title: Saikosaponin-a Attenuates Oxidized LDL Uptake and Prompts Cholesterol Efflux in THP-1 Cells.
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.
authors: *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.
authors: Dan
authors: D
authors: He
authors: Hongyan
authors: H
authors: Wang
authors: Ling
authors: L
authors: Xu
authors: Xiaoqing
authors: X
authors: Wang
authors: Kuang
authors: K
authors: Peng
authors: Lili
authors: L
authors: Wang
authors: Pixu
authors: P
authors: Liu
authors: Peng
authors: P
authors: Qu
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000096:biosynthesis; D050197:Atherosclerosis / Q000503:physiopathology*; D018955:CD36 Antigens / Q000378:metabolism; D018929:Cell Culture Techniques; D002784:Cholesterol / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D008074:Lipoproteins / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects*; D016328:NF-kappa B / Q000096:biosynthesis; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000378:metabolism; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D047495:PPAR gamma / Q000096:biosynthesis; D018110:Receptors, Lipoprotein / Q000378:metabolism; D012503:Saponins / Q000494:pharmacology*
chemical_list: D064286:ATP Binding Cassette Transporter 1; D018955:CD36 Antigens; D016207:Cytokines; D008074:Lipoproteins; D008077:Lipoproteins, LDL; D016328:NF-kappa B; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D047495:PPAR gamma; D018110:Receptors, Lipoprotein; D012503:Saponins; C099252:oxidized low density lipoprotein; D009828:Oleanolic Acid; D002784:Cholesterol; C025759:saikosaponin D