Quercetin exhibits neuroprotective effect by reduc-ing amyloid precursor protein expression and oxida-tive stress in Neuro2a/APPswe cell model / 中国药理学与毒理学杂志

OBJECTIVE The abnormal amyloid-β(Aβ)and oxidative stress assiociated with the progression of Alzheimer disease(AD).Quercetin has been reported to possess antioxidant and anti-inflammatory properties in neurodegenerative disorders.In this present study,we designed to characterize the mechanisms by which quer-cetin exerts neuroprotective effects in murine neuroblas-toma N2a cells stably expressing human Swedish mutant amyloid precursor protein(N2a/APP).METHODS N2a/APP cells were treated with quercetin at concentrations of 10,20 and 50 μ mol·L-1 for 24 h.Cell viability was examined with CCK-8 assays.The protein levels of ERK1/2 and Akt were detected by Western blotting.Intra-cellular reactive oxygen species(ROS)was detected by a fluorescent probe 2,7-dichlorofluorescein diacetate(DCFH-DA).The mitochondrial membrane potential(Δψ m)in N2a/APP cells was detected by using JC-1 staining method.Immunofluorescence was used to detect the generation of 8-hydroxy-2′-deoxyguanosine(8-OHdG)and 4-hydroxynonenal(4-HNE).RESULTS Quercetin attenuated the enhancement of p-ERK1/2,reductions of p-Akt,and decreased levels of APP expression.More-over,quercetin alleviated loss of mitochondria membrane potential(MMP)since it attenuates these oxidative stress,as reflected in the levels of ROS,4-HNE and 8-OHdG,was elevated in N2a/APP cells and these effects were again ameliorated by quercetin.CONCLUSION Neuroprotection by quercetin in N2a/APP cells involves normalizing the impaired mitochondrial function and reducing oxidative stress via inactivation of the ERK1/2 and activation of the Akt pathways.

The protective effect of trigonelline on H / 中国药理学通报

Aim To study the protective effect of trigonelline on H

Role of MDA in the pathogenesis of GERD esophagus mucosal inflammatory injury / 中国医师杂志

Objective To investigate the expression of malondialdehyde ( MDA) in esophageal mu-cosa of different types of gastroesophageal reflux disease ( GERD) patients and its role in the esophageal in-flammation. Methods According to the inclusion and exclusion criteria, 42 patients hospitalized in the the Xinjiang Uygur Autonomous Region People's Hospital from December 2017 to October 2018 were selected as the research group. 8 healthy subjects completed physical examination were set up as healthy control group. GERD completed GERDQ score, 24 h pH monitoring, and taken 3 cm on the dentate line of the esophagus as a specimen. The study group was divided into non-erosive reflux disease (NERD) group (17 cases) and Ero-sive reflux disease [erosive esophagitis (RE)] group (25 cases). Then hematoxylin-eosin (HE) staining, immunohistochemistry, real-time polymerase chain reaction ( qPCR ) , enzyme-linked immunosorbent assay (ELISA) methods were used to detect inflammation, oxidative stress (MDA), antioxidant enzyme [manga-nese superoxide dismutase (Mn SOD), glutathione (GSH), catalase (CAT)], and proinflammatory cyto-kines [monocyte chemotactic protein-1 (MCP-1), interlukin-8 (IL-8), tumor necrosis factorα(TNF-α)]. Results There was no significant difference in body mass index ( BMI ) between the three groups ( P >0. 05). 24 h pH monitoring of esophagus showed that the indexes of weak acid reflux (4<pH<7), acid re-flux ( pH<4 ) , esophageal near end acid reflux (％) and DeMeester score in RE group were significantly higher than those in NERD group, with statistical significance between the groups (P<0. 05). There was no significant difference in esophageal pressure between high resolution groups (P>0. 05). In RE group , the infiltration of immune cells (neutrophils, eosinophils), nipple lengthening, edema and other inflammatory changes were found in the esophageal mucosa, and the inflammation score reached the peak, which was signif-icantly higher than that in NERD group, with statistical significant difference (P<0. 001). The positive ex-pression of MDA in the two groups ( NERD, RE) was higher than that in the control group, and the MDA ex-pression in the RE group was almost covered with the full layer esophagus. The serum MDA concentration in the NERD and RE groups was significantly higher than that in the control group (P<0. 001). Compared with the NERD group, the serum MDA in the RE group reached the peak (P<0. 01). The relative expression of mRNA ( Mn SOD, GSH and CAT) in NERD group and RE group was significantly decreased, and there was a significant difference between the three groups (P<0. 001). Compared with the NERD group, the mRNA expression level of Mn SOD and CAT in RE group was significantly decreased (P<0. 01). The relative ex-pression of mRNA (MCP-1, IL-8, TNF- α) increased significantly in the two groups (NERD, RE), and there was a statistically significant difference between the three groups ( P <0. 001 ) . Compared with the NERD group, the expression of its inflammatory factors in the RE group significantly increased (P<0. 01). Conclusions The expression level of MDA in different types of GERD is significantly higher, which may be closely related to esophageal inflammation induced by acid reflux.

