Inhibition of hypoxia-induced cyclooxygenase-2 by Korean Red Ginseng is dependent on peroxisome proliferator-activated receptor gamma

Background: Korean Red Ginseng (KRG) is a traditional herbal medicine made by steaming and drying fresh ginseng. It strengthens the endocrine and immune systems to ameliorate various inflammatory responses. The cyclooxygenase-2 (COX-2)/prostaglandin E2 pathway has important implications for inflammation responses and tumorigenesis. Peroxisome proliferator-activated receptor gamma (PPARγ) is a transcription factor that regulates not only adipogenesis and lipid homeostasis, but also angiogenesis and inflammatory responses.

Methods: The effects of the KRG on inhibition of hypoxia-induced COX-2 via PPARγ in A549 cells were determined by luciferase assay, Western blot, and/or quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The antimigration and invasive effects of KRG were evaluated on A549 cells using migration and matrigel invasion assays.

Results and conclusion: We previously reported that hypoxia-induced COX-2 protein and mRNA levels were suppressed by KRG. This study examines the possibility of PPARγ as a cellular target of KRG for the suppression of hypoxia-induced COX-2. PPARγ protein levels and PPARγ-responsive element (PPRE)-driven reporter activities were increased by KRG. Reduction of hypoxia-induced COX-2 by KRG was abolished by the PPARγ inhibitor GW9662. In addition, the inhibition of PPARγ abolished the effect of KRG on hypoxia-induced cell migration and invasion.

Discussion: Our results show that KRG inhibition of hypoxia-induced COX-2 expression and cell invasion is dependent on PPARγ activation, supporting the therapeutic potential for suppression of inflammation under hypoxia. Further studies are required to demonstrate whether KRG activates directly PPARγ and to identify the constituents responsible for this activity.