RESUMEN
Importance: Use of herbal and dietary supplements (HDSs) accounts for an increasing proportion of drug hepatotoxicity cases. Turmeric or curcumin, green tea extract, Garcinia cambogia, black cohosh, red yeast rice, and ashwagandha are the most frequently reported hepatoxic botanicals, but their prevalence and reasons for use in the general population are unknown. Objective: To assess the prevalence and clinical characteristics of adult consumers of 6 potentially hepatoxic botanicals. Design, Setting, and Participants: This survey study analyzed nationally representative data from the National Health and Nutrition Examination Survey (NHANES), a nationally representative, cross-sectional survey of the general US population. Prescription drug and HDS exposure data in the past 30 days were analyzed, and 2020 US Census data were used for population estimates. Data were analyzed July 1, 2023, to February 1, 2024. Exposures: Adult NHANES participants enrolled between January 2017 and March 2020. Main Outcomes and Measures: Baseline weighted characteristics of HDS users and users of 6 potentially hepatotoxic botanical products were compared with non-HDS users. Multivariable analysis was undertaken to identify factors associated with HDS use or at-risk botanical use. Results: Among 9685 adults enrolled in this NHANES cohort, the mean (SE) age was 47.5 (0.5) years, and 51.8% (95% CI, 50.2%-53.4%) were female. The overall prevalence of HDS product use was 57.6% (95% CI, 55.9%-59.4%), while the prevalence of using the 6 botanicals of interest was 4.7% (95% CI, 3.9%-5.7%). Turmeric-containing botanicals were most commonly used (n = 236), followed by products containing green tea (n = 92), ashwagandha (n = 28), Garcinia cambogia (n = 20), red yeast rice (n = 20), and black cohosh (n = 19). Consumers of these 6 botanicals were significantly older (adjusted odds ratio [AOR], 2.36 [95% CI, 1.06-5.25]; P = .04 for 40-59 years of age and AOR, 3.96 [95% CI, 1.93-8.11]; P = .001 for ≥60 years of age), had a higher educational level (AOR, 4.78 [95% CI, 2.62-8.75]; P < .001), and were more likely to have arthritis (AOR, 2.27 [95% CI, 1.62-3.29]; P < .001) compared with non-HDS users. An estimated 15â¯584â¯599 (95% CI, 13â¯047â¯571-18â¯648â¯801) US adults used at least 1 of the 6 botanical products within the past 30 days, which was similar to the estimated number of patients prescribed potentially hepatotoxic drugs, including simvastatin (14â¯036â¯024 [95% CI, 11â¯202â¯460-17â¯594â¯452]) and nonsteroidal anti-inflammatory drugs (14â¯793â¯837 [95% CI, 13â¯014â¯623-16â¯671â¯897]). The most common reason for consuming turmeric and green tea was to improve or maintain health. Conclusions and Relevance: In this survey study, an estimated 15.6 million US adults consumed at least 1 botanical product with liver liability within the past 30 days, comparable with the number of people who consumed nonsteroidal anti-inflammatory drugs and a commonly prescribed hypolipidemic drug. Given a lack of regulatory oversight on the manufacturing and testing of botanical products, clinicians should be aware of possible adverse events from consumption of these largely unregulated products.
Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas , Suplementos Dietéticos , Encuestas Nutricionales , Humanos , Femenino , Masculino , Adulto , Persona de Mediana Edad , Estados Unidos/epidemiología , Estudios Transversales , Enfermedad Hepática Inducida por Sustancias y Drogas/epidemiología , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Suplementos Dietéticos/efectos adversos , Curcuma , Anciano , Extractos Vegetales/efectos adversos , Adulto Joven , Garcinia cambogia , Prevalencia , Preparaciones de Plantas/efectos adversos , Cimicifuga/efectos adversosRESUMEN
Garcinia cambogia, a weight control herbal, can cause mild liver toxicity with nonspecific histologic changes. Herein, we reported a case of herbal-induced fulminant cholestatic giant cell hepatitis due to garcinia cambogia use. A 65-year-old woman with breast cancer treated 18 years earlier was admitted for obstructive jaundice for 2 weeks. She started using garcinia cambogia 3 months ago for weight loss. Physical exam showed scleral icterus. Serum studies excluded Wilson's disease, systemic infection including COVID-19 (coronavirus disease 2019), autoimmune hepatitis, and metabolic or toxicologic causes. An urgent liver biopsy showed severe giant cell hepatitis in absence of HSV-1/2, cytomegalovirus, HBsAg and HBcAg (immunostain), and EBV (in situ hybridization). Despite supportive therapy, the patient developed grade 2-3 hepatic encephalopathy and necessitated liver transplant. The explanted liver was markedly atrophy, in which the most striking histologic finding was diffuse distribution of multinucleated giant hepatocytes with syncytial pattern in a background of extensive zone-1 accentuated, geographic, hemorrhagic, confluent hepatocytic necrosis, along with remarkable hepatocytic and canalicular cholestasis. Marked hepatocellular and sinusoidal iron orverload present. The patient recovered uneventfully.
