AIM:The direct renin inhibitor aliskiren displays antihypertensive and antialbuminuric effects in humans and in animal models . Emerging evidence has shown that aliskiren localizes and persists in medullary collecting ducts even after treatment was discontinued . The purpose of the present study was to investigate whether aliskiren regulates renal aquaporin expression and improves urinary concen -trating defect induced by lithium .METHODS:The mice were either fed with normal chow or LiCl diet (40 mmol/kg dry food per day for first 4 days and 20 mmol/kg dry food per day for last 3 days ) for seven days .Some mice were intraperitoneally injected aliskiren ( 50 mg/kg BW per day in saline ) .RESULTS:Mice injected aliskiren developed decreased urine output and increased urine osmolal -ity when compared with controls .Aliskiren significantly increased protein abundance of AQP 2 and phosphorylated-S256 AQP2 in the kidney inner medulla .Immunohistochemistry and immunofluoresence showed increased apical and intracellular labeling of AQP 2 and pS256-AQP2 in collecting duct principal cells of kidneys in mice treated with aliskiren .Aliskiren treatment prevented urinary concen-trating defect in lithium-treated mice , and improved the downregulation of AQP 2 and pS256-AQP2 protein abundance in inner medulla of the kidney .In primary cultured rat inner medulla collecting duct cells , aliskiren dramatically increased AQP 2 protein abundance which was significantly inhibited either by PKA inhibitor H 89 or by adenylyl cyclase inhibitor MDL 12330, indicating an involvement of the cAMP signalling pathway in mediating aliskiren-induced increased AQP 2 expression .CONCLUSION: The direct renin inhibitor aliskiren upregulates AQP 2 protein expression in inner medullary collecting duct principal cells and prevents lithium -induced nephro-genic diabetes insipidus ( NDI) likely via PKA-cAMP pathways .

Aim To investigate the influence of Ramu-lus mori polysaccharides ( RMP) on blood glucose and anti-oxidative effect in streptozotocin ( STZ )-induced diabetic mice .Methods Diabetic mice were induced by intraperitoneal injection with 120 mg? kg -1 STZ and were randomly divided into the following 5 groups with 20 animals per group: model group , valsartan group ( 20 mg? kg -1 ) , low-, medium-, high-dose (0.3,0.6,1.2 g? kg -1 ) of RMP groups.Other 20 normal mice were treated as normal control group .The mice were administered orally for 90 d.On 45 d of ad-ministration , the 24 h urine was collected through met-abolic cages for urine protein detection .Pathological changes of kidney tissues were observed through HE staining .The serum levels of urea nitrogen ( BUN) and creatinine ( Cr ) were detected by automatic biochemical analyzer; and the manganese superoxide dismutase (Mn-SOD), catalase(CAT), malonaldehyde(MDA) and mitochondrial respiratory chain complex Ⅰ,Ⅲac-tivity of kidney tissues were also determined .ELISA method was used to detect ROS content in renal cortex . The SIRT1 , FOXO1 and NF-κB protein expressions were analyzed by Western blot .Results Compared with model group, the FBG, microalbuminuria, BUN and Cr were decreased by RMP medication ( P <0.05).The activities of Mn-SOD, CAT and mitochon-drial respiratory chain complex Ⅰ,Ⅲ in RMP groups were enhanced , while MDA and ROS levels were re-duced. Moreover, the expressions of SIRT1 and FOXO1 were up-regulated by RMP , the expression of NF-κB was down-regulated ( P<0.05) .Conclusion RMP exerts renal protective effect through up-regula-ting the expressions of SIRT1 and FOXO1 in renal cor-tex , which may relate to the improvement of anti-oxida-tive capability .

ObjectiveTo establish a rat model of hyperuricemia （HUA）， to study the effect of Liqing granules on lowering serum uric acid， and to evaluate its safety . MethodsMale SD rats were randomly divided into solvent control group and model group according to their body weight. For the model group， serum uric acid （SUA） was determined after 7 days of intra-gastric administration of potassium oxyazinate. The model group were randomly divided into model control group， positive control group， and low， medium， high dose group based on SUA level. Each group from the model group continued to receive potassium oxyazinate in the morning. The animals in the model groups received 0.5% CMC-Na， 10 mg·kg^-1 benzbromarone （Doses by body weight） and Liqing granules 0.6， 1.2， 2.4 g·kg^-1 （Doses by body weight）， respectively in the afternoon. 0.5% CMC-Na suspension with the same volume was given both in the morning and afternoon for the solvent control group. Levels of SUA， creatinine （CREA）， alanine aminotransferase （ALT） and aspartate transaminase （AST） were determined after 32 and 45 days administration of the test substance. ResultsSUA of the model group was （218±23） μmol·L^-1 after 7 days of modeling， which was significantly higher than that of the solvent control group （P<0.001）. After 32 days administration of the test substance， SUA didn’t significantly decrease in each dose group （P>0.05）. CREA in the medium and high dose groups significantly decreased （P<0.05）. After 45 days administration of the test substance， SUA in each dose group was significantly decreased （P<0.001）， but CREA， ALT， and AST were not significantly different in each dose group in comparison with the model control group （P>0.05）. ConclusionLiqing granules can assist in lowering blood serum uric acid in the rat HUA model， and no damage to liver and kidney function is found.

Dopamine D₃ receptor (D₃R) is implicated in multiple psychotic symptoms. Increasing the D₃R selectivity over dopamine D₂ receptor (D₂R) would facilitate the antipsychotic treatments. Herein, novel carbazole and tetrahydro-carboline derivatives were reported as D₃R selective ligands. Through a structure-based virtual screen, ZLG-25 (D₃R K_i = 685 nmol/L; D₂R K_i > 10,000 nmol/L) was identified as a novel D₃R selective bitopic ligand with a carbazole scaffold. Scaffolds hopping led to the discovery of novel D₃R-selective analogs with tetrahydro-β-carboline or tetrahydro-γ-carboline core. Further functional studies showed that most derivatives acted as hD₃R-selective antagonists. Several lead compounds could dose-dependently inhibit the MK-801-induced hyperactivity. Additional investigation revealed that 23j and 36b could decrease the apomorphine-induced climbing without cataleptic reaction. Furthermore, 36b demonstrated unusual antidepressant-like activity in the forced swimming tests and the tail suspension tests, and alleviated the MK-801-induced disruption of novel object recognition in mice. Additionally, preliminary studies confirmed the favorable PK/PD profiles, no weight gain and limited serum prolactin levels in mice. These results revealed that 36b provided potential opportunities to new antipsychotic drugs with the multiple antipsychotic-like properties.