Anti-inflammatory effects of Lacto-Wolfberry in a mouse model of experimental colitis

作者:Philippe David; Brahmbhatt Viral*; Foata Francis; Saudan Yen; Serrant Patrick; Blum Stephanie; Benyacoub Jalil; Vidal Karine
来源:World Journal of Gastroenterology, 2012, 18(38): 5351-5359.
DOI:10.3748/wjg.v18.i38.5351

摘要

AIM: To investigate the anti-inflammatory properties of Lacto-Wolfberry (LWB), both in vitro and using a mouse model of experimental colitis. METHODS: The effects of LWB on lipopolysaccharide (LPS)-induced reactive oxygen species (ROS) and interleukin (IL)-6 secretion were assessed in a murine macrophage cell line. in vitro assessment also included characterizing the effects of LWB on the activation of NF-E2 related 2 pathway and inhibition of tumor necrosis factor-alpha (TNF-alpha)-induced nuclear factor-kappa B (NF kappa B) activation, utilizing reporter cell lines. Following the in vitro assessment, the anti-inflammatory efficacy of an oral intervention with LWB was tested in vivo using a preclinical model of intestinal inflammation. Multiple outcomes including body weight, intestinal histology, colonic cytokine levels and anti-oxidative measures were investigated. RESULTS: LWB reduced the LPS-mediated induction of ROS production [+LPS vs 1% LWB + LPS, 1590 +/- 188.5 relative luminescence units (RLU) vs 389 +/- 5.9 RLU, P < 0.001]. LWB was more effective than wolfberry alone in reducing LPS-induced IL-6 secretion in vitro (wolfberry vs 0.5% LWB, 15% +/- 7.8% vs 64% +/- 5%, P < 0.001). In addition, LWB increased reporter gene expression via the anti-oxidant response element activation (wolfberry vs LWB, 73% +/- 6.9% vs 148% +/- 28.3%, P < 0.001) and inhibited the TNF-a-induced activation of the NF-kappa B pathway (milk vs LWB, 10% +/- 6.7% vs 35% +/- 3.3%, P < 0.05). Furthermore, oral supplementation with LWB resulted in a reduction of macroscopic (-LWB vs +LWB, 5.39 +/- 0.61 vs 3.66 +/- 0.59, P = 0.0445) and histological scores (-LWB vs +LWB, 5.44 +/- 0.32 vs 3.66 +/- 0.59, P = 0.0087) in colitic mice. These effects were associated with a significant decrease in levels of inflammatory cytokines such as IL-1 beta (-LWB vs +LWB, 570 +/- 245 mu g/L vs 89 +/- 38 mu g/L, P = 0.0106), keratinocyte-derived chemokine/growth regulated protein-a (-LWB vs +LWB, 184 +/- 49 mu g/L vs 75 +/- 20 mu g/L, P = 0.0244), IL-6 (-LWB vs +LWB, 318 +/- 99 mu g/L vs 117 +/- 18 mu g/L, P = 0.0315) and other pro-inflammatory proteins such as cyclooxygenase-2 (-LWB vs +LWB, 0.95 +/- 0.12 AU vs 0.36 +/- 0.11 AU, P = 0.0036) and phosphorylated signal transducer and activator of transcription-3 (-LWB vs +LWB, 0.51 +/- 0.15 AU vs 0.1 +/- 0.04 AU, P = 0.057). Moreover, antioxidant biomarkers, including expression of gene encoding for the glutathione peroxidase, in the colon and the plasma anti-oxidant capacity were significantly increased by supplementation with LWB (-LWB vs +LWB, 1.2 +/- 0.21 mmol/L vs 2.1 +/- 0.19 mmol/L, P = 0.0095). CONCLUSION: These results demonstrate the anti-inflammatory properties of LWB and suggest that the underlying mechanism is at least in part due to NF-kappa B inhibition and improved anti-oxidative capacity.

  • 出版日期2012-10-14