OBJECTIVETo investigate effects of total paeony glucosides (TPGs) on the expressions of Toll receptors (TLR4) and interleukin-33 (IL-33) in the brain tissue of D-galactose-induced aging rats. METHODS; Fifty SD rats were randomly divided into 5 groups, i.e., the blank control group, the model group, the high dose TPG group, the middle dose TPG group, and the low dose TPG group, 10 in each group. Equal volume of normal saline was subcutaneously injected to rats in the blank control group, while 10% D-galactose was subcutaneously injected to rats in the rest groups at 0.125 mL/g, once a day for 8 successive weeks to induce the aging rat model. TPG was administered at 300 mg/kg, 150 mg/kg, and 75 mg/kg to rats in the high, middle, and low dose TPG groups while injecting D-galactose from the 5th week of model preparation, once daily for 4 successive weeks. Equal volume of normal saline was administered to rats in the blank control group and the model group, once daily. The capability for learning and memory was detected using Morris water. The mRNA expressions of TLR4 and IL-33 in the brain tissue were detected using ELISA.

RESULTSCompared with the blank control group, the capability for learning and memory decreased in the model group with statistical difference (P < 0.05). Compared with the model group, the capability for learning and memory was obviously improved in all the medicated groups in a dose-dependent manner, showing statistical difference (P < 0.05). Compared with the blank control group, mRNA expressions of TLR4 and IL-33 in the brain tissue obviously increased after medication in the model group, showing statistical difference (P < 0.05). Compared with the model group, mRNA expressions of TLR4 and IL-33 in the brain tissue obviously decreased after medication in all the medicated groups in a dose-dependent manner, showing statistical difference (P < 0.05).

CONCLUSIONTPGs improved D-galactose induced aging rats' capability for learning and memory through regulating changes of TLR4 and IL-33 expressions.

Aging ; drug effects ; Animals ; Brain ; drug effects ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Galactose ; adverse effects ; Interleukins ; metabolism ; Learning ; drug effects ; Male ; Memory ; drug effects ; Paeonia ; chemistry ; RNA, Messenger ; genetics ; Rats ; Rats, Sprague-Dawley ; Toll-Like Receptor 4 ; metabolism

OBJECTIVETo evaluate the key indicators in the pituitary-target gland axes in the animal model of Shen-yang deficiency syndrome (SYDS).

METHODSThe 8 biological indicators [thyroid stimulating hormone (TSH), 3, 3', 5-triiodothyronine (T3), thyroxine (T4), luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T), adrenocorticotropic hormone (ACTH), and cortisol (CORT)] in the pituitary-target gland axes were grouped using factor analysis. Then the sensitivity of every indicator was calculated according to the sensitivity function defined in this paper, so as to find all the most sensitive indicators in every group as key indicators of SYDS.

RESULTSThe key indicators in the early period of SYDS were T, LH, T4, and CORT. The key indicators in the middle period were LH,T, CORT, and ACTH. The key indicators in the late period were LH, T, CORT, and FSH.

CONCLUSIONST, LH, and CORT were the common key indicators of the three periods, and other different key indicator of SYDS in the early, middle and late period were T4, ACTH, and FSH respectively, which changed from the thyroid axis to the adrenal axis and then to the gonadal axis as the period changed. The key indicators in the late period were mainly in the gonadal axis, showing gonadal dysfunction in the late period.

Animals ; Disease Models, Animal ; Estradiol ; analysis ; Factor Analysis, Statistical ; Follicle Stimulating Hormone ; analysis ; Hydrocortisone ; analysis ; Luteinizing Hormone ; analysis ; Male ; Pituitary-Adrenal System ; physiopathology ; Rats ; Rats, Sprague-Dawley ; Testosterone ; analysis ; Thyrotropin ; analysis ; Thyroxine ; analysis ; Yang Deficiency ; physiopathology

OBJECTIVETo investigate the regulative mechanism of the diterpene phenol extract of Rosmarinus Officinalis (DERO) on the imbalance of collagen metabolism of the lung tissue in pulmonary fibrosis rats.