Asunto(s)
Hemocromatosis , Hepatitis , Fallo Hepático Agudo , Femenino , Humanos , Anciano , Garcinia cambogia , Hepatitis/complicaciones , Hepatitis/patología , Hemocromatosis/complicaciones , Hígado/patología , Fallo Hepático Agudo/inducido químicamenteRESUMEN
Garcinia cambogia (GC) has antioxidant, anticancer, antihistamine, and antimicrobial properties. To determine the effect of GC on lipid profiles, a systematic review and meta-analysis was carried out. Up to February 9, 2023, six electronic databases (Web of Science, Cochrane Library, Embase, PubMed, Scopus, and Google Scholar) were searched at any time without limitations. Trials examining the impact of GC on serum levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol (HDL-C) in adults were included. The total effect was shown as a weighted mean difference (WMD) and 95% confidence interval (CI) in a random-effects meta-analysis approach. This systematic review and meta-analysis included 14 trials involving 623 subjects. Plasma levels of TC (WMD: -6.76 mg/dL; CI: -12.39 to -0.59, p-value = 0.032), and TG (WMD: -24.21 mg/dL; CI: -37.84 to -10.58, p < 0.001) were significantly reduced after GC use, and plasma HDL-C (WMD: 2.95 mg/dL; CI: 2.01 to 3.89, p < 0.001) levels increased. low-density lipoprotein cholesterol levels (WMD: -1.15 mg/dL; CI: -16.08 to 13.78, p-value = 0.880) were not significantly affected. The effects of lowering TC and TG were more pronounced for periods longer than 8 weeks. Consuming GC has a positive impact on TC, TG, and HDL-C concentrations. The limitations of this study include the short duration of analyzed interventions and significant heterogeneity. Nevertheless, it is imperative to conduct well-structured, and high-quality long-term trials to comprehensively evaluate the clinical effectiveness of GC on lipid profile, and validate these findings.
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Garcinia cambogia , Humanos , Colesterol/sangre , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Citratos , Garcinia cambogia/química , Lípidos/sangre , Extractos Vegetales/farmacología , Ensayos Clínicos Controlados Aleatorios como Asunto , Triglicéridos/sangreRESUMEN
Garcinia cambogia extract (GCE) is a popular weight-loss supplement that also lowers plasma triglyceride (TG) levels. We hypothesized that GCE-mediated inhibition of ATP citrate lyase and thereby hepatic TG production could lead to compensatory mechanisms, including increased hepatic TG uptake via lipoprotein receptors. GCE (20 mg/day) administered 40 days orally to female C57BL/6Rj mice on a standard chow diet led to a decrease in both plasma fasting and post-prandial TG-rich lipoprotein levels, but with no significant change in body weight gain. Lipolysis stimulated lipoprotein receptor (LSR) protein levels, but not those of LDL-receptor, were increased as compared to controls. Mouse Hepa1-6 cells treated with the GCE active ingredient, hydroxycitrate, also led to increased LSR protein levels. Hepatic total cholesterol, TG, and muscle TG contents were higher in GCE-treated animals as compared to controls, whereas adipose TG levels were unchanged. LSR and LDL-receptor protein levels were correlated with liver total cholesterol, but only LDL-receptor was associated with liver TG. These results show that GCE treatment in mice on a standard chow diet led to significantly increased liver and muscle lipids, with no significant change in adipose tissue TG levels, which should be considered in the long-term use of GCE.
