Objective To investigate the inhibitory effect of running combined with chitosan on high-fat diet(HFD)induced obesity in rats through the expression of fatty acid transporter 4(FATP4)and Toll like receptor 4(TLR4)and its mechanism.Methods 50 male Wistar rats were randomly divided into normal control(NC)group,HFD group,chitosan(Chi)group,running exercise(Run)and chitosan+running exercise(Chi+Run)group,with 10 rats in each group.The levels of serum total cholesterol(TC),triglyceride(TG),high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),very low density lipoprotein cholesterol(VLDL-C),alanine aminotransferase(ALT)and aspartate aminotransferase(AST)were detected.ELISA was used to detect serum TNF-α,IL-6,APN,Ghrelin,Leptin(LP),and Ins levels.Western blot was used to test the expression of FATP4 and TLR4 proteins in liver and adipose tissue,and HE staining was used to evaluate liver and adipose tissue pathology.Results Compared with the HFD group,the Chi,Run,and Chi+Run groups showed an increase in HDL-C,serum APN,and Ghrelin(P<0.05),as well as an decreased in body weight,fat mass,obesity index,TC,TG,LDL-C,VLDL-C,ALT,AST,TNF-α,IL-6,LP,Ins,FATP4 protein expression,TLR4 protein expression,adipocyte size and quantity in liver and adipose tissue(P<0.05).The HDL-C was higher in Chi+Run group than in Chi and Run groups(P<0.05),and the final weight,LDL-C,TG,AST,IL-6,the expression of FATP4 protein,TLR4 protein,and adipocyte size in the liver and adipose tissue were lower in Chi+Run group than in Chi and Run groups(P<0.05).Conclusions The inhibitory effect of running combined with Chi on HFD induced obesity was superior to that of running or Chi alone,and its mechanism may be related to the downregulation of FATP4 and TLR4.

Objective To investigate the inhibitory effect of running combined with chitosan on high-fat diet(HFD)induced obesity in rats through the expression of fatty acid transporter 4(FATP4)and Toll like receptor 4(TLR4)and its mechanism.Methods 50 male Wistar rats were randomly divided into normal control(NC)group,HFD group,chitosan(Chi)group,running exercise(Run)and chitosan+running exercise(Chi+Run)group,with 10 rats in each group.The levels of serum total cholesterol(TC),triglyceride(TG),high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),very low density lipoprotein cholesterol(VLDL-C),alanine aminotransferase(ALT)and aspartate aminotransferase(AST)were detected.ELISA was used to detect serum TNF-α,IL-6,APN,Ghrelin,Leptin(LP),and Ins levels.Western blot was used to test the expression of FATP4 and TLR4 proteins in liver and adipose tissue,and HE staining was used to evaluate liver and adipose tissue pathology.Results Compared with the HFD group,the Chi,Run,and Chi+Run groups showed an increase in HDL-C,serum APN,and Ghrelin(P<0.05),as well as an decreased in body weight,fat mass,obesity index,TC,TG,LDL-C,VLDL-C,ALT,AST,TNF-α,IL-6,LP,Ins,FATP4 protein expression,TLR4 protein expression,adipocyte size and quantity in liver and adipose tissue(P<0.05).The HDL-C was higher in Chi+Run group than in Chi and Run groups(P<0.05),and the final weight,LDL-C,TG,AST,IL-6,the expression of FATP4 protein,TLR4 protein,and adipocyte size in the liver and adipose tissue were lower in Chi+Run group than in Chi and Run groups(P<0.05).Conclusions The inhibitory effect of running combined with Chi on HFD induced obesity was superior to that of running or Chi alone,and its mechanism may be related to the downregulation of FATP4 and TLR4.

