Paeoniflorin inhibits PDGF-BB induced pulmonary arterial smooth muscle cells proliferation via p 38 MAPK / JNK pathways and alleviate inflammation

Objective: The objective of this study was to determine the effect of Paeoniflorin (PF), a monoterpene glycoside isolated from the roots of Paeonia lactiflora Pallas, on rat pulmonary arterial smooth muscle cells (PASMCs) pretreated with platelet-derived growth factor (PDGF)-BB. Methods: PASMCs were pretreated with PDGF-BB (60 ng/ml) or PF (20 μmol/L) under normal conditions. Cell viability was detected by Cell Counting Kit-8 (CCK-8) assay. Western Blot was used to measure the expression of p38 MAPK, ERK1/2, JNK, phospho-p38 MAPK (p-p38 MAPK), phospho-ERK1/2 (p-ERK1/2), and phospho-JNK (p-JNK). The cell cycle was analyzed by flow cytometry. Real-time PCR and enzyme-linked immunosorbent assay were used to measure the expression of pro-inflammatory cytokines. Results: CCK-8 analysis indicated that PDGF-BB induced the proliferation of PASMCs, and this effect was significantly inhibited by PF treatment (PF treatment = 0.63 ± 0.02, PDGF-BB = 0.71 ± 0.01, n = 3, P < 0.01). Under PDGF-BB pretreatment conditions, PF significantly decreased the proportion of S-phase (PF treatment = 24.63 ± 0.13, PDGF-BB =51.35 ± 0.40, n = 3, P < 0.01) increased the proportion of G0/G1 and G2/M, and inhibited the phosphorylations of p38 MAPK and JNK, but not ERK1/2. In addition, PF markedly down-regulated the expression of PDGF-BB-induced pro-inflammatory cytokines, interleukin (IL)-1β, IL-6, tumor necrosis factor-α, and transforming growth factor-β1, in PASMCs. Conclusions: This study demonstrated that PF inhibited the proliferation of PASMCs induced by PDGF-BB. The underlying mechanism is in part mediated by the down-regulation of the activation of p38 MAPK/JNK pathways. Moreover, PF alleviated inflammation.