Asunto(s)
Garcinia cambogia , Lipólisis , Ratones , Femenino , Animales , Ratones Endogámicos C57BL , Ratones Endogámicos , Triglicéridos/metabolismo , Hígado/metabolismo , Colesterol/metabolismo , Dieta , Extractos Vegetales/farmacología , Extractos Vegetales/metabolismoRESUMEN
Obesity is a major global health problem which is associated with various diseases and psychological conditions. Increasing understanding of the relationship between obesity and gut microbiota has led to a worldwide effort to use microbiota as a treatment for obesity. However, several clinical trials have shown that obesity treatment with single strains of probiotics did not achieve as significant results as in animal studies. To overcome this limitation, we attempted to find a new combination that goes beyond the effects of probiotics alone by combining probiotics and a natural substance that has a stronger anti-obesity effect. In this study, we used a diet-induced obesity mouse (DIO) model to investigate the effects of combining Lactobacillus plantarum HAC03 with Garcinia cambogia extract, as compared to the effects of each substance alone. Combining L. plantarum HAC03 and G. cambogia, treatment showed a more than two-fold reduction in weight gain compared to each substance administered alone. Even though the total amount administered was kept the same as for other single experiments, the combination treatment significantly reduced biochemical markers of obesity and adipocyte size, in comparison to the treatment with either substance alone. The treatment with a combination of two substances also significantly decreased the gene expression of fatty acid synthesis (FAS, ACC, PPARγ and SREBP1c) in mesenteric adipose tissue (MAT). Furthermore, 16S rRNA gene sequencing of the fecal microbiota suggested that the combination of L. plantarum HAC03 and G. cambogia extract treatment changed the diversity of gut microbiota and altered specific bacterial taxa at the genus level (the Eubacterium coprostanoligenes group and Lachnospiraceae UCG group) and specific functions (NAD salvage pathway I and starch degradation V). Our results support that the idea that the combination of L. plantarum HAC03 and G. cambogia extract has a synergistic anti-obesity effect by restoring the composition of the gut microbiota. This combination also increases the abundance of bacteria responsible for energy metabolism, as well as the production of SCFAs and BCAAs. Furthermore, no significant adverse effects were observed during the experiment.
Asunto(s)
Lactobacillus plantarum , Probióticos , Animales , Ratones , Garcinia cambogia , Ratones Obesos , ARN Ribosómico 16S/genética , Obesidad/tratamiento farmacológico , Obesidad/etiología , Obesidad/metabolismo , Dieta , Probióticos/farmacología , Probióticos/uso terapéuticoRESUMEN
Garcinia gummi-gutta, also known as Garcinia cambogia, is a member of the Guttiferae family. Garcinia is a polygamous genus consisting 200 species of trees and shrubs. It is found in different zones of the planet including Asia's tropical regions. In India alone, around 30 species have been discovered. They are widely used as a flavoring agent to garnish fish curry in southern India, particularly in Kerala and Karnataka. The fruit rind of G. gummi-gutta has traditionally been used to treat gastrointestinal problems, diarrhea, and ulcers. South Indian people have been utilizing it traditionally as evidenced by its ethnobotanical properties. In vivo and in vitro effects of the crude fruit extract showed anti-inflammatory, anti-cancer, anthelmintic, anti-microbial, and antioxidant activities. G. gummi-gutta fruit rind is medicinally significant and is frequently used in ayurvedic and traditional medicine for many diseases. Various secondary metabolites such as organic acids-hydroxycitric acid (HCA), flavonoids, terpenes, polysaccharides and polyisoprenylated benzophenones-garcinol, xanthochymol, guttiferone, benzophenone, xanthone, biflavonoids, alkaloids, tannins, phenols, and saponins isolated from the G. gummi-gutta have diverse pharmacological activities. This review provides a summary of G. gummi-gutta, including its biological activities, phytochemistry, and ethnobotanical applications.
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Garcinia , Animales , Garcinia/química , India , Garcinia cambogia/química , Antioxidantes/farmacología , Extractos Vegetales/farmacología , Extractos Vegetales/química , Fitoquímicos/farmacologíaRESUMEN
BACKGROUND AND PURPOSE: Pharmacological intervention to induce browning of white adipose tissue provides a promising anti-obesity therapy. The fruits of Garcinia cambogia (Clusiaceae) have been widely applied to manage body weight; however, the chemical principles remain unclear. The current study aims to discover browning inducers from the fruits of G. cambogia and investigate the underlying mechanisms. EXPERIMENTAL APPROACH: The bioactivity-based molecular networking and Oil Red O staining on 3T3-L1 and C3H10T1/2 adipocytes were applied for guided isolation. High-fat diet-induced obese mice were recruited to evaluate the anti-obesity activity. KEY RESULTS: The bioactivity-based molecular networking-guided isolation yielded several polycyclic polyprenylated acylphloroglucinols from the fruits of G. cambogia with lipid-lowering effect in adipocytes, including guttiferone J (GOJ), garcinol and 14-deoxygarcinol. As the most potent one, GOJ (10 µM) reduced lipid accumulation by 70% and 76% in 3T3-L1 and C3H10T1/2 adipocytes, respectively. Furthermore, GOJ (2.5-10 µM) increased the expression of the deacetylase sirtuin 3 (SIRT3) and activated it, which, in turn, reduced the acetylation level of PPARγ coactivator-1α to boost mitochondrial biogenesis and promoted uncoupling protein 1 expression to enhance thermogenesis, resulting in browning of adipocytes. In high-fat diet-induced-obese mice, GOJ (10 and 20 mg·kg-1 ·day-1 for 12 weeks) protected against adiposity, hyperlipidaemia, insulin resistance and liver lipotoxicity, through boosting SIRT3-mediated browning of inguinal adipose tissue. CONCLUSION AND IMPLICATIONS: GOJ represents a new scaffold of thermogenic inducer, which is responsible for the anti-obesity property of G. cambogia and can be further developed as a candidate for treating obesity and its related disorders.
