The attenuating effects of 1,2,3,4,6 Penta‐o‐Galloyl‐β‐D‐Glucose on the inflammatory cytokines release from activated BV‐2 microglial cells

Abstract

Inflammation is a critical pathogenic mechanism involved in neurodegenerative diseases, including Alzheimer's (AD) and Parkinson's diseases. One of the hallmarks of AD is the abnormal extracellular deposition of neurotoxic amyloid‐β (Aβ) peptides which are toxic to neurons. An inflammatory process and the activation of glial cells by a variety of factors appear to have an important role in the pathway leading to neuronal cell death. Many natural compounds derived from plants have showed antiinflammatory activity, such as 1,2,3,4,6 Penta‐O‐Galloyl‐β‐D‐Glucose (PGG), which is a polyphenolic compound isolated from Rhus chinensis Mill that exhibits multiple pharmacological activities. Moreover, PGG is a potent inhibitor of IAPP (islet amyloid polypeptide, amylin) aggregation, which can slow or possibly prevent the toxic effects of IAPP oligometic intermediates. In this study, we investigated the protective effect of PGG in BV2 microglia cells activated by LPS/IFNγ. In this experiment, BV2‐immortalized murine microglial cells were used and cytokine antibody arrays were used to assess the effect of PGG in the release of proinflammatory cytokines, and ELISA experiments were performed to validate the results from the arrays. The results obtained from the cytokine arrays showed that PGG decreased the expression of monocyte chemotactic protein‐5 (MCP‐5) and matrix metallopeptidase 9 (MMP‐9). Both of these cytokines are up regulated during the inflammatory process. The results obtained demonstrate the ability of PGG to inhibit MCP‐5 and MMP‐9 synthesis in activated BV2 microglia cell. Up‐regulation of MMP‐9 and MCP‐5 has a great effect upon brain injury, inflammation, and neurodegeneration. Therefore, PGG inhibition effects on the release of these cytokines may provide novel therapeutic agent to treat brain inflammation and may be useful in delaying the onset of microglia‐mediated neurodegenerative disordersSupport or Funding InformationNIH Grants G12 MD007582 and P20 MD 006738