Effects of the proliferation, migration and apoptosis of AHVAC - on gastric cancer MKN-28 cells / 中国临床药理学与治疗学

AIM: To investigate the effects of agkis-trodon halys venom anti-tumor component (AHVAC-) on the biological behavior of gastric cancer MKN-28 cells. METHODS: Gastric cancer MKN-28 cells were treated with the experimental concentrations (5, 10, 15 μg/mL) of AHAVC- for 24 h. Cell proliferation and toxicity assay (cell counting kit-8, CCK-8) was used to detect the inhibition rates of the cells in different concentrations of AHVAC-. The migration ability of the cells was evaluated by wound-healing and Transwell assay. The apoptosis were observed by laser confocal microscopy with annexin V-mCherry/DAPI double staining, and the apoptosis rates were analyzed by flow cytometry with annexin V-FITC/PI double fluorescence staining. The protein level of Caspease-3 was determined by Western blot. RESULTS: Compared with normal control group, the results of AHVAC- concentration groups showed that with the increase of AHVAC- concentration, the proliferative activity of MN-28 cells decreased gradually (P<0.01), the cell migration ability decreased gradually (P<0.01), and the cell apoptosis rate increased (P<0.05). The expression of apoptosis-related protein Caspease-3 was up-regulated (P<0.01). CONCLUSION: AHVAC- inhibits proliferation and migration of gastric cancer MSN-28 cells and induces apoptosis.

Geraniol attenuates cerebral ischemia-reperfusion injury in rats by regulating oxidative stress via Nrf2/HO-1 pathway / 中国药理学通报

Aim To investigate the regulatory effect of geraniol on Nrf2/HO-1 signaling pathway after cerebral ischemia-reperfusion(I/R)in rats. Methods In this experiment,all the male SD rats were randomly divided into nine groups receiving the following treatments:sham operation(sham); sham operation+200 mg·kg-1 geraniol; I/R; I/R+50 mg·kg-1 geraniol; I/R+100 mg/kg geraniol; I/R+200 mg·kg-1 geraniol; edaravone; I/R+ brusatol(Nrf2 inhibitor); I/R+200mg·kg-1 geraniol+brusatol. All rats received intraperitoneal injection of geraniol for five consecutive days before MCAO and again after MCAO. During the construction of cerebral I/R injury models,the blood vessels were isolated without any suture in the sham operation and the sham operation +200 mg·kg-1 geraniol groups while the blood vessels with suture in other groups. The damage of neurological function was evaluated by the modified rating scale for neurological function. The TTC,HE and Tunel staining methods were used to determine the cerebral infarction volume,the damage of the ischemic cortex and the apoptosis of cortical cells,respectively. The oxidative stress-related parameters then were measured. The protein expressions of Nrf2 and HO-1 were detected by immunohistochemical staining and the target protein expressions of the injured cortex were detected by Western blot. Results Compared with the model group,it was found that the geraniol treatment significantly repaired neural injury,reduced cerebral infarction volume,cerebral cortex damage and cell apoptosis. Meanwhile,geraniol intervention could significantly increase the expression of Nrf2/HO-1 protein in the right-sided cortex and reduce oxidative stress level. Conclusion Geraniol can attenuate cerebral injury induced by ischemia-reperfusion in rats via activating Nrf2/HO-1 signaling pathway.

Research progress in RIPK3 and its inhibitors / 中国药理学通报

Receptor-interacting serine/threonine-protein kinase 3(RIPK3),a member of the RIP kinase family,plays an important role in cell death,especially in necroptosis. In addition,RIPK3 is also involved in apoptosis and pyroptosis,suggesting that RIPK3 may be the intersection of multiple cell death and it possesses the potential to be a target for precise regulation of cell death. According to the kinase binding mode,current RIPK3 inhibitors can be classified into type ,type Ⅱ and other types. This review summarizes the research progress in the role of RIPK3 in cell death and its inhibitors,which is of great significance in seeking drugs for the treatment of injury-related diseases.