Asunto(s)
Garcinia cambogia , Sirtuina 3 , Ratones , Animales , Ratones Obesos , Sirtuina 3/metabolismo , Obesidad/tratamiento farmacológico , Obesidad/metabolismo , Tejido Adiposo Blanco/metabolismo , Lípidos , Células 3T3-L1 , Dieta Alta en Grasa , Tejido Adiposo Pardo/metabolismoRESUMEN
OBJECTIVE: The purpose of this study is to assess the effects of applying Garcinia cambogia to cultured human nasal epithelial cells. MATERIALS AND METHODS: A cell culture was set up consisting of human primary nasal epithelial cells harvested during septorhinoplasty from volunteers. The cells came from individuals with no history of rhinosinusitis. One assay for assessing cytotoxicity in cell culture utilizes MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide). This method allows visualization of fragmented DNA, condensation of nuclei and changes to the external cellular membrane or cytoskeleton. Our study employed this method. Nasal epithelial cells at 37°C were exposed in culture to G. cambogia for a period of 24 hours. Afterwards an MTT assay was used in conjunction with confocal microscopy to assess evidence of toxicity. The proliferative capability of the nasal epithelial cells was also evaluated by inducing a scratch injury to cultured cells followed by light microscopic examination. RESULTS: Testing for cytotoxicity in this manner indicates that G. cambogia does not appear harmful to cultured nasal epithelial cells when applied directly. The cells exposed to this plant extract were still fully viable 24 hours afterwards. There was no increase in viability at the level of statistical significance. It was noted, however, that proliferation did increase slightly within the exposure period. The MTT assay and confocal microscopy confirm these findings. Under confocal microscopic examination, a compact morphology with unaltered nuclear and cytoskeletal appearances was observed. Thus, there is no evidence suggesting viability is impaired or that cytotoxicity occurs. Ordinary light microscopic examination showed the area denuded of cells had become re-covered completely within 24 hours in the cultures where G. cambogia had been applied. The result suggests that exposure to G. cambogia has no significant effect in terms of stimulating or inhibiting cellular proliferation. CONCLUSIONS: G. cambogia may offer clinical benefit as a supplementary topical treatment for inflammation of the nose and sinuses, as seen in chronic and acute rhinosinusitis, or nasal polyps. The plant appears to increase nasal epitheliocytic proliferation slightly, as revealed by the MTT assay. There were no indications of a cytotoxic effect on epithelial cells of the nose.
Asunto(s)
Pólipos Nasales , Sinusitis , Humanos , Garcinia cambogia , Células Cultivadas , Sinusitis/tratamiento farmacológico , Células EpitelialesRESUMEN
Food supplements of plant origin for weight control are increasingly being demanded by consumers as a way to promote good health. Among them, those based on Garcinia cambogia (GCFS) are widely commercialized considering their bioactive properties, mainly due to (-)-hydroxycitric acid ((-)-HCA). However, recently, controversy has arisen over their safety; thus, further research and continuous monitoring of their composition is required. Hence, in this work, a multi-analytical approach was followed to determine not only (-)-HCA but also other constituents of 18 GCFS, which could be used as quality markers to detect fraudulent practices in these samples. Discrepancies between the declared (-)-HCA content and that experimentally determined were detected by LC-UV in 33% of the samples. Moreover, GC-MS analyses of GCFS allowed the detection of different compounds not present in G. cambogia fruits and not declared on supplement labels, probably related to heat exposure or to the addition of excipients or other extracts. This multi-analytical methodology is shown to be advantageous to address different fraudulent practices affecting the quality of these supplements.
Asunto(s)
Fármacos Antiobesidad , Garcinia cambogia , Fármacos Antiobesidad/análisis , Suplementos Dietéticos/análisis , Frutas/química , Extractos Vegetales , Pérdida de PesoRESUMEN
SCOPE: Garcinia cambogia (G. cambogia) is known to have antiobesity effects. In this study, the therapeutic effects of G. cambogia on glucose homeostasis in obesity-induced diabetes are explored and the underlying mechanisms are investigated. METHODS AND RESULTS: C2C12 myotubes are treated with G. cambogia; glucose uptake, intracellular Ca2+ levels, and related alterations in signaling pathways are examined. High-fat diet (HFD)-fed mice are administered G. cambogia for 8 weeks; oral glucose tolerance is evaluated, and the regulation of identified targets of signaling pathways in quadriceps skeletal muscle are examined in vivo. G. cambogia increases glucose uptake in C2C12 myotubes and induces the upregulation of AMPK, ACC, and p38 MAPK phosphorylation. Notably, G. cambogia markedly elevates both intracellular Ca2+ levels, activating CaMKII, a Ca2+ -sensing protein, and TBC1D4-mediated GLUT4 translocation, to facilitate glucose uptake. Furthermore, high-glucose-induced inhibition of glucose uptake and signal transduction is reverted by G. cambogia. In an HFD-induced diabetes mouse model, G. cambogia administration results in significant blood glucose-lowering effects, which are attributed to the regulation of targets that have been identified in vitro, in quadricep skeletal muscle. CONCLUSION: These findings provide new insights into the mechanism by which G. cambogia regulates glucose homeostasis in obesity-induced diabetes.