METHODSFifty healthy Sprague-Dawley rats were randomly divided into the normal saline group (NS), the bleomycin-induced lung injury group (BLM), the low dose DERO group (at the daily dose of 50 mg/kg), the moderate dose DERO group (at the daily dose of 100 mg/kg), and the high dose DERO group (at the daily dose of 200 mg/kg), 10 in each group (abbreviated as DERO 1, 2, 3, respectively). The pulmonary fibrosis rat model was prepared by disposable intratracheal instillation of bleomycin. DERO was administered by gastrogavage as intervention during the repairing process of lung injury. On the morning of the 29th day, the rats' lung tissue was extracted. The karyocyte number, collagen protein, type I collagen (collagen I) and transforming growth factor-beta type II receptor (TGFbetaR II), Smad4 mRNA expressions were semi-quantitatively determined using tissue microarray, HE staining, collagen fiber dyeing, immunohistochemical assay, and in situ hybridization. Using real-time fluorescent quantification RT-PCR, the mRNA expression of transforming growth factor-beta1 (TGF-beta1) were detected.

RESULTSCompared with the NS group, the collagen deposition of the lung tissue was obvious and the inflammatory infiltration was more severe in the BLM group (P < 0.05, P < 0.01). There was no statistical difference in the aforesaid 4 indices between the DERO1 group and the BLM group (P > 0.05). The collagen deposition and the inflammatory infiltration were obviously alleviated in the DERO2 and DERO3 groups (P < 0.05, P < 0.01). Compared with the NS group, the mRNA expressions of collagen-I, TGF-beta1 R II, Smad4, and TGF-beta1 were obviously up-regulated in the BLM group (P < 0.05, P < 0.01). Compared with the BLM group, the aforesaid four indices were not statistically changed in the DERO1 group (P > 0.05). But the mRNA expressions of collagen-I, TGF-beta1 R II, Smad4, and TGF-beta1 were obviously downregulated in the DERO2 and DERO3 groups (P < 0.05, P < 0.01). But the down-regulation of Smad4 expression was not obvious in the DERO2 and the DERO3 groups (P > 0.05). Compared with the DERO1 group, the mRNA expressions of collagen-I, TGF-beta1, R II, TGFbeta1 were all obviously lower in the DERO2 and the DERO3 groups (P < 0.05). But there was no statistical difference in the aforesaid 4 indices between the DERO2 group and the DERO3 group (P > 0.05).

CONCLUSIONSDERO could regulate imbalanced collagen metabolism of pulmonary fibrosis. It could inhibit excessive deposition of collagen fibers, especially excessive deposition of collagen- I. Its mechanisms might be realized by inhibiting up-regulation of TGF-beta1 and TGFbetaR II mRNA expressions, thus interfering the activation of TGF-beta-Smad signaling pathway on target genes, especially on type I procollagen target gene.

Animals ; Collagen Type I ; metabolism ; Diterpenes ; pharmacology ; Female ; Lung ; drug effects ; metabolism ; Male ; Plant Extracts ; pharmacology ; Protein-Serine-Threonine Kinases ; metabolism ; Pulmonary Fibrosis ; metabolism ; RNA, Messenger ; genetics ; Rats ; Rats, Sprague-Dawley ; Receptors, Transforming Growth Factor beta ; metabolism ; Rosmarinus ; chemistry ; Signal Transduction ; Transforming Growth Factor beta1 ; metabolism

OBJECTIVETo observe the effects of Dioscornin Tablet (DT) containing serum on nuclear factor of kappa B (NF-kappaB) p65, signal transducer and activator of transcription 3 (STAT3), and vascular endothelial growth factor (VEGF) mRNA expressions in rats' synovial cell strain 364 (RSC-364) induced by interleukin-17 (IL-17) and tumor necrosis factor-alpha (TNF-alpha), and to investigate the underlying mechanisms for DT to inhibit angiogenesis of rheumatoid arthritis (RA).

METHODSIn this experiment, the vehicle control group, the cell model group, the DT containing serum group, and the positive control group (Tripterygium containing serum) were set up. The DT containing serum and the Tripterygium containing serum were prepared. The RA cell model was established by IL-17 combined TNF-alpha induced injury in RSC-364. The RA cells were intervened by DT containing serum and Tripterygium containing serum respectively. The DNA binding activity of NF-kappaB p65 was detected using TransAM NF-kappaB p65. The expression of STAT3 was observed using Western blot. The VEGF mRNA expressions were detected by real-time quantitative PCR.

