Effects of ethanolic extracts of Euonymus alatus on CCl4-induced hepatic fibrosis in mice based on JAK2/STAT3 signaling pathway and its mechanism北大核心CSCD

Aim To explore the mechanism of ethanolic extracts of euonymus alatus on CCl4-induced hepatic fibrosis in mice by regulating JAK2/STAT3 signaling pathway. Methods Sixty C57BL/6J mice were randomly divided into control group,model group,EAL,EAM),EAH,and Silybin(n=10). Except for the control group,mice in other groups were injected with 25% CCl4 of 1.6 mL·kg-1 to induce HF model. Moreover,the positive group was administered 12.6 mg·kg-1 Silybin by gavage once a day,and EAL,EAM,and EAH were administered 72,140 and 280 mg·kg-1 ethanolic extracts of euonymus alatus once by gavage once a day,and the intervention lasted for six weeks. After 6th week,mouse blood was collected,the body weight and liver weight were measured and liver mass index calculated,the liver appearance was observed,and ALT,AST,TNF-α,IL-6,IL-1β were detected in serum. The protein expression levels of collagen Ⅰ,α-SMA,and JAK2/STAT3 signaling pathway-related protein(JAK2,STAT3,p-JAK2,pSTAT3)in mouse liver tissues were detected. Results Compared with the model group,EAM and EAH significantly decreased liver mass index,and the ALT,AST,α-SMA,collagen I levels of serum. After treatment,the liver morphology and structure,cellular inflammatory infiltration,fiber changes and collagen deposition in euonymus alatus intervention group were dose-dependently better than those of the model group. Compared with the model group,the expression of TNF-α,IL-6 and IL-1β in EAM and EAH serum decreased significantly(P<0.05). Compared with the model group,the protein expression levels of JAK2,STAT3,p-JAK2,pSTAT3 in EAM and EAH mouse liver tissues decreased significantly(P<0.05). Conclusion Ethanolic extracts of euonymus alatus have an anti-CCl4-induced HF effect in mice,and its mechanism may be related to the regulation of the JAK2/STAT3 signaling pathway. © 2023 Publication Centre of Anhui Medical University. All rights reserved.     

Effect of Lulong Zaisheng Decoction II on chemotherapy-induced bone marrow suppression and its mechanism北大核心CSCD

Aim To investigate the effect of Lulong Zaisheng Decoction II on chemotherapy-induced bone marrow suppression in nude mice bearing colorectal cancer. Methods Male BALB/C nude mice were inoculated with human colon cancer cell HT-29 under the armpit. The tumor bearing nude mice were randomly divided into five groups: control group, chemotherapy group, positive drug group, Lulong Zaisheng Decoction II groups with high and low doses. The mice were given drugs by gavage once a day for 10 consecutive days. From the fourth day of the experiment, except for the control group, the nude mice were intraperitoneally injected with 5-FU at dose of 25 mg • kg-1 for 7 consecutive days. The mice in control group were injected with the same volume of normal saline. On the 11th day, blood was collecled from the orbit to measure peripheral hemogram. The mice were killed after cervical dislocation, then the morphology of bone marrow cells was observed - Bone marrow cell cycle, apoplosis rate and CD34+ were detected by flow cytometiy, mRNA expressions of granulocyle-macrophage colony stimulating factor (GM-CSF), granulocyte-macrophage colony stimulating factor receptor (GM-CSFR), inlerleukin-1 p (IL-1 (3) and inlerleukin-3 (IL-3) were tested by quantitative real-lime PCR, and the protein expressions of vascular endothelial growth factor (VEGF) and intercellular cell adhesion molecule-1 (VCAM-1) were tested by Western blot. Results Lulong Zaisheng Decoction II significantly elevated the number of white cells, increased the proportion of CD34 positive cells and the percentage of S cells, and reduced the apoplosis rate of bone marrow cells. Furthermore, it obviously up-regulated the mRNA expressions of GM-CSF, GM-CSFR, IL-1 (3 and IL-3, and promoted the protein expressions of VEGF and VCAM-1 in bones. Conclusions Lulong Zaisheng Decoction II can significantly alleviate bone marrow suppression caused by chemotherapy. Its mechanism is closely related to regulating cell cycle, preventing bone marrow cell apoptosis, promoting the secretion and expression of hematopoietic growth factors, and improving bone marrow hematopoietic microenvironment. © Food and Fermentation Industries. All rights reserved.     

