Journal
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
Volume 46, Issue 5, Pages 415-425Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejps.2012.03.004
Keywords
Berberine; Neuroprotection; Antioxidant defense; PI3K/Akt; Nrf2/HO-1
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Funding
- National Science Council of Taiwan [NSC 99-2320-B-037-023-MY3]
- Kaohsiung Medical University Research Foundation [KMUR007]
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Berberine (BBR) is a well-known anti-diabetic herbal medicine in Asia due to its beneficial effects on insulin sensitivity, glucose metabolism and glycolysis. Here, we identified the critical role of phosphatidylinositol 3-kinase (PI3K)/Akt involved BBR cellular defense mechanisms and first revealed the novel effect of BBR on nuclear factor (erythroid-derived 2)-related factor-2 (Nrf2)/heme oxygenase (HO)-1 induction in NSC34 motor neuron-like cells. BBR (0.1-10 nM) led to increasing insulin receptor expression, Akt phosphorylation and enhanced oxidant-sensitive Nrf2/HO-1 induction, which were blocked by a PI3K inhibitor, LY294002. In H2O2-treated cells, BBR significantly attenuated ROS production and increased cell viability, antioxidant defense (GSH and SOD) and oxidant-sensitive proteins (HO-1 and Nrf2), which also were blocked by LY294002. Furthermore, BBR improved mitochondrial function by increasing mitochondrial membrane potential and decreasing the oxygen consumption rate. BBR-induced anti-apoptotic function was demonstrated by increasing anti-apoptotic protein Bcl-2 and survival of motor neuron protein (SMN) and by decreasing apoptotic proteins (cytochrome c, Bax and caspase). These results suggest that BBR, which is active at nanomolar concentration, is a potential neuroprotective agent via PI3K/Akt-dependent cytoprotective and antioxidant pathways. (C) 2012 Elsevier B.V. All rights reserved.
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