RESULTSCompared with the vehicle control group, the NF-kappaB p65 activity, the expressions of STAT3 and VEGF mRNA increased significantly in RSC-364 induced by IL-17 +TNF-alpha (P < 0.01, P < 0.05). Compared with the model group, the NF-kappaB p65 activity, the expressions of STAT3 and VEGF mRNA decreased significantly in the DT containing serum group and the positive control group (P < 0.01, P < 0.05). There was no statistical difference between the two groups (P > 0.05).

CONCLUSIONDT inhibited the VEGF mRNA expression through inhibiting the NF-kappaB p65 activity and the STAT3 protein expression in the Janus kinase (JAK)-signal transducer and activating transcription factor pathway, thus inhibiting the angiogenesis of RA.

Animals ; Arthritis, Rheumatoid ; pathology ; Cells, Cultured ; Diosgenin ; analogs & derivatives ; pharmacology ; Interleukin-17 ; adverse effects ; Male ; Neovascularization, Pathologic ; pathology ; RNA, Messenger ; pharmacology ; Rats ; Rats, Wistar ; STAT3 Transcription Factor ; metabolism ; Serum ; Signal Transduction ; Synovial Membrane ; cytology ; drug effects ; metabolism ; Transcription Factor RelA ; metabolism ; Tumor Necrosis Factor-alpha ; adverse effects ; Vascular Endothelial Growth Factor A ; metabolism

OBJECTIVETo observe the effect of curcumin combined folinic acid fluorouracil oxaliplatin (FOLFOX) on the gastric adenocarcinoma cell line BGC-823 and to explore its possible mechanisms.

METHODSCells were divided into five groups, i.e. the blank control group, the curcumin group, the FOLFOX group (0.1 mmol/L 5-FU +5 micromol/L oxaliplatin), and the curcumin combined FOLFOX group. CCK-8 was used to detect cell activity. The cell apoptosis was observed using Hoechst dyeing. Caspase-3 test kit was applied to test Caspase-3 vitality. The mRNA expressions of Bcl-2 and Bax were detected by real time fluorescent quantitative PCR. The expressions of Bcl-2 and Bax protein were determined by Western blot.

RESULTSThe BGC-823 cells' proliferation could be inhibited, apoptosis induced, the Caspase-3 activity increased, expressions of Bcl-2 mRNA and Bcl-2 protein lowered, while Bax mRNA and Bax protein expressions increased in each medicated group. Besides, the efficacy of the curcumin combined FOLFOX group was superior to that of the curcumin group and the FOLFOX group, showing statistical difference (P < 0.01).

CONCLUSIONCurcumin combined FOLFOX could significantly inhibit the proliferation of BGC-823 cells possibly via promoting Bax expression and Caspase-3 activity, inhibiting Bcl-2 expression, thus inducing apoptosis.

Antineoplastic Combined Chemotherapy Protocols ; pharmacology ; Apoptosis ; drug effects ; Caspase 3 ; metabolism ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Curcumin ; pharmacology ; Fluorouracil ; pharmacology ; Humans ; Leucovorin ; pharmacology ; Organoplatinum Compounds ; pharmacology ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Stomach Neoplasms ; pathology ; bcl-2-Associated X Protein ; metabolism

OBJECTIVETo study the inhibitory effects of Taxus chinensis var. mairei Aqueous Extract (TAE) on SGC-7901 and MCF-7 cells, and to explore its mechanisms.

METHODSThe inhibitory effects of TAT and Paclitaxel on the proliferation of SGC-7901 and MCF-7 cells were tested by MTT method. Their effects on the morphology of SGC-7901 and MCF-7 cells were observed by microscope. Its effects on the cell apoptosis were detected by flow cytometry.

RESULTSThe TAE had inhibitory effects on the proliferation of tumor cells, and its mechanisms were correlated to inducing the apoptosis of tumor cells.

CONCLUSIONTAE had inhibitory effects on the proliferation of tumor cells.

Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Humans ; MCF-7 Cells ; Plant Extracts ; pharmacology ; Taxus ; chemistry

OBJECTIVETo establish a social defeat stress model for simulating the human mental disease, thus laying a foundation for in-depth laboratory research on depression.

