BackgroundThe initiation of atherosclerosis (AS) is attributed to the dysfunction of endothelial cells (ECs) via the inhibition of g protein-coupled estrogen receptor (GPER). In the current study, we assessed the potential of Ginsenoside Rb1 (Rb1) to attenuate the dysfunction of ECs via GPER-mediated PI3K/Akt pathway.Material/MethodsAS was induced in rabbits and then the AS rabbits were treated with Rb1. Thereafter, the ECs were isolated from AS and healthy rabbits, and treated with Rb1. The effect of Rb1 on blood lipid levels in AS rabbits and on apoptosis, inflammatory response, and GPER/PI3K/Akt axis activity in ECs was detected. Furthermore, the activities of GPER and PI3K were modulated to verify the key role of the axis in the anti-AS effect of Rb1.ResultsThe levels of total cholesterol, low-density lipoprotein (LDL), and triglyceride in AS rabbits were suppressed by Rb1 while the high-density lipoprotein (HDL) level was increased. In in vitro assays, Rb1 administration inhibited apoptosis process and the production of pro-inflammation cytokines in AS ECs. The expression levels of GPER, p-PI3K, and p-Akt were upregulated by Rb1, associated with the increased level of Bcl-2 and reduced level of Bax. When the activity of GPER was inhibited by GP-15 in AS ECs, the treatment effect of Rb1 was blocked. However, the activation of PI3K could restore the protective effect of Rb1 after the inhibition of GPER.ConclusionsThe anti-AS potential of Rb1 was exerted by restoring the regular function of ECs via the activation of GPER-mediated PI3K/Akt signaling.
Ischemia‐reperfusion injury (
IRI
) occurs when blood supply returns to tissue after interruption, which is associated with life‐threatening inflammatory response. Tranilast is a widely used antiallergic agent in the treatment against bronchial asthma and keloid. To study the function of tranilast, we used
IRI
in rat models. The brain tissues of
IRI
rats with or without tranilast treatment were collected. Neuronal apoptosis in the brain was detected by terminal deoxynucleotidyl transferase nick end labeling assay, and proinflammatory cytokine levels were measured by quantitative real‐time polymerase chain reaction and enzyme‐linked immunosorbent assay. The expression levels of nuclear factor‐kappa B (
NF
‐κB), inhibitor of κB (IκB) and peroxisome proliferator‐activated receptors (
PPAR
s) were detected by Western blot. The results showed that tranilast treatment reduced neuronal apoptosis in the brain of
IRI
rats. Tranilast enhanced the short‐term memory and long‐term memory to novel object recognition paradigm. Tranilast treatment decreased the messenger RNA (
mRNA
) and protein levels of multiple proinflammatory cytokines, and affected
NF
‐κB and inhibitor of kappa B protein expressions. Tranilast promoted the expressions of
PPAR
‐α and
PPAR
‐γ. Our findings demonstrate that tranilast treatment could attenuate cerebral
IRI
by regulating the inflammatory cytokine production and
PPAR
expression. Tranilast is a potential drug for
IRI
treatment in the clinic.
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