A growing body of evidence demonstrates the efficacy of Garcinia cambogia-derived natural (–)-hydroxycitric acid (HCA) in weight management by curbing appetite and inhibiting body fat biosynthesis. However, the exact mechanism of action of this novel phytopharmaceutical has yet to be fully understood. In a previous study, we showed that in the rat brain cortex a novel HCA extract (HCA-SX, Super CitriMax™) increases the release/availability of radiolabeled 5-hydroxytryptamine or serotonin ([3H]-5-HT), a neurotransmitter implicated in the regulation of eating behavior and appetite control. The aim of the present study was 2-fold: (a) to determine the effect of HCA-SX on 5-HT uptake in rat brain cortex in vitro; and (b) to evaluate the safety of HCA-SX in vivo. Isolated rat brain cortex slices were incubated in oxygenated Krebs solution for 20 min and transferred to buffer solutions containing [3H]-5-HT for different time intervals. In some experiments, tissues were exposed to HCA-SX (10 μM – 1 mM) and the serotonin receptor reuptake inhibitors (SRRI) fluoxetine (100 μM) plus clomipramine (10 μM). 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 min. HCA-SX, and fluoxetine plus clomipramine inhibited the time-dependent uptake of [3H]-5-HT. At 90 min, HCA-SX (300 μM) caused a 20% decrease, whereas fluoxetine plus clomipramine inhibited [3H]-5-HT uptake by 30%. In safety studies, acute oral toxicity, acute dermal toxicity, primary dermal irritation and primary eye irritation, were conducted in animals using various doses of HCA-SX. Results indicate that the LD50 of HCA-SX is greater than 5000 mg/kg when administered once orally via gastric intubation to fasted male and female Albino rats. No gross toxicological findings were observed under the experimental conditions. Taken together, these in vivo toxicological studies demonstrate that HCA-SX is a safe, natural supplement under the conditions it was tested. Furthermore, HCA-SX can inhibit [3H]-5-HT uptake (and also increase 5-HT availability) in isolated rat brain cortical slices in a manner similar to that of SRRIs, and thus may prove beneficial in controlling appetite, as well as treatment of depression, insomnia, migraine headaches and other serotonin-deficient conditions.
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.Sergio W: A natural food, the Malabar Tamarind, may be effective in the treatment of obesity. Med Hypotheses 29: 39–40, 1988
Mattes DR, Bormann L: Effects of (–)-hydroxycitric acid on appetitive variables. Physiol Behav 71: 87–94, 2000
Sullivan AC, Triscari J, Hamilton JG, Miller ON, Wheatley VR: Effect of (–)-hydroxycitrate upon the accumulation of lipid in the rat. I. Lipogenesis. Lipids 9: 121–128, 1974
Sullivan AC, Triscari J, Hamilton JG, Miller ON: Effect of (–)-hydroxycitrate upon the accumulation of lipid in the rat. II. Appetite. Lipids 9: 129–134, 1974
Ramos RR, Saenz JLS, Agular RJA: Extract of Garcinia Cambogia in controlling obesity. Invest Med Int 22: 97–100, 1995
Loe YC, Bergeron N, Rodriguez N, Schwarz J-M: Gas chromatography/ mass spectrometry method to quantify blood hydroxycitrate concentration. Analyt Biochem 292: 148–154, 2001
Ohia SE, Awe O, LeDay AM, Opere CA, Bagchi D: Effect of hydroxycitric acid on serotonin release from isolated rat brain cortex. Res Commun Mol Pathol Pharmacol 109: 210–216, 2001
Leibowtz SF, Alexander JT: Hypothalamic serotonin in control of eating behavior, meal size, and body weight. Biol Psychiatry 44: 851–864, 1998
Mauri MC, Rudelli R, Somasehini E, Roncoroni L, Papa R, Mantero M, Penati G: Neurobiological and psychopharmacological basis in the therapy of bulimia and anorexia. Prog Neuropsychopharmacol Biol Psychiatry 20: 207–240, 1996
Wilding J, Widdowson P, Williams G: Neurobiology. Br Med Bull 53: 286–306, 1997
Kirksey DF, Slotkin TA: Concomitant development of [3H]-dopamine and [3H]-5-hydroxytryptamine uptake systems in rat brain regions. Br J Pharmacol 67: 387–391, 1979
Goodlet I, Mireylees SE, Sugrue MF: Effects of mianserin, a new antidepressant, on the in vitro and in vivo uptake of monoamines. Br J Pharmacol 61: 307–313, 1977
Draize JH: The Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics. Dermal Toxicity. Association of Food and Drug Officials of the US, Topeka, KA, 1965, pp 46–59
Fuller RW, Wong DT, Robertson DW: Fluoxetine, a selective inhibitor of serotonin uptake. Med Res Rev 11: 17–34, 1991
Lingjaerde O, Kildemo O: Dopamine uptake in platelets: Two different low affinity, saturable mechanisms. Agents Actions 11: 410–416, 1981
Stauderman KA, Jones DJ: Characterization of sodium-dependent, high-affinity serotonin uptake in rat spinal cord synaptosomes. Brain Res 330: 11–20, 1985
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Ohia, S.E., Opere, C.A., LeDay, A.M. et al. Safety and mechanism of appetite suppression by a novel hydroxycitric acid extract (HCA-SX). Mol Cell Biochem 238, 89–103 (2002). https://doi.org/10.1023/A:1019911205672
- Garcinia cambogia
- (–)-Hydroxycitric acid
- rat brain cortex
- serotonin release
- acute oral toxicity
- acute dermal toxicity
- primary dermal irritation
- primary eye irritation