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OBJECTIVE@#To explore the effect of Kuanxiong Aerosol (KXA) on isoproterenol (ISO)-induced myocardial injury in rat models.@*METHODS@#Totally 24 rats were radomly divided into control, ISO, KXA low-dose and high-dose groups according to the randomized block design method, and were administered by intragastric administration for 10 consecutive days, and on the 9th and 10th days, rats were injected with ISO for 2 consecutive days to construct an acute myocardial ischemia model to evaluate the improvement of myocardial ischemia by KXA. In addition, the diastolic effect of KXA on rat thoracic aorta and its regulation of ion channels were tested by in vitro vascular tension test. The influence of KXA on the expression of calcium-CaM-dependent protein kinase II (CaMK II)/extracellular regulated protein kinases (ERK) signaling pathway has also been tested.@*RESULTS@#KXA significantly reduced the ISO-induced increase in ST-segment, interventricular septal thickness, cardiac mass index and cardiac tissue pathological changes in rats. Moreover, the relaxation of isolated thoracic arterial rings that had been precontracted using norepinephrine (NE) or potassium chloride (KCl) was increased after KXA treatment in an endothelium-independent manner, and was attenuated by preincubation with verapamil, but not with tetraethylammonium chloride, 4-aminopyridine, glibenclamide, or barium chloride. KXA pretreatment attenuated vasoconstriction induced by CaCl2 in Ca2+-free solutions containing K+ or NE. In addition, KXA pretreatment inhibited accumulation of Ca2+ in A7r5 cells mediated by KCl and NE and significantly decreased p-CaMK II and p-ERK levels.@*CONCLUSION@#KXA may inhibit influx and release of calcium and activate the CaMK II/ERK signaling pathway to produce vasodilatory effects, thereby improving myocardial injury.
Subject(s)
Animals , Rats , Aerosols , Aorta, Thoracic , Calcium/metabolism , Endothelium, Vascular/metabolism , Myocardial Ischemia/metabolism , VasodilationABSTRACT
OBJECTIVE@#To evaluate the effects of Huoxin Pill (, HXP) on cardiac fibrosis and heart failure (HF) in isoproterenol (ISO)-induced HF rats.@*METHODS@#Thirty Wistar rats were randomly divided into 5 groups including control, HF, isosorbide mononitrate (ISMN), HXP low (HXP-L), and HXP high (HXP-H) groups (n=6 for each group) according to the complete randomization method. Rats were pretreated with ISMN (5 mg/kg daily), low concentration of HXP (10 mg/kg daily) or high concentration of HXP (30 mg/kg daily) or equal volume of saline by intragastric administration for 1 week, followed by intraperitoneal injection of ISO (10 mg/kg, 14 days), and continually intragastric administrated with above medicines or saline for additional 6 weeks. The effects of HXP treatment on the cardiac function, heart weight index (HWI), pathological changes, and collagen content were further assessed. Moreover, the role of HXP on activation of transforming growth factor- β 1 (TGF-β 1)/Smads pathway was further explored using immunohistochemistry (IHC) and Western-blot assay.@*RESULTS@#HXP treatment significantly alleviated the decrease of ejection fraction (EF) and fractional shortening (FS), while decreased the elevation of left ventricular end-systolic volume (LVESV) in ISO-induced HF rats (P<0.05). Moreover, HXP treatment obviously attenuated the increase of HWI and serum level of creatine kinase MB (CK-MB, P<0.05), as well as pathological changes in ISO-induced HF rats. Further determination indicated that HXP treatment alleviated the elevation of collagen I and collagen III protein expression in cardiac tissues of ISO-induced HF rats. Furthermore, HXP treatment significantly down-regulated the increase of TGF-β 1 and p-Smad2/3 protein expression in cardiac tissues of HF rats (P<0.05), while did not affect the expression of total Smad2/3.@*CONCLUSIONS@#HXP attenuated heart failure and cardiac fibrosis in ISO-induced HF rats by suppression of TGF-β 1/Smad2/3 pathway.
