Suppression of NPC1L1 and Inflammatory Cytokines by Flavonoid Compounds

Open Access
Author:
Chua, Charles
Area of Honors:
Toxicology
Degree:
Bachelor of Science
Document Type:
Thesis
Thesis Supervisors:
  • Gary H Perdew, Thesis Supervisor
  • Gary H Perdew, Honors Advisor
  • Andrew Patterson, Faculty Reader
Keywords:
  • Flavonoid
  • NPC1L1
  • aryl hydrocarbon receptor
  • AHR
  • cholesterol
  • inflammatory cytokines
  • Niemann-pick C1-like 1
Abstract:
Aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that is known for its ability to mediate responses to a wide variety of ligands, both exogenous and endogenous. Of particular interest is the ability of flavonoids, a naturally occurring compound ubiquitous in plants, to bind to this receptor. Due to their physiologically relevant concentrations in our diet, it is particularly important that we have a solid understanding of the short and long-term effects of its consumption. Flavonoids have long been associated with the modulation of cholesterol levels and the inflammatory response. However, the mechanism of action for these flavonoid-mediated effects is still not clear. Since certain abundant flavonoids are ligands of AHR, we hypothesized that cholesterol homeostasis and the attenuation of the inflammatory response is at least partially regulated by AHR. Furthermore, we hypothesized that the mechanism behind cholesterol homeostasis involves repression of Niemann-pick C1-like 1 (NPC1L1), an intestinal/hepatic cholesterol transport protein that is regulated by AHR. While we confirmed that flavonoids inhibited the expression of NPC1L1, this did not translate into any significant decreases in cholesterol absorption through NPC1L1. Furthermore, although the data suggests that flavonoids inhibit expression of inflammatory cytokines, AHR appears to have little to no role in this response.