Objective To explore the difference in myopia control efficacy between spectacle lenses with highly aspherical lenslets(HAL)combined with 0.01％atropine eye drops and spectacle lenses with HAL alone or single vision spectacle lenses(SVL)in children and adolescents.Methods A retrospective cohort study was conducted with a total of 105 myopic children aged 6-15 years.According to the specific myopia correction and control methods of each subject,they were evenly divided into the HAL+0.01％atropine(HAL+AT)group,the HAL group,and the SVL group,with 35 subjects in each group.Relevant data,such as cycloplegic refraction and axial length(AL)at baseline and 12 months after wearing spectacles,were retrieved.One-way analysis of variance,or the Kruskal-Wallis test,was used to analyze the changes in AL and spherical equivalent refraction(SER)after wearing spectacles for 12 months in comparison to those at baseline in the three groups.Results There was no statistically significant difference in the baseline parameters and duration of wearing spectacles among the three groups(P＞0.05).After wearing spectacles for 12 months,the changes in SER were-0.13(-0.25,0.00)D,-0.25(-0.63,-0.25)D,and-0.63(-1.00,-0.25)D in the HAL+AT group,HAL group,and SVL group,respectively;AL elongation in the three groups was(0.09±0.11)mm,(0.19±0.16)mm,and(0.34±0.16)mm,respectively.The HAL+AT group exhibited slower SER changes(PHAL+AT vs.HAL=0.00 1,PHAL+AT vs.SVL=0.002)and AL elongation(PHAL+AT vs.HAL=0.009,PHAL+AT vs.SVL=0.001)than those of the HAL and the SVL groups.Compared with those of the SVL group,myopia progression was reduced by 79.4％and AL elongation was slowed down by 73.5％in the HAL+AT group,while in the HAL group,myopia progression and AL elongation were reduced by 60.3％and 44.1％,respectively.According to stratified analysis based on age and myopia progression rate,among younger children aged 6 to 8 years and older children aged 9 to 15 years,the HAL+AT group had a significantly lower proportion of subjects experiencing fast AL elongation(AL＞0.36 mm/year)and a significantly higher proportion of subjects experiencing slow AL elongation(AL≤0.18 mm/year)compared to the SVL group(P＜0.017).Conclusion The combination intervention of spectacle lenses with HAL and 0.01％atropine eye drops is effective in controlling myopia progression in children and adolescents,with better myopia control effect achieved using this combination intervention in myopic children of all ages.

The EtOH extracts of the whole plants of afforded 17 new jatrophane diterpenoid esters, helioscopianoids A-Q (-), along with eight known compounds (-). Their structures were elucidated by extensive spectroscopic methods and Mo(OAc)-induced ECD analysis, and the structures of compounds , , and were confirmed by X-ray crystallography. Compounds - were evaluated for inhibitory effects on P-glycoprotein (P-gp) in an adriamycin (ADM)-resistant human breast adenocarcinoma cell line (MCF-7/ADR) and neuroprotective effects against serum deprivation-induced and rotenone-induced PC12 cell damage. Compounds and increased the accumulation of ADM in MCF-7/ADR cells by approximately 3-fold at a concentration of 20 μmol/L. Compound could attenuate rotenone-induced PC12 cell damage, and compounds , , and showed neuroprotective activities against serum deprivation-induced PC12 cell damage.

The study reports the detection of neuroprotective effect of 10 kinds of coumarin derivatives and explores their possible mechanism. MTT method was used to screen the neuroprotective effect of 10 coumarin derivatives on neurotoxic agents (Aβ25-35 and rotenone) or OGD (oxygen-glucose deprivation). A compound with better protective effect was obtained. Then the effect of this compound on neurotoxic agents on PC12 was detected by the morphological observation. Furthermore, the effect of compound 3 on microglia with lipopolysaccharide (LPS) induced inflammation was detected. And the inflammatory factor was tested. Finally, direct free radical scavenging ability was detected. Compound 3 was found to be the best compound through three neurons toxic models. Not only compound 3 ameliorated cell viability reduced by three neurons toxic models, but also significantly inhibited the production of inflammatory factor (TNF-α and IL-1β). And its free radical scavenging ability is very good, especially the effect on superoxide anion, which is comparable with vitamin C. The significant scavenging effect of compound 3 on superoxide anion might be the mechanism of the neuroprotection. Compound 3 as a potential neural cell protective agent merits further investigation.

