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- All Subjects: Cholesterol
- All Subjects: Turmeric
- Creators: Do, Ngoc Bich Thi
- Creators: Geiger, James
- Member of: Theses and Dissertations
- Member of: Barrett, The Honors College Thesis/Creative Project Collection
Description
Turmeric is the bright yellow root that has been used as a spice, healing remedy, and textile dye. Previous studies have suggested that the most active ingredient in turmeric, curcumin, could reduce serum cholesterol concentration. However, most of these studies were conducted on animals and not many have been done on controlled human trials. This randomized, double-blinded, controlled crossover study evaluates the effects of turmeric on blood cholesterol concentrations including total cholesterol, LDL cholesterol, HLD cholesterol, and triglycerides. In this study, eight healthy participants between the ages of 18 and 45 were randomized to receive either 500mg capsules of turmeric or placebo for a period of three weeks. Following a wash-out period of five weeks, all participants were crossed over to the alternative treatment for another three weeks. After comparing the 3 week treatment and placebo phases, turmeric showed no significant effect on serum lipid concentrations. Furthermore, a slight increase in total cholesterol concentrations was observed following the turmeric phase when compared to the placebo phase.
ContributorsDo, Ngoc Bich Thi (Author) / Johnston, Carol (Thesis director) / Whisner, Corrie (Committee member) / School of Nutrition and Health Promotion (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
G protein-coupled receptors (GPCRs) are known to be modulated by membrane cholesterol levels, but whether or not the effects are caused by specific receptor-cholesterol interactions or cholesterol’s general effects on the membrane is not well-understood. Results from coarse-grained molecular dynamics (CGMD) simulations coupled and structural bioinformatics offer new insights into how cholesterol modulates GPCR function by showing cholesterol interactions with β2AR that agree with previously published data. Additionally, differential and specific cholesterol binding in the CCK receptor subfamily was observed while revealing a previously unreported Cholesterol Recognition Amino-acid Consensus (CRAC) sequence that is also conserved across 38% of class A GPCRs. Mutation of this conserved CRAC sequence of the β2AR affects cholesterol stabilization of the receptor in a lipid bilayer. Serial femtosecond crystallography (SFX) with X-ray free electron lasers (XFELs) has proven highly successful for structure determination of challenging membrane proteins crystallized in lipidic cubic phase, however, as most techniques, it has limitations. Using an optimized SFX experimental setup in a helium atmosphere we determined the room temperature structure of the adenosine A2A receptor (A2AAR) at 2.0 Å resolution and compared it with previous A2AAR structures determined in vacuum and/or at cryogenic temperatures. Specifically, we demonstrated the capability of utilizing high XFEL beam transmissions, in conjunction with a high dynamic range detector, to collect high-resolution SFX data while reducing crystalline material consumption and shortening the collection time required for a complete data set.
The results of these studies provide a better understanding of receptor-cholesterol interactions that can contribute to novel and improved therapeutics for a variety of diseases. Furthermore, the experimental setups presented herein can be applied to future molecular dynamics and SFX applications for protein nanocrystal samples to aid in structure-based discovery efforts of therapeutic targets that are difficult to crystallize.
The results of these studies provide a better understanding of receptor-cholesterol interactions that can contribute to novel and improved therapeutics for a variety of diseases. Furthermore, the experimental setups presented herein can be applied to future molecular dynamics and SFX applications for protein nanocrystal samples to aid in structure-based discovery efforts of therapeutic targets that are difficult to crystallize.
ContributorsGeiger, James (Author) / Liu, Wei (Thesis advisor) / Mills, Jeremy (Committee member) / Chiu, Po-Lin (Committee member) / Arizona State University (Publisher)
Created2020