{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T14:45:02Z","timestamp":1787582702184,"version":"build-2736575974"},"reference-count":87,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2022,1,21]],"date-time":"2022-01-21T00:00:00Z","timestamp":1642723200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012176","name":"Project 211","doi-asserted-by":"publisher","award":["CPU2018GF10"],"award-info":[{"award-number":["CPU2018GF10"]}],"id":[{"id":"10.13039\/501100012176","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2018YFC1704900"],"award-info":[{"award-number":["2018YFC1704900"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2018YFC1704905"],"award-info":[{"award-number":["2018YFC1704905"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2022,5]]},"abstract":"<jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>Non\u2010alcoholic fatty liver disease (NAFLD) represents a severe public health problem. It often coexists with hypertension in the context of metabolic syndrome. We investigated the effects of amlodipine on NAFLD combined with hypertension and investigated the underlying mechanism\/s.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>\n                      Mice were fed with high\u2010fat diet (HFD) and 0.05%\n                      <jats:italic>N<\/jats:italic>\n                      \u2010nitro\u2010L\u2010arginine methylester sterile water to induce NAFLD with hypertension. Gut microbiota composition and function were assessed by 16S ribosomal DNA and metagenomic sequencing. Untargeted metabolome profiles were applied to identify differential metabolites in mice caecum.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>\n                      Amlodipine besylate and amlodipine aspartate significantly decreased liver injury and hepatic steatosis, and improved lipid metabolism with a concomitant reduction in the expression of lipogenic genes in mice with NAFLD and hypertension. Mechanistically, amlodipine besylate and amlodipine aspartate have potential to restore intestinal barrier integrity and improve antimicrobial defence, along with the elevated abundances of\n                      <jats:italic>Akkermansia<\/jats:italic>\n                      ,\n                      <jats:italic>Bacteroides<\/jats:italic>\n                      and\n                      <jats:italic>Lactobacillus<\/jats:italic>\n                      . Noteworthily, the gut microbiota in amlodipine besylate\u2010 and amlodipine aspartate\u2010treated mice had higher abundance of functional genes involved in taurine and hypotaurine metabolism. Consistently, the strengthened taurine and hypotaurine metabolism was confirmed by untargeted metabolome analysis. Based on the correlation and causal analysis, the altered gut microbiota composition and the enhancement of taurine and hypotaurine metabolism may synergistically decreased alanine aminotransferase, liver triglycerides, lipogenic genes and plasma cholesterol in HFD\u2010fed hypertensive mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and Implications<\/jats:title>\n                    <jats:p>Amlodipine besylate and amlodipine aspartate exert multifactorial improvements in NAFLD and hypertension by modulating gut microbiota. They may serve as promising therapeutic agents for treating these diseases.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.15768","type":"journal-article","created":{"date-parts":[[2021,12,3]],"date-time":"2021-12-03T20:55:12Z","timestamp":1638564912000},"page":"2054-2077","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":63,"title":["Amlodipine, an anti\u2010hypertensive drug, alleviates non\u2010alcoholic fatty liver disease by modulating gut microbiota"],"prefix":"10.1111","volume":"179","author":[{"given":"Yang","family":"Li","sequence":"first","affiliation":[{"name":"School of Basic Medicine and Clinical Pharmacy, State Key Laboratory of Natural Medicines China Pharmaceutical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danyang","family":"Zhao","sequence":"additional","affiliation":[{"name":"School of Basic Medicine and Clinical Pharmacy, State Key Laboratory of Natural Medicines China Pharmaceutical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minyi","family":"Qian","sequence":"additional","affiliation":[{"name":"School of Basic Medicine and Clinical Pharmacy, State Key Laboratory of Natural Medicines China Pharmaceutical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Basic Medicine and Clinical Pharmacy, State Key Laboratory of Natural Medicines China Pharmaceutical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuyue","family":"Pan","sequence":"additional","affiliation":[{"name":"School of Basic Medicine and Clinical Pharmacy, State Key Laboratory of Natural Medicines China Pharmaceutical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinxin","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Basic Medicine and Clinical Pharmacy, State Key Laboratory of Natural Medicines China Pharmaceutical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xubin","family":"Duan","sequence":"additional","affiliation":[{"name":"School of Basic Medicine and Clinical Pharmacy, State Key Laboratory of Natural Medicines China Pharmaceutical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yufei","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Basic Medicine and Clinical Pharmacy, State Key Laboratory of Natural Medicines China Pharmaceutical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenxin","family":"Jia","sequence":"additional","affiliation":[{"name":"School of Basic Medicine and Clinical Pharmacy, State Key Laboratory of Natural Medicines China Pharmaceutical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9285-7084","authenticated-orcid":false,"given":"Lirui","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Modern Biology Nanjing