METHODSEight C57BL/6J mice (abbreviated as C57 mice) were recruited as the stress group. They were subject to psychological stress of social defeat for 10 successive days. Besides, another 8 C57 mice were selected as the normal control group (receiving no stress). The Noldus Ethovision was used to evaluate the depressive behavior of mice. The date was acquired in the case of with or without aggressive CD-1 mice in the social defeat open field (SDOF), and it included the two groups of mice's trajectory in the SDOF and the first time of the two groups of mice's entry into the interactive area of the SDOF, the residence time of the two groups of mice in the interactive area of the SDOF, the first time of the two groups of mice's entry into the corner areas of the SDOF and the residence time of the two groups of mice in the corner areas of the SDOF. All data were used to analyze the changes in the behavior of the C57, mice, thus inferring the psychological changes of C57 mice.

RESULTSThe mice in the social stress group showed significant behavioral differences when compared with the normal control group. Their trajectories in the interactive area of the SDOF were significantly reduced. The trajectories of the mice in the social stress group were mainly distributed in the corner areas of the SDOF and its surrounding area within the smaller range. The residence time of mice in the social stress group in the interactive area of the SDOF was shortened (P < 0.05). The first time for the mice in the social stress group to enter the interactive area of the SDOF was extended (P < 0.05). Their residence time in the corner areas of the SDOF was shortened (P < 0.05). The first time for mice in the social stress group to enter the corner areas of the SDOF was extended (P < 0.05).

CONCLUSIONAn animal model of depressive behavior can be established by social defeat stress, which was consistent with human depression.

Animals ; Behavior, Animal ; Depression ; Disease Models, Animal ; Male ; Mice ; Mice, Inbred C57BL ; Stress, Psychological

OBJECTIVETo explore the effect of Chinese herbs for Shen invigorating and blood activating (CHSIBA) on the number of endothelial progenitor cells (EPCs) in the bone marrow and the peripheral blood and the signaling pathway of bone marrow matrix metalloproteinase 9 (MMP-9) of the myocardial infarction (MI) model rats.

METHODSThe MI rat model was established by ligation. Thirty successfully modeled rats were randomly divided into the high dose CHSIBA group, the low dose CHSIBA group, and the model group, 10 in each group. Besides, another 10 normal rats were recruited as the blank group. Rats in the high dose CHSIBA group and the low dose CHSIBA group were administered with CHSIBA at 3 g/kg and 1.5 g/kg body weight by gastrogavage (by adding them in 4 mL physiological saline), once daily. Rats in the model group and the blank group were administered with 4 mL physiological saline once daily. The EPCs were collected from the bone marrow and the peripheral blood 4 weeks later. Seven days later the CD34/CD133 phenotype was identified in collected sticking wall cells using flow cytometry. The MMP-9 and water soluble Kit ligand (sKitL) were detected using Western blot. The expressions of vascular endothelial growth factor (VEGF) and stromal cell-derived factor-1alpha (SDF-1alpha) were detected using ELISA.

RESULTSThe CD34/CD133 positive rate and the EPC quantity in the bone marrow and the peripheral blood were higher in the high dose CHSIBA group and the low dose CHSIBA group than in the model group (P < 0.05, P < 0.01). Besides, the expressions of VEGF, SDF-1alpha, MMP-9, and sKitL in the bone marrow and the peripheral blood were also higher in the high dose CHSIBA group and the low dose CHSIBA group than in the model group (P < 0.05, P < 0.01).

CONCLUSIONCHSIBA could activate MMP-9 signaling pathway, increase its upstream and downstream signal expression levels, and mobilize EPCs in the bone marrow to enter the blood circulation.

Animals ; Bone Marrow Cells ; drug effects ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Endothelial Cells ; drug effects ; metabolism ; Male ; Matrix Metalloproteinase 9 ; metabolism ; Myocardial Infarction ; metabolism ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; Stem Cells ; drug effects ; metabolism

OBJECTIVETo observe the protective effect of Wufu Jingfang (WJ, containing Aconitum carmichaeli Debx, Radix Aconiti Lateralis Preparatae, Rhizoma Pinelliae, and snakegourd fruit) on myocardial ischemia-reperfusion injury (I/R) of rats, thus exploring the feasibility of recipes containing eighteen incompatible pairs for specific pathological conditions.

