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Efficacy and Tolerability of Meratrim for Weight Management

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In the course of our search for natural antioxidants, the methanol extract of the fruit hulls of mangosteen (Garcinia mangostana L.) originating in Vietnam was found to exhibit a potent radical scavenging effect. By monitoring the radical scavenging effect, two xanthones, α- and γ- mangostins, were isolated together with (-)-epicatechin, procyanidins A-2 and B-2 as active principles. The antioxidative activity of these two xanthones was measured by the ferric thiocyanate method and it was found that γ- mangostin showed more potent antioxidative activity than BHA and α- tocopherol.
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Five xanthone derivatives and one flavanol were isolated from the dichloromethane extract of Garcinia mangostana. Dichloromethane, ethyl acetate extract and the major xanthone (α-mangostin) were evaluated in vitro against erythrocytic schizonts of Plasmodium falciparum, intracellular amastigotes of Leishmania infantum and Trypanosoma cruzi and free trypomastigotes of T. brucei. The major constituent α-mangostin was also checked for antimicrobial potential against Candida albicans, Escherichia coli, Pseudomonas aeruginosa, Bacillius subtilis, Staphylococcus aureus, Mycobacterium smegmatis, M. cheleneoi, M. xenopi and M. intracellulare. Activity againstP. falciparum (IC50 2.7 μg/mL) and T. brucei (IC50 0.5 μg/mL) were observed for the dichloromethane extract, however, with only moderate selectivity was seen based on a parallel cytotoxicity evaluation on MRC-5 cells (IC50 9.4 μg/mL). The ethyl acetate extract was inactive (IC50 > 30 μg/mL). The major constituent α-mangostin showed rather high cytotoxicity (IC50 7.5 μM) and a broad but non-selective antiprotozoal and antimicrobial activity profile. This in vitro study endorses that the antiprotozoal and antimicrobial potential of prenylated xanthones is non-conclusive in view of the low level of selectivity.
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In this study, we examined the effects of a hydroethanolic extract from the fruit pericarp of mangosteen that contained epicathechin based tannins as a major constituent upon acute and subchronic treatments to experimental animals. Intragastric administration of this extract to Swiss albino mice at a single dose of 2 and 5 g/kg body weight produced no toxicity signs during 14 days of observation. For the subchronic toxicity study, the mangosteen extract at 400, 600 and 1,200 mg/kg body weight was administered by oral gavage to male and female Wistar rats daily for 12 weeks. In all instances, consumption of the extract showed no effect on behavior, food and water intake, growth or health status of these animals. In both sexes, their hematology values monitored throughout the study period did not alter from those of the control. After the 12 weeks, no significant dose-related differences in blood biochemical parameters were detected among the female groups, but in all male groups, there were dose-variation increases in direct bilirubin compared with the control. However, either gross necropsy or histopathological examination of their livers as well as other internal organs did not reveal any abnormal appearances.
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Chromium(III) is an essential trace element required for normal protein, fat and carbohydrate metabolism. It also helps in energy production and increasing lean body mass. Chromium(III) dinicocysteinate (CDNC) is a unique form of bioavailable chromium(III). This study was focused on determining the broad spectrum safety of CDNC. Acute oral, acute dermal, primary dermal and eye irritation studies, Ames' bacterial reverse mutation assay, mammalian erythrocyte micronucleus test, and a 90-day dose-dependent oral toxicity study were conducted. Acute oral and dermal LD(50) of CDNC was found to be greater than 2000 mg/kg in Sprague-Dawley rats. A primary skin irritation study in New Zealand Albino rabbits demonstrated CDNC as slightly irritating. An eye irritation study exhibited that CDNC is moderately irritating. Ames' bacterial reverse mutation assay and mammalian erythrocyte micronucleus test demonstrated CDNC as non-mutagenic. A dose-dependent 90-day oral toxicity study demonstrated no significant toxicity of CDNC. Body weight, food and water consumption, selected organ weights (expressed as percentages of body or brain weights), ocular health, hematology, blood chemistry, and histopathology showed no abnormal changes. Clinical and histopathological evaluation of CDNC identified a dose level of 5.7 mg/kg/day as the no observed adverse effect level (NOAEL). Overall, these results demonstrate the broad spectrum safety of CDNC.