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Diabetes Mellitus , Glucosa , Proteínas Quinasas Activadas por AMP/metabolismo , Animales , Calcio/metabolismo , Calcio de la Dieta/farmacología , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/metabolismo , Diabetes Mellitus/metabolismo , Dieta Alta en Grasa/efectos adversos , Garcinia cambogia/metabolismo , Glucosa/metabolismo , Transportador de Glucosa de Tipo 4/metabolismo , Ratones , Fibras Musculares Esqueléticas , Músculo Esquelético/metabolismo , Obesidad/tratamiento farmacológico , Obesidad/etiología , Obesidad/metabolismoRESUMEN
BACKGROUND & AIMS: Garcinia cambogia, either alone or with green tea, is commonly promoted for weight loss. Sporadic cases of liver failure from G cambogia have been reported, but its role in liver injury is controversial. METHODS: Among 1418 patients enrolled in the Drug-Induced Liver Injury Network (DILIN) from 2004 to 2018, we identified 22 cases (adjudicated with high confidence) of liver injury from G cambogia either alone (n = 5) or in combination with green tea (n = 16) or Ashwagandha (n = 1). Control groups consisted of 57 patients with liver injury from herbal and dietary supplements (HDS) containing green tea without G cambogia and 103 patients from other HDS. RESULTS: Patients who took G cambogia were between 17 and 54 years, with liver injury arising 13-223 days (median = 51) after the start. One patient died, one required liver transplantation, and 91% were hospitalized. The liver injury was hepatocellular with jaundice. Although the peak values of aminotransferases were significantly higher (2001 ± 1386 U/L) in G cambogia group (P < .018), the median time for improvement in total bilirubin was significantly lower compared with the control groups (10 vs 17 and 13 days; P = .03). The presence of HLA-B∗35:01 allele was significantly higher in the G cambogia containing HDS (55%) compared with patients because of other HDS (19%) (P = .002) and those with acute liver injury from conventional drugs (12%) (P = 2.55 × 10-6). CONCLUSIONS: The liver injury caused by G cambogia and green tea is clinically indistinguishable. The possible association with HLA-B∗35:01 allele suggests an immune-mediated mechanism of injury. CLINICAL TRIALS: gov number: NCT00345930.
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Enfermedad Hepática Inducida por Sustancias y Drogas , Garcinia cambogia , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Suplementos Dietéticos/efectos adversos , Garcinia cambogia/efectos adversos , Antígenos HLA-B , Humanos , Té/efectos adversosRESUMEN
The overexpansion of adipose tissues leads to obesity and eventually results in metabolic disorders. Garcinia cambogia (G. cambogia) has been used as an antiobesity supplement. However, the molecular mechanisms underlying the effects of G. cambogia on cellular processes have yet to be fully understood. Here, we discovered that G. cambogia attenuated the expression of CEBPB (CCAAT/enhancer binding protein (C/EBP), beta), an important adipogenic factor, suppressing its transcription in differentiated cells. In addition, G. cambogia inhibited macroautophagic/autophagic flux by decreasing autophagy-related gene expression and autophagosome formation. Notably, G. cambogia markedly elevated the expression of KLF3 (Kruppel-like factor 3 (basic)), a negative regulator of adipogenesis, by reducing SQSTM1/p62-mediated selective autophagic degradation. Furthermore, increased KLF3 induced by G. cambogia interacted with CTBP2 (C-terminal binding protein 2) to form a transcriptional repressor complex and inhibited Cebpa and Pparg transcription. Importantly, we found that RPS6KA1 and STAT3 were involved in the G. cambogia-mediated regulation of CEBPB and autophagic flux. In an obese animal model, G. cambogia reduced high-fat diet (HFD)-induced obesity by suppressing epididymal and inguinal subcutaneous white adipose tissue mass and adipocyte size, which were attributed to the regulation of targets that had been consistently identified in vitro. These findings provide new insight into the mechanism of G. cambogia-mediated regulation of adipogenesis and suggest molecular links to therapeutic targets for the treatment of obesity.Abbreviations: 3-MA: 3-methyladenine; ACTB: actin beta; ATG: autophagy-related; Baf: bafilomycin A1; BECN1: beclin 1; CEBP: CCAAT/enhancer binding protein (C/EBP); CHX: cycloheximide; CREB: cAMP response element binding protein; CTBP: C-terminal binding protein; EGCG: (-)-epigallocatechin gallate; eWAT: epididymal white; G. cambogia: Garcinia cambogia; GFP: green fluorescent protein; H&E: hematoxylin and eosin; HFD: high-fat diet; iWAT: inguinal subcutaneous white; KLF: Kruppel-like factor; LAP: liver-enriched transcriptional activating proteins; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; ND: normal diet; PPARG: peroxisome proliferator activated receptor gamma; qPCR: quantitative real-time PCR; RFP: red fluorescent protein; RPS6KA1: ribosomal protein S6 kinase A1; siRNA: small-interfering RNA; SQSTM1/p62: sequestosome 1; STAT: signal transducer and activator of transcription; TEM: transmission electron microscopy.
