive dysfunction in DM by reducing inflammatory factor levels， decreasing neurotoxicity caused by Aβ40 deposition， and inhibiting hyperphosphorylation of tau protein in DM rats.

Study on effect of curcumin in inhibiting proliferation of multidrug resistant liver cancer HepG2/ADM cells and its mechanism / 重庆医学

Objective To observe the inhibitory effect of curcumin on the proliferation of multidrug resistance liver cancer line HepG2/ADM cells and to explore its mechanisms.Methods HepG2/ADM cells were prepared and cultured in vitro,and treated by different concentrations (5,10,20,40 μmol/L) of curcumin for 24,48,72 h respectively.The effect of curcumin on proliferation of HepG2/ADM cells was measured by CCK-8 reagent;the concentration of intracellular rhodamine-123 (Rh-123) and adriamycin (ADM) were determined by flow cytometry;the level change of intracellular mdr-1 mRNA in each group was determined by RT-PCR,the P-gp protein level was detected by Western blot.Results Compared with the blank control and DMSO group,curucmin had more obvious inhibitory effect on HepG2/ADM cells proliferation (P＜0.05),and could more remarkably inhibit the intracellular Rh-123 excretion(P＜0.05).The RT-PCR and Western blot results showed that curcumm more significantly decrease the mdr-1 mRNA and P-gp protein levels in dose-time dependent manner (P＜0.05).Conclusion Curcumin could significantly inhibit the proliferation of multidrug-resistant HepG2/ADM cells,and its mechanism may be related with inhibiting mdr-1 gene expression and its encoded P-gp protein level,which are closely related with MDR.

Preparation of sinomenine hydrochloride delayed-onset sustained-release tablets / 中国中药杂志

<p><b>OBJECTIVE</b>To prepare sinomenine hydrochloride delayed-onset sustained-release tablets.</p><p><b>METHOD</b>The tablets containing sinomenine hydrochloride were prepared by dry-compression coating technique with the ratio of HPMC in core tablet and the ratio of HPMC in coating film as the influence factors and the lag-time and release rate as the evaluation parameters. Experiments were done on the central composite design, the data were simulated by using multi-linear equation and second-order polynomial equation. The possibly optimal formulation was predicted by response surface method. The dissolution date (lag-time and release rate) of the tablets prepared under the optimum condition were compared with the predicted. The drug released mechanism of the tablet were studied by Model-fitted of drug released within 6-15 h with zero-order, Higuchi and Peppas equation, respectively.</p><p><b>RESULT</b>The lag-time and release rate were simulated using second-order polynomial equation, regression coefficients of the two parameters were 0.9901 and 0.9876, respectively. Bias between the observed and predicted values of lag-time and release rate were -3.15% and -0.34%, respectively. The lag-time of the tablet prepared under the optimum condition in vitro was about 6 h, then drug released from the tablet within 6-15 h was found to conform to zero-order kinetics and was controlled by bulk erosion mechanism.</p><p><b>CONCLUSION</b>Sinomenine hydrochloride delayed-onset sustained-release tablets release drug slowly after lag time. The models developed in this study are proved to be highly predictable.</p>

Drug delivery of sinomenine hydrochloride floating and pulsatile release tablet / 中成药

AIM : To prepare a phase-specific drug delivery system withfloating and pulsatile release of sinome-nine hydrochloride and evaluate in vitro drug release behavior. METHODS: The floating and pulsatile-release of coat-core tablets were prepared by press-coated technics. The effects of factors influencing release characteristic of the drug were investigated by dissolution test, and to elucidate the mechanism of drug releaseof the tablets with erosion and water-uptake test. RESULTS: The tablets had typical floating and pulsatile release properties with a lag time rapid release. The lag-time was shortened with the increase of expansion ratio of tablet core and rotation speed of stirrer. The lag-time was prolonged with the increase of pH and ionic strength of dissolution media.CONCLUSION: The tablet could float and rapidly release drug at the predetermined time.

Preparation of gastric retenting and chronopharmacologic drug delivery tablets of sinomenine hydrochloride / 中国中药杂志

<p><b>OBJECTIVE</b>To prepare the gastric retenting and chronopharmacologic drug delivery tablets containing sinomenine hydrochloride as a model drug, evaluate the effects of the coating layers formulation and technics on drug release behavior, and to elucidate the mechanism of drug release based on obtained results.</p><p><b>METHOD</b>The gastric retenting and chronopharmacologic drug delivery tablets were prepared by press-coated technics. The types of disintegrants were chosen according to the expanding rate and the lag-time. The effects of formulation and technics of coating layer on the release characteristic of the drug were investigated by dissolution testing. The mechanism of drug release was proved by erosion test.</p><p><b>RESULT</b>The tablets had typical chronopharmacologic drug delivery properties with a lag time followed by a rapid release phase. CMS-Na was selected as the disintegrant. The lag-time was prolonged with the increase of the ratio of HPMC/carrrageenan and the amount of matrix material in coating layer. The compressing pressure and preparation method of coat material had minor influence on the lag-time of the tablets. Coating layer erosion and tablet core swelling were involved in the mechanism of drug release.</p><p><b>CONCLUSION</b>The tablets had typical chronopharmacologic drug delivery properties. A suitable lag-time can be achieved by adjusting formulation of coating layer to meet the requirement of chronotherapy.</p>

Influencing factors of the formulation and preparation on in vitro drug release from sinomenine hydrochloride delayed-onset sustained-release tablet / 中成药

AIM: To study the formulation and preparation factors on vitro drug release from sinomenine hydrochloride delayed-onset sustained-release tablet. METHODS: With hydrophilic matrix materials as excipient,the tablets containing hydrochloride sinomenine as a model drug were prepared by direct compression. The effect of the type and amount of tablet core matrix materials(HPMC K15M,HPMC K4M,xanthan gum and carrageenan),the type and amount of coating matrix materials,the preparation of coating materials and the pressure on in vitro drug release of the tablets were studied. RESULTS: The lag time of the tablet was 4 ～ 5 h and drug release slowly in 24 h. The type and the amount of the core matix materials and the coating matrix materials play an important role on lag time and drug release(P

Drug delivery of sinomenine hydrochloride floating and pulsatile release tablet / 中成药

AIM: To prepare a phase-specific drug delivery system with floating and pulsatile release of sinomenine hydrochloride and evaluate in vitro drug release behavior. METHODS: The floating and pulsatile-release of coat-core tablets were prepared by press-coated technics.The effects of factors influencing release characteristic of the drug were investigated by dissolution test,and to elucidate the mechanism of drug release of the tablets with erosion and water-uptake test. RESULTS: The tablets had typical floating and pulsatile release properties with a lag time rapid release.The lag-time was shortened with the increase of expansion ratio of tablet core and rotation speed of stirrer.The lag-time was prolonged with the increase of pH and ionic strength of dissolution media. CONCLUSION: The tablet could float and rapidly release drug at the predetermined time.