Tipping the Scales of Inflammation One Phytonutrient at a Time: Composition and Context Matter
This is a faculty mentored scholarship project that is a completing of a Hippenhammer grant (Faculty Scholarship), the mentoring of a honors student project (Honors Program Project), and a second student project (Student Scholarship).
Abstract
The prevalence of intestinal inflammatory diseases is increasing, and pharmacologic agents for intervention are currently limited. The etiology may be diverse (e.g. allergy, infection, etc.), but ultimately intestinal inflammation results from disruption of tight junction (TJ) proteins which creates gaps between epithelial cells, allowing bacteria to enter and perpetuate a cycle of inflammation with underlying immune cells like macrophages. Interestingly, the integrity of TJs can be protected against inflammation by ingesting various phytonutrients like epigallocatechin gallate from green tea or curcumin from turmeric. It is also well documented that combinations of phytonutrients can offer synergistic benefit in other models of inflammation. However, such an approach has not yet been studied in an intestinal model of inflammation. The novel phytonutrient S7 contains a proprietary blend of 7 phytonutrients, including green tea extract, turmeric extract, green coffee bean extract, whole tart cherries, blue berry, kale, and broccoli. Here, we utilized an in vitro co-culture system of RAW 264.7 macrophages and Caco-2 intestinal epithelial cells to investigate the effects of the novel phytonutrient S7 on ameliorating macrophage inflammation and TJ integrity. Phytonutrients individually, or in combination, were tested for their ability to alter LPS-induced macrophage inflammation and subsequent TJ integrity. We further examined the effects of two variations of S7, S7-THC (tetrahydrocurcumin) and S7-C (curcumin). We found a synergistic, dose-dependent effect of phytonutrients on the reduced production of inflammatory nitric oxide by macrophages, with curcumin-containing blends exhibiting the greatest affect. A similar pattern was observed for ROS production and alteration of inflammatory cytokine profiles. Interesting, only S7-THC was able to provide TJ protection, and it appears to be dependent on preventing the upregulation of myosin light chain kinase (MLCK). Together, these findings suggest that phytonutrients such as S7-THC have prophylactic potential in the preservation of TJ integrity, and the specific composition of these phytonutrients matters.
Tipping the Scales of Inflammation One Phytonutrient at a Time: Composition and Context Matter
Reed 330
The prevalence of intestinal inflammatory diseases is increasing, and pharmacologic agents for intervention are currently limited. The etiology may be diverse (e.g. allergy, infection, etc.), but ultimately intestinal inflammation results from disruption of tight junction (TJ) proteins which creates gaps between epithelial cells, allowing bacteria to enter and perpetuate a cycle of inflammation with underlying immune cells like macrophages. Interestingly, the integrity of TJs can be protected against inflammation by ingesting various phytonutrients like epigallocatechin gallate from green tea or curcumin from turmeric. It is also well documented that combinations of phytonutrients can offer synergistic benefit in other models of inflammation. However, such an approach has not yet been studied in an intestinal model of inflammation. The novel phytonutrient S7 contains a proprietary blend of 7 phytonutrients, including green tea extract, turmeric extract, green coffee bean extract, whole tart cherries, blue berry, kale, and broccoli. Here, we utilized an in vitro co-culture system of RAW 264.7 macrophages and Caco-2 intestinal epithelial cells to investigate the effects of the novel phytonutrient S7 on ameliorating macrophage inflammation and TJ integrity. Phytonutrients individually, or in combination, were tested for their ability to alter LPS-induced macrophage inflammation and subsequent TJ integrity. We further examined the effects of two variations of S7, S7-THC (tetrahydrocurcumin) and S7-C (curcumin). We found a synergistic, dose-dependent effect of phytonutrients on the reduced production of inflammatory nitric oxide by macrophages, with curcumin-containing blends exhibiting the greatest affect. A similar pattern was observed for ROS production and alteration of inflammatory cytokine profiles. Interesting, only S7-THC was able to provide TJ protection, and it appears to be dependent on preventing the upregulation of myosin light chain kinase (MLCK). Together, these findings suggest that phytonutrients such as S7-THC have prophylactic potential in the preservation of TJ integrity, and the specific composition of these phytonutrients matters.