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Adipogénesis , Garcinia cambogia , Adipogénesis/genética , Animales , Autofagia/fisiología , Garcinia cambogia/metabolismo , Factores de Transcripción de Tipo Kruppel/genética , Factores de Transcripción de Tipo Kruppel/metabolismo , Obesidad , PPAR gamma/metabolismo , Proteínas Serina-Treonina Quinasas , Proteína Sequestosoma-1/metabolismoRESUMEN
Caffeine, a natural stimulant, is known to be effective for weight loss. On this basis, we screened the arousal-inducing effect of five dietary supplements with a weight loss effect (Garcinia cambogia, Coleus forskohlii, Camellia sinensis L., Irvingia gabonensis, and Malus pumila M.), of which the G. cambogia peel extract (GC) showed a significant arousal-inducing effect in the pentobarbital-induced sleep test in mice. This characteristic of GC was further evaluated by analysis of electroencephalogram and electromyogram in C57L/6N mice, and it was compared to that of the positive control, caffeine. Administration of GC (1500 mg/kg) significantly increased wakefulness and decreased non-rapid eye movement sleep, similar to that of caffeine (25 mg/kg), with GC and caffeine showing a significant increase in wakefulness at 2 and 6 h, respectively. Compared to that of caffeine, the shorter duration of efficacy of GC could be advantageous because of the lower possibility of sleep disturbance. Furthermore, the arousal-inducing effects of GC (1500 mg/kg) and caffeine (25 mg/kg) persisted throughout the chronic (3 weeks) administration study. This study, for the first time, revealed the arousal-inducing effect of GC. Our findings suggest that GC might be a promising natural stimulant with no side effects. In addition, it is preferential to take GC as a dietary supplement for weight loss during the daytime to avoid sleep disturbances owing to its arousal-inducing effect.
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Nivel de Alerta/efectos de los fármacos , Ondas Encefálicas/efectos de los fármacos , Encéfalo/efectos de los fármacos , Estimulantes del Sistema Nervioso Central/farmacología , Electroencefalografía , Garcinia cambogia , Extractos Vegetales/farmacología , Animales , Fármacos Antiobesidad/farmacología , Encéfalo/fisiología , Cafeína/farmacología , Estimulantes del Sistema Nervioso Central/aislamiento & purificación , Frutas , Garcinia cambogia/química , Hipnóticos y Sedantes/farmacología , Masculino , Ratones Endogámicos C57BL , Ratones Endogámicos ICR , Pentobarbital/farmacología , Extractos Vegetales/aislamiento & purificación , Sueño/efectos de los fármacosRESUMEN
Ten new polyisoprenylated benzophenone derivatives, 4,8-epi-uralione F (1), 4,8-epi-uralione G (2), uralione S (3), coccinone J (4), 6-epi-coccinone C (5), coccinone I (6), 36-hydroxy-guttiferone J (7), multiflorone I (8), garciniagifolone F (9) and 36-hydroxy-garciniagifolone F (10), were isolated from the fruits of Garcinia cambogia, along with seven known analogues. The structures of the new compounds were established based on the detailed analysis of 1D and 2D nuclear magnetic resonance (NMR) spectra and high resolution electrospray ionization mass spectrometra (HRESIMS), and their absolute configurations were determined from the electronic circular dichroism (ECD) spectra. All the isolates were tested for their inhibitory effects against nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. The results indicated that compound 1 displayed a potent NO inhibitory effect with an IC50 value of 41.60 ± 0.17 µM. Furthermore, compound 1 suppressed inducible NO synthase (iNOS) expression in a dose-dependent manner through inhibiting the activation of nuclear factor-κB (NF-κB).