Effect of Sea Cucumber Enzymolysis Fermentation Liquid on immunosuppressed mice based on metabonomics北大核心CSCD

Aim To prepare the sea cucumber enzy¬molysis fermentation liquid (SCEFL) by enzymatic hydrolysis of protease and fermentation of probiotics and to investigate the effect of SCEFL on the immunosup-pression induced by cyclophosphamide in mice and to explore its mechanism by metabomic method. Methods The immunosuppressive model was induced by in-traperitoneal injection of cyclophosphamide. C57BL/6J mice were randomly divided into normal group, model group, Levamisole group, SCEFL groups (at low, medium and high doses). The pathological changes of spleen were observed by HE staining. The proportion of CD4+and CD8+T lymphocyte subsets and the pro-portion of CD4 /CD8 T lymphocyte subsets in peripheral blood were detected by flow cytometry. The con¬tents of IL-2 ( interleukin-2 ), IgG ( immunoglobulin G) and IgM (immunoglobulin G) in serum were detected by ELISA. The changes of endogenous metabolites in mouse serum were analyzed by UPLC-Q/TOF-MS metabolomics, and the related metabolic pathways were explored. Results SCEFL could improve the pathological changes of immunosuppressed mice, in¬crease the proportion of CD4 T cells and the proportion of CD4+/CD8+T lymphocyte subsets,and increase the contents of IL-2, IgG and IgM in serum. The immune function of mice was regulated mainly through six related metabolic pathways, including glyc-erophospholipid metabolism, sphingolipid metabolism, linoleic acid metabolism, a-linoleic acid metabolism, glycophosphatidylinositol-anchored biosynthesis and arachidonic acid metabolism. Conclusion SCEFL may ameliorate the immunosuppression of mice by regulating endogenous metabolic disorder. © 2023 Publication Centre of Anhui Medical University. All rights reserved.     

The protective effect of L-Shikonin on LPS/D-GalN-induced acute liver injury in mice via inhibiting NF-κB inflammatory signaling pathway北大核心CSCD

Aim To investigate the anti-inflammatory effect of L-Shikonin ( SK ) on lipopolysaccharide ( LPS)-induced RAW 264. 7 macrophages in vitro and its protective effect on LPS/D-GalN-induced acute liver injury. Methods The mouse model of acute liver in¬jury was established in vivo experiments by LPS/D- GalN. The survival rate of the mice and the changes of liver and spleen indices in each group were examined. The levels of AST, ALT and AKP in serum and NO, superoxide dismutase ( SOD ) and malondialdehyde (MDA) in liver tissue homogenate were measured, and the histopathological sections of the liver of each group were observed by H&E staining. M I T colorimet- ric assay was used for cell viability in vitro experi¬ments, Griess method for the detection of NO content, RT-PCR assay and Western blot assay for examining the effect of levulinic acid on the expression levels of mRNA and related pathway proteins of pro-inflammato¬ry factors in LPS-induced RAW264. 7 cells. Results The results of in vivo experiments showed that L-SK significantly improved the liver and spleen indices, de¬creased AST, ALT and AKP levels in serum, de¬creased NO and MDA in liver homogenate, and in¬creased SOD activity in mice with acute liver injury. The results of in vitro experiments showed that L-SK significantly inhibited the mRNA expression of INOS, COX2, I FN-(3 and pro-inflammatory factors 1L-6, TNF-a and IL-10 in LPS-induced RAW264. 7 cells, and significantly inhibited the protein expression of IN¬OS, COX2 and the NF-kB signaling pathway. Conclu¬sions L-SK has good anti-inflammatory effects in LPS-induced inflammation in RAW 264. 7 cells in vitro. Il inhibits the protein expression of phosphorylated P65 and IKKaαβ in the NF-kB signaling pathway, thereby suppressing the anti-inflammatory effects in vitro and L- Shikonin has protective effects against acute liver injury in mice. © 2023 Publication Centre of Anhui Medical University. All rights reserved.     

