Journal
PLANTA MEDICA
Volume 76, Issue 2, Pages 120-127Publisher
GEORG THIEME VERLAG KG
DOI: 10.1055/s-0029-1186005
Keywords
16-hydroxycleroda-3,13-dien-15,16-olide; lipopolysaccharide; microglia; inflammation; neuroprotection; Polyalthia longifolia var. pendula (Annonaceae)
Categories
Funding
- National Science Council [NSC-96-2320-B-037-039-MY3]
- Kaohsiung Medical University, Taiwan [QA096001]
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Polyalthia longifolia var. pendula is used as an antipyretic agent in indigenous systems of medicine. Microglia-mediated inflammation plays an important role in the pathway leading to neuronal cell death in a number of neurodegenerative diseases. The aim of this study was to investigate the effects of 6-hydroxycleroda-3,13-dien-15,16-olide (PL3) extracted from Polyalthia longifolia var. pendula on lipopolysaccharide(LPS)-induced inflammation inmicroglia-like HAPI cells and primary microglia cultures. In microglia-neuron cocultures, LPS decreased the cell viability of neuroblastoma SH-SY5Y cells. LPS-induced cell death was attenuated by the NOS inhibitor, L-NAME, the COX-2 inhibitor, NS-398 or the NADPH oxidase inhibitor, DPI, respectively. In LPS-treated microglia cells, PL3 decreased the expression of iNOS, COX-2, gp91(phox), and NF-kappa Bp65, the degradation of I kappa B alpha, and the production of NO, PGE(2), iROS, and TNF-alpha. PL3 also enhanced the expression of HO-1, a cytoprotective and anti-inflammatory enzyme. Moreover, PL3 reduced LPS-activated microglia-induced cell death. The present results suggest that PL3 inhibits microglia-mediated inflammation and inflammation-related neuronal cell death. Therefore, PL3 has potential use for the treatment of inflammation-related neurodegenerative diseases.
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