Asunto(s)
Antiinflamatorios/farmacología , Benzofenonas/farmacología , Frutas/química , Garcinia cambogia/química , Animales , Antiinflamatorios/química , Benzofenonas/química , Supervivencia Celular/efectos de los fármacos , Dicroismo Circular/métodos , Lipopolisacáridos/farmacología , Espectroscopía de Resonancia Magnética/métodos , Ratones , FN-kappa B/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa/metabolismo , Extractos Vegetales/química , Extractos Vegetales/farmacología , Células RAW 264.7 , Espectrometría de Masa por Ionización de Electrospray/métodosRESUMEN
Nowadays, obesity is one of the great nutritional problems facing public health. The prevalence of this pathology has increased in a worrying way over recent years, currently reaching epidemic proportions. In this context, nutritional supplements are presented as a therapeutic alternative to which more and more people are turning to. Nutritional supplements to lose weight based on the Garcinia plant, specifically on Garcinia cambogia, are commonly used. The active principle of this plant to which these properties have been attributed, is hydroxycitric acid (HCA). The aim of the present review is to gather reported data concerning the effectiveness of nutritional supplements based on Garcinia extracts on weight loss and their possible negative effects. Contradictory results have been observed regarding the effectiveness of the supplements. While statistically significant weight loss was observed in some studies, no changes were found in others. Regarding safety, although Garcinia supplements have been revealed as safe in the vast majority of the studies carried out in animal models and humans, some cases of hepatotoxicity, serotonin toxicity and mania have been reported. In conclusion, the results suggest that Garcinia-based supplements could be effective in short-term weight loss, although the data are not conclusive. In addition, the safety of the complement should be further studied.
Asunto(s)
Fármacos Antiobesidad/administración & dosificación , Suplementos Dietéticos , Garcinia cambogia , Obesidad/terapia , Extractos Vegetales/administración & dosificación , Animales , Fármacos Antiobesidad/efectos adversos , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Citratos/administración & dosificación , Citratos/efectos adversos , Humanos , Manía/inducido químicamente , Extractos Vegetales/efectos adversos , Serotonina/metabolismo , Pérdida de Peso/efectos de los fármacosRESUMEN
Obesity is associated with an increase in adipose tissue, which is mediated by hyperplasia and hypertrophy. Therefore, inhibiting cell proliferation during mitotic clonal expansion (MCE) is one of the major strategies for preventing obesity. The antagonistic effects of Garcinia cambogia (G. cambogia) on obesity have been studied in animal experimental models. However, the effects of G. cambogia extract on MCE, and the underlying molecular mechanisms, are poorly understood. In this study, 3T3-L1 cells were used to investigate whether G. cambogia extract affected cell proliferation during MCE and to identify target molecules for any anti-adipogenic activity. G. cambogia extract suppressed isobutylmethylxanthine and dexamethasone-and-insulin (MDI)-induced adipogenesis at an early stage by attenuating MCE. In G. cambogia extract-treated preadipocytes, MDI-induced cell proliferation and cell cycle progression were inhibited by G0 /G1 arrest due to an increase in p21 and p27 expression, and inhibition of cyclin-dependent kinase 2, cyclin E1 expression, and retinoblastoma (Rb) phosphorylation. In addition, the MDI-induced phosphorylation and subsequent translocation into the nucleus of p90 ribosomal S6 kinase (p90RSK) and signal transducer and activator of transcription (Stat) 3 were suppressed. Specific inhibitors of p90RSK (FMK) and Stat3 (stattic) regulated cell proliferation and adipogenesis. In conclusion, this study demonstrated that G. cambogia extract inhibited MCE by regulating p90RSK, Stat3, and cell cycle proteins, leading to G0 /G1 arrest. These findings provide new insight into the mechanism by which G. cambogia suppresses adipocyte differentiation and show that p90RSK is critical for adipogenesis as a new molecular target.