Mechanism of Modified Danggui Shaoyao San in treatment of chronic atrophic gastritis based on network pharmacology and experimental verification北大核心CSCD

Aim To predict the targets of Modified Danggui Shaoyao San ( MDSS) in the treatment of chronic atrophic gastritis ( CAG) based on network pharmacology and vertify the results based on experim-ention. Methods TCMSP, SWISS TARGETS, GENE CARDS and OMIM databases were used to screen the therapeutic targets of MDSS for CAG. STRING database and Cytoscape software were used to construct the protein interaction network and screen the core targets. Metascape database was used for GO analysis and KEGG enrichment pathways. And molecular docking was used for target validation. CAG rat model was pre¬pared by N-methyl-N'-nitroso-N-nitroguanidine free drink combined with sodium salicylate gastric lavage. The pathology of rat gastric mucosa was observed by hematoxylin-eosin staining,and the ultrastructure of ep¬ithelial cells was observed by transmission electron mi-croscopy. The serum IL-6 and IL-10 content was detected by enzyme-linked immunosorbent assay, and the expression of JAK2, STAT3 , p-STAT3 , c-MYC mRNA and protein in rats was detected by qPCR and Western blot. Results MDSS acted on 189 targets, mainly involved in response to oxidative stress and apoptotic signaling pathway. KEGG analysis related to pathways in cancer and JAK-STAT signaling pathway. The experimental results showed that the MDSS could improve the degree of atrophy of gastric mucosa in CAG rats and improve the status of epithelial cells, down-regulate the serum IL-6 content of CAG rats, up-regulate the IL-10 content, and reduce the expression of JAK2, STAT3 , p-STAT3 , c-MYC mRNA and protein in gastric mucosa with statistical significance. Conclusions MDSS treats CAG through multiple active ingredients, targets, and pathways, the mechanism of which may be related to the inhibition of the JAK2/STAT3 signaling pathway. © 2023 Publication Centre of Anhui Medical University. All rights reserved.     

Effect of a novel phosphodiesterase type 5 inhibitor,CPD1, on carbon tetrachloride-induced liver fibrosis in mice北大核心CSCD

Aim To investigate the effects of CPD1, a novel phosphodiesterase 5 inhibitor, on liver pathological phenotype and hepatic stellate cells (HSCs) activation in hepatic fibrosis model mice caused by carbon tetrachloride ( CCl4). Methods Male C57BL/6 J mice were divided into four groups randomly ( control group, CCl4group, CCl4+ CPD1 group and CCl4+ tadalafil group) . Hepatic fibrosis model was construc¬ted by intraperitoneal injection of CCl4( twice a week) . Four weeks after CCl4injection, the mice were treated with CPD1 (2 mg kg-1• d-1) , or Tadalafil (10 mg • kg-1• d-1) by intragastric administration, respec¬tively, for four weeks. Hematoxylin-eosin staining and Sirius Red staining were used to observe the distribu¬tion of liver tissue structural lesions and fibrosis. Im-munohistochemical staining was used to detect the ex¬pression of a-smooth muscle actin ( a-SMA) and fi-bronectin. Results Compared with control group, the liver tissue structure was seriously damaged in CCl4group with many hepatocytes necrosis and inflammatory cell infiltration, indicating that liver injury occurred in the CCl4-induced hepatic fibrosis model mice. Moreo¬ver, the expressions of a-SMA increased significantly in CCl4group. Compared to CCl4group, the liver tissue damage was significantly improved in PDE5 inhibitors group,most notably, CPD1 had a better curative effect than tadalafil did. Furthermore, CPD1 inhibited the ex¬pression of a-SMA markedly and reduced the expres-sion of ECM-related proteins induced by transforming growth factor pi ( TGF-f31 ) in Lieming Xu-2 ( LX-2 ) cells. Conclusions Phosphodiesterase 5 inhibitor CPD1 strongly alleviates CCl4-induced hepatic damage by inhibiting the activation of HSCs and expression of collagen fibers. © 2023 Publication Centre of Anhui Medical University. All rights reserved.     

吗多明和N-硝基-L-精氨酸甲基酯抑制小鼠胚胎着床以及子宫内膜的细胞凋亡

AIM: To investigate the possible effect of nitric oxide on receptivity and apoptosis of mouse endometrium and the possible pathway. METHODS: Female pregnant mice were treated with either molsidomine, a generator of nitric oxide (NO), or N-omega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthase. The pregnancy rates of each group were calculated; 3'-end-labeling was used to detect DNA fragmention of apoptotic cells;immunohistochemistry, in situ hybridization, and Western blot were applied respectively to estimate expression levels of Fas/FasL proteins and mRNA. RESULTS: The pregnancy rate in the drug treated group was reduced in a dose-dependent manner; apoptosis, Fas protein and mRNA levels in the endometrium of drug treated mice were correlatively decreased during the peri-implantation period. CONCLUSION: The decreased pregnant rate in mice by abnormal levels of nitric oxide may be brought about by inhibiting the normally occurrence of apoptosis in the receptive endometrium.     