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OBJECTIVE@#To evaluate the inhibitory effect of bear bile powder (BBP) on hepatocellular carcinoma (HCC) growth in vivo and investigate the underlying mechanisms.@*METHODS@#A HCC xenograft mouse model was developed by producing with huh7 cells. After 5 days following xenograft implantation, ten HCC xenograft mice were given intra-gastric administration with 10 mg/(kg•d) dose of BBP or saline for 3 weeks. Tumor growth in HCC xenograft mice was evaluated by measuring the tumor weight and volume. Cell apoptosis, proliferation or tumor angiogenesis were examined via immunohistochemical (IHC) staining for transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL), proliferating cell nuclear antigen (PCNA) or cluster of differentiation 31 (CD31), respectively. Phosphorylation of signal transducer and activator of transcription 3 (STAT3) were determined by Western blot. The mRNA and protein expressions of Bcl-2, Bax, Cyclin D1 and Cyclin-dependent kinase 4 (CDK4) in HCC tumor tissues were respectively determined by reverse transcription polymerase chain reaction (RT-PCR) and Western blot. The protein expression of vascular endothelial growth factor A (VEGF-A) in tumor tissues was examined by IHC staining.@*RESULTS@#BBP treatment led to a significant decrease on tumor volume and tumor weight in HCC mice (P<0.05) and had no effect on the change of body weight. In addition, BBP profoundly promoted cell apoptosis, inhibited cell proliferation and intratumoral microvessel density in HCC tumor tissues (P<0.05). Moreover, BBP treatment remarkably suppressed the STAT3 phosphorylation and modulated the expression of critical target genes including Bcl-2, Bax, Cyclin D1, CDK4 and VEGF-A in HCC mice.@*CONCLUSION@#BBP exerts its anti-cancer activities via suppressing STAT3 signaling pathway and affecting multiple intracellular targets.
Subject(s)
Animals , Mice , Bile , Biological Products , Pharmacology , Carcinoma, Hepatocellular , Drug Therapy , Cell Line, Tumor , Disease Models, Animal , Liver Neoplasms , Drug Therapy , Medicine, Chinese Traditional , Mice, Inbred BALB C , Powders , STAT3 Transcription Factor , Metabolism , UrsidaeABSTRACT
OBJECTIVES@#To investigate the protective effects of Shexiang Tongxin Dropping Pill (, STP) on NaSO-induced hypoxia-reoxygenation injury in cardiomyoblast H9c2 cells.@*METHODS@#The cell viability and levels of mRNA and protein expression in H9c2 cells were determined following NaSO-induced hypoxia using Hoechst staining, annexin V/propidium iodide (PI) flow cytometry, real-time polymerase chain reaction and Western blot analysis.@*RESULTS@#STP pretreatment significantly increased the viability and inhibited aberrant morphological changes in H9c2 cardiomyoblast cells induced by NaSO treatment (P<0.05). In addition, STP pretreatment attenuated NaSO-induced hypoxic damage, down-regulated the expression of pro-apoptotic Bax, and up-regulated the expression of anti-apoptotic Bcl-2 in H9c2 cells (P<0.05).@*CONCLUSIONS@#STP was strongly cardioprotective in hypoxia-reoxygenation injury by preventing hypoxic damage and inhibiting cellular apoptosis. These results further support the use of STP as an effective drug for the treatment of ischemic heart disease.
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OBJECTIVE@#To evaluate the effect of Pien Tze Huang (, PZH) on breast cancer chemoresistance and related epithelial-mesenchymal transition (EMT) and investigate the underlying mechanisms.@*METHODS@#3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay was used to determine the cell viability. Adriamycin (ADR) staining observed by fluorescence microscope was performed to detect the accumulation of ADR. Transwell assay was used to analyze the cell migration and invasion. Western-blot was performed to detect the protein expression of related genes.@*RESULTS@#MCF-7/ADR cells were resistant to ADR treatment, and PZH treatment inhibited the viability of MCF-7/ADR cells in a dose-dependent manner. PZH treatment also increased the intercellular accumulation of ADR and down-regulated the expression of ABCG2 and ABCB1 in MCF-7/ADR cells (P<0.05). In addition, PZH treatment inhibited EMT, migration and invasion of MCF-7/ADR cells (P<0.05). Moreover, PZH suppressed activation of transforming growth factor β1 (TGF-β) signaling in MCF-7/ADR cells (P<0.05).@*CONCLUSION@#PZH treatment can effectively overcome chemoresistance via down regulating ABCG2, ABCB1 and inhibit EMT in ADR resistant human breast cancer cells via suppression of the TGF-β1 pathway.