Effect of exogenous hydrogen sulfide on hypoxia/reoxygenation injury in glomerular mesangial cells and its mechanism / 中国药理学通报

Aim To explore the effect of exogenous hydrogen sulfide ( H2 S ) on hypoxia/reoxygenation ( H/R) injury in glomerular mesangial cells and elucidate its relevant mechanism. Methods H/R induced mouse mesangial cell line ( SV40MES13 ) to establish cell damage model. Cell viability was detected by cell proliferation kit ( CCK8 ), the content of H

Benzyl isothiocyanate induces cell cycle arrest and apoptosis in cervical cancer through activation of p53 and AMPK-FOXO1a signaling pathways / 中国药理学通报

Aim To investigate the effect of benzyl iso-thiocyanate (BITC) on the proliferation of mouse U14 cervical cancer cells and to explore the mechanism of cytotoxicity based on transcriptomic data analysis. Methods The effect of BITC on U14 cell activity was detected by MTT, nuclear morphological changes were observed by Hochest 33258 and fluorescent inverted microscope, cell cycle and apoptosis were determined by flow cytometry, and the transcriptome database of U14 cells before and after BITC (20 μmol · L

Mechanism of oxymatrine promoting the apoptosis of osteosarcoma MG63 cell line through mitophagy mediated by COX-2/PINK1/Parkin signaling pathway / 中国药房

OBJECTIVE To study the mechanism of oxymatrine inducing apoptosis of osteosarcoma MG63 cell line based on mitophagy mediated by cyclooxygenase-2 （COX-2）/PTEN-induced putative kinase-1 （PINK1）/Parkinson disease protein-2 （Parkin） signaling pathway. METHODS MG63 cells were treated with 2.0， 4.0， 8.0 mg/mL oxymatrine and 6 μmol/L 5-fluorouracil， then the apoptotic rate， the expression of apoptosis-related proteins [B-cell lymphoma-2 （Bcl-2）， Bcl-2 related X protein （Bax）]， the proportion of decrease in mitochondrial membrane potential， the level of mitophagy as well as the protein expressions of PINK1， Parkin， and microtubule-associated protein 1 light chain-3Ⅱ （LC3-Ⅱ） were detected. PINK1 small interfering RNA （siRNA） was adopted to intervene in the expression of PINK1， the cells were divided into control group， PINK1 siRNA group， oxymatrine group， and PINK1 siRNA+oxymatrine group； the protein expressions of PINK1， Parkin， and LC3-Ⅱ， the proportion of decrease in mitochondrial membrane potential （MMP） as well as apoptotic rate were detected. The lentivirus infection technique was used to overexpress COX-2， the cells were divided into control group， oxymatrine group， COX-2 group， and COX-2+oxymatrine group. The protein expressions of COX-2， PINK1， and Parkin， as well as the proportion of decrease in MMP were detected. RESULTS After being treated with oxymatrine， the apoptotic rate， the protein expressions of Bax， PINK1， Parkin， and LC3-Ⅱ， the level of mitophagy as well as the proportion of decrease in MMP were significantly increased （P＜0.05）， while the protein expression of Bcl-2 was significantly decreased （P＜0.05）. Compared with the oxymatrine group， the protein expressions of PINK1， Parkin， and LC3-Ⅱ， apoptotic rate and the proportion of decrease in MMP were significantly decreased in PINK1 siRNA+oxymatrine group （P＜0.05）. Compared with the oxymatrine group， the protein expression of COX-2 in the COX-2+oxymatrine group was increased significantly （P＜0.05）， while the protein expressions of PINK1 and Parkin as well as the proportion of 526087266@qq.com decrease in MMP were decreased significantly （P＜0.05）. CONCLUSIONS Oxymatrine can mediate the overactivity of mitophagy based on the PINK1/Parkin signaling pathway by inhibiting COX-2 expression， thus promoting the apoptosis of the MG63 osteosarcoma cell line.

