{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T14:10:29Z","timestamp":1789135829022,"version":"build-2803163510"},"reference-count":46,"publisher":"American Chemical Society (ACS)","issue":"9","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/501100001412","name":"Council of Scientific and Industrial Research, India","doi-asserted-by":"publisher","award":["MLP2129"],"award-info":[{"award-number":["MLP2129"]}],"id":[{"id":"10.13039\/501100001412","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease characterized by aberrant fibroblast activation and excessive extracellular matrix accumulation, predominantly collagen, leading to irreversible lung remodeling. Sinigrin (SNG), a naturally occurring glucosinolate with reported anti-inflammatory and antioxidant activities, has not been investigated in the context of pulmonary fibrosis. In the present study, we evaluated the therapeutic activity of SNG using complementary in vitro and in vivo models of IPF. In the current investigation, inflammatory responses were induced by lipopolysaccharide (LPS) in RAW 264.7 macrophages and precision-cut lung slices (PCLS), whereas fibrotic activation was elicited by TGF-\u03b2 in LL29, DHLF cells, and PCLS. Treatment with sinigrin and dexamethasone significantly suppressed LPS-induced inflammatory mediators (IL-6, TNF-\u03b1, IL-1\u03b2, CCL2, MMP-9, and COX-2). In TGF-\u03b2-stimulated fibroblasts\/PCLS, SNG and pirfenidone markedly attenuated collagen accumulation and downregulated the expression of key fibrotic markers (FN-1, \u03b1-SMA, TIMP-1, TIMP-3, COL1\u03b11, and COL3\u03b11). SNG administration in a bleomycin-induced pulmonary fibrosis mouse model significantly improved body weight, survival rate, and pulmonary index. Histopathological analyses revealed reduced collagen deposition and lowered Ashcroft scores, accompanied by decreased oxidative stress and improved lung function in SNG treatment compared to BLM and PFD groups. Consistently, gene and protein expression analyses demonstrated that SNG dose-dependently attenuated the bleomycin-induced inflammatory and fibrotic marker expression. Further mechanistic investigations, including an AMPK siRNA-based approach, demonstrated that SNG exerts its anti-inflammatory and antifibrotic effects partly through activation of AMPK signaling. Collectively, these findings suggest that SNG may represent a therapeutic candidate for the treatment of IPF.<\/jats:p>","DOI":"10.1021\/acsptsci.5c00826","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T07:01:50Z","timestamp":1786518110000},"page":"2438-2453","source":"Crossref","is-referenced-by-count":0,"title":["Sinigrin Mitigates\nPulmonary Inflammation and Fibrosis\nPartly through Adenosine Monophosphate-Activated Protein Kinase (AMPK)\nSignaling"],"prefix":"10.1021","volume":"9","author":[{"given":"Suriya","family":"Panneerselvam","sequence":"first","affiliation":[{"name":"CSIR-Indian Institute of Chemical Technology , , , ,","place":["Hyderabad, Telangana, India, 500 007"]},{"name":"Academy of Scientific and Innovative Research (AcSIR) , , ,","place":["Ghaziabad, India, 201002"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeyasankari","family":"S","sequence":"additional","affiliation":[{"name":"CSIR-Indian Institute of Chemical Technology , , , ,","place":["Hyderabad, Telangana, India, 500 007"]},{"name":"Manipal Academy of Higher Education , , Manipal, , ,","place":["Udupi, Karnataka, India, 576104"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anoop","family":"Kishore","sequence":"additional","affiliation":[{"name":"Manipal Academy of Higher Education , , Manipal, , ,","place":["Udupi, Karnataka, India, 576104"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7591-737X","authenticated-orcid":true,"given":"Sai Balaji","family":"Andugulapati","sequence":"additional","affiliation":[{"name":"CSIR-Indian Institute of Chemical Technology , , , ,","place":["Hyderabad, Telangana, India, 500 007"]},{"name":"Academy of Scientific and Innovative Research (AcSIR) , , ,","place":["Ghaziabad, India, 201002"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,12]]},"reference":[{"issue":"8","key":"2026091109134071100_cit1","doi-asserted-by":"publisher","first-page":"201","DOI":"10.3390\/jcm7080201","article-title":"Idiopathic\nPulmonary Fibrosis (IPF): An Overview","volume":"7","author":"Barratt","year":"2018","journal-title":"J. Clin.