Submitted to: Antioxidants
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/9/2016
Publication Date: 9/22/2016
Citation: Shukitt Hale, B., Kelly, M.E., Bielinski, D.F., Fisher, D.R. 2016. Tart cherry extracts reduce inflammatory and oxidative stress signaling in microglial cells . Antioxidants. doi: 10.3390/antiox5040033. Interpretive Summary: Tart cherries contain an array of chemical compounds that can decrease the inflammation and cellular stress which contribute to the declines in brain function seen in the elderly. Previous studies have shown that certain chemical compounds from dark-colored fruits can reduce the molecular signs of cellular stress in mouse brain tumor-derived cultured cells. Thus, the present study sought to determine if tart cherries, which improved brain function in aged rats, would be efficacious in reducing the molecular signs of inflammation and cellular stress in rat brain-derived immortalized cells. Cells were pretreated with different concentrations of Montmorency tart cherry powder for 1-4 hours, then treated (or not) with a bacterially-derived chemical to induce inflammation. Application of this inflammation-inducer increased the molecular signs of stress and inflammation in the cells, while pretreatment with tart cherry decreased these molecular signs in a dose- and time-dependent manner. Therefore, tart cherries, like other dark-colored fruits, may be effective in reducing inflammatory and stress-mediated signs of brain aging.
Technical Abstract: Tart cherries contain an array of polyphenols that can decrease inflammation and oxidative stress (OS), which contribute to cognitive declines seen in aging populations. Previous studies have shown that polyphenols from dark-colored fruits can reduce stress-mediated signaling in BV-2 mouse microglial cells, leading to decreases in nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression. Thus, the present study sought to determine if tart cherries, which improved cognitive behavior in aged rats, would be efficacious in reducing inflammatory and OS signaling in HAPI rat microglial cells. Cells were pretreated with different concentrations (0-1.0mg/ml) of Montmorency tart cherry powder for 1-4 hours, then treated with 0 or 100ng/ml lipopolysaccharide (LPS) overnight. LPS application increased extracellular levels of NO and tumor necrosis factor-alpha (TNF-a), and intracellular levels of iNOS and cyclooxygenase-2 (COX-2). Pretreatment with tart cherry decreased levels of NO, TNF-a and COX-2 in a dose- and time-dependent manner versus those without pretreatment; the optimal combination was between 0.125 and 0.25 mg/ml tart cherry for 2 hours. Higher concentrations of tart cherry powder and longer exposure times negatively affected cell viability. Therefore, tart cherries, like other dark-colored fruits, may be effective in reducing inflammatory and OS-mediated signals.