phenanthrenes and Hypertrophy

We have reported that triptolide inhibited pulmonary inflammation in patients with steroid-resistant asthma. In the present study, we investigated whether suppresses airway remodeling and goblet cell hyperplasia, studied the mechanism of triptolide on mucin5ac (Muc5ac) expression in a murine model of asthma.. BALB/c mice were sensitized to intraperitoneal ovalbumin (OVA) followed by repetitive ovalbumin challenge for 6 weeks. Treatments included triptolide (40 μg/kg) and dexamethasone (2mg/kg). The area of bronchial airway (WAt/Pbm), smooth muscle (WAm/Pbm) and mucus index were assessed 24h after the final OVA challenge. Levels of Muc5ac were assessed by ELISA, immunohistology and real-time PCR. Western blot was performed to analyze the phosphorylation of NF-κB p65.. Triptolide and dexamethasone significantly reduced allergen-induced increases in the thickness of bronchial airway, smooth muscle and goblet cell hyperplasia. Levels of lung Muc5ac and Muc5ac mRNA were significantly reduced in mice treated with triptolide and dexamethasone. Phosphorylation of NF-κB p65 was significantly reduced in mice treated with triptolide and dexamethasone.. Triptolide may inhibit airway goblet cell hyperplasia and Muc5ac expression in asthmatic mice via NF-κB. It may be a potential drug for the treatment of patients with severe asthma.

Topics: Airway Remodeling; Animals; Asthma; Blotting, Western; Bronchi; Bronchoalveolar Lavage Fluid; Disease Models, Animal; Diterpenes; Epoxy Compounds; Female; Goblet Cells; Hyperplasia; Hypertrophy; Mice, Inbred BALB C; Mucin 5AC; Mucus; NF-kappa B; Phenanthrenes; Phosphorylation; RNA, Messenger; Transcription Factor RelA

To observe the effects of sodium tanshinone II A sulfonate (STS) on angiotensin II (Ang II)-induced hypertrophy of myocardial cells through the expression of phosphorylated extracellular signal-regulated kinase (p-ERK1/2).. In the primary culture of neonatal rat myocardial cells, the total protein content in myocardial cells was determined by coomassie brilliant blue and the protein synthesis rate was measured by [3H]-Leucine incorporation as indexes for hypertrophy of myocardial cells. The expression of p-ERK1/2 was determined using Western blot and immunofluorescence labeling.. (1) The total protein and protein synthesis rate increased significantly in contrast to the control group after the myocardial cells were stimulated by Ang II (1 micromol/L) for 24 h; STS markedly inhibited the increment of the total protein level induced by Ang II and the syntheses of protein. (2) After pretreatment of myocardial cells with Ang II (1 micromol/L) for 5 min, the p-ERK1/2 protein expression was increased, with the most obvious effect shown at about 10 min; pretreatment of myocardial cells with STS at different doses (2, 10, 50 micromol/L) for 30 min resulted in obvious inhibition of the expression of p-ERK1/2 stimulated by Ang II in a dose-dependent manner. (3) After the myocardial cells were stimulated by Ang II (1 micromol/L), the immunofluorescence of ERK1/2 rapidly appeared in the nucleus. The activation and translocation process of ERK1/2 induced by Ang II was blocked distinctly by STS.. STS inhibited the myocardial cell hypertrophy induced by Ang II, and the mechanism may be associated with the inhibition of p-ERK1/2 expression.

Topics: Angiotensin II; Animals; Hypertrophy; Leucine; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Myocytes, Cardiac; Phenanthrenes; Phosphorylation; Protein Biosynthesis; Protein Transport; Rats; Rats, Wistar; Tritium

To investigate the effects of sodium tanshinone II A sulfonate (STS) on the hypertrophy induced by angiotensin II (Ang II) in primary cultured neonatal rat cardiac myocytes.. The effect of STS on cytotoxicity was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-3,5-phenytetrazoliumromide (MTT) assay. As indexes for cardiocyte hypertrophy, cell size was determined by phase contrast microscopy and protein synthesis rate was measured by 3H-leucine incorporation. The proto-oncogene c-fos mRNA expression of cardiocytes was assessed using reverse transcription polymerase chain reaction (RT-PCR).. STS could inhibit cardiocyte hypertrophy, increase the protein synthesis rate and enhance proto-oncogene c-fos mRNA expression in cardiocytes induced by Ang II (P<0.01), with an effect similar to that of Valsartan, the Ang II receptor antagonist.. STS can prevent the hypertrophy of cardiac myocytes induced by Ang II, which may be related to its inhibition of the expression of proto-oncogene c-fos mRNA.

Topics: Angiotensin II; Animals; Animals, Newborn; Cell Survival; Gene Expression Regulation; Hypertrophy; Leucine; Myocytes, Cardiac; Phenanthrenes; Proto-Oncogene Proteins c-fos; Rats; Rats, Wistar; RNA, Messenger; Time Factors; Tritium