Molecular medicine reports
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The proliferation of pulmonary artery smooth muscle cells (PASMCs) contributes to the development of pulmonary vascular remodeling, ultimately leading to pulmonary hypertension. In this study, the effects and molecular mechanisms of salidroside on the platelet‑derived growth factor (PDGF)‑BB‑induced proliferation of primary cultured rat PASMCs were investigated. The presented data demonstrated that salidroside significantly inhibited the proliferation and DNA synthesis of PASMCs induced by PDGF‑BB in a dose‑ and time‑dependent manner, without cell cytotoxicity. ⋯ The salidroside‑induced inhibition of the cell cycle was associated with the inhibition of cyclin D1, cyclin E, cyclin‑dependent kinase 2 (CDK2) and CDK4 mRNA expression, as well as an increase in the mRNA expression of p27 in PDGF‑BB‑stimulated PASMCs. Further experiments showed that the beneficial effect of salidroside on blocking the proliferation of PASMCs was associated with the suppression of the AKT/glycogen synthase kinase 3 β (GSK3β) signaling pathway, but did not involve the extracellular signal‑regulated kinase 1/2, p38 and c‑Jun‑N‑terminal kinase signaling pathways. These results indicate that salidroside suppresses PDGF‑BB‑induced PASMC proliferation through the AKT/GSK3β signaling pathway and suggests that it may be a feasible therapy for pulmonary vascular remodeling diseases.
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Leptin, an adipokine synthesized mainly by non‑neuronal tissues, has been reported to contribute to the pathogenesis of neuropathic pain. It has been hypothesized that morphine tolerance and neuropathic pain share some common pathological mechanisms. The present study was designed to examine whether spinal leptin is implicated in the development of morphine antinociceptive tolerance, and whether spinal leptin induces the activation of signal transducer and activator of transcription 3 (STAT3) signaling pathway and the NR1 subunit of N‑methyl‑D‑aspartate (NMDA) receptor, in morphine antinociceptive tolerance in rats. ⋯ The increased activation of STAT3 and the NR1 subunit was markedly attenuated by i.t. treatment with LA. In addition, the spinal administration of AG490 or MK‑801 (a non‑competitive NMDA receptor inhibitor) blocked the development of morphine antinociceptive tolerance. Taken together, these results have demonstrated, for the first time, to the best of our knowledge, that spinal leptin contributes to the development of morphine antinociceptive tolerance by activating the spinal STAT3‑NMDA receptor pathway.
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Resveratrol (Res) or trans-3,4',5-trihydroxystilbene, has been proven to exert neuroprotective effects in cerebral ischemia. The aim of the present study was to investigate whether Res has neuroprotective effects in primary cortical neurons subjected to transient oxygen-glucose deprivation (OGD) via inhibiting the expression of the gene encoding stromelysin-1, also known as matrix metalloproteinase-3 (MMP-3), and via inhibiting cell apoptosis. Primary cortical cells were exposed to OGD, followed by reoxygenation to induce transient ischemia. ⋯ MMP-3 expression induced by NO was attenuated by Res treatment and was partially restored by exogenous NO using NOC-18. Taken together, these findings indicate that OGD induces apoptosis through canonical apoptosis signaling and by modulating the expression of MMP-3; Res can reverse the OGD-induced MMP-3 expression and cell apoptosis via the NF-κB-iNOS/NO pathway. Therefore, Res may be a promising agent for the treatment of neuronal injury associated with stroke.
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Perilla leaves are widely used in Chinese herbal medicine and in Japanese herbal agents used to treat respiratory diseases. This study aimed to investigate the anti‑inflammatory effects and the underlying mechanisms of Perilla frutescens leaf extract (PLE). Murine macrophage RAW264.7 cells were used as a model. ⋯ In addition, PLE reduced NO production and PGE2 secretion induced by LPS. PLE also inhibited activation of mitogen‑activated protein kinases (MAPKs), increased the cytosolic IκBα level, and reduced the level of nuclear factor (NF)‑κB. Taken together, these findings indicate that PLE significantly decreases the mRNA expression and protein production of pro‑inflammatory mediators, via the inhibition of extracellular‑signal‑regulated kinase (ERK)1/2, c‑Jun N‑terminal kinase (JNK), p38, as well as NF‑κB signaling in RAW264.7 cells stimulated with LPS.
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Hepatic ischemia reperfusion (HI/R) injury may occur during liver transplantation and remains a serious concern in clinical practice. Huperzine A (HupA), an alkaloid isolated from the Chinese traditional medicine Huperzia serrata, has been demonstrated to possess anti‑oxidative and anti‑apoptotic properties. In the present study, a rat model of HI/R was established by clamping the hepatic artery, the hepatoportal vein and the bile duct with a vascular clamp for 30 min followed by reperfusion for 6 h under anesthesia. ⋯ Furthermore, HupA treatment enhanced the activity of hepatic tissue SOD, CAT and GSH, but decreased the MDA tissue content. Western blot analysis revealed elevated levels of Bcl‑2 expression but decreased Bax and caspase‑3 tissue expression at the protein level in the HupA‑treated group. The present data suggest that HupA attenuates the HI/R injury of rats through its anti‑oxidative and anti‑apoptotic signaling pathways.