Notoginsenoside Rb1 inhibits activation of ERK and p38 MAPK pathways induced by hypoxia and hypercapnia

Qiu,Xiaoxiao; Zheng,Mengxiao; Song,Dong; Huang,Linjing; Tang,Lanlan; Ying,Lei; Wang,Wantie

doi:10.3892/etm.2016.3217

Notoginsenoside Rb1 inhibits activation of ERK and p38 MAPK pathways induced by hypoxia and hypercapnia

Authors:
- Xiaoxiao Qiu
- Mengxiao Zheng
- Dong Song
- Linjing Huang
- Lanlan Tang
- Lei Ying
- Wantie Wang
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Affiliations: Department of Pathophysiology, Wenzhou Medical University, Wenzhou, Zhejiang 325035, P.R. China
Published online on: April 1, 2016 https://doi.org/10.3892/etm.2016.3217
Pages: 2455-2461

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Abstract

The aim of the present study was to investigate the effect of notoginsenoside Rb1 (Rb1) on the ERK and p38 MAPK pathways in primary cultured pulmonary arterial smooth muscle cells (PASMCs) exposed to hypoxia and hypercapnia, in order to elucidate the mechanism underlying the effect of Rb1 on hypoxia and hypercapnia-induced pulmonary vasoconstriction (HHPV). PASMCs were isolated from Sprague-Dawley rats. The cells were divided into five groups: Normal (N), hypoxia and hypercapnia (H), RbL, RbM and RbH groups. N group cells were cultured under 5% CO2 and 21% O2. H, RbL, RbM and RbH groups were cultured under 6% CO2 and 1% O2. Prior to the hypoxia and hypercapnia exposure, RbL, RbM and RbH groups were treated with 8, 40 and 100 mg/ml Rb1 for 30 min, respectively. Phosphorylated extracellular signal-regulated kinase (P‑ERK) and P‑p38 protein, and ERK1/2 and p38 mRNA expression levels were detected using western blot and semi‑quantitative reverse transcription‑polymerase chain reaction (RT‑PCR) analyses, respectively. The correlations between P-ERK protein and ERK1/2 mRNA, and between P‑p38 protein and p38 mRNA were evaluated. Results of western blot and RT‑PCR showed hypoxia and hypercapnia increased P‑ERK and P‑p38 protein, and ERK1/2 mRNA, respectively (P<0.05). Rb1 suppressed the increased P‑ERK and P‑p38 protein, and ERK1/2 and p38 mRNA by hypoxia and hypercapnia (P<0.05). P-ERK protein was positively correlated with ERK1 (r=0.5, P<0.01) and ERK2 mRNA (r=0.977, P<0.01). P‑p38 protein was positively correlated with p38 mRNA (r=0.884, P<0.01). Thus, the present results indicate that Rb1 may ameliorate HHPV by suppressing ERK and p38 pathways. The study provides an experimental basis for investigating the clinical use of Rb1 in the management of HHPV-related disorders.

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