Modulation of ovine neutrophil function and apoptosis by standardized extracts of Echinacea angustifolia, Butea frondosa and Curcuma longa

Impaired neutrophil function has been associated with increased infectious diseases in ruminants. Attachment of neutrophils to endothelium and superoxide production is critical features of their immune activity. Once the infection is cleared, programmed cell death ensures the rapid resolution of inflammation. To develop new natural therapeutics for ruminants, standard extracts of Echinacea angustifolia (Polinacea™), Butea frondosa and Curcuma longa (Curcuvet™) were first evaluated on ovine neutrophil functions. Curcuvet™ strongly reduced PMA-stimulated adhesion and superoxide production. Polinacea™ and B. frondosa extract also reduced these functions, but with less efficacy than Curcuvet™. We analyzed the effect of extracts on spontaneous apoptosis and gene expression in neutrophils aged in vitro for up to 22 h. IL8 is critical for neutrophil recruitment and the immune response; Bcl2-related proteins, Bcl2A1 and Bax, are key regulators of neutrophil fate. Spontaneous apoptosis strongly increased in ovine neutrophils cultured for 22 h (T22), accompanied by an upregulation of IL8 and a decreased Bcl2A1:Bax ratio. Curcuvet™ stimulated spontaneous apoptosis and inhibited IL8 and Bcl2A1 gene expression at T22, whereas Polinacea™ and B. frondosa extract inhibited spontaneous apoptosis and stimulated IL8 expression at T22. These results suggest that Curcuvet™ has antiinflammatory activity, whereas Polinacea™ and B. frondosa have an immunomodulatory action on sheep neutrophils.