\nMed."},{"issue":"7","key":"2026091109134071100_cit2","doi-asserted-by":"publisher","first-page":"1028","DOI":"10.1016\/j.bbadis.2012.11.021","article-title":"Oxidative Stress\nand Pulmonary Fibrosis","volume":"1832","author":"Cheresh","year":"2013","journal-title":"Biochim. Biophys. Acta,\nMol. Basis Dis."},{"issue":"4","key":"2026091109134071100_cit3","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1007\/s13665-018-0210-7","article-title":"Risk Factors for\nthe Development of Idiopathic Pulmonary\nFibrosis: A Review","volume":"7","author":"Zaman","year":"2018","journal-title":"Curr. Pulmonol Rep."},{"issue":"3","key":"2026091109134071100_cit4","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1111\/resp.14194","article-title":"Incidence, Prevalence and Mortality\nof Idiopathic Pulmonary Fibrosis in Australia","volume":"27","author":"Cox","year":"2022","journal-title":"Respirology"},{"issue":"11","key":"2026091109134071100_cit5","doi-asserted-by":"publisher","first-page":"1069","DOI":"10.1038\/nbt1114-1069","article-title":"Landmark Approvals\nin Idiopathic Pulmonary Fibrosis","volume":"32","author":"Ratner","year":"2014","journal-title":"Nat. Biotechnol."},{"issue":"1","key":"2026091109134071100_cit6","doi-asserted-by":"publisher","first-page":"12062","DOI":"10.1038\/s41598-019-48593-4","article-title":"Gastrointestinal\nAdverse Effects of Nintedanib and\nthe Associated Risk Factors in Patients with Idiopathic Pulmonary\nFibrosis","volume":"9","author":"Kato","year":"2019","journal-title":"Sci. Rep."},{"key":"2026091109134071100_cit7","doi-asserted-by":"publisher","first-page":"1031890","DOI":"10.3389\/fphar.2022.1031890","article-title":"Metabolic Reprogramming of Pulmonary\nFibrosis","volume":"13","author":"Li","year":"2022","journal-title":"Front. Pharmacol."},{"issue":"8","key":"2026091109134071100_cit8","doi-asserted-by":"publisher","first-page":"1121","DOI":"10.1038\/s41591-018-0087-6","article-title":"Metformin\nReverses Established Lung\nFibrosis in a Bleomycin Model","volume":"24","author":"Rangarajan","year":"2018","journal-title":"Nat. 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Biol."},{"key":"2026091109134071100_cit18","doi-asserted-by":"publisher","first-page":"2017","DOI":"10.1002\/ptr.8453","article-title":"Sinigrin Selectively Mitigates the\nAcute-Cardiac Inflammatory\nResponse Through an AMPK -Dependent Mechanism","volume":"39","author":"Veeram","year":"2025","journal-title":"Phytother. Res."},{"issue":"1","key":"2026091109134071100_cit19","doi-asserted-by":"publisher","first-page":"3439","DOI":"10.1038\/s41598-017-03676-y","article-title":"Protective\nand Therapeutic Effect\nof Felodipine against Bleomycin-Induced Pulmonary Fibrosis in Mice","volume":"7","author":"Tanaka","year":"2017","journal-title":"Sci. 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Scientific Opinion on the Safety of Allyl\nIsothiocyanate for the Proposed Uses as a Food Additive","volume":"8","author":"EFSA.","year":"2010","journal-title":"EFSA J."},{"issue":"4","key":"2026091109134071100_cit23","doi-asserted-by":"publisher","first-page":"83","DOI":"10.3390\/medicina55040083","article-title":"Epithelial\u2013Mesenchymal Transition\nin the Pathogenesis of Idiopathic Pulmonary Fibrosis","volume":"55","author":"Salton","year":"2019","journal-title":"Medicina"},{"issue":"1","key":"2026091109134071100_cit24","doi-asserted-by":"publisher","first-page":"2592","DOI":"10.1080\/10717544.2022.2105445","article-title":"Histopathological, Physiological\nand Biochemical Assessment of Resveratrol Nanocapsules Efficacy in\nBleomycin-Induced Acute and Chronic Lung Injury in Rats","volume":"29","author":"Albanawany","year":"2022","journal-title":"Drug Delivery"},{"issue":"10","key":"2026091109134071100_cit25","doi-asserted-by":"publisher","DOI":"10.1002\/mco2.744","article-title":"Pulmonary Fibrosis:\nPathogenesis and Therapeutic Strategies","volume":"5","author":"Wang","year":"2024","journal-title":"MedComm"},{"issue":"1","key":"2026091109134071100_cit26","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1186\/s12931-021-01711-1","article-title":"Idiopathic\nPulmonary Fibrosis beyond the Lung: Understanding Disease Mechanisms\nto Improve Diagnosis and Management","volume":"22","author":"Luppi","year":"2021","journal-title":"Respir\nRes."