Effect of Guipitang on ERK1/2 and p38 MAPK in Rats with Myocardial Ischemia / 中国实验方剂学杂志

ObjectiveTo explore the therapeutic effect and mechanism of Guipitang on rats with myocardial ischemia. MethodFifty SD rats were divided into five groups： a control group， a model group， low and high-dose Guipitang （7.52， 15.04 g·kg-1） groups， and a trimetazidine group （0.002 g·kg-1）. By intragastric administration of vitamin D3 and feeding rats with high-fat forage and injecting isoproterenol， the rat model of myocardial ischemia was established. After drug treatment of 15 d， an electrocardiogram （ECG） was performed to analyze the degree of myocardial injury. A fully automatic biochemical analyzer was used to detect the changes in the serum levels of total cholesterol （TC）， high-density lipoprotein cholesterol （HDL-C）， triglyceride （TG）， and low-density lipoprotein cholesterol （LDL-C）. Hematoxylin-eosin （HE） staining and Masson staining were used to observe myocardial histopathological changes. TdT-mediated dUTP nick end labeling （TUNEL） staining was used to detect cardiomyocyte apoptosis. Western blot was adopted to detect the protein levels of extracellular signal-regulated kinase 1/2 （ERK1/2）， phospho-ERK1/2 （p-ERK1/2）， p38 mitogen-activated protein kinase （p38 MAPK）， phospho-p38 MAPK （p-p38 MAPK）， B-cell lymphoma-2 （Bcl-2）-associated X （Bax）， Bcl-2， and cleaved cysteine aspartate proteolytic enzyme （cleaved Caspase-3）. ResultCompared with the control group， the ECG S-T segment decreased in the model group. The serum levels of TC， TG， and LDL-C were increased significantly （P<0.05）. The arrangement of myocardial tissue was disordered， and the proportion of cardiomyocyte apoptosis increased. The protein levels of cleaved Caspase-3， Bax， and p-p38 MAPK in the heart were increased， and the Bcl-2 expression was decreased （P<0.05）. Compared with the model group， the S-T segment downward shift was restored in the low and high-dose Guipitang groups and trimetazidine group， and the levels of TC， TG， and LDL-C were decreased. The protein expression of cleaved Caspase-3 and Bax in the heart dropped， and p-p38 MAPK and p-ERK1/2 protein expressions increased significantly （P<0.05）. The degree of myocardial injury was alleviated， and the proportion of cardiomyocyte apoptosis decreased. Bcl-2 protein expression was increased significantly in the low-dose Guipitang group （P<0.05）. ERK1/2 and p38 MAPK proteins had no significant difference among different groups. ConclusionGuipitang could alleviate myocardial injury and inhibit cardiomyocyte apoptosis in rats by activating the expression of ERK1/2 and p38 MAPK.

Cordycepin, a metabolite of Cordyceps militaris, inhibits xenograft tumor growth of tongue squamous cell carcinoma in nude mice / 南方医科大学学报

OBJECTIVE@#To evaluate the inhibitory effect of cordycepin on oral cancer xenograft in nude mice and explore the underlying mechanisms.@*METHODS@#Sixteen BALB/c mice bearing subcutaneous human tongue squamous cell carcinoma (TSCC) TCA-8113 cell xenografts were randomized into model group and cordycepin treatment group for daily treatment with saline and cordycepin for 4 weeks. After the treatment, the tumor xenografts were dissected and weighed to assess the tumor inhibition rate. Histological changes in the heart, spleen, liver, kidney, and lung of the mice were evaluated with HE staining, and tumor cell apoptosis was examined using TUNEL staining; The expressions of Bax, Bcl-2, GRP78, CHOP, and caspase-12 in the xenografts were detected using RT-qPCR and Western blotting.@*RESULTS@#Cordycepin treatment resulted in a tumor inhibition rate of 56.09% in the nude mouse models, induced obvious changes in tumor cell morphology and significantly enhanced apoptotic death of the tumor cells without causing pathological changes in the vital organs. Cordycepin treatment also significantly reduced Bcl-2 expression (P < 0.05) and increased Bax, GRP78, CHOP, and caspase-12 expressions at both the RNA and protein levels in the tumor tissues.@*CONCLUSION@#Cordycepin treatment can induce apoptotic death of TCA-8113 cell xenografts in nude mice via the endogenous mitochondrial pathway and endoplasmic reticulum stress pathways.