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Many tropical plants have interesting biological activities with potential therapeutic applications. Garcinia mangostana Linn. (GML) belongs to the family of Guttiferae and is named "the queen of fruits". It is cultivated in the tropical rainforest of some Southeast Asian nations like Indonesia, Malaysia, Sri Lanka, Philippines, and Thailand. People in these countries have used the pericarp (peel, rind, hull or ripe) of GML as a traditional medicine for the treatment of abdominal pain, diarrhea, dysentery, infected wound, suppuration, and chronic ulcer. Experimental studies have demonstrated that extracts of GML have antioxidant, antitumoral, antiallergic, anti-inflammatory, antibacterial, and antiviral activities. The pericarp of GML is a source of xanthones and other bioactive substances. Prenylated xanthones isolated from GML have been extensively studied; some members of these compounds possess antioxidant, antitumoral, antiallergic, anti-inflammatory, antibacterial, antifungal and antiviral properties. Xanthones have been isolated from pericarp, whole fruit, heartwood, and leaves. The most studied xanthones are alpha-, beta-, and gamma-mangostins, garcinone E, 8-deoxygartanin, and gartanin. The aim of this review is to summarize findings of beneficial properties of GML's extracts and xanthones isolated from this plant so far.
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Overweight and obesity in adulthood are linked to an increased risk for death and disease. Their potential effect on life expectancy and premature death has not yet been described. To analyze reductions in life expectancy and increases in premature death associated with overweight and obesity at 40 years of age. Prospective cohort study. The Framingham Heart Study with follow-up from 1948 to 1990. 3457 Framingham Heart Study participants who were 30 to 49 years of age at baseline. Mortality rates specific for age and body mass index group (normal weight, overweight, or obese at baseline) were derived within sex and smoking status strata. Life expectancy and the probability of death before 70 years of age were analyzed by using life tables. Large decreases in life expectancy were associated with overweight and obesity. Forty-year-old female nonsmokers lost 3.3 years and 40-year-old male nonsmokers lost 3.1 years of life expectancy because of overweight. Forty-year-old female nonsmokers lost 7.1 years and 40-year-old male nonsmokers lost 5.8 years because of obesity. Obese female smokers lost 7.2 years and obese male smokers lost 6.7 years of life expectancy compared with normal-weight smokers. Obese female smokers lost 13.3 years and obese male smokers lost 13.7 years compared with normal-weight nonsmokers. Body mass index at ages 30 to 49 years predicted mortality after ages 50 to 69 years, even after adjustment for body mass index at age 50 to 69 years. Obesity and overweight in adulthood are associated with large decreases in life expectancy and increases in early mortality. These decreases are similar to those seen with smoking. Obesity in adulthood is a powerful predictor of death at older ages. Because of the increasing prevalence of obesity, more efficient prevention and treatment should become high priorities in public health.
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Obesity and overweight are linked with a cluster of metabolic and vascular disorders that have been termed the metabolic syndrome. Although there is not yet a universally-accepted set of diagnostic criteria, most expert groups agree that the syndrome is characterised by impaired insulin sensitivity and hyperglycaemia, dyslipidaemia (elevated blood triacyglycerols with depressed HDL-cholesterol), abdominal obesity and hypertension. Based on existing published criteria estimates suggest that the syndrome affects a substantial percentage of the middle-aged and elderly populations of most European countries (10-20%) and confers increased risk of type 2 diabetes (2-8.8-fold) and CVD (1.5-6-fold), as well as having a marked effect on morbidity. Although the pathophysiology is incompletely understood, insulin resistance and abdominal obesity are central to subsequent abnormalities in circulating glucose and lipoproteins, and vascular function that lead to type 2 diabetes, atherosclerosis and CVD. The link between metabolic syndrome, type 2 diabetes and CVD, as well as inability to reverse the present rising rates of obesity, will lead to economically-unsustainable costs of health care in the next 10-20 years. Preventative strategies for metabolic syndrome are required to slow rates of progression and to reduce dependence on costly medical management. A notable development is recent evidence that shows that diet and exercise are more effective than drug treatment in preventing the development of type-2 diabetes in high-risk individuals. The LIPGENE project will investigate dietary fat quality as a strategy for the prevention of metabolic syndrome and identify food chain approaches that can support consumer attempts to alter their dietary patterns.
