{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T13:37:27Z","timestamp":1790257047842,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2020,5,19]],"date-time":"2020-05-19T00:00:00Z","timestamp":1589846400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Physiology"],"published-print":{"date-parts":[[2020,6]]},"abstract":"<jats:sec><jats:title>New Findings<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p><jats:bold>What is the central question of this study?<\/jats:bold><\/jats:p>\n<jats:p>We previously demonstrated that quercetin transiently preserved respiratory function in dystrophin\u2010deficient mice. To gain lasting therapeutic benefits, we tested quercetin in combination with nicotinamide riboside, lisinopril and prednisolone in the D2\u2010mdx model.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p><jats:bold>What is the main finding and its importance?<\/jats:bold><\/jats:p>\n<jats:p>We demonstrated that these quercetin\u2010based cocktails did not preserve respiratory or diaphragmatic function or reduce histological damage after 7 months of treatment starting at 4 months of age.<\/jats:p>\n<\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Duchenne muscular dystrophy is characterized by the absence of dystrophin protein and causes muscle weakness and muscle injury, culminating in respiratory failure and cardiomyopathy. Quercetin transiently improved respiratory function but failed to maintain long\u2010term therapeutic benefits in <jats:italic>mdx<\/jats:italic> mice. In this study, we combined quercetin with nicotinamide riboside (NR), lisinopril and prednisolone to assess the efficacy of quercetin\u2010based cocktails. We hypothesized that quercetin, NR and lisinopril independently would improve respiratory function and decrease diaphragmatic injury and when combined would have additive effects. To address this hypothesis, <jats:italic>in vivo<\/jats:italic> respiratory function, <jats:italic>in vitro<\/jats:italic> diaphragmatic function and histological injury were assessed in DBA (healthy), D2\u2010mdx (dystrophic) and D2\u2010mdx mice treated with combinations of quercetin, NR and lisinopril from 4 to 11\u00a0months of age. Respiratory function, assessed using whole\u2010body plethysmography, was largely similar between healthy and dystrophin\u2010deficient mice. Diaphragm specific tension was decreased by \u223c50% in dystrophic mice compared with healthy mice (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05), but fatigue resistance was similar between groups. Contractile area was decreased by \u223c10% (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05) and fibrotic area increased from 3.5% in healthy diaphragms to 27% (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05) in dystrophic diaphragms. Contrary to expectations, these functional and histological parameters of disease were not offset by any intervention. These data suggest that quercetin, NR and lisinopril, independently and in combination, did not prevent diaphragmatic injury or preserve respiratory function.<\/jats:p><\/jats:sec>","DOI":"10.1113\/ep087887","type":"journal-article","created":{"date-parts":[[2020,4,8]],"date-time":"2020-04-08T13:30:10Z","timestamp":1586352610000},"page":"989-999","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Nutraceutical and pharmaceutical cocktails did not preserve diaphragm muscle function or reduce muscle damage in D2\u2010mdx mice"],"prefix":"10.1113","volume":"105","author":[{"given":"H. R.","family":"Spaulding","sequence":"first","affiliation":[{"name":"Department of Animal Science Iowa State University  Ames IA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4655-0086","authenticated-orcid":false,"given":"T.","family":"Quindry","sequence":"additional","affiliation":[{"name":"Health and Human Performance University of Montana  Missoula MT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. C.","family":"Quindry","sequence":"additional","affiliation":[{"name":"Health and Human Performance University of Montana  Missoula MT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3797-7539","authenticated-orcid":false,"given":"J. T.","family":"Selsby","sequence":"additional","affiliation":[{"name":"Department of Animal Science Iowa State University  Ames IA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,5,19]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2012.06.007"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00552.2016"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1113\/EP086091"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1113\/expphysiol.2014.083360"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.1916"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(18)30024-3"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clnu.2011.01.010"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1988.sp017279"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1004490"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.06-7353com"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/2044-5040-4-2"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddv460"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/135.10.2299"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M038786"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-8966(02)00140-2"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.23819"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1525107"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00221.2012"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1113\/EP085339"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clnu.2014.06.008"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.21848"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0088360"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1006868130002"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1183\/20734735.012716"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.3233\/JND-150099"},{"key":"e_1_2_8_27_1","first-page":"e50036","article-title":"Isometric and eccentric force generation assessment of skeletal muscles isolated from murine models of muscular dystrophies","author":"Moorwood C.","year":"2013","journal-title":"Journal of visualized experiments: JoVE"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M501485200"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.128.3.355"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12576-015-0408-1"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.111.031716"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aaf5504"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP272057"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0030063"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0102737"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.3390\/jpm9010001"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0168293"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/apha.12944"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00162.2019"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1249\/MSS.0000000000001639"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaf2693"}],"container-title":["Experimental Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1113%2FEP087887","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/EP087887","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1113\/EP087887","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/EP087887","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T03:56:05Z","timestamp":1693972565000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.1113\/EP087887"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,19]]},"references-count":40,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2020,6]]}},"alternative-id":["10.1113\/EP087887"],"URL":"https:\/\/doi.org\/10.1113\/ep087887","archive":["Portico"],"relation":{},"ISSN":["0958-0670","1469-445X"],"issn-type":[{"value":"0958-0670","type":"print"},{"value":"1469-445X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,5,19]]},"assertion":[{"value":"2019-05-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-04-03","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-05-19","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}