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By using pharmacodynamics, pharmacokinetics, and metabolomics, our present study discusses whether the combination of individual herbs or major active components of MJCPF possess synergistic neuroprotective effects against ischemic stroke (IS). 108 adult male Sprague\u2010Dawley rats were randomly and equally divided into 9 groups, including sham group (N, vehicle), middle cerebral artery occlusion (MCAO) model group (M, vehicle), positive group (P, 36\u2009mg\/kg\/day nimodipine), crocin I (A1, 40\u2009mg\/kg\/day), <jats:italic>\u03b2<\/jats:italic>\u2010asarone (B1, 15\u2009mg\/kg\/day), crocin I\u2009+\u2009<jats:italic>\u03b2<\/jats:italic>\u2010asarone (A1B1, 55\u2009mg\/kg\/day), <jats:italic>C<\/jats:italic>. <jats:italic>sativus<\/jats:italic> (A, 580\u2009mg\/kg\/day), <jats:italic>A. tatarinowii<\/jats:italic> (B, 480\u2009mg\/kg\/day), and <jats:italic>C. sativus<\/jats:italic>\u2009+\u2009<jats:italic>A. tatarinowii<\/jats:italic>, also named MJCPF (AB, 1060\u2009mg\/kg\/day) groups. All drugs were orally administered to rats once a day for 14 consecutive days. Neurological deficit score, cerebral infarct volume, body weight change, TTC, HE and IHC staining, behavioral evaluation, metabolic profiles, and pharmacokinetic parameters were determined. MCAO led to severe brain damage including large infarct volume, more severe brain tissue injury, and worse neurological function as compared to the sham rats. All treatment groups showed a significant neuroprotective effect on MCAO rats. Furthermore, the pharmacodynamics\u2019 results demonstrated that MJCPF had a synergistic effect evidenced by small infarct volume, more regular arrangement of neuronal cells, and more improved neural function, and the levels of inflammatory factors were closer to normality. A total of 53 differential metabolites between MCAO and sham groups were screened by integration of serum and brain metabolisms, all of which were restored at varying degrees in treatment. PCA and PLS\u2010DA analysis showed that the levels of differential metabolites treated with MJCPF were closer to the sham group than the individual herb and single compound alone or A1B1 combination. The pharmacokinetic parameters further verified the above results that MJCPF could synergistically promote drug absorption greater than others. Our integrated pharmacodynamics, metabolomics, and pharmacokinetic approach reveals the synergistic effect of MJCPF on treatment of IS, which powerfully contribute to the understanding of scientific connotation of TMC formula.<\/jats:p>","DOI":"10.1155\/2022\/9365760","type":"journal-article","created":{"date-parts":[[2022,10,18]],"date-time":"2022-10-18T22:20:05Z","timestamp":1666131605000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Combination of Individual Herb of Mi\u2010Jian\u2010Chang\u2010Pu Formula Exerts a Synergistic Effect in the Treatment of Ischemic Stroke in Rats"],"prefix":"10.1155","volume":"2022","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2002-7898","authenticated-orcid":false,"given":"Fangfang","family":"Lu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7067-0067","authenticated-orcid":false,"given":"Xiaojuan","family":"Su","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6039-0619","authenticated-orcid":false,"given":"Jingjing","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3370-8246","authenticated-orcid":false,"given":"Rong","family":"Zong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5105-1030","authenticated-orcid":false,"given":"Shuqin","family":"Ding","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1149-3237","authenticated-orcid":false,"given":"Lingling","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4872-9867","authenticated-orcid":false,"given":"Jing","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5231-8884","authenticated-orcid":false,"given":"Gidion","family":"Wilson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4170-7080","authenticated-orcid":false,"given":"Liuyan","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0266-4137","authenticated-orcid":false,"given":"Youyue","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6622-5275","authenticated-orcid":false,"given":"Xiaoying","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0049-0604","authenticated-orcid":false,"given":"Weibiao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4818-5967","authenticated-orcid":false,"given":"Xueqin","family":"Ma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,10,18]]},"reference":[{"key":"e_1_2_12_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2020.113518"},{"key":"e_1_2_12_2_2","doi-asserted-by":"publisher","DOI":"10.1136\/svn-2020-000457"},{"key":"e_1_2_12_3_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21186454"},{"key":"e_1_2_12_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10571-019-00709-0"},{"key":"e_1_2_12_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clineuro.2022.107238"},{"key":"e_1_2_12_6_2","doi-asserted-by":"publisher","DOI":"10.2147\/IJN.S210035"},{"key":"e_1_2_12_7_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0209184"},{"key":"e_1_2_12_8_2","doi-asserted-by":"publisher","DOI":"10.1017\/S1092852919000804"},{"key":"e_1_2_12_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1875-5364(18)30047-5"},{"key":"e_1_2_12_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2019.112051"},{"key":"e_1_2_12_11_2","first-page":"1001","article-title":"Effects of Zha-Li-nu-Si decoction and Mi-Jian-Chang-Pu decoction on neuron injury in cerebral ischemia rats","volume":"33","author":"Liu J. 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