METHODSFifty male Wistar rats were randomly divided into five groups, i.e., the sham-operative control group (the SH group), the I/R group, the low dose WJ I/R group (the I/R +JFL group), the middle dose WJ I/R group (the I/R +JFM group), the high dose WJ I/R group (the I/R +JFH group), 10 in each group. Rats in the latter three groups were administered with WJ at 0.75 mL/100 g, 1.50 mL/100 g, and 3.00 mL/100 g body weight for 14 consecutive days by gastrogavage. All groups except the SH group received ligation of left anterior descending branch of coronary artery for 30-min ischemia followed by 120-min reperfusion. The micro-structural changes of myocardial mitochondria were observed by transmission electron microscope. The ischemic cardiomyocyte apoptosis was detected in each group using one-step terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL). The mRNA expressions of B-cell leukemia/lymphoma 2 (Bcl-2) and Bcl-2 associated x protein (Bax) were detected by RT-PCR. The activities of lactic dehydrogenase (LDH) and creatine kinase (CK) were detected using ELISA. The myocardial infarct size was detected.

RESULTSCompared with the I/R group, WJ pretreatment significantly suppressed the release of LDH and CK (Besides, the release of LDH and CK reduced along with increased dose.), reduced the myocardial infarct size, and lowered myocardial apoptosis index (P < 0.05). WJ pretreatment also modulated Bcl-2/Bax ratio by up-regulating Bcl-2 expression level while decreasing Bax expression level.

CONCLUSIONSWJ pretreatment might protect the heart from I/R injury via decreasing myocardial cell apoptosis. The results suggested that eighteen incompatible pairs is not absolute, but relative. Chinese medical preparation containing opposite Chinese herbs could be used in specific pathological states such as ischemic cardiomyopathy.

Animals ; Apoptosis ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Ischemic Preconditioning, Myocardial ; methods ; Male ; Myocardial Reperfusion Injury ; pathology ; Rats ; Rats, Wistar

OBJECTIVETo investigate the effects of Xinfuli Granule (XG) on cardiomyocyte apoptosis in rats with adriamycin-induced dilated cardiomyopathy (DCM).

METHODSSeventy-two male SD rats were randomly divided into 6 groups, i.e., the normal control group, the model group, the irbesartan group, the low dose XG group, the medium dose XG group, and the high dose XG group. The DCM heart failure rat model was established using peritoneal injection of ADR. Equal volume of normal saline was injected to those in the normal control group, once per week for 6 consecutive weeks. The medication was started from the 5th week by gastrogavage. XG was dispensed into 0.5 g/mL suspension with distilled water. The XG was administered at the daily dose of 0.675 g/kg, 1.350 g/kg, and 2.700 g/kg to those in the low dose XG group, the medium dose XG group, and the high dose XG group, respectively. Irbesartan was administered to rats in the irbesartan group at the daily dose of 50 mg/kg. Equal volume of normal saline was administered to those in the normal control group and the model group by gastrogavage, once in the morning for 4 consecutive weeks. Myocardial apoptosis was measured by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), and the expressions of the Bcl-2 and Bax protein of cardiomyocytes were measured by immunohistochemical assay.

RESULTSCompared with the normal control group, the cardiomyocyte apoptosis rate and Bax expression level obviously increased, but the expression of Bcl-2 and the Bcl-2/Bax ratio decreased significantly in the model group (P < 0.05). Compared with the model group, the expression of Bax and the Bcl-2/Bax ratio increased significantly in the high dose XG group and the irbesartan group (P < 0.01). The Bax expression level obviously decreased in all groups except the normal control group (P < 0.01).

CONCLUSIONSXG could obviously attenuate cardiomyocyte apoptosis in the adriamycin-induced DCM rats, and reverse the occurrence and development of heart reconstruction. The underlying mechanism might be related to regulating and controlling the expressions of Bax and Bcl-2.

Animals ; Apoptosis ; drug effects ; Cardiomyopathy, Dilated ; chemically induced ; complications ; Doxorubicin ; adverse effects ; Drugs, Chinese Herbal ; pharmacology ; Heart Failure ; chemically induced ; pathology ; Male ; Myocytes, Cardiac ; drug effects ; metabolism ; Rats ; Rats, Sprague-Dawley