Open AccessSalidroside suppressing LPS ‐induced myocardial injury by inhibiting ROS ‐mediated PI 3K/Akt/ mTOR pathway in vitro and in vivo
Author(s) -
Chen Lvyi,
Liu Peng,
Feng Xin,
Ma Chunhua
Publication year - 2017
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12871
Subject(s) - salidroside , protein kinase b , pi3k/akt/mtor pathway , superoxide dismutase , lactate dehydrogenase , glutathione peroxidase , glutathione , chemistry , pharmacology , western blot , oxidative stress , apoptosis , biochemistry , biology , enzyme , gene
The purpose of the present study was to investigate the effect of salidroside (Sal) on myocardial injury in lipopolysaccharide ( LPS )‐induced endotoxemic in vitro and in vivo . SD rats were randomly divided into five groups: control group, LPS group (15 mg/kg), LPS plus dexamethasone (2 mg/kg), LPS plus Sal groups with different Sal doses (20, 40 mg/kg). Hemodynamic measurement and haematoxylin and eosin staining were performed. Serum levels of creatine kinase ( CK ), lactate dehydrogenase, the activities of the antioxidant enzymes catalase ( CAT ), superoxide dismutase ( SOD ), glutathione peroxidase ( GSH ‐px), glutathione, tumour necrosis factor‐α ( TNF ‐α), interleukin‐6 ( IL ‐6), and interleukin‐1β ( IL ‐1β) were measured after the rats were killed. iNOS , COX ‐2, NF ‐κB and PI 3K/Akt/ mTOR pathway proteins were detected by Western blot. In vitro , we evaluated the protective effect of Sal on rat embryonic heart‐derived myogenic cell line H9c2 induced by LPS . Reactive oxygen species ( ROS ) in H9c2 cells was measured by flow cytometry, and the activities of the antioxidant enzymes CAT , SOD , GSH ‐px, glutathione‐S‐transferase, TNF ‐α, IL ‐6 and IL ‐1β in cellular supernatant were measured. PI 3K/Akt/ mTOR signalling was examined by Western blot. As a result, Sal significantly attenuated the above indices. In addition, Sal exerts pronounced cardioprotective effect in rats subjected to LPS possibly through inhibiting the iNOS , COX ‐2, NF ‐κB and PI 3K/Akt/ mTOR pathway in vivo . Furthermore, the pharmacological effect of Sal associated with the ROS ‐mediated PI 3K/Akt/ mTOR pathway was proved by the use of ROS scavenger, N ‐acetyl‐ l ‐cysteine, in LPS ‐stimulated H9C2 cells. Our results indicated that Sal could be a potential therapeutic agent for the treatment of cardiovascular disease.