Total Panax notoginseng saponin inhibits balloon injury-induced neointimal hyperplasia in rat carotid artery models by suppressing pERK/p38 MAPK pathways

Total Panax notoginseng saponin (TPNS) is the main bioactivity compound derived from the roots and rhizomes of Panax notoginseng (Burk.) F.H. Chen. The aim of this study was to investigate the effectiveness of TPNS in treating vascular neointimal hyperplasia in rats and its mechanisms. Male Sprague-Dawley rats were randomly divided into five groups, sham (control), injury, and low, medium, and high dose TPNS (5, 10, and 20 mg/kg). An in vivo 2F Fogarty balloon-induced carotid artery injury model was established in rats. TPNS significantly and dose-dependently reduced balloon injury-induced neointimal area (NIA) (P<0.001, for all doses) and NIA/media area (MA) (P<0.030, for all doses) in the carotid artery of rats, and PCNA expression (P<0.001, all). The mRNA expression of smooth muscle (SM) α-actin was significantly increased in all TPNS groups (P<0.005, for all doses) and the protein expression was significantly increased in the medium (P=0.006) and high dose TPNS (P=0.002) groups compared to the injury group. All the TPNS doses significantly decreased the mRNA expression of c-fos (P<0.001). The medium and high dose TPNS groups significantly suppressed the upregulation of pERK1/2 protein in the NIA (P<0.025) and MA (P<0.004). TPNS dose-dependently inhibited balloon injury-induced activation of pERK/p38MAPK signaling in the carotid artery. TPNS could be a promising agent in inhibiting cell proliferation following vascular injuries.

Effect of Phosphocreatine on Angiotensin II Induced Proliferation and Collagen Synthesis of Cardiac Fibroblasts in Neonatal Rats With its Mechanism / 中国循环杂志

Objective: To investigate the effect of phosphocreatine (PCr) on angiotensin II (Ang II) induced proliferation and collagen synthesis of cardiac ifbroblasts in neonatal rats with its mechanism. Methods: The cardiac ifbroblasts (CF) from neonatal rats were cultured in vitro and were divided into 4 groups.①Control group, the CF was cultured in non-serum DMEM,②Ang II group, the CF was cultured with Ang II at (1×10-6) mol/L,③PCr treated group, the CF was cultured with PCr at 10 mmol/L, and④Ang II+PCr group. The CF cell cycle percentage was detected by lfow cytometric assay, myocardial collagen content was observed by VG staining and protein expression of phosphorylated extracellular signal-regulated kinase (pERK1/2) was detected by immuneohistochemistry. Results: ① Compared with Control group, the CF in Ang II group showed increased percentage of S phase and decreased percentage of G0/G1 and G2/M phases, increased collagen content and pERK1/2 protein expression, all P0.05. ③ Compared with Control group, Ang II + PCr group had elevated pERK1/2 protein expression, P0.05.④Compared with Ang II group, the CF in Ang II + PCr group had increased percentage of G0/G1 and G2/M phases, decreased percentage of S phase, decreased collagen content and pERK1/2 protein expression, all P Conclusion: PCr may partially inhibit Ang II induced CF proliferation and collagen synthesis which might be related to the inhibition of excessively activated ERK1/2. Therefore, PCr could improve Ang II induced myocardial ifbrosis in neonatal rats.

Effects of DA-9701, a Novel Prokinetic Agent, on Phosphorylated Extracellular Signal-Regulated Kinase Expression in the Dorsal Root Ganglion and Spinal Cord Induced by Colorectal Distension in Rats

BACKGROUND/AIMS: DA-9701, a standardized extract of Pharbitis Semen and Corydalis Tuber, is a new prokinetic agent that exhibits an analgesic effect on the abdomen. We investigated whether DA-9701 affects visceral pain induced by colorectal distension (CRD) in rats. METHODS: A total of 21 rats were divided into three groups: group A (no CRD+no drug), group B (CRD+no drug), and group C (CRD+DA-9701). Expression of pain-related factors, substance P (SP), c-fos, and phosphorylated extracellular signal-regulated kinase (p-ERK) in the dorsal root ganglion (DRG) and spinal cord was determined by immunohistochemical staining and Western blotting. RESULTS: The proportions of neurons in the DRG and spinal cord expressing SP, c-fos, and p-ERK were higher in group B than in group A. In the group C, the proportion of neurons in the DRG and spinal cord expressing p-ERK was lower than that in group B. Western blot results for p-ERK in the spinal cord indicated a higher level of expression in group B than in group A and a lower level of expression in group C than in group B. CONCLUSIONS: DA-9701 may decrease visceral pain via the downregulation of p-ERK in the DRG and spinal cord.