Pharmaceutical biology, 2021-01, Vol.59 (1), p.1104-1114
2021
Details
- Autor(en) / Beteiligte
- Titel
- Kaempferol-induced GPER upregulation attenuates atherosclerosis via the PI3K/AKT/Nrf2 pathway
- Ist Teil von
- Pharmaceutical biology, 2021-01, Vol.59 (1), p.1104-1114
- Ort / Verlag
- England: Taylor & Francis
- Erscheinungsjahr
- 2021
- Link zum Volltext
- Quelle
- Taylor & Francis Journals Auto-Holdings Collection
- Beschreibungen/Notizen
- The effect of kaempferol, a regulator of oestrogen receptors, on atherosclerosis (AS) and the underlying mechanism is elusive. To explore the effect and mechanism of kaempferol on AS. In vivo, C57BL/6 and apolipoprotein E (APOE) -/- mice were randomly categorized into six groups (C57BL/6: control, ovariectomy (OVX), high-fat diet (HFD); APOE -/- : OVX-HFD, OVX-HFD + kaempferol (50 mg/kg) and OVX-HFD + kaempferol (100 mg/kg) and administered with kaempferol for 16 weeks, intragastrically. Oil-Red and haematoxylin-eosin (HE) staining were employed to examine the effect of kaempferol. In vitro, human aortic endothelial cells (HAECs) were pre-treated with or without kaempferol (5, 10 or 20 μM), followed by administration with kaempferol and oxidized low-density lipoprotein (ox-LDL) (200 μg/mL). The effect of kaempferol was evaluated using flow cytometry, and TdT-mediated dUTP Nick-End Labelling (TUNEL). In vivo, kaempferol (50 and 100 mg/kg) normalized the morphology of blood vessels and lipid levels and suppressed inflammation and apoptosis. It also activated the G protein-coupled oestrogen receptor (GPER) and PI3K/AKT/nuclear factor-erythroid 2-related factor 2 (Nrf2) pathways. In vitro, ox-LDL (200 μg/mL) reduced the cell viability to 50% (IC 50 ). Kaempferol (5, 10 or 20 μM) induced-GPER activation increased cell viability to nearly 10%, 19.8%, 30%, and the decreased cellular reactive oxygen species (ROS) generation (16.7%, 25.6%, 31.1%), respectively, consequently attenuating postmenopausal AS. However, the protective effects of kaempferol were blocked through co-treatment with si-GPER. The beneficial effects of kaempferol against postmenopausal AS are associated with the PI3K/AKT/Nrf2 pathways, mediated by the activation of GPER.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1388-0209eISSN: 1744-5116DOI: 10.1080/13880209.2021.1961823Titel-ID: cdi_proquest_journals_2691141947
- Format
- –
- Schlagworte
- 1-Phosphatidylinositol 3-kinase, AKT protein, Animals, Aorta, Aorta - cytology, Apolipoprotein E, Apoptosis, Apoptosis - drug effects, Arteriosclerosis, Atherosclerosis, Atherosclerosis - drug therapy, Atherosclerosis - pathology, Blood vessels, Cell activation, Cell Survival - drug effects, Cell viability, Cells, Cultured, DNA nucleotidylexotransferase, Dose-Response Relationship, Drug, Endothelial cells, Endothelial Cells - drug effects, Endothelial Cells - metabolism, Female, Flow cytometry, High fat diet, Humans, Inflammation, Kaempferol, Kaempferols - administration & dosage, Kaempferols - pharmacology, Labelling, Lipoproteins, LDL - administration & dosage, Low density lipoprotein, Mice, Mice, Inbred C57BL, Mice, Knockout, ApoE, NF-E2-Related Factor 2 - metabolism, Ovariectomy, oxidized low-density lipoprotein (ox-LDL), Phosphatidylinositol 3-Kinase - metabolism, Post-menopause, Proto-Oncogene Proteins c-akt - metabolism, Reactive oxygen species, Reactive Oxygen Species - metabolism, Receptors, Estrogen - genetics, Receptors, G-Protein-Coupled - genetics, traditional Chinese medicines (TCM), Up-Regulation - drug effects