Molsidomine and N-omega-nitro-L-arginine methyl ester inhibit implantation and apoptosis in mouse endometrium

AIM: To investigate the possible effect of nitric oxide on receptivity and apoptosis of mouse endometrium and the possible pathway. METHODS: Female pregnant mice were treated with either molsidomine, a generator of nitric oxide (NO), or N-omega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthase. The pregnancy rates of each group were calculated; 3'-end-labeling was used to detect DNA fragmention of apoptotic cells; immunohistochemistry, in situ hybridization, and Western blot were applied respectively to estimate expression levels of Fas/FasL proteins and mRNA. RESULTS: The pregnancy rate in the drug treated group was reduced in a dose-dependent manner; apoptosis, Fas protein and mRNA levels in the endometrium of drug treated mice were correlatively decreased during the peri-implantation period. CONCLUSION: The decreased pregnant rate in mice by abnormal levels of nitric oxide may be brought about by inhibiting the normally occurrence of apoptosis in the receptive endometrium.     

Effect of total flavonoids of Rosa rugosa on PI3K/AKT pathway and endoplasmic reticulum stress apoptosis in rats with cerebral ischemia-reperfusion injury北大核心CSCD

Aim To investigate the effects of total flavonoids from Rosa rugosa (TFR) on cerebral ischemia reperfusion injury (CIRI) in rats, and to investigate whether TFR inhibited neuronal apoptosis by regulating phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) signaling pathway and endoplasmic reticulum stress (ERS) pathways. Methods SD rats were randomly divided into sham operation group, model group, low-dose group (50 mg · kg -1 · d -1), medium-does group (100 mg · kg -1 · d -1), and high-does group (200 mg· kg -1 · d -1). The injury model of middle cerebral artery occlusion/reperfusion (MCAO/R) was prepared following suture method. Neurobehavioral changes, cerebral infarct size and brain tissue water content were detected 24 h after surgery. HE and Nissl staining were performed to observe pathological indicators. TUNEL staining was used to detect the apoptosis of ischemic nerve cells in brain. Western blot was used to detect the protein levels of Bcl-2, Bax, and cleaved Caspase-3, PI3K, p-PI3K, AKT, p-AKT, GRP78, CHOP and Caspase-12. Results Compared with MCAO/R group, the rats in medium-dose group and high-dose group showed improvement in the neurobehavioral function, decrease in the cerebral infarction area and the degree of cerebral edema, and reduction of the pathological damage of cerebral cortex. Moreover, there was a significantly decrease in the apoptosis rate of nerve cells in medium-dose group and high-dose group. The expression of anti-apoptotic protein Bcl-2 increased, and the pro-apoptotic protein Bax and cleaved-Caspase-3 decreased, the expression of pPI3K/PI3K, p-Akt/AKT increased, and the expression of ERS-related protein GRP78, CHOP, Caspase-12 decreased. Conclusions TFR can inhibit neuronal apoptosis by regulating the PI3K/AKT signaling pathway and ERS pathway, thus playing a protective role in CIRI rats. © 2023 Publication Centre of Anhui Medical University. All rights reserved.     

The antitumor effect of cisplatin chemotherapy promoted by Taohong Siwu Decoction on mice with lung adenocarcinoma北大核心CSCD

Aim To study the antitumor effect of cispl-atin ( DDP) chemotherapy promoted by Taohong Siwu Decoction (TSD) on mice with lung adenocarcinoma mice. Methods Lewis lung carcinoma cell line was used to make homologous lung adenocarcinoma trans¬plantation mouse model. Normal control, Model, TSD, DDP, TSD + DDP groups were set up. The change of transplanted tumor volume after administration was observed, the weight of transplanted tumor was weighed, the expression of Ki67 in transplanted tumor tissue was detected by immunohistochemistry, TUNEL was detected by fluorescence staining, Bcl-2, Bax, cleaved Caspase-3 and cleaved Caspase-9 were detected by immunoblotting, and the content of D-dirtier in plasma was measured by ELISA. Results DDP plus TSD significantly inhibited the growth of transplanted tumor. Ki67 expression in tumor tissue was lower than that in DDP group (28. 3% ±3. 1% vs 40. 3% ±2.1% ). The combined use of TSD and DDP significantly promoted the apoptosis level of transplanted tumor. The positive rate of TUNEL was significantly higher than that of DDP group (41. 0% ±3.0% vs 30.7% ± 4.5%). Bax, cleaved Caspase-3 and cleaved Caspase-9 expressions in tumor tissue were also higher than those of DDP group, while the expression of Bcl-2 was significantly lower than that of DDP group. Moreover, we found a significant interaction between TSD and DDP on the expression of four apoptotic proteins ( P < 0.05 ) . The plasma D-dimer content in TSD + DDP group was significantly lower than that in DDP group (188. 50 ± 28. 46 vs 269.80 ± 35.92) μg • L-1(P < 0.05). Conclusion TSD may promote the inhibitory effect of DDP chemotherapy on transplanted lung adenocarcinoma by alleviating carcinoma hy-percoagulale state. © 2023 Publication Centre of Anhui Medical University. All rights reserved.     

