BACKGROUND AND PURPOSE: 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. EXPERIMENTAL APPROACH: 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. KEY RESULTS: 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. CONCLUSION AND IMPLICATIONS: 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.
BACKGROUND AND PURPOSE: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. EXPERIMENTAL APPROACH: 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. KEY RESULTS: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. CONCLUSION AND IMPLICATIONS: AL-1 has a hypoglycaemic effect and improves insulin resistance in type 2 diabeticrats. 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.
Authors: B A S Reyes; N D Bautista; N C Tanquilut; R V Anunciado; A B Leung; G C Sanchez; R L Magtoto; P Castronuevo; H Tsukamura; K-I Maeda Journal: J Ethnopharmacol Date: 2005-11-18 Impact factor: 4.360
Authors: Adam J Pawson; Joanna L Sharman; Helen E Benson; Elena Faccenda; Stephen P H Alexander; O Peter Buneman; Anthony P Davenport; John C McGrath; John A Peters; Christopher Southan; Michael Spedding; Wenyuan Yu; Anthony J Harmar Journal: Nucleic Acids Res Date: 2013-11-14 Impact factor: 16.971
Authors: Leonardo C Souza; Marcos K Andrade; Evellyn M Azevedo; Daniele C Ramos; Ellen L Bail; Maria A B F Vital Journal: Neurotox Res Date: 2022-08-27 Impact factor: 3.978