},{"issue":"4","key":"2026091109134071100_cit27","doi-asserted-by":"publisher","first-page":"3149","DOI":"10.3390\/ijms24043149","article-title":"Immune Mechanisms of\nPulmonary Fibrosis with Bleomycin","volume":"24","author":"Ishida","year":"2023","journal-title":"IJMS"},{"issue":"12","key":"2026091109134071100_cit28","doi-asserted-by":"publisher","first-page":"2404","DOI":"10.3390\/antiox11122404","article-title":"Broccoli-Derived\nGlucoraphanin Activates AMPK\/PGC1\u03b1\/NRF2 Pathway and Ameliorates\nDextran-Sulphate-Sodium-Induced Colitis in Mice","volume":"11","author":"Tian","year":"2022","journal-title":"Antioxidants"},{"issue":"1","key":"2026091109134071100_cit29","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.70321","article-title":"Orderly Regulation\nof Macrophages and Fibroblasts by Axl in Bleomycin-Induced Pulmonary\nFibrosis in Mice","volume":"29","author":"Zhao","year":"2025","journal-title":"J. Cell. Mol. Med."},{"issue":"10","key":"2026091109134071100_cit30","doi-asserted-by":"publisher","first-page":"4733","DOI":"10.4049\/jimmunol.153.10.4733","article-title":"Lung Monocyte\nChemoattractant Protein-1 Gene Expression in Bleomycin-Induced Pulmonary\nFibrosis","volume":"153","author":"Zhang","year":"1994","journal-title":"J. Immunol."},{"issue":"2","key":"2026091109134071100_cit31","doi-asserted-by":"publisher","first-page":"31","DOI":"10.29245\/2689-999X\/2019\/2.1149","article-title":"Epithelial-Mesenchymal\nTransition Contributes to Pulmonary Fibrosis via Aberrant Epithelial\/Fibroblastic\nCross-Talk","volume":"3","author":"Hill","year":"2019","journal-title":"J. Lung Health Dis."},{"issue":"12","key":"2026091109134071100_cit32","doi-asserted-by":"publisher","first-page":"1053","DOI":"10.1136\/thx.2009.121798","article-title":"SNAI Transcription\nFactors Mediate Epithelial-Mesenchymal Transition in Lung Fibrosis","volume":"64","author":"Jayachandran","year":"2009","journal-title":"Thorax"},{"key":"2026091109134071100_cit33","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1016\/B978-0-12-394311-8.00012-1","article-title":"N-Cadherin-Mediated\nAdhesion and Signaling from Development to Disease","volume-title":"Progress in Molecular Biology and Translational Science","author":"Radice","year":"2013"},{"key":"2026091109134071100_cit34","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/j.toxlet.2018.10.019","article-title":"Pirfenidone Inhibits Epithelial-Mesenchymal\nTransition and Pulmonary\nFibrosis in the Rat Silicosis Model","volume":"300","author":"Guo","year":"2019","journal-title":"Toxicol.\nLett."},{"issue":"4","key":"2026091109134071100_cit35","doi-asserted-by":"publisher","first-page":"1622","DOI":"10.1172\/JCI71386","article-title":"Fibrotic Extracellular Matrix Activates a Profibrotic\nPositive Feedback Loop","volume":"124","author":"Parker","year":"2014","journal-title":"J. Clin. Invest"},{"issue":"2","key":"2026091109134071100_cit36","doi-asserted-by":"publisher","first-page":"67","DOI":"10.2174\/157340810791233033","article-title":"TGF-\u03b2:\nTitan of Lung Fibrogenesis","volume":"6","author":"Yue","year":"2010","journal-title":"Curr. Enzym Inhib"},{"issue":"1","key":"2026091109134071100_cit37","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1007\/s10522-023-10072-9","article-title":"AMPK Signaling\nInhibits the Differentiation of Myofibroblasts: Impact on Age-Related\nTissue Fibrosis and Degeneration","volume":"25","author":"Salminen","year":"2024","journal-title":"Biogerontology"},{"issue":"1","key":"2026091109134071100_cit38","doi-asserted-by":"publisher","first-page":"19060","DOI":"10.1038\/s41598-025-01314-6","article-title":"Allicin Induced AMPK Signaling Attenuated\nSmad3 Pathway Mediated Lung Fibrosis","volume":"15","author":"Nakazawa","year":"2025","journal-title":"Sci. Rep."