Dihydromyricetin Alleviates H9C2 Cell Apoptosis and Autophagy by Regulating CircHIPK3 Expression and PI3K/AKT/mTOR Pathway / 中国结合医学杂志

OBJECTIVE@#To investigate the effect and potential mechanism of dihydromyricetin (Dmy) on H9C2 cell proliferation, apoptosis, and autophagy.@*METHODS@#H9C2 cells were randomly divided into 7 groups, namely control, model, EV (empty pCDH-CMV-MCS-EF1-CopGFP-T2A-Puro vector), IV (circHIPK3 interference), Dmy (50 µ mol/L), Dmy+IV, and Dmy+EV groups. Cell proliferation and apoptosis were detected by cell counting kit-8 assay and flow cytometry, respectivley. Western blot was used to evaluate the levels of light chain 3 II/I (LC3II/I), phospho-phosphoinositide 3-kinase (p-PI3K), protein kinase B (p-AKT), and phospho-mammalian target of rapamycin (p-mTOR). The level of circHIPK3 was determined using reverse transcriptase polymerase chain reaction. Electron microscopy was used to observe autophagosomes in H9C2 cells.@*RESULTS@#Compared to H9C2 cells, the expression of circHIPK in H9C2 hypoxia model cells increased significantly (P<0.05). Compared to the control group, the cell apoptosis and autophagosomes increased, cell proliferation rate decreased significantly, and the expression of LC3 II/I significantly increased (all P<0.05). Compared to the model group, the rate of apoptosis and autophagosomes in IV, Dmy, and Dmy+IV group decreased, the cell proliferation rate increased, and the expression of LC3 II/I decreased significantly (all P<0.05). Compared to the control group, the expressions of p-PI3K, p-AKT, and p-mTOR in the model group significantly reduced (P<0.05), whereas after treatment with Dmy and sh-circHIPK3, the above situation was reversed (P<0.05).@*CONCLUSION@#Dmy plays a protective role in H9C2 cells by inhibiting circHIPK expression and cell apoptosis and autophagy, and the mechanism may be related to PI3K/AKT/mTOR pathway.

Effects of VALD-3,a derivative of o-vanilla Schiff base ligand,on proliferation,migration and apoptosis of colorectal cancer cells and its mechanism / 中国生物制品学杂志

@#Objective To the effects of VALD-3,a derivative of o-vanilla Schiff base ligand,on proliferation,migration and apoptosis of colorectal cancer cells and evaluate its mechanism.Methods HT-29 and HCT116 cells were cultured in vitro,and the inhibitory effects of VALD-3(5,10,20 and 40 mg/L) on proliferation of the two kinds of cells were detected by MTT assay;The effects of VALD-3(10,20 and 40 mg/L) on the morphological changes of the cells were observed by inverted microscope,while the effects on the migration ability of HT-29 cells were detected by cell scratch test,and the effects on the apoptosis of HT-29 cells were detected by flow cytometry and Hoechst 33258 fluorescence staining;The effects of VALD-3(5,10,20 and 40 mg/L) on the expression of apoptosis-related proteins in HT-29 cells were detected by Western blot.Negative control groups were set up(with no VALD-3).Results Compared with the negative control group,the survival rates of HT-29 and HCT116 cells in 10,20 and 40 mg/L VALD-3 treated groups significantly decreased(t=7.717～2 006.148,each P <0.05);the number of HT-29 and HCT116 cells in 10,20 and 40 mg/L VALD-3groups decreased significantly with the increase of VALD-3 concentration,the cells appeared irregular morphology and gradually became round and smaller,and cell fragments increased;In 10,20 and 40 mg/L VALD-3 treated groups,the migration rate of HT-29 cell scratches decreased significantly(t=7.596～73.780,each P <0.01),the apoptosis rate increased significantly(t=7.092～8.057,each P <0.01),and the number of apoptotic cells increased significantly with strong bright blue fluorescence,chromatin concentration and nuclear fragmentation;The levels of cleaved caspase-3 and Bax protein in HT-29 cells treated with 5,10,20 and 40 mg/L VALD-3 significantly increased(t=2.998～24.901,each P <0.05),the level of Bcl-2 protein in 40 mg/L VALD-3 group decreased significantly(t=10.035,P <0.05),and the levels of cleaved caspase-8 in 20 and 40 mg/L VALD-3 group significantly increased(t=12.630 and 8.064 respectively,each P <0.01).Conclusion VALD-3 inhibited the proliferation and migration of colorectal cancer cells and induced apoptosis by regulating the expression of cleaved caspase-3,cleaved caspase-8,Bax and Bcl-2 proteins.

