On the binding ratio of α-cyclodextrin to dietary fat in humans

KL Catherine Jen,1,2 George Grunberger,3 Joseph D Artiss2,4 1Department of Nutrition and Food Science, Wayne State University, Detroit, MI, USA; 2ArtJen Complexus Inc, Windsor, ON, Canada; 3The Grunberger Diabetes Institute, Bloomfield Hills, MI, USA; 4Department of Pathology, School of Medicine, Wayne State University, Detroit, MI, USA Abstract: &alpha;-Cyclodextrin (&alpha;-CD), a soluble dietary fiber, has been shown to bind and eliminate nine times of its own weight in dietary fat. Studies with different animal models have reported that &alpha;-CD preferentially binds saturated fatty acids, reducing saturated and trans fatty acid levels in blood. A clinical trial demonstrated that &alpha;-CD prevented weight gain in obese diabetic patients. The present study was designed to examine whether &alpha;-CD also shows a preference in binding saturated fatty acids in humans and to confirm the 1:9 binding ratio in humans. Sixty-six obese diabetic patients were recruited at the beginning of this 3-month, double-blind, and placebo-controlled study. Patients were randomly assigned to the Active or Placebo group. Blood samples and 3-day dietary records were collected at baseline and at the end of months 1, 2, and 3. A bottle of 180 tablets of active or placebo tablets was dispensed to each participant at the beginning of each month. Dietary records were analyzed using The Food Processor software. It was observed that &alpha;-CD has a higher affinity towards saturated fats than to unsaturated fats. Participants with higher intakes of total and saturated fat lost more weight than those with lower intakes (P < 0.05 and < 0.01, respectively). These data support the earlier observation in both in vitro and animal studies that &alpha;-CD binds with dietary fat in a 1:9 ratio and further demonstrate the efficacy of &alpha;-CD in binding to and eliminating dietary fat, especially saturated fats. &alpha;-CD may play a significant role in reducing blood cholesterol and triglyceride levels as well as stopping chronic weight gain. Keywords: FBCx&reg;, fat binding capacity, 1:9 binding ratio, reducing blood cholesterol levels, saturated, dietary analysi

'Inhibition of polyamine and spermine oxidases by polyamine analogues'

Polyamine oxidase (PAO) and spermine oxidase (SMO) are involved in the catabolism of polyamines--basic regulators of cell growth and proliferation. The discovery of selective inhibitors of PAO and SMO represents an important tool in studying the involvement of these enzymes in polyamine homeostasis and a starting point for the development of novel antineoplastic drugs. Here, a comparative study on murine PAO (mPAO) and SMO (mSMO) inhibition by the polyamine analogues 1,8-diaminooctane, 1,12-diaminododecane, N-prenylagmatine (G3), guazatine and N,N1-bis(2,3-butadienyl)-1,4-butanediamine (MDL72527) is reported. Interestingly, 1,12-Diaminododecane and G3 behave as specific inhibitors of mPAO, values of K(i) for mPAO inhibition being lower than those for mSMO inactivation by several orders of magnitude. The analysis of molecular models of mPAO and mSMO indicates a significant reduction of the hydrophobic pocket located in maize PAO (MPAO) at the wider catalytic tunnel opening. This observation provides a rationale to explain the lower affinity displayed by G3, guazatine and MDL72527 for mPAO and mSMO as compared to MPAO. The different behaviour displayed by 1,12-diaminododecane towards mPAO and mSMO reveals the occurrence of basic differences in the ligand binding mode of the two enzymes, the first enzyme interacting mainly with substrate secondary amino groups and the second one with substrate primary amino groups. Thus, the data reported here provide the basis for the development of novel and selective inhibitors able to discriminate between mammalian SMO and PAO activities

History of Cyclodextrins

Cyclodextrins are cyclic oligosaccharides obtained by enzymatic degradation of starch. They are remarkable macrocyclic molecules that have led major theoretical and practical advances in chemistry, biology, biochemistry, health science, and agriculture. Their molecular structure is composed of a hydrophobic cavity that can encapsulate other substances to form inclusion complexes through host-guest interactions. This unique feature is at the origin of many applications. Cyclodextrins and their derivatives have a wide variety of practical applications in almost all sectors of the industry, including pharmacy, medicine, foods, cosmetics, chromatography, catalysis, biotechnology, and the textile industry.Villiers published the first reference to cyclodextrins in 1891. Since the beginning of the twentieth century, major researchers, such as Schardinger, Pringsheim, Karrer, Freudenberg, French, Cramer, Casu, Bender, Saenger, Nagai, Szejtli, and Pitha, have paved the history of the cyclodextrins. Several time periods have marked their history. After their discovery and characterization from 1891 to 1911, there has been a period of doubt and disagreement from 1911 to 1935. Then, the 1935–1950 exploration period was marked by structural results on the “Schardinger dextrins.” In 1949, Cramer introduced the cyclodextrin-based nomenclature. Research between 1950 and 1970, the period of maturation, focused on conformations and spectroscopic data of cyclodextrins and their inclusion complexes, with applications in catalysis and as enzyme models. Finally, the period of use has been ongoing since 1970 and has seen cyclodextrins find many industrial applications. Cyclodextrins have then found many industrial applications, initially in the pharmaceutical and food sectors. In 1984, the first chromatographic columns were commercialized. At that time, many cyclodextrin-based catalysts were developed for biomimetic chemistry and other applications such as artificial enzymes. Currently, more than 2000 publications on cyclodextrins are published each year.In this chapter, we present a historical overview of the discovery, development, and applications of cyclodextrins