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<p><b>OBJECTIVE</b>To investigate the effect of the ethanol extract of Scutellaria barbata D. Don (EESB) on colorectal cancer (CRC) growth and Wnt/β-catenin signaling pathway in vivo and in vitro.</p><p><b>METHODS</b>In vivo experiment, CRC xenograft mouse model was constructed with injection of HT-29 cells. Following xenograft implantation, twenty mice were randomly divided into EESB-treated group (n=10) and control group (n=10) by a random number table, and were given with intra-gastric administration of 2 g/kg EESB or saline, 5 days a week for 16 days, respectively. At the end of experiment, tumors were removed and weighed by electronic scales. The proliferation biomarker Ki-67 of tumor was evaluated by immunohistochemistry (IHC) assay. In vitro study, HT-29 cells were treated with 0, 0.5, 1.5, 2.5 mg/mL EESB for 24 h. At the end of the treatment, the viability and survival of HT-29 cells were determined by methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay and colony formation assay, respectively. The mRNA expression of c-Myc, Survivin and adenomatous polyposis coli (APC) was examined by reverse transcription-polymerase chain reaction (RT-PCR) both in tumor tissues of CRC xenograft mice and HT-29 cells. Protein expression of c-Myc, Survivin, APC, and β-catenin as well as β-catenin phosphorylation level were evaluated by IHC assay or Western blotting.</p><p><b>RESULTS</b>EESB significantly reduced tumor weight in CRC xenografts mice, compared with the control group (P<0.05). IHC assay showed that EESB significantly inhibited protein expression of Ki-67 in tumor tissues (P<0.05). MTT assay showed that EESB significantly reduced HT-29 cell viability in a dose-dependent manner (P<0.05). Colony formation assay showed that EESB dose-dependently decreased the survival of HT-29 cells (P<0.05). In addition, RT-PCR assay showed that EESB decreased the mRNA expression of c-Myc and Survivin and increased APC expression, both in tumor tissues of CRC xenograft mice and HT-29 cells (P<0.05). IHC assay or Western blotting showed that EESB decreased protein expression of β-catenin, c-Myc and Survivin, as well as increased APC expression and β-catenin phosphorylation in tumor tissues or HT-29 cells (P<0.05).</p><p><b>CONCLUSIONS</b>EESB significantly reduced tumor growth in CRC xenografts mice, and inhibited the viability and survival of HT-29 cells. EESB could suppress the activation of the Wnt/β-catenin pathway, which might be one of the mechanisms whereby Scutellaria barbata D. Don exerts its anticancer activity.</p>
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<p><b>OBJECTIVE</b>To systematically assess the efficacy and safety of Rhodiola in treating chronic stable angina pectoris.</p><p><b>METHODS</b>Our group searched the Cochrane library, PubMed, Embase, Chinese biomedical literature database (CBM), VIP database (VIP), Chinese Journal Full-text Database (CNKI) for the literature published in English and Chinese till April 2013. Randomized controlled trials (RCTs) were included on the therapeutic effect of Rhodiola or Rhodiola plus conventional Western medicine in comparison with the conventional Western medicine treatment on stable angina. Data were extracted according the data extraction form. The literature methodological quality was assessed by using the Cochrane handbook, and data analyzed by Rev-Man 5.2 Software for Meta-analysis. The effect indicators of outcomes was expressed by odds ratio (OR) and 95% CI.</p><p><b>RESULTS</b>A total of 7 randomized controlled trials, 662 cases of stable angina pectoris patients met the inclusion criteria and all published in Chinese, without one scientific design and high quality literature. Compared with the conventional Western medicine treatment, combined with oral administration of Rhodiola could improve the efficiency of anti-angina (OR = 2.49, 95% CI: 1.02 - 6.09). Combined with intravenous infusion of Rhodiola could also improve the efficacy of angina pectoris (OR = 4.86, 95% CI: 2.4 - 9.82). Oral administration of Rhodiola couldn't improve ECG efficacy (OR = 1.25, 95% CI: 0.67 - 2.34). Intravenous infusion of Rhodiola could improve the clinical efficacy (OR = 2.94, 95% CI: 1.61 - 5.35). Combined with the conventional treatment, intravenous infusion of Rhodiola could improve the whole blood viscosity (low and high shear rates) and inverse variance (IV) (-1.36 and -0.99, 95% CI: -1.65 - 1.07 and -1.26 - 0.71), but could not reduce serum fibrinogen and D-dimer level. The incidence rate of adverse reactions was higher than that of the conventional treatment combined with Rhodiola (OR = 0.1, 95% CI: 0.02 - 0.51).</p><p><b>CONCLUSIONS</b>On the basis of routine treatment, Rhodiola could further improve patients' symptoms. Combined with intravenous medication, Rhodiola could increase the ECG improvement rate, and reduce adverse reactions. But the methodological quality of included studies was poor, the number of samples was small, and influence factors such as the intervention period was short. This conclusion needs scientific and rational design in a larger sample, multicenter clinical trial to verify.</p>