Scutellarin inhibits oleic acid induced vascular smooth muscle foam cell formation via activating autophagy and inhibiting NLRP3 inflammasome activation

作者全名："Gao, Wen-Cong; Yang, Tie-Hua; Wang, Bin-Bao; Liu, Qian; Li, Qing; Zhou, Xiao-Huan; Zheng, Chang-Bo; Chen, Peng"

作者地址："[Gao, Wen-Cong; Yang, Tie-Hua; Wang, Bin-Bao; Liu, Qian; Li, Qing; Zhou, Xiao-Huan; Zheng, Chang-Bo; Chen, Peng] Kunming Med Univ, Sch Pharm, Kunming, Peoples R China; [Gao, Wen-Cong; Yang, Tie-Hua; Wang, Bin-Bao; Liu, Qian; Li, Qing; Zhou, Xiao-Huan; Zheng, Chang-Bo; Chen, Peng] Yunnan Prov Key Lab Nat Drug Pharmacol, Kunming, Peoples R China; [Yang, Tie-Hua] Yunnan Univ Tradit Chinese Med, Sch Tradit Chinese Med, Kunming, Peoples R China; [Liu, Qian] Chongqing Med Univ, Sch Pharm, Chongqing, Peoples R China; [Li, Qing] Chinese Acad Sci, Kunming Inst Zool, Human Dis Mech Chinese Acad Sci, Ctr Biosafety Mega Sci,Key Lab Anim Models & Human, Kunming, Peoples R China; [Zheng, Chang-Bo; Chen, Peng] Kunming Med Univ, Coll Modern Biomed Ind, Kunming, Peoples R China; [Zheng, Chang-Bo] Yunnan Vaccine Lab, Kunming, Peoples R China; [Zheng, Chang-Bo; Chen, Peng] Kunming Med Univ, Sch Pharm, Yunnan Prov Key Lab Nat Drug Pharmacol, Kunming 650500, Yunnan, Peoples R China; [Zheng, Chang-Bo; Chen, Peng] Yunnan Prov Key Lab Nat Drug Pharmacol, Kunming 650500, Yunnan, Peoples R China"

通信作者："Zheng, CB; Chen, P (通讯作者)，Kunming Med Univ, Sch Pharm, Yunnan Prov Key Lab Nat Drug Pharmacol, Kunming 650500, Yunnan, Peoples R China.; Zheng, CB; Chen, P (通讯作者)，Yunnan Prov Key Lab Nat Drug Pharmacol, Kunming 650500, Yunnan, Peoples R China."

来源：CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:001173778100001

JCR分区：Q2

影响因子：2.4

年份：2024

卷号：51

期号：4

开始页：　

结束页：　

文献类型：Article

关键词：autophagy; inflammation; oleic acid; scutellarin; VSMC foam cells

摘要："Abnormalities in vascular smooth muscle cells (VSMCs) are pivotal in the pathogenesis of cardiovascular pathologies such as atherosclerosis and hypertension. Scutellarin (Scu), a flavonoid derived from marigold flowers, exhibits a spectrum of biological activities including anti-inflammatory, antioxidant, antitumor, immunomodulatory and antimicrobial effects. Notably, Scu has demonstrated the capacity to mitigate vascular endothelial damage and prevent atherosclerosis via its antioxidative properties. Nevertheless, the influence of Scu on the formation of VSMC-derived foam cells remains underexplored. In this study, Scu was evidenced to efficaciously attenuate oleic acid (OA)-induced lipid accumulation and the upregulation of adipose differentiation-associated protein Plin2 in a dose- and time-responsive manner. We elucidated that Scu effectively diminishes OA-provoked VSMC foam cell formation. Further, it was established that Scu pretreatment augments the protein expression of LC3B-II and the mRNA levels of Map1lc3b and Becn1, concurrently diminishing the protein levels of the NLRP3 inflammasome compared to the OA group. Activation of autophagy through rapamycin attenuated NLRP3 inflammasome protein expression, intracellular lipid droplet content and Plin2 mRNA levels. Scu also counteracted the OA-induced decrement of LC3B-II levels in the presence of bafilomycin-a1, facilitating the genesis of autophagosomes and autolysosomes. Complementarily, in vivo experiments revealed that Scu administration substantially reduced arterial wall thickness, vessel wall cross-sectional area, wall-to-lumen ratio and serum total cholesterol levels in comparison to the high-fat diet model group. Collectively, our findings suggest that Scu attenuates OA-induced VSMC foam cell formation through the induction of autophagy and the suppression of NLRP3 inflammasome activation."

基金机构：Key Laboratory of Sustainable Utilization of Southern Medicine in Yunnan Province

基金资助正文："This work was supported by the Scientific Research Fund Project of Yunnan Provincial Department of Education (2023Y0779), the National Natural Science Foundation of China (82200550 and 82360088), the Graduate Student Innovation Foundation of Kunming Medical University (2023B016), the Basic Research Program of Yunnan Province (202101AT070154 and 202201AT070562), the Key Laboratory of Sustainable Utilization of Southern Medicine in Yunnan Province (202105AG070012XS23097).r No Statement Availabler No Statement Availabler No Statement Availabler No Statement Available"