University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,1,21]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000164570.20420.67"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2017.10.095"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00081.2016"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15542"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14112"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-018-2901-1"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01984"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21155214"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.03.024"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14153"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20942"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2015.09.030"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1080\/17474124.2019.1595589"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btq461"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1219451110"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1219451110"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0127252"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41401-019-0310-0"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00161.2019"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-020-01855-9"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.niox.2019.10.008"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btt086"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajh\/hpt138"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.291.5505.881"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm8081090"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.3390\/md17080455"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1097\/FJC.0b013e3181c37d86"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2019.109258"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/molbev\/msx148"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2020.e03209"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12012-020-09587-1"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12876-015-0330-2"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2014.07.006"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.03004-19"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201809302"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2016.5875"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2017.07.026"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.118.010823"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-981-13-8023-5_82"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.3350\/cmh.2020.0125"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1080\/19490976.2020.1712984"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15178"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2019.01.041"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13238-020-00724-8"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2017.09.021"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2016.09.022"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2018.01082"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.14044"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v25.i24.3009"},{"key":"e_1_2_12_51_1","doi-asserted-by":"publisher","DOI":"10.1111\/1440-1681.13387"},{"key":"e_1_2_12_52_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00726-018-2605-8"},{"key":"e_1_2_12_53_1","doi-asserted-by":"publisher","DOI":"10.1097\/MOL.0b013e3283347ebb"},{"key":"e_1_2_12_54_1","doi-asserted-by":"publisher","DOI":"10.1097\/MEG.0000000000001191"},{"key":"e_1_2_12_55_1","doi-asserted-by":"publisher","DOI":"10.4161\/15548627.2014.984268"},{"key":"e_1_2_12_56_1","doi-asserted-by":"publisher","DOI":"10.1080\/19490976.2019.1638722"},{"key":"e_1_2_12_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4197"},{"key":"e_1_2_12_58_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3000410"},{"key":"e_1_2_12_59_1","doi-asserted-by":"publisher","DOI":"10.1002\/mnfr.201900487"},{"key":"e_1_2_12_60_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.14316"},{"key":"e_1_2_12_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(21)02614-7"},{"key":"e_1_2_12_62_1","doi-asserted-by":"publisher","DOI":"10.3390\/md17070391"},{"key":"e_1_2_12_63_1","doi-asserted-by":"publisher","DOI":"10.1080\/19490976.2021.1927633"},{"key":"e_1_2_12_64_1","doi-asserted-by":"publisher","DOI":"10.1038\/hr.2016.85"},{"key":"e_1_2_12_65_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14965"},{"key":"e_1_2_12_66_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.116.309006"},{"key":"e_1_2_12_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhepr.2021.100255"},{"key":"e_1_2_12_68_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu153"},{"key":"e_1_2_12_69_1","doi-asserted-by":"publisher","DOI":"10.1021\/ac051437y"},{"key":"e_1_2_12_70_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41569-018-0108-7"},{"key":"e_1_2_12_71_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature07540"},{"key":"e_1_2_12_72_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40168-018-0541-1"},{"key":"e_1_2_12_73_1","doi-asserted-by":"publisher","DOI":"10.3164\/jcbn.18-116"},{"key":"e_1_2_12_74_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1904360116"},{"key":"e_1_2_12_75_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41366-019-0332-1"},{"key":"e_1_2_12_76_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14095"},{"key":"e_1_2_12_77_1","doi-asserted-by":"publisher","DOI":"10.1097\/HJH.0000000000001961"},{"key":"e_1_2_12_78_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00726-020-02823-6"},{"key":"e_1_2_12_79_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0013858"},{"key":"e_1_2_12_80_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00726-009-0340-x"},{"key":"e_1_2_12_81_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2020.117292"},{"key":"e_1_2_12_82_1","doi-asserted-by":"publisher","DOI":"10.1291\/hypres.29.457"},{"key":"e_1_2_12_83_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2017.109"},{"key":"e_1_2_12_84_1","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.b19-00057"},{"key":"e_1_2_12_85_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-49462-w"},{"key":"e_1_2_12_86_1","doi-asserted-by":"publisher","DOI":"10.1080\/10408398.2018.1517725"},{"key":"e_1_2_12_87_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2015-008204"},{"key":"e_1_2_12_88_1","first-page":"519","article-title":"\u95e8\u51ac\u6c28\u9178\u6c28\u6c2f\u5730\u5e73\u4e34\u5e8a\u5e94\u7528\u4e13\u5bb6\u5efa\u8bae","volume":"28","author":"\u674e\u8389","year":"2020","journal-title":"\u4e2d\u534e\u9ad8\u8840\u538b\u6742\u5fd7"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.15768","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/bph.15768","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.15768","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,25]],"date-time":"2023-08-25T06:33:58Z","timestamp":1692945238000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bph.15768"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,21]]},"references-count":87,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2022,5]]}},"alternative-id":["10.1111\/bph.15768"],"URL":"https:\/\/doi.org\/10.1111\/bph.15768","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,21]]},"assertion":[{"value":"2021-05-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-11-21","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-01-21","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}