Effect of Shui Medicine Asarum insigne Polysaccharide on Glycolipid Metabolis,Renal Function and Oxi-dative Stress in Model Rats with Experimental Type 2 Diabetes / 中国药房

OBJECTIVE:To study the effect of Shui medicine Asarum insigne polysaccharide on glycolipid metabolism,renal function and oxidative stress in rats with experimental type 2 diabetes,and provide reference for its development and use. METH-ODS:60 SD rats were randomly divided into normal control group,model control group,positive control group (Irbesartan tab-lets,0.02 g/kg) and A. insigne polysaccharide low-dose,medium-dose,high-dose groups (calculated by crude drug as 2,4,8 g/kg),10 in each group. Except for normal control group,rats in other groups were intraperitoneally injected streptozotocin 75 mg/(kg·d)to induce model with diabetes. After modeling,rats in each administration group were intraperitoneally injected relevant medicines,and rats in normal control group and model control group were intragastrically administrated 5% carboxymet hylcellu-lose sodium solution,twice a day,for 42 d. After administration,UV spectrophotometer was used to detect the glycogen content in liver tissue. Automatic biochemical analyzer was used to detect 24 h urine output,24 h urinary protein content of rats,levels of tri-glyceride (TG),cholesterol (TC),low-density lipoprotein cholesterol (LDL-C),high-density lipoprotein cholesterol (HDL-C), creatinine (Cr),urea nitrogen (BUN) in serum,and levels of superoxide dismutase (SOD),glutathione peroxidase (GSH-Px), catalase(CAT),superoxide dismutase(ROS),malondialdehyde(MDA)in kidney tissue. RESULTS:Compared with normal con-trol group,glycogen content in liver tissue of rats in model control group was decreased(P<0.05);24 h urine output and 24 h uri-nary protein content were increased(P<0.05);levels of TG,TC,LDL-C in serum were increased(P<0.05),and HDL-C level was decreased (P<0.05);levels of SOD,CAT,GSH-Px in kidney tissue were decreased (P<0.05),and levels of ROS,MDA were increased(P<0.05). Compared with model group,except that there were no significant differences in the improvement of uri-nary protein content,HDL-C level in serum,24 h urine out-put in A. insigne polysaccharide low-dose group,above-men-tioned indexes in each administration group were obviously im-proved (P<0.05). CONCLUSIONS:A. insigne polysaccha-ride can regulate lipid metabolic disorders,and improve renal function and antioxidant capacity of rats.

Effects of metformin on inflammation and oxidative levels in hypothalamic paraventricular nucleus of salt-sensitive hypertensive rats / 中国基层医药

Objective To explore central mechanism of metformin(MET)in salt -sensitive hypertensive rats by assessing the effect of metformin on inflammation and oxidative stress in hypothalamic paraventricular nucleus (PVN),sympathetic nerve activity and blood pressure.Methods Eight -week -old male Dahl salt -sensitive rats were divided into 4 groups:the normal -salt diet control group[0.3% NaCl +intracerebroventricular(ICV)artificial cerebrospinal fluid(aCSF)],the normal -salt diet with MET group(0.3% NaCl +ICV MET 25μg/d],the high -salt diet control group (8% NaCl +ICV aCSF),the high -salt diet with MET group (8% NaCl +ICV MET 25μg/d). Mean arterial pressure(MAP)was determined every week by a tail -cuff occlusion.After 6 weeks,all rats were eutha-nized,and blood and brain tissues were collected.Then,the plasma norepinephrine(NE,an indicator of sympathetic activity)was detected by enzyme linked immune sorbent assay(ELISA).The expression levels of interleukin(IL)-1β,IL -10 and NOX -2[a subunit of NAD(P)H oxidase],superoxide dismutase(SOD)in the PVN were detected by immunofluorescence,immunohistochemistry and Western blot methods.Reactive oxygen species(ROS)was detec-ted by dihydroethidium(DHE)staining.Results The MAP level of high -salt diet with metformin group was attenu-ated compared with that of the high -salt diet control group[(129.55 ±6.52)mmHg vs.(154.47 ±6.57)mmHg, F =121.90,P <0.05].The change of plasma NE level of high -salt diet with metformin group was lower compared with that of the high -salt diet control group[(364.57 ±30.73)pg/mL vs.(547.68 ±25.08)pg/mL,F =179.24, P <0.05].The expression levels of IL -1β,IL -6,NOX -2 and ROS were markedly higher in high -salt diet with metformin than those of the high -salt diet control group(F =27.80,21.20,22.48,31.99,all P <0.05),which of IL -10 and SOD was lower(F =17.69,23.69,all P <0.05).Conclusion Metformin may attenuate blood pressure in salt -sensitive hypertensive rats,at least partly via decreasing inflammatory molecules and inhibiting oxidative stress in the PVN,subsequently inhibiting sympathoexcitation.

