Oxidative medicine and cellular longevity · 2019
LOX-1, the Common Therapeutic Target in Hypercholesterolemia: A New Perspective of Antiatherosclerotic Action of Aegeline.
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Singh Abhilasha, Srinivasan Ashok Kumar, Chakrapani Lakshmi Narasimhan, Kalaiselvi Periandavan
Аннотация
BACKGROUND: Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is the major receptor for oxidized low-density lipoprotein (Ox-LDL) in the aorta of aged rats. Ox-LDL initiates LOX-1 activation in the endothelium of lipid-accumulating sites of both animal and human subjects of hypercholesterolemia. Targeting LOX-1 may provide a novel diagnostic strategy towards hypercholesterolemia and vascular diseases.
HYPOTHESIS: This study was planned to address whether aegeline (AG) could bind to LOX-1 with a higher affinity and modulate the uptake of Ox-LDL in hypercholesterolemia.
STUDY DESIGN: Thirty-six Wistar rats were divided into six groups. The pathology group rats were fed with high-cholesterol diet (HCD) for 45 days, and the treatment group rats were fed with HCD and aegeline/atorvastatin (AV) for the last 30 days. In vivo and in vitro experiments were carried out to assay the markers of atherosclerosis like Ox-LDL and LOX-1 levels. Histopathological examination was performed. Oil Red O staining was carried out in the IC-21 cell line. Docking studies were performed.
RESULTS: AG administration effectively brought down the lipid levels induced by HCD. The lowered levels of Ox-LDL and LOX-1 in AG-administered rats deem it to be a potent antihypercholesterolemic agent. Compared to AV, AG had a pronounced effect in downregulating the expression of lipids evidenced by Oil Red O staining. AG binds with LOX-1 at a higher affinity validated by docking.
CONCLUSION: This study validates AG to be an effective stratagem in bringing down the lipid stress induced by HCD and can be deemed as an antihypercholesterolemic agent.
HYPOTHESIS: This study was planned to address whether aegeline (AG) could bind to LOX-1 with a higher affinity and modulate the uptake of Ox-LDL in hypercholesterolemia.
STUDY DESIGN: Thirty-six Wistar rats were divided into six groups. The pathology group rats were fed with high-cholesterol diet (HCD) for 45 days, and the treatment group rats were fed with HCD and aegeline/atorvastatin (AV) for the last 30 days. In vivo and in vitro experiments were carried out to assay the markers of atherosclerosis like Ox-LDL and LOX-1 levels. Histopathological examination was performed. Oil Red O staining was carried out in the IC-21 cell line. Docking studies were performed.
RESULTS: AG administration effectively brought down the lipid levels induced by HCD. The lowered levels of Ox-LDL and LOX-1 in AG-administered rats deem it to be a potent antihypercholesterolemic agent. Compared to AV, AG had a pronounced effect in downregulating the expression of lipids evidenced by Oil Red O staining. AG binds with LOX-1 at a higher affinity validated by docking.
CONCLUSION: This study validates AG to be an effective stratagem in bringing down the lipid stress induced by HCD and can be deemed as an antihypercholesterolemic agent.