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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: Andrographis, Animals, Diabetes Mellitus, Experimental, Diabetes Mellitus, Type 2, Diterpenes, Dose-Response Relationship, Drug, Down-Regulation, Hypoglycemic Agents, Inflammation, Insulin Resistance, Insulinoma, Islets of Langerhans, Male, NF-kappa B, Pancreatic Neoplasms, Rats, Rats, Sprague-Dawley, Reactive Oxygen Species, Signal Transduction, Streptozocin, Thioctic Acid.
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Does andrographolide derivative AL-1 improve insulin resistance through down-regulation of NF-κB signalling pathway? Context: Andrographolide is the most active constituent of the medicinal plant Andrographis paniculata. Previously, we synthesized a novel andrographolide derivative AL-1, conjugating andrographolide with lipoic acid. Although the antioxidative and/or anti-inflammatory activity of AL-1 contributes to its cytoprotective effects, whether AL-1 can improve insulin resistance and the mechanisms responsible for its action have not been elucidated. We investigated the anti-hyperlipidaemic and anti-hyperglycaemic effects of AL-1 in a high-fat diet/streptozocin-induced animal diabetic model. In addition, we investigated the effect of AL-1 on the NF-κB signalling pathway in rat islet derived insulinoma cells (RIN-m cells) with a focus on the link between reactive oxygen species-associated inflammation and insulin resistance. AL-1, at doses of 40 and 80 mg · kg(-1), had a significant hypoglycaemic effect; it significantly reduced the level of cholesterol and increased HDL. AL-1 also reduced the homeostasis model assessment of insulin resistance and enhanced insulin sensitivity. In addition, AL-1 improved the morphology of pancreatic islets and their function. Furthermore, AL-1 suppressed high glucose-induced phosphorylation of p65 and IκBα in RIN-m cells.
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AL-1 has a hypoglycaemic effect and improves insulin resistance in type 2 diabetic rats. It protected islet from high glucose-induced oxidative damage by down-regulating the NF-κB signalling pathway. Further investigations of AL-1 as a promising new agent for treatment and/or prevention of diabetes are warranted. Final Decision: yes