Protective effect of emodin on rats with pulmonary fibrosis and its partial mechanisms / 中国药理学通报

Aim To observe the influence of emodin on bleomycin-induced pulmonary fibrosis in rats, and explore its protective mechanisms. Methods Sixty SD rats were randomly divided into normal control group, sham operation group, model group, low-dose inter-vention group, high-dose intervention group and pred-nisone group. Each group included 10 animals. Rats in the latter 4 groups were intratracheally administered with bleomycin to establish pulmonary fibrosis model. From the second day, rats in low-and high-dose inter-vention groups were intragastrically treated with 2 mL of 20 and 80 mg · kg-1 emodin, respectively. Predni-sone group were intragastrically administrated with 2 mL of 5 mg·kg-1 prednisone acetate. However, con-trol and model groups were treated with 2 mL of normal saline. All rats were sacrificed on day 28. Pulmonary tissues were then removed, and HE and Masson stai-ning were performed. The contents of hydroxyproline ( HYP ) , malondialdehyde ( MDA ) , superoxide dis-mutase ( SOD) , glutathione-peroxidase ( GSH-Px) and catalase (CAT) in pulmonary tissues were measured. Serum concentrations of tumor necrosis factor-α ( TNF-α) , interleukin ( IL )-6 and IL-17 were detected by enzyme linked immunosorbent assay ( ELISA ) . The expression of Kelch-like ECH-associated protein 1 ( Keap 1 ) , nuclear factor-erythroid 2-related factor 2 (Nrf2) and nuclear factor-κB (NF-κB) p65 in pulmo-nary tissues was analyzed using Western blot. Results The pulmonary inflammation and fibrosis in low-and high-dose intervention as well as prednisone groups was significantly improved when compared with model group ( P0. 05 ) . Conclusion Emodin may protect against rats with pulmonary fibrosis by enhan-cing antioxidative ability and inhibiting inflammatory response.

Effect of deamination reaction mediated by semicarbazide-sensitive amine oxidase on 3 T3-L1 adipocytes / 中国病理生理杂志

[ ABSTRACT] AIM:To observe the effect of the metabolites generated from oxidative deamination of methylamine ( MA) or benzylamine ( BZA ) catalyzed by semicarbazide-sensitive amine oxidase ( SSAO ) on 3T3-L1 adipocytes. METHODS:3T3-L1 preadipocytes were induced to differentiation.SSAO activity was determined by high performance liquid chromatography ( HPLC) at different differentiation time points.MTT assay was applied to detect cell vitality after exposure to different concentrations of MA or BZA.Fluorescence probe DCFH-DA was used to determine the production of reactive oxygen species after incubation of 3T3-L1 adipocytes with MA or BZA.After exposure to 0.5 mmol/L MA or BZA for 4 h, malondialdehyde ( MDA) , total superoxide dismutase ( T-SOD) and glutathione ( GSH) in the adipocytes or prea-dipocytes were measured.RESULTS:SSAO activity increased with the increase in the differentiation days, and reached a maximum at the 8th day.Incubation of the cells with different concentrations of MA or BZA for 4 h did not significantly de-creased the cell vitality (P>0.05).After exposure to 0.5 mmol/L MA or BZA, the reactive oxygen species in adipocytes significantly increased, and were about 3 to 4 times as compared with control group (P0.05 ) .CONCLUSION: MA or BZA induces oxidative stress in the mature adipocytes, which might result from the deamination products catalyzed by SSAO.