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The fruit hull of Garcinia mangostana Linn (Guttiferae) is used as an anti-inflammatory drug in Southeast Asia. Two xanthones, alpha- and gamma-mangostins, were isolated from the fruit hull of G. mangostana, and both significantly inhibited nitric oxide (NO) and PGE(2) production from lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. The IC(50) values for the inhibition of NO production by alpha- and gamma-mangostins were 12.4 and 10.1 microM, respectively. After iNOS enzyme activity was stimulated by LPS for 12 h, treatment with either alpha- or gamma-mangostin at 5 microg/ml (12.2 and 12.6 microM, respectively) for 24 h did not significantly inhibit NO production. The data show that the inhibitory activities of alpha- and gamma-mangostins are not due to direct inhibition of iNOS enzyme activity. On the other hand, expression of iNOS was inhibited by alpha- and gamma-mangostins in LPS-stimulated RAW 264.7 cells, but not by COX-2. However, the level of PGE(2) production was reduced by the two xanthones. In an in vivo study, alpha-mangostin significantly inhibited mice carrageenan-induced paw edema. In conclusion, alpha- and gamma-mangostins from G. mangostana are bioactive substances with anti-inflammatory effects.
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Ethanolic extracts from fruit pericarp of mangosteen (Garcinia mangostana L.) possess many biological and pharmacological activities. However, chronic toxicity study of ethanolic extract has never been investigated. The objective of this study was to evaluate the safety of 95% ethanolic extract from mangosteen pericarp in animal model. The oral administration of the extract was performed in 180 Wistar rats randomly allocated to six groups, each of 15/sex. Group 1 was control group receiving distilled water. Group 2 to 6 were treatment groups receiving the extract at the doses of 10, 100, 500, 1000 and 1000 mg/kg/day for six months respectively. The last group was assigned to be the satellite group for the study of reversibility of the extract effects after two-week of extract withdrawal. The results revealed that the highest dose extract produced significantly lower body weights in both male and female rats, compared to their corresponding control groups. The extract at any tested doses did not affect the animals' behavior, health status and nor did produce any abnormality of clinical manifestations and hematological values. Clinical chemistry results showed that the male rats treated with 500 mg/kg/day extract onward had significantly higher ALT than their control group. Both male and female receiving the highest dose extract had significantly higher AST, whereas their glucose levels were significantly lower when compared to their corresponding control groups. The male rats of the highest dose and satellite groups had significantly higher BUN values than their control group. The female rats receiving the extract at the dose of 500 mg/kg/day onward had significantly higher BUN and creatinine values than their control group. Histopathological results of visceral organs revealed no significant lesion related to the extract; except the satellite group of both sexes, which had significantly higher lesion of centrilobular hydropic degeneration in their livers than the corresponding control groups. Such alteration may be caused by the highest dose mangosteen pericarp extract. In conclusion, the high dose mangosteen pericarp extract affected liver and kidney. Safety of chemical constituents in the extract should be further investigated before the usage for health promotion.
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Objective: To evaluate the efficacy of an herbal blend. Design and methods: A randomized, double-blind, clinical trial in 60 subjects with body mass index (BMI) between 30 and 40 kg/m(2) . Participants were randomized into two groups receiving either 400 mg herbal capsules or 400 mg placebo capsules twice daily. The herbal blend comprises of extracts from Sphaeranthus indicus and Garcinia mangostana. Participants received a standard diet (2,000 kcal per day) and walked 30 min 5 days per week. Results: After 8 weeks, significant net reductions in body weight (3.74 kg; P < 0.0001), BMI (1.61 kg/m(2) ; P < 0.0001), and waist circumference (5.44 cm; P < 0.05) were observed in the herbal group compared with placebo. Additionally, a significant increase in serum adiponectin concentration was found in the herbal group versus placebo (P = 0.001). Adverse events were mild and were equally distributed between the two groups. In vitro studies in the 3T3-L1 adipocyte cell line showed that the herbal extract markedly downregulated the expression of peroxisome proliferator-activated receptor gamma, adipocyte-differentiation related protein, and cluster of differentiation 36 but increased adiponectin expression. The herbal extract also reduced the expression and the recruitment of perilipin onto the membrane of lipid droplets. Conclusion: Supplementation with the herbal blend resulted in a greater degree of weight loss than placebo over 8 weeks.