Inhibitory effect of combination of tanshinone I,metformin and aspirin on malignant melanoma model mice北大核心CSCD

OBJECTIVE: To explore the antitumor effects of combined tanshinone I (Tan I), metformin (Met) and aspirin (Asp) on malignant melanoma in mice and the possible mechanisms. METHODS: C57BL/6 mice were injected with 0.1 mL B16F10 cells (2.8×109 L-1) to establish the subcutaneous transplantation tumor model at the right forelimbs axillary. Then, the mice were divided into 8 groups according to body mass, including model group, Tan I group (20 mg.kg-1 ip), Asp group (210 mg.kg-1, orally in drinking water), Met group (70 mg.kg-1, orally in drinking water), Asp+Met group, Tan I +Asp group, Tan I +Met group and Tan I +Asp+Met group, 10 mice in each group. Each mouse drank about 7 mL of water every day for a total of 18 d. The mouse body mass was measured every other day and the tumor diameter was calculated every day. The mice were sacrificed after treatment, the tumor mass was measured and the tumor inhibitory rates were counted. The histopathological changes of the liver and spleen were observed with HE staining. The percentage of lymphocytes in the tumor tissue such as CD8T, CD4+T and Treg cells was detected by flow cytometry. Inflammatory factors such as interleukin-6 (IL-6), IL-1β and tumor necrosis factor-α (TNF-α) were detected by ELISA. RESULTS: The body mass (including tumor mass) of mice in different groups increased during the experiment, but that of Tan I + Asp+Met group increased more slower than in model group (P<0.01). At the end of the experiment, no lesions were seen in any liver or spleen tissue by pathological observation, and the number of survivors was 8/10 (model group), 8/10 (Tan I group), 7/10 (Asp group), 7/10 (Met group), 8/10 (Tan I +Asp group), 8/10 (Tan I +Met group), 7/10 (Asp + Met group) and 5/10 (Tan I +Asp+ Met group), respectively. Compared with model group, there were no obvious changes in tumor volume or tumor mass in Tan I, Asp and Met groups and other two-two joint groups, but the tumor volume and tumor mass in Tan I + Asp+ Met group were significantly decreased (P<.01, P<0.05), and the tumor inhibitory rate in this group was 46.2%. Compared with the model group, the percentage of CD8+T cells increased (P<0.05) in Tan I + Asp+ Met group, but there were no significant changes in other groups. The contents of IL-6, IL-1β and TNF-α in tumor tissue of Tan I +Met group were much higher than in model group (P<0.01, P<.05, P<0.05) and the content of IL-6 increased in Tan I +Asp+Met group (P<0.01). CONCLUSION: Combination of Tan I, Asp and Met can effectively inhibit the growth of melanoma in mice, which may be related to the increasing percentage of CD8+T lymphocytes and IL-6 in tumor tissue. However there are possibly some side effects. © 2017 Chinese Journal of Pharmacology and Toxicology. All rights reserved.     

Effect and mechanism of baicalein on 2,4,6-trinitrobenzene sulfonic acid-induced experimental colitis of mice北大核心CSCD

