{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:45:05Z","timestamp":1760060705558,"version":"build-2065373602"},"reference-count":57,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T00:00:00Z","timestamp":1758672000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007300","name":"China Medical University and the Asia University","doi-asserted-by":"publisher","award":["CMU105-ASIA-11","CSMU-INT-113-06"],"award-info":[{"award-number":["CMU105-ASIA-11","CSMU-INT-113-06"]}],"id":[{"id":"10.13039\/501100007300","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008641","name":"Chung Shan Medical University","doi-asserted-by":"publisher","award":["CMU105-ASIA-11","CSMU-INT-113-06"],"award-info":[{"award-number":["CMU105-ASIA-11","CSMU-INT-113-06"]}],"id":[{"id":"10.13039\/501100008641","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Obesity is closely associated with the development of insulin resistance (IR) and type 2 diabetes mellitus (T2DM), primarily due to dysfunctional adipose tissue expansion and the secretion of pro-inflammatory cytokines such as interleukin-1\u03b2 (IL-1\u03b2). 14-Deoxy-11,12-didehydroandrographolide (deAND), a major diterpenoid component of Andrographis paniculata, has demonstrated notable antioxidant and anti-inflammatory activities. This study aimed to investigate the protective effects and mechanisms of deAND against IL-1\u03b2-induced IR in 3T3-L1 adipocytes. Network pharmacology analysis indicated that deAND targets several IR-related signaling pathways, particularly the MAPK and IRS-1\/AKT pathways. The experimental results show that IL-1\u03b2 stimulated p67phox membrane translocation and reactive oxygen species (ROS) production, contributing to impaired insulin signaling by activating ERK and JNK and reducing IRS-1\/AKT phosphorylation, which ultimately decreased insulin-stimulated glucose uptake. Pretreatment with deAND effectively inhibited NOX2-derived ROS generation, suppressed ERK\/JNK activation, restored IRS-1\/AKT phosphorylation, and reversed the reduction in glucose uptake caused by IL-1\u03b2. These findings suggest that deAND can alleviate IR by inhibiting NOX2-mediated oxidative stress, restoring insulin signaling and improving glucose uptake, highlighting its potential as a therapeutic agent for obesity-related IR.<\/jats:p>","DOI":"10.3390\/antiox14101155","type":"journal-article","created":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T08:19:45Z","timestamp":1758701985000},"page":"1155","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["14-Deoxy-11,12-didehydroandrographolide Alleviates IL-1\u03b2-Induced Insulin Resistance by Modulating NOX2-Driven ROS Generation and Restoring Insulin Signaling in 3T3-L1 Adipocytes"],"prefix":"10.3390","volume":"14","author":[{"given":"Chih-Ching","family":"Yen","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, China Medical University Hospital, Taichung 404328, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chia-Wen","family":"Lo","sequence":"additional","affiliation":[{"name":"Department of Nutrition, College of Medical and Health Care, Hung-Kuang University, Taichung 433304, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jyun-Lin","family":"Lee","sequence":"additional","affiliation":[{"name":"School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung 404328, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kai-Li","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Nutrition, Chung Shan Medical University, Taichung 402306, Taiwan"},{"name":"Department of Nutrition, Chung Shan Medical University Hospital, Taichung 402306, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chien-Chun","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Nutrition, Chung Shan Medical University, Taichung 402306, Taiwan"},{"name":"Department of Nutrition, Chung Shan Medical University Hospital, Taichung 402306, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chong-Kuei","family":"Lii","sequence":"additional","affiliation":[{"name":"Department of Nutrition, China Medical University, No. 100, Section 1, Jingmao Road, Beitun District, Taichung 406040, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chia-En","family":"Hsu","sequence":"additional","affiliation":[{"name":"Department of Nutrition, China Medical University, No. 100, Section 1, Jingmao Road, Beitun District, Taichung 406040, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ya-Chen","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Health and Nutrition Biotechnology, Asia University, Taichung 413305, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7611-5515","authenticated-orcid":false,"given":"Haw-Wen","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Nutrition, China Medical University, No. 100, Section 1, Jingmao Road, Beitun District, Taichung 406040, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1723","DOI":"10.1001\/jama.288.14.1723","article-title":"Prevalence and trends in obesity among US adults, 1999\u20132000","volume":"288","author":"Flegal","year":"2002","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.febslet.2007.11.057","article-title":"Inflammation and insulin resistance","volume":"582","author":"Olefsky","year":"2008","journal-title":"FEBS Lett."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2959","DOI":"10.1093\/eurheartj\/ehn387","article-title":"Adipose tissue dysfunction in obesity, diabetes, and vascular diseases","volume":"29","author":"Hajer","year":"2008","journal-title":"Eur. 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