Progress in the effect of fluorosis on skeletal muscle and its related molecular mechanisms / 中华地方病学杂志

Fluoride has dual health effects. Proper amount of fluoride plays an important role in bone development, prevention of dental caries and nervous system activity. Excessive fluoride causes chronic systemic diseases with dental fluorosis and skeletal fluorosis as the main symptoms. Fluorosis causes morphological and structural changes and function damage in skeletal muscle. Low concentration of fluoride induces muscle canal hypertrophy in skeletal muscle, while high concentration of fluoride leads to skeletal muscle atrophy by causing a series of signal pathway abnormalities. Abnormal changes in phosphatidylinositol-3-hydroxykinase/protein kinase B (PI3K/Akt) signal pathway, oxidative stress, and ubiquitin-proteasome pathway all play important roles in skeletal muscle injury caused by fluorosis. In this paper, the effect of fluoride on skeletal muscle and its related molecular mechanisms are reviewed.

Effects of orlistat on the viability of human gallbladder cancer cells / 中华消化外科杂志

Objective:To investigate the effects of orlistat on the viability of human gall-bladder cancer (GBC) cells.Methods:The experimental study was conducted. The human GBC NOZ cells with high expression of FSAN was screened out through in vitro cultivating human GBC-SD, SGC-996 and NOZ cells. The cell proliferation assay, clone formation assay and protein detection experiment were used to analysis of the effects of orlistat on the viability of human GBC cells. Cell grouping: NOZ cells cultured with medium were set as the control group, cultured with medium + 10 μmol/L orlistat were set as the low-dose orlistat group, cultured with medium + 100 μmol/L orlistat were set as the high-dose orlistat group, respectively. Observation indicators: (1) expression of FASN protein in human GBC cells; (2) effects of orlistat on the proliferation of human GBC NOZ cells; (3) effects of orlistat on apoptosis of human GBC NOZ cells. Measurement data with normal distribution were represented as Mean± SD, the ANOVA test was used for comparison between groups and the least significant difference method was used for pairwise comparison. Results:(1) Expression of FASN protein in human GBC cells. Results of western blot showed that the relative expression of FASN protein in human GBC NOZ, GBC-SD and SGC-996 cells was 0.57±0.06, 0.12±0.04 and 0.10±0.02, respectively, showing a significant difference among them ( F=115.67, P<0.05). There were significant differences between the NOZ cells and the GBC-SD or the SGC-996 cells ( P<0.05), and there was no significant difference between the GBC-SD cells and the SGC-996 cells ( P>0.05). (2) Effects of orlistat on the proliferation of human GBC NOZ cells. ① Results of cell proliferation assay showed that the absorbance value of NOZ cells was 2.34±0.12, 1.57±0.08 and 1.07±0.13 in the control group, low-dose orlistat group and high-dose orlistat group, respectively, showing a significant difference among them ( F=205.88, P<0.05). ② Results of clone formation assay showed that the number of NOZ cells clones was 257±23, 153±11 and 83±11 in the control group, low-dose orlistat group and high-dose orlistat group, respectively, showing a significant difference among them ( F=92.64, P<0.05). ③Results of western blot showed that the relative expression of Cyclin-D1 protein of NOZ cells was 2.31±0.10, 1.52±0.05 and 1.23±0.11 in the control group, low-dose orlistat group and high-dose orlistat group, respectively, showing a significant difference among them ( F=120.73, P<0.05). The relative expression of CDK-4 protein of NOZ cells was 1.58±0.04, 1.21±0.02 and 1.19±0.04 in the control group, low-dose orlistat group and high-dose orlistat group, respectively, showing a signifi-cant difference among them ( F=110.45, P<0.05). (3) Effects of orlistat on apoptosis of human GBC NOZ cells. Results of western blot showed that the relative expression of Bcl-2 protein of NOZ cells was 1.07±0.03, 0.36±0.03 and 0.15±0.02 in the control group, low-dose orlistat group and high-dose orlistat group, respectively, showing a significant difference among them ( F=1 242.93, P<0.05). The relative expression of Bax protein of NOZ cells was 0.51±0.03, 0.38±0.05 and 1.38±0.04 in the control group, low-dose orlistat group and high-dose orlistat group, respectively, showing a signifi-cant difference among them ( F=583.51, P<0.05). Conclusion:Orlistat can inhibit the growth of human GBC NOZ cells and promote their apoptosis.