OBJECTIVE: To explore the effect and mechanisms of baicalein on 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced experimental colitis in mice. METHODS: BALB/c mice were randomly placed into three groups (n=10): normal control group, TNBS group, and TNBS+baicalein (20 mg.kg-1, once per day) group. Mouse colitis was induced by intrarectal injection of TNBS. Baicalein was administered by oral gavage two days prior to TNBS treatment and until the end of the study (a total of 9 d). The colon length was measured before HE staining was performed for histological damage assessment. The remaining colon pieces were collected to measure the content of tumor necrosis factor-α(TNF-α). Lipopolysaccharide (LPS)-stimulated RAW264.7 mouse macrophage was used as a cell model to determine the content of nitric oxide (NO) in cell culture medium, the mRNA levels of TNF-α, interleukin-6(IL-6), IL-1β, inducible nitric oxide synthase(iNOS), cyclooxygenase 2(COX-2) and monocyte chemoattractant protein-1 (MCP-1), and the protein expression of phosphatidylinositol 3-kinase/protein kinase B/nuclear factor-κB (PI3K/AKT/NF-κB) pathway. RESULTS: Baicalein significantly attenuated TNBS-induced colon shortening and histological injury (P<0.05), which was correlated with the decline in the content of TNF-α in the colon. According to the in vivo results, baicalein exposure down-regulated the secretion of NO and the mRNA expression of pro-inflammatory mediators (iNOS, COX-2, MCP-1, TNF-α, IL-1β and IL-6) in LPS-stimulated RAW264.7 cells (P<0.05, P<0.01). Additionally, the phosphorylation/activation of LPS-stimulated PI3K/AKT/NF-κB pathway was inhibited by baicalein treatment. CONCLUSION: The beneficial effect of baicalein in TNBS-induced experimental colitis may be due to PI3K/AKT/NF-κB signaling inhibition.     

Study on effect and mechanism of Celastrus Orbiculatus total terpenoids in regulating lipid metabolism

Objective To investigate the effect and mechanism of Celastrus Orbiculatus total terpenoids on lipid metabolism in hyperlipidemia mice.Methods ICR mice were selected as investigated subject.The hyperlipemia mice models were made with feeding high-fat forage and were randomly divided into six groups:the normal group,the model group,the positive control group(treated with simvastatin)and the three groups treated with Celastrus Orbiculatus total terpenoids with low,medium and high dosage,respectively.Each group included eight mice.The control group was fed normal forage,but other groups were fed high fat forage.All groups were allowed to drink water freely.Since the first day when the models were made,intragastric administration had been adopted.The normal group was fed normal forage without intragastric administration;the model group was received physiological saline 20 mL·kg-1·d-1 with intragastric administration;the positive control group received simvastatin 2.6 mg·kg-1·d-1 with intragastric administration;the three treated groups received Celastrus Orbiculatus total terpenoids 60 mg·kg-1·d-1,120 mg·kg-1·d-1,200 mg·kg-1·d-1 with intragastric administration respectively.Each group was weighed once a week.On the basis of establishing hyperlipidemia mice model,blood lipids,lipid metabolic enzyme,antioxidative capacity were investigated after 21 days feeding of high-fat forage.Results Compared with model group,TC and TG in mice treated with Celastrus Orbiculatus total terpenoids all reduced and HDL-C raised obviously(P<0.01).Celastrus orbiculatus total terpenoids was shown to decreased MDA content in both serum and liver,increased serum SOD activity and inhibited the activity of the cholesteryl ester transfer protein(CETP).Conclusions Celastrus Orbiculatus total terpenoids could remarkably modulate the lipid metabolic disorder in hyperlipidemia mice,and has a certain regulating function on lipoprotein,inferring that it could reduce the occur of atherosclerosis.The mechanism of regulating lipid metabolism might be related with decreasing the activity of CETP and increasing antioxidative capacity.     

Effects of valsartan with or without benazepril on blood pressure,angiotensin Ⅱ,and endoxin in patients with essential hypertension

AIM：To eveluate the effects of valsartan(Val)with or without benazepril(Ben)on blood pressure and plasma levels of angiotensin(Ang Ⅱ)and digoxin-immunoreactive factors(endoxin)in patients with essential hypertension. METHODS:Ninety patients with essential hypertension were randomly divided into 3 groups(n=30 per group):Ben group(Ben 10 mg/d,po);Val group(Val 80mg/d,po);combination drug therapy group(Val 80mg/d Ben 10mg/d,po);all patients were treated for 12 weeks.Age and sex-matched 20 normal subjects were served as control group.RESULTS:The levels of plasma endoxin and ang Ⅱ in patients with essential hypertension were remarkably higher than those in normal subjects.The levels of plasma ang Ⅱ and endoxin were all obvious positive correlation with systolic blood pressure(SBP)and diastolic blood pressure(DBP)(Ang Ⅱ:r=0.5151,0.7978;endoxin:r= 0.4706,0.7274,respectively),within 6 weeks of drug intervene,SBP and DBP were remarkably decreased in 3 groups.After 6 weeks,SBP and DBP were continuously decreased in Ben group and Val Ben group,but not in Val group.Level of plasma AngⅡ was remarkably decreased as SBP and DBP decreased in Ben group and Val Ben group;level of plasma AngⅡ was remarkably increased in Val group.CONCLUSION:Val with or without Ben remarkably decreased SBP and DBP in patients with essential hypertension within 6 weeks.Antihypertensive efficacy was weakened after long-term use of Val alone.The antihypertensive effect of Val Ben group was the most remarkable among 3 groups and could avoid the side effects of high plasma AngⅡ.     

