Society of Toxicology Abstract 41st Annual Meeting & ToxExpo™ Nashville March 17-21, 2002 Volume 66, Number1-S March 19, 2002 921 MECHANISM OF APPETITE SUPPRESSION BY A NOVEL, NATURAL HYDROXYCITRIC ACID S.E. Ohia, C.A. Perre, A.M. LeDay, M. Bagchi and D. Bagchi School of Pharmacy & Allied Health Professions, Creighton University, Omaha, NE. Although evidence available indicates that Garcinia cambogia-derived natural extract, (-)-hydroxycitric acid (HCA, Super Citrimax®) is a potent appetite suppressant and an inhibitor of body fat biosynthesis, its exact mechanism of action is yet to be fully elucidated. In a previous study, we showed that in the rat brain cortex, HCA can increase the release/availability of radiolabeled 5-HT ([3H]-5-HT), a neurotransmitter implicated in the regulation of eating behavior (Ohia et al., FASEB J. 15: Abs. No 207.13, 2001). The aim of the present study was two-fold: (a) to evaluate the safety of HCA in vivo and (b) to determine the effect of HCA on 5-HT uptake in rat brain cortex in vitro. In safety studies, acute oral toxicity, dermal toxicity, dermal irritation and eye irritation, were conducted in animals with different doses of HCA yielding an LD50 greater than 5000mg/kg following oral administration of this compound. Isolated rat brain cortex slices were incubated in oxygenated Krebs solution for 20 minutes and then transferred to buffer solutions containing [3H]-5-HT for different time intervals. In some experiments, tissues were exposed to HCA (10 uM -1 uM), fluoxetine (100 uM) and clomipramine (10 uM ). Uptake of [3H]-5-HT was expressed as d.p.m./mg wet weight. A time dependent uptake of [3H]-5-HT occurred in cortical slices reaching a maximum at 60 mins. HCA (300 uM) caused a 20% decrease whereas fluoxetine and/or clomipramine inhibited the time-dependent uptake of [3H]-5-HT. At 90 min HCA (300 uM) caused a 20% decrease whereas fluoxetine plus clomipramine inhibited [3H]-5-HT uptake by 30%. We conclude that HCA is a safe compound that can inhibit [3H]-5-HT uptake (and increase 5-HT availability) in isolated rat brain cortical slices in a manner similar to that of selective serotonin reuptake inhibitors (SSRIs). Amino Acid Supplements.

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