Shara Michael, Ohia Sunny E, Schmidt Robert E, Yasmin Taharat, Zardetto-Smith Andrea, Kincaid Anthony, Bagchi Manashi, Chatterjee Archana, Bagchi Debasis, Stohs Sidney J
Department of Pharmacy Sciences, School of Pharmacy and Health Professions, Creighton University Medical Center, Omaha, NE 68178, USA.
Mol Cell Biochem. 2004 May;260(1-2):171-86. doi: 10.1023/b:mcbi.0000026069.53960.75.
Garcinia cambogia-derived (-)-hydroxycitric acid (HCA) is a popular and natural supplement for weight management. HCA is a competitive inhibitor of the enzyme ATP citrate lyase, which catalyzes the conversion of citrate and coenzyme A to oxaloacetate and acetyl coenzyme A (acetyl CoA) in the cytosol. Acetyl CoA is used in the synthesis of fatty acids, cholesterol and triglycerides, and in the synthesis of acetylcholine in the central nervous system. Studies have demonstrated the efficacy of a novel 60% calcium-potassium salt of HCA derived from Garcinia cambogia (HCA-SX, Super CitriMax) in weight management. Results have shown that HCA-SX promotes fat oxidation, enhances serotonin release and availability in the brain cortex, normalizes lipid profiles, and lowers serum leptin levels in obese subjects. Acute oral, acute dermal, primary dermal irritation and primary eye irritation toxicity, as well as Ames bacterial reverse mutation studies and mouse lymphoma tests have demonstrated the safety of HCA-SX. However, no detailed long-term safety of HCA-SX or any other HCA extract has been previously assessed. We evaluated the dose- and time-dependent effects of HCA-SX in Sprague-Dawley rats on body weight, selected organ weights, hepatic lipid peroxidation and DNA fragmentation, hematology and clinical chemistry over a period of 90 days. Furthermore, a 90-day histopathological evaluation was conducted. The animals were treated with 0, 0.2, 2.0 and 5.0% HCA-SX of feed intake and were sacrificed on 30, 60 or 90 days of treatment. The body weight and selected organ weights were assessed and correlated as a % of body weight and brain weight at 90 days of treatment. A significant reduction in body weight was observed in treated rats as compared to control animals. An advancing age-induced marginal increase in hepatic lipid peroxidation was observed in both male and female rats, while no such difference in hepatic DNA fragmentation was observed as compared to the control animals. Furthermore, selected organ weights individually and as a % of body weight and brain weight at 90 days of treatment exhibited no significant difference between the groups. No difference was observed in hematology and clinical chemistry or the histopathological evaluation. Taken together, these results show that 90 day treatment of HCA-SX results in a reduction in body weight, and does not cause any changes in major organs or in hematology, clinical chemistry, and histopathology.
藤黄果提取物(-)-羟基柠檬酸(HCA)是一种广受欢迎的天然体重管理补充剂。HCA是一种竞争性的ATP柠檬酸裂解酶抑制剂,该酶催化柠檬酸和辅酶A在细胞质中转化为草酰乙酸和乙酰辅酶A(乙酰CoA)。乙酰CoA用于脂肪酸、胆固醇和甘油三酯的合成,以及中枢神经系统中乙酰胆碱的合成。研究已经证明了一种从藤黄果中提取的新型60%钙钾盐HCA(HCA-SX,超级藤黄果提取物)在体重管理方面的功效。结果表明,HCA-SX可促进脂肪氧化,增强大脑皮层中血清素的释放和可用性,使脂质谱正常化,并降低肥胖受试者的血清瘦素水平。急性口服、急性皮肤、原发性皮肤刺激性和原发性眼刺激性毒性,以及艾姆斯细菌回复突变试验和小鼠淋巴瘤试验均已证明HCA-SX的安全性。然而,此前尚未对HCA-SX或任何其他HCA提取物的详细长期安全性进行评估。我们评估了HCA-SX在90天内对Sprague-Dawley大鼠体重、选定器官重量、肝脏脂质过氧化和DNA片段化、血液学和临床化学的剂量和时间依赖性影响。此外,还进行了为期90天的组织病理学评估。动物分别给予0、0.2、2.0和5.0%的HCA-SX饲料,并在治疗的第30、60或90天处死。评估体重和选定器官重量,并将其作为治疗90天时体重和脑重的百分比进行关联。与对照动物相比,治疗组大鼠的体重显著降低。在雄性和雌性大鼠中均观察到随着年龄增长肝脏脂质过氧化有轻微增加,而与对照动物相比肝脏DNA片段化未观察到差异。此外,治疗90天时选定器官重量单独以及作为体重和脑重的百分比在各组之间均未显示出显著差异。在血液学、临床化学或组织病理学评估中未观察到差异。综上所述,这些结果表明,90天的HCA-SX治疗可导致体重减轻,且不会引起主要器官、血液学、临床化学和组织病理学的任何变化。