Studies on the anti-inflammatory effects and mechanisms of andrographolide in mouse BV-2 microglia

Autor: Chin-Hsiang Chen, 陳致翔
Rok vydání: 2007
Druh dokumentu: 學位論文 ; thesis
Popis: 95
Andrographolide (Andro) is one of the active components of Andrographis paniculat, a Chinese official herbal medicine used as an anti-inflammatory drug. Andro is known to display anti-inflammatory activity in peripheral neutrophils and macrophage, but its protective effects and mechanisms in microglia and neuron are not clear. Microglia, a macrophage-like resident brain cell, has been proposed to play a key role in host defense and tissue repair in the central nervous system (CNS). Microglial cells become activated and play deleterious roles during brain injury and various neurodegenerative diseases such as ischemic stroke by over-responsiveness or improper regulation through producing excessive pro-inflammatory mediators including nitric oxide (NO), cytokines (e.g., interleukin-1β (IL-1β) and tissue necrosis factor-α (TNF-α)), and reactive oxygen species (ROS) in CNS. In the present work, I examined the effects of Andro on LPS- and IFN-γ-stimulated microglia cells (BV-2) and in oxygen-glucose deprivation (OGD)-activated microglia and neurons. Andro concentration-dependently reduced iNOS and NO production in LPS- and IFN-γ-stimulated BV-2 possibly through inhibition of nuclear factor-κB by suppressing I κB activation and ERK activation. Andro also inhibited LPS-induced ROS and cytokine (TNF-α and IL-1β) production in BV-2 possibly through modulation of intracellular calcium mobilization. Furthermore, Andro decreased OGD-induced protein nitrotyrosine formation in BV-2 by reducing iNOS expression. OGD trigger a mitochondria dysfunction-dependent ROS production leading to neuronal cell death. Andro prevented OGD-induced neuronal death but did not reverse the OGD-triggered mitochondria dysfunction. Based on these results, I conclude that Andro is a potent anti-inflammatory drug in compromising microglia activation during inflammation and hypoxia condition. It is also protective against hypoxia-induced neuronal death. These effects confer Andro beneficial properties for the treatment of inflammation-related CNS disease.
Databáze: Networked Digital Library of Theses & Dissertations
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