Effect of ECR on the Expression of Tau from the Brain of the Mice Induced by Overload Aluminum Salt

Aim: To study the effect of Ecdysterone (ECR) on the expression of Tau from the cerebral cortice and hippocampus and behaviors in passive avoidance reaction and spatial discrimination of the mice induced by overload aluminum salt.Methods Fourty-five NIH mice were randomly divided into five groups, the control group, the model group, the treated     

Effect of phillygenin on inflammatory response of A549 cells induced by lipopolysaccharide and normal human plasma北大核心CSCD

Aim To investigate the effect of phillygenin ( PHI) on lipopolysacchride ( LPS) and normal human plasma ( NHP) induced inflammatory injury on alveolar type II epithelial A549 cells and the related mechanism. Methods A549 cells were exposured to 1 mg • L -1 of LPS and 5% NHP to build the inflammatory injury model. The effects of PHI on cell viability, cell number, area, morphology, and DNA content of A549 cells were detected by thiazole blue colorimetric (MTT) and Hoechst 33342 staining. The A549 cells were pretreated with PHI for 2 h, and then exposed to 1 mg • L -1 of LPS and 5% NHP. The contents of inflammatory cytokines and NF-κB p65 were determined by ELISA and quantitative real-time PCR. The transfer of NF-κB p65 from cytoplasm to nucleus was detected by cellular immunofluorescence. The protein expres¬sions of NF-κB and MAPK signaling pathways were de¬tected by Western blot. Results The contents of IL-6 and IL-8 and the transfer of NF-κB p65 from cytoplasm to nucleus were significantly up-regulated in LPS combined with NHP co-stimulated group. PHI at 1, 10, 50, and 100 jjimol • L -1decreased the mRNA and protein expressions of IL-6 and IL-8 , inhibited the transfer of NF-κB p65 from cytoplasm to nucleus, reduced the NF-κB p65 mRNA level, down-regulated the phospho-rylation levels of IκBα, NF-κB p65, p38, JNK, and ERK, and up-regulated the protein expression of IκBα in a dose-dependent manner. Conclusions LPS combined with NHP successfully induces inflammatory injury in alveolar type II epithelial A549 cells. PHI could improve the inflammatory response by inhibiting the activation of LPS-TLR4-NF-κB/MAPK signaling pathways. © 2023 Publication Centre of Anhui Medical University. All rights reserved.     

Effect of telmisartan on expression of protein kinase C-α in kidneys of diabetic mice

Aim： To investigate the effects of angiotensin receptor blocker （ARB） telmisartan on the expression and distribution of protein kinase C （PKC）-α in the kidneys of diabetic mice. Methods： Diabetic mice were induced with streptozotocin and a group of them were randomly selected for treatment with telmisartan. After 6 weeks, the expression and localization of PKC-α in the renal cortex, and the outer and inner medulla were assessed by immunohistochemistry and semiquantitative Western blotting. In addition, expressions of PKC-α, transforming growth factor- β1 （TGF-β1）, and vascular endothelial growth factor （VEGF） in glomeruli were measured by semiquantitative immunohistochemistry. Results： Diabetic and normal mice showed similar distributions of PKC-α in the kidneys. The expression of PKC-α was found in glomeruli, epithelial cells of proximal tubules, and medullary- collecting duct, while not in the medullary and cortical thick ascending limb, and was different in the epithelial cells of proximal tubules of diabetic nephropathy （DN） mice, PKC-α was mostly translocated from the basement membrane to the apical membrane, whereas it was largely translocated from the apical membrane to the basement membrane in epithelial cells of the inner medullary-collecting duct. Western blotting detected increased expression of PKC-α in the renal cortex and outer medulla, but not in the inner medulla of DN mice. Enhanced expressions of PKC-α, TGF-β1, and VEGF were shown in the glomeruli of DN mice, where PKC-α exhibited a correlation to VEGF, but no correlation to TGF-β1. ARB telmisartan attenuated alterations of PKC-α as mentioned earlier in the DN mice. Conclusion： Our findings suggest that PKC-α may play a role in the pathogenesis of DN, and that the nephroprotective effects of ARB telmisartan may be partly associated with its influence on PKC-α.     