},{"key":"2026091109134071100_cit39","doi-asserted-by":"publisher","first-page":"104280","DOI":"10.1016\/j.jff.2020.104280","article-title":"Natural Product Mogrol\nAttenuates Bleomycin-Induced\nPulmonary Fibrosis Development through Promoting AMPK Activation","volume":"77","author":"Liu","year":"2021","journal-title":"J. Funct. Foods"},{"key":"2026091109134071100_cit40","doi-asserted-by":"publisher","first-page":"105844","DOI":"10.1016\/j.phrs.2021.105844","article-title":"Activated\nAMPK by Metformin Protects against Fibroblast Proliferation\nduring Pulmonary Fibrosis by Suppressing FOXM1","volume":"173","author":"Gu","year":"2021","journal-title":"Pharmacol. Res."},{"key":"2026091109134071100_cit41","doi-asserted-by":"publisher","first-page":"719589","DOI":"10.3389\/fphar.2021.719589","article-title":"Metformin\nAttenuates Silica-Induced Pulmonary Fibrosis by Activating Autophagy\nvia the AMPK-mTOR Signaling Pathway","volume":"12","author":"Li","year":"2021","journal-title":"Front.\nPharmacol"},{"issue":"15","key":"2026091109134071100_cit42","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.182578","article-title":"Impaired AMPK Control of Alveolar Epithelial Cell Metabolism\nPromotes Pulmonary Fibrosis","volume":"10","author":"Rodri\u0301guez","year":"2025","journal-title":"JCI Insight"},{"issue":"5","key":"2026091109134071100_cit43","doi-asserted-by":"publisher","first-page":"918","DOI":"10.1161\/HYPERTENSIONAHA.108.114702","article-title":"AMP Activated\nProtein Kinase-Alpha2 Deficiency Exacerbates Pressure-Overload-Induced\nLeft Ventricular Hypertrophy and Dysfunction in Mice","volume":"52","author":"Zhang","year":"2008","journal-title":"Hypertension"},{"key":"2026091109134071100_cit44","doi-asserted-by":"publisher","first-page":"175820","DOI":"10.1016\/j.ejphar.2023.175820","article-title":"Dehydrozingerone Alleviates\nPulmonary Fibrosis via Inhibition of Inflammation and Epithelial-Mesenchymal\nTransition by Regulating the Wnt\/\u03b2-Catenin Pathway","volume":"953","author":"Shaikh","year":"2023","journal-title":"Eur. J. Pharmacol."},{"issue":"1","key":"2026091109134071100_cit45","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1165\/rcmb.2007-0340OC","article-title":"Male Sex\nHormones Exacerbate Lung Function Impairment after Bleomycin-Induced\nPulmonary Fibrosis","volume":"39","author":"Voltz","year":"2008","journal-title":"Am. J. Respir. Cell Mol.\nBiol."},{"key":"2026091109134071100_cit46","doi-asserted-by":"publisher","first-page":"3101","DOI":"10.1021\/acsptsci.5c00280","article-title":"Design and Synthesis of Novel Pirfenidone\nAnalogues\nfor Targeting Fibroblast Differentiation via Transforming Growth Factor-\u03b2\/Smad\nPathway Using In Vitro and In Vivo Models","volume":"8","author":"Nandawadekar","year":"2025","journal-title":"ACS\nPharmacol. Transl. Sci."}],"container-title":["ACS Pharmacology &amp; Translational\nScience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acsptsci.5c00826","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/aptsfn\/article-pdf\/9\/9\/2438\/66506489\/acsptsci.5c00826.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/aptsfn\/article-pdf\/9\/9\/2438\/66506489\/acsptsci.5c00826.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T13:37:26Z","timestamp":1789133846000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/aptsfn\/article\/9\/9\/2438\/5253170\/Sinigrin-Mitigates-Pulmonary-Inflammation-and"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,12]]},"references-count":46,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,8,12]]},"published-print":{"date-parts":[[2026,9,11]]}},"URL":"https:\/\/doi.org\/10.1021\/acsptsci.5c00826","relation":{},"ISSN":["2575-9108"],"issn-type":[{"value":"2575-9108","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,12]]}}}