{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:30:05Z","timestamp":1786977005501,"version":"build-2736575974"},"reference-count":26,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2022,12,9]],"date-time":"2022-12-09T00:00:00Z","timestamp":1670544000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81573761"],"award-info":[{"award-number":["81573761"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82004262"],"award-info":[{"award-number":["82004262"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["LQ20H290002"],"award-info":[{"award-number":["LQ20H290002"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["LGF22H290001"],"award-info":[{"award-number":["LGF22H290001"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["anatomypubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Anatomical Record"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Aim<\/jats:title>\n                    <jats:p>Nonalcoholic steatohepatitis (NASH) is a critical stage in the prognosis of nonalcoholic fatty liver disease (NAFLD). Pure total flavonoids from circus (PTFC) play essential roles in the improvement of NASH symptoms, but the underlying regulatory mechanism remains elusive. Our previous high\u2010throughput omics screening results indicate that the CCL2\/CCR2\u2010PI3K\u2010Akt signaling pathway is a key pathway that regulates the liver inflammatory response. PTFC may regulate the CCL2\/CCR2\u2010PI3K\u2010Akt signaling pathway to improve the liver inflammatory response.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A mice model of NASH was established by a high\u2010fat diet, and PTFC was used as treatment. Hematoxylin\u2010eosin and oil red O staining were used to observe the pathological changes in the liver tissue. Western blotting and real\u2010time PCR were used to measure the mRNA and protein levels in the liver. The expression of proinflammatory cytokines in the peripheral blood and liver tissues was measured by liquid suspension array. An automatic biochemical method was used to examine serum transaminases and lipids levels, as well as liver lipids.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Compared with the mice in the high\u2010fat diet group, mice in the HFD\u2009+\u2009PTFC group showed significantly improved liver histopathology, and levels of serum transaminase and lipids, liver lipids and serum proinflammatory cytokines. Moreover, the mRNA and protein expression and phosphorylation levels of key signaling molecules in the CCL2\/CCR2\u2010PI3K\u2010Akt signal transduction pathway were obviously reduced by PTFC treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusive Remarks<\/jats:title>\n                    <jats:p>PTFC can ameliorate NASH symptoms, and the mechanism may be related to regulating the CCL2\/CCR2\u2010PI3K\u2010Akt signal transduction pathway to reduce the liver inflammatory response.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ar.25117","type":"journal-article","created":{"date-parts":[[2022,12,9]],"date-time":"2022-12-09T04:30:06Z","timestamp":1670560206000},"page":"3169-3177","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Pure total flavonoids from citrus improve nonalcoholic steatohepatitis liver inflammatory responses by regulating the\n                    <scp>CCL2<\/scp>\n                    \/\n                    <scp>CCR2\u2010PI3K\u2010Akt<\/scp>\n                    signal transduction pathway"],"prefix":"10.1002","volume":"306","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9832-397X","authenticated-orcid":false,"given":"Liyan","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Gastroenterology Tongde Hospital of Zhejiang Province  Hangzhou Zhejiang China"},{"name":"The Second Central Laboratory The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine)  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8697-0574","authenticated-orcid":false,"given":"Zengsheng","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases Tongde Hospital of Zhejiang Province  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6170-8481","authenticated-orcid":false,"given":"Beihui","family":"He","sequence":"additional","affiliation":[{"name":"The Second Central Laboratory The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine)  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianshun","family":"Yu","sequence":"additional","affiliation":[{"name":"The Second Central Laboratory The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine)  Hangzhou Zhejiang China"},{"name":"Department of Gastroenterology Hangzhou Hospital of Traditional Chinese Medicine  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7805-4899","authenticated-orcid":false,"given":"Maoxiang","family":"Yan","sequence":"additional","affiliation":[{"name":"The Second Central Laboratory The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine)  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0929-3618","authenticated-orcid":false,"given":"Jianping","family":"Jiang","sequence":"additional","affiliation":[{"name":"The Second Central Laboratory The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine)  Hangzhou Zhejiang China"},{"name":"Department of Pharmacy, School of Medicine Zhejiang University City College  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7654-5080","authenticated-orcid":false,"given":"Zhiyun","family":"Chen","sequence":"additional","affiliation":[{"name":"The Second Central Laboratory The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine)  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,12,9]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2011-300304"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1901427"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2021.105849"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinre.2021.101710"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2019.10.028"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2019.00582"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2014.10.039"},{"key":"e_1_2_9_9_1","first-page":"2644","article-title":"Regulation of pure total flavonoids from citrus on TH17\/Treg balance in mice with NASH","volume":"40","author":"Li J. S.","year":"2015","journal-title":"Zhongguo Zhong Yao Za Zhi"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1142\/S0192415X21500130"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/mnfr.201400913"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2014.6108"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1055\/a-1250-8221"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.2741\/4892"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.15024"},{"issue":"571","key":"e_1_2_9_16_1","article-title":"CCL2CCR2 signaling in the skin drives surfactant\u2010induced irritant contact dermatitis through IL\u20101beta mediated neutrophil accumulation","volume":"142","author":"Shibuya R.","year":"2022","journal-title":"The Journal of Investigative Dermatology"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14938"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41387-020-00130-3"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2017.04.128"},{"key":"e_1_2_9_20_1","first-page":"403","article-title":"An interpretation of European guidelines for the diagnosis and treatment of nonalcoholic fatty liver disease","volume":"24","author":"Xin F. Z.","year":"2016","journal-title":"Zhonghua Gan Zang Bing Za Zhi"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01076-21"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/cpr.13115"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2022.824597"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2019.11.017"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.687095"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2016.06.036"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2019.04.050"}],"container-title":["The Anatomical Record"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ar.25117","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ar.25117","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/anatomypubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ar.25117","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T17:15:17Z","timestamp":1759943717000},"score":1,"resource":{"primary":{"URL":"https:\/\/anatomypubs.onlinelibrary.wiley.com\/doi\/10.1002\/ar.25117"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,9]]},"references-count":26,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2023,12]]}},"alternative-id":["10.1002\/ar.25117"],"URL":"https:\/\/doi.org\/10.1002\/ar.25117","archive":["Portico"],"relation":{},"ISSN":["1932-8486","1932-8494"],"issn-type":[{"value":"1932-8486","type":"print"},{"value":"1932-8494","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,9]]},"assertion":[{"value":"2022-07-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-10-10","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-12-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}