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Abstract The clinical effects and tolerability of a novel herbal formulation comprising the extracts of Sphaeranthus indicus and Garcinia mangostana were assessed in two similarly designed randomized, double-blind, placebo-controlled, clinical trials in 100 human subjects with a body mass index (BMI) between 30 and 40 kg/m(2). Participants were randomized into two groups receiving either 400 mg of herbal blend twice daily or two identical placebo capsules. All subjects received three meals (2000 kcal/day) throughout the study and walked 5 days a week for 30 min. The primary outcome was reduction in body weight. Secondary outcomes were reduction in BMI and in waist and hip circumference. Serum glycemic, lipid, and adiponectin levels were also measured. Ninety-five subjects completed the trials, and data from these two studies were pooled and analyzed. At study conclusion (8 weeks), statistically significant reductions in body weight (5.2 kg; P<.0001), BMI (2.2 kg/m(2); P<.0001), as well as waist (11.9 cm; P<.0001) and hip circumferences (6.3 cm; P=.0001) were observed in the herbal group compared with placebo. An increase in serum adiponectin concentration was also found in the herbal group versus placebo (P=.0008) at study conclusion along with reductions in fasting blood glucose (12.2%, P=.01), cholesterol (13.8%, P=.002), and triglyceride (41.6%, P<.0001) concentrations. No changes were seen across organ function panels, multiple vital signs, and no major adverse events were reported. The minor adverse events were equally distributed between the two groups. Our findings suggest that the herbal blend appears to be a well-tolerated and effective ingredient for weight management.
Article
Mangosteen (Garcinia mangostana) has been widely used in the traditional medicine of Thailand to treat various ailments, especially diseases of the digestive system and infections. Many reports show antiproliferation of crude extracts and active constituents from mangosteen against many cancer cell lines. Therefore, the current study is proposed to demonstrate in vivo evidence on the antitumor activity of mangosteen. Crude methanolic extract (CME) from mangosteen pericarp including 25.19 % α-mangostin as an active xanthone was used in this study. The inhibition on tumor cell proliferation of CME was preliminarily evaluated against the murine colon cancer cell line NL-17 with an IC(50) value of 17 and 84 μg/ml based on WST-1 and LDH assays, respectively. The safety dose for animal application was assessed by in vivo toxicity studies using female BALB/c mice. Acute toxicity showed an LD(50) value and approximate lethal dose at 1,000 mg/kg, whereas the suitable dose for short-term study should be ≤200 mg/kg. The effective dose for antitumor activity of CME was found to be between 100 and 200 mg/kg, with a tumor size reduction of 50-70 %. Histological staining clearly illustrated a decrease of tumor cell density in the footpad in a dose-dependent manner. The median survival time and life span significantly increased in tumor-bearing mice with CME treatment. This study suggests that CME possesses a powerful antitumor activity. Therefore, it is worth undertaking further investigation to identify active compounds and obtain a deeper understanding of their mechanism, in order to acquire novel effective anticancer drugs.
Article
Sphaeranthus indicus Linn. (Asteraceae) is widely used in Ayurvedic system of medicine to treat vitiated conditions of epilepsy, mental illness, hemicrania, jaundice, hepatopathy, diabetes, leprosy, fever, pectoralgia, cough, gastropathy, hernia, hemorrhoids, helminthiasis, dyspepsia and skin diseases. There are reports providing scientific evidences for hypotensive, anxiolytic, neuroleptic, hypolipidemic, immunomodulatory, antioxidant, anti-inflammatory, bronchodialatory, antihyperglycemic and hepatoprotective activities of this plant. A wide range of phytochemical constituents have been isolated from this plant including sesquiterpene lactones, eudesmenolides, flavanoids and essential oil. A comprehensive account of the morphology, phytochemical constituents, ethnobotanical uses and pharmacological activities reported are included in this review for exploring the immense medicinal potential of this plant.
