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Previously, we synthesized a novel andrographolide derivative <jats:styled-content style=\"fixed-case\">AL<\/jats:styled-content>\u20101, conjugating andrographolide with lipoic acid. Although the antioxidative and\/or anti\u2010inflammatory activity of <jats:styled-content style=\"fixed-case\">AL<\/jats:styled-content>\u20101 contributes to its cytoprotective effects, whether <jats:styled-content style=\"fixed-case\">AL<\/jats:styled-content>\u20101 can improve insulin resistance and the mechanisms responsible for its action have not been elucidated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>We investigated the anti\u2010hyperlipidaemic and anti\u2010hyperglycaemic effects of <jats:styled-content style=\"fixed-case\">AL<\/jats:styled-content>\u20101 in a high\u2010fat diet\/streptozocin\u2010induced animal diabetic model. In addition, we investigated the effect of <jats:styled-content style=\"fixed-case\">AL<\/jats:styled-content>\u20101 on the <jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">\u03baB<\/jats:styled-content> signalling pathway in rat islet derived insulinoma cells (<jats:styled-content style=\"fixed-case\">RIN<\/jats:styled-content>\u2010m cells) with a focus on the link between reactive oxygen species\u2010associated inflammation and insulin resistance.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">AL<\/jats:styled-content>\u20101, at doses of 40 and 80\u2009mg\u00b7kg<jats:sup>\u22121<\/jats:sup>, had a significant hypoglycaemic effect; it significantly reduced the level of cholesterol and increased <jats:styled-content style=\"fixed-case\">HDL<\/jats:styled-content>. <jats:styled-content style=\"fixed-case\">AL<\/jats:styled-content>\u20101 also reduced the homeostasis model assessment of insulin resistance and enhanced insulin sensitivity. In addition, <jats:styled-content style=\"fixed-case\">AL<\/jats:styled-content>\u20101 improved the morphology of pancreatic islets and their function. Furthermore, <jats:styled-content style=\"fixed-case\">AL<\/jats:styled-content>\u20101 suppressed high glucose\u2010induced phosphorylation of p65 and <jats:styled-content style=\"fixed-case\">I\u03baB\u03b1<\/jats:styled-content> in <jats:styled-content style=\"fixed-case\">RIN<\/jats:styled-content>\u2010m cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">AL<\/jats:styled-content>\u20101 has a hypoglycaemic effect and improves insulin resistance in type 2 diabetic rats. It protected islet from high glucose\u2010induced oxidative damage by down\u2010regulating the <jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">\u03baB<\/jats:styled-content> signalling pathway. Further investigations of <jats:styled-content style=\"fixed-case\">AL<\/jats:styled-content>\u20101 as a promising new agent for treatment and\/or prevention of diabetes are warranted.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.13118","type":"journal-article","created":{"date-parts":[[2015,2,25]],"date-time":"2015-02-25T09:50:49Z","timestamp":1424857849000},"page":"3151-3158","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Andrographolide derivative <scp>AL<\/scp>\u20101 improves insulin resistance through down\u2010regulation of <scp>NF<\/scp>\u2010<scp>\u03baB<\/scp> signalling pathway"],"prefix":"10.1111","volume":"172","author":[{"given":"Yongmei","family":"Li","sequence":"first","affiliation":[{"name":"Institute of New Drug Research and Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine, College of Pharmacy Jinan University  Guangzhou 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