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Andrographolide derivative AL-1 improves insulin resistance through down-regulation of NF-κB signalling pathway.
Br J Pharmacol. 2015 Jun; 172(12):3151-8.BJ

Abstract

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.

Links

Authors+Show Affiliations

Institute of New Drug Research and Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine, College of Pharmacy, Jinan University, Guangzhou, China.

Institute of New Drug Research and Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine, College of Pharmacy, Jinan University, Guangzhou, China.

Institute of New Drug Research and Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine, College of Pharmacy, Jinan University, Guangzhou, China.

Institute of New Drug Research and Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine, College of Pharmacy, Jinan University, Guangzhou, China.

Institute of New Drug Research and Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine, College of Pharmacy, Jinan University, Guangzhou, China.

Institute of New Drug Research and Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine, College of Pharmacy, Jinan University, Guangzhou, China.

Institute of New Drug Research and Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine, College of Pharmacy, Jinan University, Guangzhou, China.

Institute of New Drug Research and Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine, College of Pharmacy, Jinan University, Guangzhou, China.

Pub Type(s)

Journal Article

Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25712508

Citation

Li, Yongmei, et al. "Andrographolide Derivative AL-1 Improves Insulin Resistance Through Down-regulation of NF-κB Signalling Pathway." British Journal of Pharmacology, vol. 172, no. 12, 2015, pp. 3151-8.

Li Y, Yan H, Zhang Z, et al. Andrographolide derivative AL-1 improves insulin resistance through down-regulation of NF-κB signalling pathway. Br J Pharmacol. 2015;172(12):3151-8.

Li, Y., Yan, H., Zhang, Z., Zhang, G., Sun, Y., Yu, P., Wang, Y., & Xu, L. (2015). Andrographolide derivative AL-1 improves insulin resistance through down-regulation of NF-κB signalling pathway. British Journal of Pharmacology, 172(12), 3151-8. https://doi.org/10.1111/bph.13118

Li Y, et al. Andrographolide Derivative AL-1 Improves Insulin Resistance Through Down-regulation of NF-κB Signalling Pathway. Br J Pharmacol. 2015;172(12):3151-8. PubMed PMID: 25712508.

* Article titles in AMA citation format should be in sentence-case

TY - JOUR T1 - Andrographolide derivative AL-1 improves insulin resistance through down-regulation of NF-κB signalling pathway. AU - Li,Yongmei, AU - Yan,Hui, AU - Zhang,Zaijun, AU - Zhang,Gaoxiao, AU - Sun,Yewei, AU - Yu,Pei, AU - Wang,Yuqiang, AU - Xu,Lipeng, Y1 - 2015/04/10/ PY - 2014/10/04/received PY - 2015/02/13/revised PY - 2015/02/16/accepted PY - 2015/2/26/entrez PY - 2015/2/26/pubmed PY - 2016/3/2/medline SP - 3151 EP - 8 JF - British journal of pharmacology JO - Br J Pharmacol VL - 172 IS - 12 N2 - 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. SN - 1476-5381 UR - https://www.unboundmedicine.com/medline/citation/25712508/Andrographolide_derivative_AL_1_improves_insulin_resistance_through_down_regulation_of_NF_κB_signalling_pathway_ DB - PRIME DP - Unbound Medicine ER -