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Zusammenfassung
Upon activation, microglia, the immunocompetent cells in the brain, get highly phagocytic and release pro-inflammatory mediators like nitric oxide (NO). Excessive NO prodn. is pivotal in neurodegenerative disorders, and there is evidence that abnormalities in NO prodn. and inflammatory responses may at least support a range of neuropsychiatric disorders, including depression. Although exts. of ...
Zusammenfassung
Upon activation, microglia, the immunocompetent cells in the brain, get highly phagocytic and release pro-inflammatory mediators like nitric oxide (NO). Excessive NO prodn. is pivotal in neurodegenerative disorders, and there is evidence that abnormalities in NO prodn. and inflammatory responses may at least support a range of neuropsychiatric disorders, including depression. Although exts. of St. John's wort (Hypericum perforatum L.) have been used for centuries in traditional medicine, notably for the treatment of depression, there is still considerable lack in scientific knowledge about the impact on microglia. We used N11 and BV2 mouse microglia, as well as RAW 264.7 macrophages to investigate the effects of St. John's wort ext. and constituents thereof on NO prodn. Moreover, flow cytometry and fluorescence microscopy were employed to analyze the influence on phagocytosis, transcription factor activation states, and cell motility. We found that exts. of St. John's wort efficiently suppress lipopolysaccharide-induced NO release and identified hyperforin as the responsible compd., being effective at concns. between 0.25 and 0.75 micro M. The reduced NO prodn. was mediated by diminished inducible nitric oxide synthase expression on the mRNA and protein level. In addn., at similar concns., hyperforin reduced zymosan phygocytosis to 20-40% and putatively acted by downregulating the CD206 macrophage mannose receptor and modulation of cell motility. We found that the obsd. effects correlate with a suppression of the activated state of Nf-kappaB and phospho-CREB, while c-JUN, STAT1, and HIF-1alpha activity and cyclooxygenase-2 expression remained unaffected by hyperforin. These results reveal that hyperforin influences pro-inflammatory and immunol. responses of microglia that are involved in the progression of neuropathol. disorders.