Role and mechanism of tubastatin A in alleviating brain injury after cardiopulmonary resuscitation by inhibiting endoplasmic reticulum stress-mediated cell apoptosis in swine / 中华急诊医学杂志

Objective:To explore the role and mechanism of tubastatin A (TubA) in alleviating brain injury after cardiac arrest and cardiopulmonary resuscitation (CA-CPR) by inhibiting endoplasmic reticulum stress-mediated cell apoptosis in swine.Methods:Twenty-three conventional male white swine, weighing 33-40 kg, aged 4 to 6 months, were divided into 3 groups by random number table method: sham group ( n=6), CA-CPR group ( n=9), and TubA group ( n=8). The CA-CPR swine model was established by 9 min of electrically induced CA through pacing catheter in the right ventricle and then 6 min of CPR in the CA-CPR group. The CA-CPR swine model was established by the same method, and then a dose of 4.5 mg/kg of TubA at 5 min after resuscitation was intravenously infused in the TubA group. The serum concentrations of neuron specific enolase (NSE) and S100β protein (S100β) were measured using ELISA before modeling and at 1, 2, 4 and 24 h after resuscitation. Neurological deficit score (NDS) was evaluated at 24 h after resuscitation. Thereafter, the animals were euthanized, and brain cortex tissues were harvested, and the expression levels of caspase-12 and caspase-3 were measured using immunohistochemistry. Cell apoptosis index was detected by TUNEL assay. The variables among the three groups were compared with one-way analysis of variance and the Bonferroni hoc test using SPSS software. Results:Twenty-four h after resuscitation, the serum concentrations of NSE and S100β were significantly increased, and NDS was markedly elevated in the CA-CPR and TubA groups compared with the sham group (all P<0.05). Compared with the CA-CPR group, serum concentration of NSE starting 2 h after resuscitation and serum concentration of S100β starting 1 h after resuscitation were significantly decreased in the TubA group [NSE (ng/mL): (23.1±2.0) vs. (20.2±2.0) at 2 h, (28.4±2.3) vs. (23.7±1.9) at 4 h, (32.1±2.7) vs. (26.6±2.0) at 24 h; S100β (pg/mL): (2239±193) vs. (1923±101) at 1 h, (2817±157) vs. (2360±141) at 2 h, (3384±250) vs. (2691±210) at 4 h, (3965±303) vs. (3119±260) at 24 h, all P<0.05], and NDS was markedly reduced (240±30 vs. 63±44, P<0.05). At 24 h after resuscitation, brain cortex tissue detection showed that the expression levels of caspase-12 and caspase-3 were significantly increased, and cell apoptosis index was markedly elevated in the CA-CPR and TubA groups compared with the sham group (all P<0.05). However, the expression levels of caspase-12 and caspase-3 were significantly decreased [caspase-12:(7.1±0.7) vs. (4.2±0.4); caspase-3: (13.3±1.6) vs. (7.7±0.8), all P<0.05], and cell apoptosis index was markedly reduced in the TubA group compared to the CA-CPR group [(31.1±8.6) vs. (17.3±2.2), P<0.05]. Conclusions:TubA alleviates brain injury and neurological dysfunction after CA-CPR in swine, which may be related to the inhibition of cell apoptosis mediated by endoplasmic reticulum stress.