This study is to investigate the amelioration effect of glucocorticoid receptor (GR) antagonist mifepristone on the changes of learning and memory abilities in rat model of depression. In the present study, a 35-day rat chronic unpredictable stress (CUS) model was used to observe both depression-like behaviors with sucrose preference test and open-field test and learning and memory-associated behaviors with Morris water maze test. A total of 45 male adult Sprague-Dawley rats were randomly assigned to three groups of equal size: control group (CON); CUS group (CUS); CUS + mifepristone group (CM). Animals in CM group were first exposed to CUS for 14 days, and then were administered with 50 mg x kg(-1) x d(-1) of mifepristone with continued CUS procedure. Corticosterone EIA Kit was used to detect the concentration of plasma corticosterone (CORT). Nissl staining was used to observe the structure of hippocampus. The results demonstrated that CUS exposure induced both depressive-like and learning and memory-associated behaviors and these deficits were reversed by mifepristone. Compared to CON group, the concentration of plasma CORT increased significantly in CUS group. CUS exposure damaged the structure of hippocampus, whereas mifepristone had an amelioration effect. Together, the structural deficits of hippocampus resulting from long-term stress exposure, which could contribute to the impairment of learning and memory in depression, are reversed by the GR receptor antagonist mifepristone.

Objective To investigate the effect of morroniside on cycloxygenase (Cox) in the condition of platelet aggregation inducedby adenosine diphosphate (ADP) in rabbits. Methods The levels of Cox induced by ADP in different groups were detected by enzyme-linked immunosorbent assay (ELISA). Results Compared with the control group, all the morroniside groups significantly inhibited theincrease of Cox induced by ADP (P<0.001), which had concentration dependence, and the inhibition rate of high dose group was 30%. ConclusionMorroniside can decrease the level of Cox and it may be the mechanism of morroniside on inhibiting the platelet aggregation inducedby ADP in rabbits.

Objective To investigate the suppression of mrp1 and MRP1 induced by small interfering RNA and the restoration of sensitivity to chemotherapeutic drugs in the multidrug-resistant hepatocellular carcinoma cell lines HepG2/mrp1. Methods mrp1-targeted small interfering RNA duplexes were designed and composed and introduced into multidrug-resistant hepatocellular carcinoma cell lines HepG2/mrp1. The suppression of mrp1 mRNA and its gene product MRP1 was examined by RT-PCR and flow cytometry (FCM), respectively. MTT assay was performed to measure the reverse effect of small interfering RNA based on the results of ICs0. Results The overexpression of mrp1 mRNA and MRP1 was effectively suppressed by small interfering RNAs. The level of mrp1 mRNA in the transfected HepG2/mrp1 cells was reduced to (86.36±2.76)% and MRP1 to (89.38±3.76)%compared with those of the controls. The resistance to ADR was reversed five-fold, which indicated the restoration of sensitivity to drugs. Conclusion Small interfering RNA can inhibit mrp1 expression effectively and reverse the multidrug resistance mediated by MRP1.

OBJECTIVETo investigate the chemical constituents of Heteroplexis micocephal and their bioactivities.

METHODThe constituents were isolated by using a combination of various chromatographic techniques including column chromatography over macroporous adsorbent resin, silica gel, Pharmadex LH-20, and C-18, as well as reversed-phase HPLC. Structures of the isolates were identified by spectroscopic data analysis. In vitro cytotoxic, HIV-1 replication, neuroprotective, and anti-inflammatory activities were screened by using cell-based models.

