Longxuetongluo capsule inhibits atherosclerosis progression in high-fat diet-induced ApoE−/− mice by improving endothelial dysfunction. (December 2016)

• Record Type: Journal Article
• Authors: Zheng, Jiao; Liu, Binglin; Lun, Qixing; Gu, Xiaopan; Pan, Bo; Zhao, Yunfang; Xiao, Wei; Li, Jun; Tu, Pengfei
• Is Part Of: Atherosclerosis. Volume 255(2016)
• Page Start: 156
• Page End: 163
• Publication Date: 2016-12
• Subjects: Chinese dragon's blood -- Longxuetongluo capsule -- Anti-atherosclerosis -- Endothelial dysfunction; CG chow diet group -- COX-2 cyclooxygenase-2 -- DMEM Dulbecco's modified Eagle's medium -- EG ezetimibe-treated group -- eNOS endothelial nitric oxide synthase -- FBS fetal bovine serum -- HDLc high density lipoprotein cholesterol -- HE hematoxylin and eosin -- HFD high-fat diet -- HG HFD-induced group -- HUVECs human umbilical vein endothelial cells -- IκB inhibitor of kappa B -- IKK inhibitor of kappa B kinase -- LTC Longxuetongluo capsule -- LTC100 (low), LTC200 (medium), and LTC300 (high) oral administration at doses of 100, 200, and 300 mg/kg/d, respectively -- MAPK mitogen-activated protein kinase -- MCP-1 monocyte chemotactic protein-1 -- NF-κB nuclear factor kappa B -- NO nitric oxide -- OCT optimum cutting temperature -- Ox-LDL oxidized low-density lipoprotein -- ORO oil Red O -- PBS phosphate buffered saline -- SEM standard error of the mean -- TC total cholesterol -- TG triglycerides -- VCAM-1 vascular cell adhesion molecule-1; Arteriosclerosis -- Periodicals; Electronic journals; 616.136
• DOI: 10.1016/j.atherosclerosis.2016.08.022
• Languages: English
• ISSNs: 0021-9150

Abstract

Abstract: Background and aims: Chinese dragon's blood has been used to treat blood stasis for thousands of years. Its total phenolic extract (Longxuetongluo capsule, LTC) is used for the treatment of ischemic stroke; however, its protective effect against atherosclerosis remains poorly understood. This paper aims to investigate the antiatherosclerotic effect of LTC and the underlying mechanisms in high-fat diet (HFD)-induced ApoE −/− mice. Methods: The levels of plasma lipid and areas of atherosclerotic lesions in the aortic sinus in ApoE −/− mice were evaluated. The effect of LTC on the nitric oxide (NO) production in oxidized low-density lipoprotein (ox-LDL)-stimulated human umbilical vein endothelial cells ( HUVECs ) was determined. The adhesion of monocytes to ox-LDL-stimulated HUVECs was further studied. Results: LTC at low, medium, and high doses markedly decreased the atherosclerotic lesion areas of the aortic sinus in HFD-induced ApoE −/− mice by 26.4% ( p < 0.05), 30.1% ( p < 0.05), and 46.5% ( p < 0.01), respectively, although it did not improve the dyslipidemia. Furthermore, LTC restored the diminished NO production of ox-LDL-stimulated HUVECs ( p < 0.001) and inhibited the adhesion between monocytes and endothelial cells ( p < 0.01). LTC appeared to alleviate ox-LDL-stimulated dysfunction of HUVECs, and inhibit the adhesion of monocytes to HUVECs via the MAPK/IKK/I κ B/NF- κ B signaling pathway, thus decrease atherosclerotic lesions in the aortic sinus in HFD-induced ApoE −/− mice. Conclusions: These findings suggest the potential of LTC for use as an effective agent against atherosclerosis. Highlights: Longxuetongluo capsule (LTC) delays atherosclerosis development. LTC increased NO production and the eNOS protein expression level of HUVECs stimulated by ox-LDL. LTC inhibited adhesion of THP-1 cells to ox-LDL-stimulated HUVECs. LTC regulated NF-κB and MAPK signaling pathway in ox-LDL-stimulated HUVECs.