Study on the protective mechanism of Bawei chenxiang powder containing serum on H9c2 cells injured by oxygen-glucose deprivation / 中国药房

OBJECTIVE To study the protective mechanism of Bawei chenxiang powder containing serum on H9c2 cells injured by oxygen-glucose deprivation （OGD）. METHODS H9c2 cells were divided into blank group， model group and Bawei chenxiang powder low-dose， medium-dose and high-dose groups （the dose of drug containing serum 2.5， 8， 12 g/kg）. H9c2 cells were cultured in vitro to establish OGD model. After intervention with drug-containing serum， survival rate of cell was detected. The cell morphology was observed； the levels of lactate dehydrogenase （LDH）， creatine kinase （CK）， superoxide dismutase （SOD）， catalase （CAT）， respiratory chain complexⅠ （ComplexⅠ）， glutathione peroxidase （GSH-Px） and malondialdehyde （MDA） were detected. The contents of reactive oxygen species （ROS）， mitochondrial membrane potential and apoptosis were also detected. The expressions of oxidative stress-related proteins [Kelch ECH association protein 1 （Keap1）， nuclear factor erythroid 2- related factor 2 （Nrf2）， heme oxygenase 1 （HO-1）， NADH oxidoreductase coenzyme 10 （Ndufa10）， thioredoxin （Trx）] and apoptosis-related proteins [B-cell lymphoma 2 （Bcl-2）， Bcl-2 associated X protein （Bax）， Caspase-3 and cytochrome C （Cytc）] were detected. RESULTS Compared with blank group， the cell morphology of model group was damaged； the levels of LDH， CK and MDA were significantly increased （P＜0.01）， while the levels of CAT， ComplexⅠ， SOD and GSH-Px and mitochondrial membrane potential were significantly decreased （P＜0.01）. The content of intracellular ROS and apoptotic rate were significantly increased （P＜0.01）； the expressions of oxidative stress-related proteins （Keap1， Nrf2， HO-1， Ndufa10 and Trx） and pro- apoptosis proteins （Bax， Caspase-3 and Cytc） were significantly increased （P＜0.05）， while the expression of anti-apoptotic protein Bcl-2 was significantly decreased （P＜0.05）. After administration of Bawei chenxiang powder containing serum， the cell morphology improved， and most of the above indexes were significantly reversed （P＜0.05 or P＜0.01）.CONCLUSIONS Bawei chenxiang powder containing serum E-mail：345783110@qq.com has a good protective effect on H9c2 cells damaged by OGD，the mechanism of which is related to the reduction of oxidative damage and inhibition of cell apoptosis.

Effects and mechanism of dapagliflozin on myocardial injury in type 1 diabetes mice / 中国临床药理学与治疗学

AIM: To investigate the effect of dapagliflozin on myocardial injury in type 1 diabetes mice and its mechanism. METHODS: Normal C57BL / 6J male mice were randomly divided into normal control group (Control), diabetes cardiomyopathy group (DCM) and dapagliflozin group (DAPA). The model of diabetes was induced by streptozotocin (STZ) and given maintenance feed. DAPA group was given 10 mg · kg

Hippo-YAP pathway is involved in the effect of NaAsO / 中国药理学通报

Aim To explore the effects of NaAsO

Gabapentin effectively alleviates pain sensitization and regulates CACNA2D1 expression in postherpetic neuralgia rats / 中国药理学通报

Aim To identify the molecular target of gabapentin in the treatment of postherpetic neuralgia(PHN). Methods The molecular target of gabapentin for PHN was analyzed by network pharmacology and molecular docking and confirmed by coprecipitation test. Rats were randomly divided into control group, model group, model+50 mg·kg-1 gabapentin group, model+100 mg·kg-1 gabapentin group, and model+200 mg·kg-1 gabapentin group, with nine rats in each group. The pain-related behaviors of the rats were measured at different time points. The mRNA and protein expressions of CACNA2D1, Bax, and Bcl-2 in rat spinal cord were determined by immunofluorescence, Western blot, and qPCR. Results CACNA2D1 was the target gene of gabapentin that determined via network pharmacology, molecular docking, and co-precipitation tests. After modeling, mechanical pain threshold and thermal pain threshold significantly decreased, and the number of apoptotic GABA cells significantly increased. However, after intraperitoneal injection of 50, 100, and 200 mg·kg-1 gabapentin, mechanical pain threshold and thermal pain threshold significantly increased(P<0.05), and the number of apoptotic GABA cells significantly decreased(P<0.01). Immunofluorescence and Western blot results showed that compared with the model group, with the increase of gabapentin concentration, the positive expression rate of Bax significantly decreased, and the positive expression rate of Bcl-2 and CACNA2D1 significantly increased. The mRNA expression levels of Bax, Bcl-2 and CACNA2D1 detected by qPCR were consistent with the results of immunofluorescence and Western blot. Conclusions Gabapentin up-regulates the expression of target protein CACNA2D1, inhibits the proapoptotic protein Bax, and promotes the expression of apoptotic inhibitor Bcl-2.

