{"doi":"10.3389/fcvm.2022.907490","title":"Anemoside B4 Inhibits Vascular Smooth Muscle Cell Proliferation, Migration, and Neointimal Hyperplasia","abstract":"Vascular smooth muscle cell (VSMC) phenotypic transformation, proliferation, and migration play a pivotal role in developing neointimal hyperplasia after vascular injury, including percutaneous transluminal angioplasty and other cardiovascular interventions. Anemoside B4 (B4) is a unique saponin identified from the Pulsatilla chinensis (Bge.) Regel, which has known anti-inflammatory activities. However, its role in modulating VSMC functions and neointima formation has not been evaluated. Herein, we demonstrate that B4 administration had a potent therapeutic effect in reducing neointima formation in a preclinical mouse femoral artery endothelium denudation model. Bromodeoxyuridine incorporation study showed that B4 attenuated neointimal VSMC proliferation in vivo . Consistent with the in vivo findings, B4 attenuated PDGF-BB-induced mouse VSMC proliferation and migration in vitro . Moreover, quantitative RT-PCR and Western blot analysis demonstrated that B4 suppressed PDGF-BB-induced reduction of SM22α, SMA, and Calponin, suggesting that B4 inhibited the transformation of VSMCs from contractile to the synthetic phenotype. Mechanistically, our data showed B4 dose-dependently inhibited the activation of the phosphatidylinositol 3-kinase (PI3K)/AKT and p38 mitogen-activated protein kinase MAPK signaling pathways. Subsequently, we determined that B4 attenuated VSMC proliferation and migration in a p38 MAPK and AKT dependent manner using pharmacological inhibitors. Taken together, this study identified, for the first time, Anemoside B4 as a potential therapeutic agent in regulating VSMC plasticity and combating restenosis after the vascular intervention.","journal":"Frontiers in Cardiovascular Medicine","year":2022,"id":252583,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":23,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9571,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":276184,"name":"Ping Qu","orcid":null,"position":1,"is_corresponding":false},{"id":270574,"name":"Chao Zhong","orcid":"0000-0003-1744-6378","position":2,"is_corresponding":false},{"id":897777,"name":"Luling He","orcid":null,"position":3,"is_corresponding":false},{"id":897099,"name":"Qingshan Zhang","orcid":"0009-0001-2559-5253","position":4,"is_corresponding":false},{"id":897100,"name":"Guoyue Zhong","orcid":"0000-0001-7882-9765","position":5,"is_corresponding":false},{"id":297243,"name":"Wenhui Hu","orcid":"0000-0001-8152-6116","position":6,"is_corresponding":false},{"id":270575,"name":"Yulin Feng","orcid":"0000-0002-8472-3091","position":7,"is_corresponding":false},{"id":897101,"name":"Shilin Yang","orcid":"0000-0001-9665-5834","position":8,"is_corresponding":false},{"id":233133,"name":"Xiaofeng Yang","orcid":"0000-0002-6854-6195","position":9,"is_corresponding":false},{"id":270576,"name":"Jun Yu","orcid":"0000-0003-4530-2179","position":10,"is_corresponding":false},{"id":862004,"name":"Dan Shan","orcid":"0009-0008-5153-5917","position":0,"is_corresponding":true}],"reference_count":58,"raw_metadata":null,"created_at":"2026-07-19T00:24:50.819822Z","pmid":"35620517","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}