{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T12:29:00Z","timestamp":1790080140412,"version":"4.0.1"},"reference-count":38,"publisher":"Wiley","issue":"16","license":[{"start":{"date-parts":[[2020,6,1]],"date-time":"2020-06-01T00:00:00Z","timestamp":1590969600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100011744","name":"National University Health System","doi-asserted-by":"publisher","award":["R\u2010184\u2010000\u2010267\u2010733"],"award-info":[{"award-number":["R\u2010184\u2010000\u2010267\u2010733"]}],"id":[{"id":"10.13039\/501100011744","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001381","name":"National Research Foundation Singapore","doi-asserted-by":"publisher","award":["R\u2010184\u2010000\u2010269\u2010592"],"award-info":[{"award-number":["R\u2010184\u2010000\u2010269\u2010592"]}],"id":[{"id":"10.13039\/501100001381","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":[[2020,8]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Corticosteroid resistance poses a major barrier to an effective anti\u2010inflammatory therapy for chronic obstructive pulmonary disease (COPD). The present study aimed to investigate potential corticosteroid re\u2010sensitization actions of andrographolide, a bioactive molecule from the herb <jats:styled-content style=\"fixed-case\"><jats:italic>Andrographis paniculata<\/jats:italic><\/jats:styled-content>, in COPD models, particularly in peripheral blood mononuclear cells (PBMCs) from COPD patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Corticosteroid sensitivity in PBMCs collected from COPD patients, or in human monocytic U937 cells exposed to cigarette smoke extract (CSE), was determined by measuring LPS\u2010induced IL\u20108 production, in the presence and absence of andrographolide. The mechanisms of corticosteroid re\u2010sensitization action of andrographolide were evaluated in a mouse cigarette smoke (CS)\u2010induced acute lung injury model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Impaired inhibition of IL\u20108 production by dexamethasone was detected in PBMCs from COPD patients and in CSE\u2010exposed U937 cells, together with reduced levels of nuclear factor erythroid 2\u2010related factor 2 (Nrf2) and histone deacetylase\u20102 (HDAC2). In both PBMCs and CSE\u2010exposed U937 cells, andrographolide restored dexamethasone inhibition of IL\u20108 production, accompanied by the up\u2010regulation of Nrf2 and HDAC2 levels. In the U937 cells, andrographolide was able to block CSE\u2010induced Akt and reduce the level of c\u2010Jun. Besides, andrographolide also augmented dexamethasone actions on lowering total and neutrophil counts, cytokine levels, and oxidative damage markers in bronchoalveolar lavage fluid from CS\u2010exposed mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>We report here for the first time a novel corticosteroid re\u2010sensitization property of andrographolide in human PBMCs and provide mechanistic evidence to support clinical evaluation of andrographolide in reversing steroid resistance in COPD.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.15080","type":"journal-article","created":{"date-parts":[[2020,4,26]],"date-time":"2020-04-26T01:58:28Z","timestamp":1587866308000},"page":"3662-3673","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Restoration of HDAC2 and Nrf2 by andrographolide overcomes corticosteroid resistance in chronic obstructive pulmonary disease"],"prefix":"10.1111","volume":"177","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2291-6063","authenticated-orcid":false,"given":"Wupeng","family":"Liao","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Yong Loo Lin School of Medicine National University Health System  Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert Y. 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