RESULTThirty-one compounds were obtained. Twelve of them are phenylpropanols, and the structures were elucidated as (+)-(7S,8R)-guaiacylglycerol (1), ferulic acid (2), cinnamate methyl ester (3), 1-eicosanyl 3,4-dihydroxycinnamate (4), morinin B (5), sinapyl diangelate (6), chlorogenic acid (7), 4-O-caffeoylquinic acid (8), 5-O-caffeoylquinic acid (9), 5-O-caffeoylquinic acid methyl ester (10), 1,5-di-O-caffeoylquinic acid (11) and 4,5-di-O-caffeoylquinic acid methyl ester (12). Three lignans, (+)-pinoresinol (13), prinsepiol (14) and (+)-pinoresinol-O-beta-D-glucopyranoside (15). Four acetophenones, 2,4-diacetylanisole (16), espeleton (17), viscidone (18) and 12-hydroxytremetone-12-O-beta-D-glucopyranoside (19). Nine flavones, isosakuranetin (20), hesperetin (21), 3-methoxy-5,7,3',4'-tetrahydroxyflavone (22), acacetin (23), 5-hydroxy-7,4'- dimethoxyflavone (24), 7-methoxy-4',5, 6-trihydroxyflavone (25), 3,3'-dimethylquercetin (26), kaempferol 3-O-rutinoside (27), rutin (28). And three coumarins scopoletin (29), umbelliferone (30) and ayapin (31). Compound 6 and 22 showed selective cytotoxicities against a human stomach cancer cell line(BGC-823) and a human lung cancer cell line (A549) with IC50 values of 3.74 x 10(-5) and 7.17 x 10(-5) mol L(-1), respectively. In addition, Compound 6 showed a potent activity inhibiting HIV-1 replication with an IC50 value of 4.04 x 10(-6) mol L(-1), while 22 showed neuroprotective activity Against the MPP+ induced PC12-syn cell damage, with a relative protection ratio of 105.2% (P < 0.01) at a concentration of 10(-5) mol L(-1). Compound 26 and 31 showed inhibitory activities against the release of beta-glucuronidase of the polymorphous nuclear leukocytes induced by platelet activating factor (PAF), with inhibitory rates of 75.6% (P < 0.001) and 53. 9% (P < 0.01), respectively.

CONCLUSIONCompounds 1-31 were obtained from the genus Heteroplexis for the first time. Compound 6 and 22 possessed selective cytotoxicities against human cancer cell lines BGC-823 and A549, respectively. In addition, Compound 6 showed a potent activity inhibiting HIV-1 replication while 22 showed neuroprotective activity against the MPP+ induced PC12-syn cell damage. Compound 26 and 31 were potent anti-inflammatory agents.

Animals ; Antiviral Agents ; analysis ; pharmacology ; Cell Line, Tumor ; HIV-1 ; drug effects ; physiology ; Humans ; Myrtaceae ; chemistry ; Neurons ; cytology ; drug effects ; Neuroprotective Agents ; analysis ; pharmacology ; Plant Extracts ; analysis ; pharmacology ; Rats ; Virus Replication ; drug effects

Abstract:Aim To study the effect of rotenone on α-synuclein in rat midbrain of Parkinson's disease(PD).Methods Rats were subcutaneouly injected with chronic low dose rotenone(1.0 mg·kg~(-1)·d~(-1)).Movements within 5 minutes were evaluated in open field test.Tyrosine hydroxylase(TH)-positive neuronsin the midbrain were measured with immunofluorescence staining.α-SYN protein level in the midbrain was demonstrated with immunohistochemical staining and Western blot.Results Compared to the control group,latency time,crossing,rearing and rearing time were changed significantly(P<0.05,0.01)in the rotenone group,TH-positive neurons were reduced(P<0.05)and α-SYN protein level in the midbrain was increased(P<0.05).Conclusion Injection with rotenone can induce PD symptom,which may be correlated to α-SYN protein level in the midbrain.