Molecular mechanism of a Matijin-su derivative for inhibiting proliferation, invasion and migration of prostate cancer cells / 中国药理学通报

Aim To investigate the effects of HXL130 on the proliferation, invasion and migration of prostate cancer PC3 cells and its molecular mechanism. Methods MTT assay was used to detect the effect of HXL130 on the proliferation of prostate cancer PC3 cells. Hoechst 33258 staining and flow cytometry were used to detect the effects on apoptosis and cell cycle of cancer cells. Transwell was used to detect the effects of compounds on the invasion and migration of cancer cells. Proteomic sequencing was employed to detect differentially expressed proteins (DEPs) induced by compound treatment of cancer cells. Bioinformatics was used to analyze the functions of DEPs and the related signaling pathways regulated by DEPs, and Western blot was used to verify the result. Results The survival rate of PC3 cells decreased with the increase of HXL130 concentration and treatment time. HXL130 could significantly induce cell apoptosis and block G

Licochalcone A inhibits osteosarcoma proliferation by Akt/ERK signaling pathway / 中国药理学通报

Aim To investigate the effect of licochalcone A (LCA) on proliferation and apoptosis of osteosarcoma HOS and U2OS cells and to explore its possible molecular mechanism. Methods The HOS and U2OS cells were cultured in vitro. MTT assay was used to detect the proliferation of the cells after being treated with different concentrations of LCA at different intervention time. Then HOS and U2OS cells were treated with 0. 1% DMSO, or different concentrations of LCA (5, 10, 20 μmol/L), and flow cytometry was used to assess the cell apoptosis. The expression of apoptosis-related protein cleaved PARP1, Bcl-2, Bax, and Akt, ERK were detected by Western blot. The antitumor effect of LCA was detected on U2OS xenograft mice in vivo. Results LCA could inhibit the proliferation of HOS and U2OS cells in a time-and dose-dependent manner. Flow cytometry showed that LCA treatment could induce cell apoptosis. Western blot results showed that LCA could inhibit the phosphorylation of Akt and ERK, increase the expression of cleaved PARP1 and Bax, and decrease the expression of Bcl-2. In the tumor-bearing mouse models, LCA significantly decreased the tumor volume (P < 0. 05) and weight (P < 0. 01). Conclusions LCA could inhibit the proliferation of HOS and U2OS and induce apoptosis possibly by inhibiting the Akt/ERK signaling pathway.

Mediation of mitochondrial translocator protein by tanshinone ⅡA in apoptosis of HepG2 cells / 中国药理学通报

Aim To investigate the role of mitochondrial translocator protein(TSPO)in the apoptosis of HepG2 cells induced by tanshinone IIA(Tan II A)and the involved mechanism. Methods Following the HepG2 cells treated with Tan ⅡA at 2.5, 5 and 10 μmol·L-1, the cell viability was determined by MTT assay, and intracellular ATP content was determined by luciferin-luciferase method. Oxygen utilization was measured polarographically with a Clark oxygen electrode. Cell apoptosis was determined by Hoechst 33342 staining and flow cytometry. The mitochondrial membrane potential was assessed with JC-1 staining. The intracellular distribution of TSPO was examined by TSPO immunostaining, and the expressions of TSPO, Cyto C, caspase-3, caspase-9 were determined by immunoblotting analysis. Results Tan II A inhibited the proliferation of HepG2 cells in a dose-and time-dependent manner. The treatment with Tan II A inhibited ATP production and oxygen utilization of mitochondria. In addition, Tan ⅡA enhanced TSPO expression and accumulation in nuclei and up-regulated the expression of Cyto C, caspase-3 and caspase-9. Conclusions Tan II A induces the apoptosis of HepG2 cells, which may be related to the TSPO-mediated mitochondrial dysfunction.