Article
Garcinia mangostana L. (mangosteen, Clusiaceae) has a long history of use as a medical plant, mostly in Southeast Asia. This is a review of the phytochemistry and pharmacology of mangosteen. Traditionally mangosteen is famous for its antiinflammatory properties and is used in the treatment of skin infections and wounds. Other applications include the therapy of various conditions such as dysentery, different urinary disorders, cystitis and gonorrhoea. This review highlights the development of this botanical drug into a widely used nutraceutical. Products derived from G. mangostana are now distributed increasingly all over the world. This has given rise to a concomitant increase in research on the phytochemical constituents and biological activity of mangosteen. Central to the biological activity of the species are xanthones which are reviewed in detail. A comprehensive assessment of the biological activities of individual xanthones as well as extracts of G. mangostana is included. In addition, its potential in terms of developing novel drug leads is assessed. Products containing its fruits are now sold widely as 'liquid botanical supplements', but evidence for the health benefits of these products is still lacking. As shown here, a serious weakness in our knowledge is the lack of clinical data and it is not yet clear to what extent the findings about pharmacological activities are of potential clinical relevance.
Article
The fruit hull of Garcinia mangostana Linn. has been used in Thai traditional medicine for treatment of abscess and skin infection. The mangosteen fruit hull and its compounds were carried out to investigate for anti-inflammatory activity. The extract of Garcinia mangostana together with alpha- and gamma-mangostins were tested for anti-inflammatory effect against lipopolysaccharide (LPS)-induced nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor alpha (TNF-alpha) and interleukin-4 (IL-4) releases as well as their mechanisms in transcriptional levels using RAW264.7 macrophage cells. Mangosteen extract possessed potent NO inhibitory effect with an IC50 value of 1.0 microg/ml. The isolated compounds from the extract including alpha-mangostin and gamma-mangostin, possessed marked inhibitory effect against NO release with IC50 values of 3.1 and 6.0 microM, respectively. The extract exhibited potent inhibitory effect on PGE2 release (IC50=6.0 microg/ml), whereas those of alpha- and gamma-mangostins were 13.9 and 13.5 microM, respectively. However, mangostins possessed only moderate effects towards TNF-alpha and IL-4 releases with IC50 values ranging from 31.8 to 64.8 microM. Both extract and alpha-mangostin suppressed transcription of gene encoding inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in dose-dependent manners, whereas gamma-mangostin had only an inhibitory effect on transcription of iNOS. The present study may support the Thai traditional use of Garcinia mangostana fruit hull for treatment of inflammatory-related diseases through the inhibition of NO and PGE2 releases, but moderate effect through TNF-alpha and IL-4.
Article
Studies on the stem of Garcinia mangostana have led to the isolation of one new xanthone mangosharin (1) (2,6-dihydroxy-8-methoxy-5-(3-methylbut-2-enyl)-xanthone) and six other prenylated xanthones, alpha-mangostin (2), beta-mangostin (3), garcinone D (4), 1,6-dihydroxy-3,7-dimethoxy-2-(3-methylbut-2-enyl)-xanthone (5), mangostanol (6) and 5,9-dihydroxy-8- methoxy-2,2-dimethyl-7-(3-methylbut-2-enyl)-2H,6H-pyrano-[3,2-b]-xanthene-6-one (7). The structures of these compounds were determined by spectroscopic methods such as 1H NMR, 13C NMR, mass spectrometry (MS) and by comparison with previous studies. All the crude extracts when screened for their larvicidal activities indicated very good toxicity against the larvae of Aedes aegypti. This article reports the isolation and identification of the above compounds as well as bioassay data for the crude extracts. These bioassay data have not been reported before.
Article
The tropical mangosteen fruit has long been prized in Southeast Asia for its traditional healing properties. Mangosteen fruit juice is now available in the United States and marketed for its purported health benefits. We describe a case of severe lactic acidosis associated with the use of mangosteen juice as a dietary supplement.
Article
Twelve xanthone constituents of the botanical dietary supplement mangosteen (the pericarp of Garcinia mangostana) were screened using a noncellular, enzyme-based microsomal aromatase inhibition assay. Of these compounds, garcinone D (3), garcinone E (5), alpha-mangostin (8), and gamma-mangostin (9) exhibited dose-dependent inhibitory activity. In a follow-up cell-based assay using SK-BR-3 breast cancer cells that express high levels of aromatase, the most potent of these four xanthones was gamma-mangostin (9). Because xanthones may be consumed in substantial amounts from commercially available mangosteen products, the consequences of frequent intake of mangosteen botanical dietary supplements require further investigation to determine their possible role in breast cancer chemoprevention.
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