Abstract
Hemp seed (Fructus cannabis) is rich in lignanamides, and initial biological screening tests showed their potential anti-inflammatory and anti-oxidative capacity. This study investigated the possible effects and underlying mechanism of cannabisin F, a hempseed lignanamide, against inflammatory response and oxidative stress in lipopolysaccharide (LPS)-stimulated BV2 microglia cells. Cannabisin F suppressed the production and the mRNA levels of pro-inflammatory mediators such as interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) in a concentration-dependent manner in LPS-stimulated BV2 microglia cell. Furthermore, cannabisin F enhanced SIRT1 expression and blocked LPS-induced NF-κB (Nuclear factor kappa B) signaling pathway activation by inhibiting phosphorylation of IκBα (Inhibit proteins of nuclear factor kappaB) and NF-κB p65. And the SIRT1 inhibitor EX527 significantly inhibited the effect of cannabisin F on pro-inflammatory cytokines production, suggesting that the anti-inflammatory effects of cannabisin F are SIRT1-dependent. In addition, cannabisin F reduced the production of cellular reactive oxygen species (ROS) and promoted the expression of Nrf2 (Nuclear factor erythroid-2 related factor 2) and HO-1 (Heme Oxygenase-1), suggesting that the anti-oxidative effects of cannabisin F are related to Nrf2 signaling pathway. Collectively, these results suggest that the neuro-protection effect of cannabisin F against LPS-induced inflammatory response and oxidative stress in BV2 microglia cells involves the SIRT1/NF-κB and Nrf2 pathway.
Highlights
Hemp seed (Fructus cannabis, the dried fruit of Cannabis sativa L.) has been documented as a folk source of food for a long time [1,2]
We evaluated the neuro-protective effect of cannabisin F using LPS-stimulated BV2 microglia cells and investigated the underlying molecular mechanisms involving silent information regulator transcript-1 (SIRT1) and Nuclear factor erythroid-2 related factor 2 (Nrf2) modulation
Our results demonstrated that cannabisin F promoted the expression of Nrf2 and HO-1 protein, suggesting that cannabisin F attenuates the oxidative stress through the modulation of the expression of Nrf2
Summary
Hemp seed (Fructus cannabis, the dried fruit of Cannabis sativa L.) has been documented as a folk source of food for a long time [1,2]. Hemp seed extracts were reported for their anti-aging effects and the potential to improve impaired learning and memory induced by chemical drugs in mice [8,9]. It is reasonable to assume that lignanamides contribute to the neuroprotective effect of hemp seed [14,15,16]. To know more about the neuroprotective effect of hemp seed lignanamides, this study selects cannabisin F (Figure 1) as representative to investigate the underlying anti-neuroinflammatory mechanism using lipopolysaccharide (LPS)-induced BV2 microglia cells, based on its good performance in a previous screening study [11]
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