Original ArticleSaikosaponin-a Attenuates Oxidized LDL Uptake and Prompts Cholesterol Efflux in THP-1 CellsHe, Dan PhD; Wang, Hongyan PhD; Xu, Ling MSc; Wang, Xiaoqing PhD; Peng, Kuang PhD; Wang, Lili PhD; Liu, Pixu PhD; Qu, Peng MDAuthor Information *Department of Cardiology, Institute of Heart and Vessel Diseases of Dalian Medical University, The Second Affiliated Hospital of Dalian Medical University, Dalian, China; †Department of Neurology, Xinhua Hospital Affiliated of Dalian University, Dalian, China; ‡Department of Cardiology, The First Affiliated Hospital of Nanhua University, Hengyang, China; and §Department of Cancer Center, Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China. Reprints: Pixu Liu, Department of Cancer Center, Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China, 116023 (e-mail: firstname.lastname@example.org). Supported by the National Natural Science Foundation of China (30670836). The authors report no conflicts of interest. D. He and H. Wang contributed equally to this work. Received September 29, 2015 Accepted January 19, 2016 Journal of Cardiovascular Pharmacology: June 2016 - Volume 67 - Issue 6 - p 510-518 doi: 10.1097/FJC.0000000000000373 Buy Metrics Abstract Saikosaponins-a (Ssa) is a major bioactive extract of Radix Bupleuri which is a traditional Chinese medicine. The roles of inflammatory response and lipid transportation in the process of atherosclerosis have drawn increasing attention. We explored the regulation of lipid transportation and immune-inflammatory role of Ssa in early atherosclerosis. The antiatherogenic actions and possible molecular mechanisms of Ssa were texted in THP-1 cells. We examined the effect of Ssa on oxidized low-density lipoprotein (ox-LDL)-induced lipid uptake, cholesterol efflux, immune-inflammatory response. THP-1 macrophages were treated with Ssa followed by ox-LDL for 24 hours. Results from western blot showed that Ssa obviously reduced lipoprotein uptake to block foam cell formation and the expression of Density Lipoprotein Receptor-1 and CD36. Ssa also significantly boosted cholesterol efflux and the expression of ATP binding cassettetransporter A1 and peroxisome proliferator-activated receptor γ. The results also indicated that Ssa inhibited ox-LDL–induced activation of AKT and nuclear factor-κB, assembly of NLRP3 inflammasome and production of proinflammatory cytokines. It is suggested that the ability against immune inflammatory response of Ssa is due to modulation of the PI3K/AKT/NF-κB/NLRP3 pathway. In conclusion, this study provides new insight into Ssa's molecular mechanism and its therapeutic potential in the treatment of atherosclerosis. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.