Tetramethylpyrazine protected photoreceptor cells of rats by modulating nuclear translocation of NF-κB

Aim: To evaluate the effect of tetramethylpyrazine (TMP) injection on retinal damage induced by N-methyl-N-nitrosourea (MNU) in rats and on nuclear factorkappa B (NF-κB) family members. Methods: Female Sprague-Dawley (SD) rats were randomly divided into groups: (i), control group; (ii), model group; and (iii), TMP-injection groups, in which the rats were subdivided into 40 mg/kg, 80 mg/kg and 160 mg/kg groups. Drugs were injected ip into 47-day-old SD rats once a day. At 50 days of age, all rats in the model group and drug groups also received a single ip injection of 60 mg/kg MNU. Rats in group 1 received ip injection of physiological saline. All rats were killed at different times after MNU or physiological saline treatment. The apoptotic index of photoreceptor ceils was calculated by TUNEL labeling; retinal damage was evaluated based on retinal thickness and the expression of NF-nB family members was detected by Western blot. Results: TMP injections, in a dose-dependent manner, suppressed photoreceptor cell apoptosis and decreased its loss in the peripheral retina. As compared with the MNU-treated group, TMP injection at a dose of 160 mg/kg also timedependently upregulated the NF-κB/p65 protein level in the nucleus and downregulated the IκBα protein level in the cytoplasm. However, no protective effect of TMP injection on MNU-induced central retinal damage was found. Conclusion: TMP injection partially protects against MNU-induced retinal damage by upregulating the nuclear translocation of p65 to inhibit photoreceptor cells apoptosis.     

Effect of α-asarone on ethanol-induced learning and memory impairment in mice and its underlying mechanism

OBJECTIVE To investigate the effect ofα-asarone on ethanol-impaired cognitive ability and explore the underlying mechanism in mice. METHODS A mouse model of impaired learning and memory was created by ethanol(2.0 g · kg~(-1), ig). α-Asarone(7.5, 15 and 30 mg·kg~(-1), ip) was delivered 10 min prior to ethanol administration. After 40 min, the locomotor activity of mice with learning and memory impairment was evaluated by the open field test and the behavioral effect of α-asarone was evaluated using the novel object recognition test.Glutamate(Glu) and γ-aminobutyric acid(GABA) levels in the hippocampus were determined by ELISA, and the proteins expression levels of hippocampal α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid(AMPA) receptor(Glu R2), N-methyl-D-aspartic acid(NMDA)receptor(NMDAR2 B), synaptophysin I(SYNΙ), glutamate transporter type 1(GLT-1) and calcium/calmodulindependent protein kinaseⅡ(Ca MKⅡ) were detected by Western blotting. RESULTS There was no significant difference in the horizontal or vertical locomotor activity between the ethanol and normal groups or the 7.5, 15 and 30 mg·kg~(-1)α-asarone groups[F(5, 48)=0.6536, P>0.05; F(5, 49)=1.995, P>0.05]. The recognition index in the ethanol group was significantly decreased as compared with that in the normal group[F(5, 46) =6.739, P<0.05]and was markedly increased in the α-asarone groups as compared with that in the ethanol group(P<0.05), with the exception of the 7.5 mg · kg~(-1)α-asarone group(P>0.05). The hippocampal Glu: GABA ratio in mice was significantly elevated in the ethanol group as compared with that in the normal group(33.42±0.8972 vs 30.79±0.2102, P<0.05) and significantly lower in the α-asarone groups(31.99±0.4986 vs. 33.42±0.8972; 30.97±0.1757 vs. 33.42±0.8972; 30.83 0.1723 vs. 33.42±0.8972, P<0.05). The expression levels of GluR2, NMDAR2B, pSYNⅠand p Ca MKII were significantly higher in the ethanol group as compared with those in the normal group(P<0.05) and obviously lower in the α-asarone groups(P<0.05), with the exception of GluR2, NMDAR2B and pCaMKⅡ in the 7.5 mg·kg~(-1)α-asarone group(P>0.05).And the expression level of GLT-1 was significantly lower in the ethanol group as compared with that in the normal group(P<0.05) and obviously higher in the α-asarone groups(P<0.05). CONCLUSION Pretreatment with α-asarone significantly improved the learning and memory impairment. A possible underlying mechanism is regulation of the calcium signaling cascade to correct functioning of related proteins, and thus, maintain the level of Glu.