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This study aimed to investigate the combinational mechanisms of SBP against AS by comprehensive network pharmacology and fecal metabolomic analysis. Bufonis venenum, one of the adjuvant medicines in SBP, is an animal medicine with a narrow therapeutic window. Considering animal protection, we evaluated the anti-AS effect of SBP without BV (SBP-BV) using ApoE\u2212\/\u2212 mouse models, culture cells, and metabolomic methods. Our data suggested that SBP showed remarkable anti-atherosclerotic effects through multiple targets and multiple pathways, while each component in SBP played different roles in their synergistic effect. Notably, SBP-BV showed comparable effects with SBP in the treatment of AS. Both SBP and SBP-BV could reduce cholesterol uptake in RAW264.7 cells and prevent the occurrence and development of AS in WD-induced ApoE\u2212\/\u2212 mice by attenuating the atherosclerotic plaque area, and reducing inflammatory cytokines and cholesterol levels in vivo. Our finding might provide new insights into the research and development of new anti-atherosclerosis drugs.<\/jats:p>\n                  <jats:p\/>","DOI":"10.1039\/d3mo00067b","type":"journal-article","created":{"date-parts":[[2023,5,23]],"date-time":"2023-05-23T21:42:05Z","timestamp":1684878125000},"page":"653-667","update-policy":"https:\/\/doi.org\/10.1039\/rsc_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Integrated network pharmacology and fecal metabolomic analysis of the combinational mechanisms of Shexiang Baoxin Pill against atherosclerosis"],"prefix":"10.1093","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8042-0413","authenticated-orcid":false,"given":"Zhicong","family":"Wang","sequence":"first","affiliation":[{"name":"School of Pharmacy, Fujian University of Traditional Chinese Medicine b , Fuzhou, 350122, China"},{"name":"School of Pharmacy, Naval Medical University a , Shanghai, 200433, China \u00a0 1391485750@qq.com \u00a0 991210766@qq.com \u00a0 437010612@qq.com \u00a0 xkxu@smmu.edu.cn \u00a0 lyliurh@126.com \u00a0 +020 81871245 \u00a0 +020 81871245"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianqian","family":"Wan","sequence":"additional","affiliation":[{"name":"Department of Integrated Chinese and Western Medicine, The Third Affiliated Hospital of Naval Medical University c , Shanghai 200438, China \u00a0 18317091985@163.com"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Xie","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Naval Medical University a , Shanghai, 200433, China \u00a0 1391485750@qq.com \u00a0 991210766@qq.com \u00a0 437010612@qq.com \u00a0 xkxu@smmu.edu.cn \u00a0 lyliurh@126.com \u00a0 +020 81871245 \u00a0 +020 81871245"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zifan","family":"Zhu","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Fujian University of Traditional Chinese Medicine b , Fuzhou, 350122, China"},{"name":"School of Pharmacy, Naval Medical University a , Shanghai, 200433, China \u00a0 1391485750@qq.com \u00a0 991210766@qq.com \u00a0 437010612@qq.com \u00a0 xkxu@smmu.edu.cn \u00a0 lyliurh@126.com \u00a0 +020 81871245 \u00a0 +020 81871245"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xike","family":"Xu","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Naval Medical University a , Shanghai, 200433, China \u00a0 1391485750@qq.com \u00a0 991210766@qq.com \u00a0 437010612@qq.com \u00a0 xkxu@smmu.edu.cn \u00a0 lyliurh@126.com \u00a0 +020 81871245 \u00a0 +020 81871245"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Fu","sequence":"additional","affiliation":[{"name":"Changhai Hospital, Naval Medical University d , Shanghai, 200433, China \u00a0 fucaofan@126.com \u00a0 +020 31162301 \u00a0 +020 31162301"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Runhui","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Fujian University of Traditional Chinese Medicine b , Fuzhou, 350122, China"},{"name":"School of Pharmacy, Naval Medical University a , Shanghai, 200433, China \u00a0 1391485750@qq.com \u00a0 991210766@qq.com \u00a0 437010612@qq.com \u00a0 xkxu@smmu.edu.cn \u00a0 lyliurh@126.com \u00a0 +020 81871245 \u00a0 +020 81871245"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,5,24]]},"reference":[{"key":"2026010813052964800_cit1","doi-asserted-by":"crossref","first-page":"113436","DOI":"10.1016\/j.jep.2020.113436","article-title":"Dingxin recipe iv attenuates atherosclerosis by regulating lipid metabolism through lxr-\u03b1\/srebp1 pathway and modulating the gut microbiota in ApoE\u2212\/\u2212 mice fed with hfd","volume":"266","author":"Zhang","year":"2021","journal-title":"J. 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