Asunto(s)
Adipogénesis , Garcinia cambogia/química , Mitosis , Proteínas Quinasas S6 Ribosómicas 90-kDa/antagonistas & inhibidores , Factor de Transcripción STAT3/antagonistas & inhibidores , 1-Metil-3-Isobutilxantina/farmacología , Células 3T3-L1 , Adipocitos/citología , Adipocitos/efectos de los fármacos , Adipocitos/metabolismo , Adipogénesis/efectos de los fármacos , Animales , Apoptosis/efectos de los fármacos , Puntos de Control del Ciclo Celular/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Núcleo Celular/efectos de los fármacos , Núcleo Celular/metabolismo , Proliferación Celular/efectos de los fármacos , Células Clonales , Dexametasona/farmacología , Insulina/farmacología , Ratones , Mitosis/efectos de los fármacos , Modelos Biológicos , Fosforilación/efectos de los fármacos , Transporte de Proteínas/efectos de los fármacos , Proteínas Quinasas S6 Ribosómicas 90-kDa/metabolismo , Factor de Transcripción STAT3/metabolismoRESUMEN
Garcinia cambogia extract (GCE)/(-) - hydroxycitric acid (HCA) has been identified as a potential antiobesity agent. However, controversial clinical trial results have been published on its biological effect and poor pharmacokinetic (PK) information increases its dubious efficacy. The aim of this study was to determine the main PK parameters of GCE/HCA in healthy women, and to evaluate food effects on HCA absorption. Healthy women ages 21-41 years with body mass index (BMI; kg/m2) 20.29-25.82 participated in a phase I, open-label, randomized, single-dose, cross-over study. In the fasted- and fed-conditions subjects received 1500/750 mg of GCE/HCA under 8 h of fasting. In the fed-period was given a high calorie breakfast (~600 calories) after dosing. Plasma HCA concentrations were substantially reduced in fed-state. Peak plasma concentration (Cmax) and area under the curve of time-concentration (AUC0-10h) were 3-fold and 2-fold lower (p < 0.001, 0.01) in fed-condition, respectively. Higher volume of distribution (Vd/F) and clearance (Cl/F) were achieved in fed state, probably due to the lower fraction (F) of HCA absorbed induced by food effect. Large inter-individual variations were observed for the main pharmacokinetics parameters in both periods. These findings suggest that HCA might suffer an active absorption uptake and intense adsorption on food.
Asunto(s)
Garcinia cambogia , Extractos Vegetales , Administración Oral , Adulto , Área Bajo la Curva , Citratos , Estudios Cruzados , Femenino , Interacciones Alimento-Droga , Humanos , Adulto JovenAsunto(s)
Fármacos Antiobesidad/farmacología , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Garcinia cambogia/efectos de los fármacos , Pérdida de Peso/efectos de los fármacos , Suplementos Dietéticos , Ingestión de Alimentos/efectos de los fármacos , Femenino , Humanos , Persona de Mediana Edad , Pérdida de Peso/fisiologíaRESUMEN
OBJECTIVE: Several trials have examined the effect of Garcinia cambogia supplement on the weight and body composition, but their results are conflicting. This systematic review and dose-response meta-analysis was designed to determine the effect of Garcinia cambogia supplement on the obesity indices in human randomized controlled trials (RCTs). METHODS: PubMed/Medline, Scopus, Cochrane library, and Web of Science databases were searched up to 1th January, 2020, to screen relevant trials. The mean changes in the weight, body mass index (BMI), percentage of fat mass (PFM), and waist circumference (WC) from the baseline were used to conduct the present dose response meta-analysis. RESULTS: In the current study, eight trials (including 530 subjects) were included. Garcinia cambogia supplement significantly reduced the weight by -1.34 kg (95% CI: -2.62 to -0.07, P = 0.03), BMI by -0.99 kg/m2 (95% CI: -1.48 to -0.49, P < 0.001), PFM by -0.42% (95% CI: -0.77 to -0.06, P = 0.02), and WC by -4.16 cm (95% CI: -7.83 to -0.49, P = 0.02) compared with the placebo group. Dose-response analysis revealed that there is a nonlinear association between Garcinia cambogia dosage and changes in the body weight (Pnonlinearity = 0.04) and BMI (Pnonlinearity < 0.001) not PFM (Pnonlinearity = 0.68). There was no publication bias among the studies. CONCLUSION: Our results suggested that Garcinia cambogia supplement had a significant effect on the body weight, BMI, PFA, and WC as compared with the placebo.
Asunto(s)
Suplementos Dietéticos , Garcinia cambogia , Obesidad/tratamiento farmacológico , Pesos y Medidas Corporales , Relación Dosis-Respuesta a Droga , Humanos , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
The main active compound of Garcinia hanburyi (referred to as gamboge) is gambogic acid (GA), which has long been a Chinese herbal medicine for treating several types of cancer. However, the potential therapeutic role and mechanisms of GA in Tcell acute lymphoblastic leukemia (TALL) remain unclear. In the present study, the effects of GA on proliferation, cell cycle, apoptosis, and autophagy in TALL cell lines were investigated. The possible mechanisms underlying GA activity were also examined. The results showed that GA inhibited proliferation, induced apoptosis, and activated autophagy in TALL cell lines (Jurkat and Molt4 cells). Findings confirmed that GA has an antileukemia effect against peripheral blood lymphocyte cells in patients with ALL. GA inhibited phosphoGSK3ß S9 (pGSK3ß S9) protein levels to inactivate Wnt signaling and suppress ßcatenin protein levels. In addition, the inhibitory effect of GA on TALL was reversed by overexpression of ßcatenin. Thus, GA can inhibit the growth and survival of TALL cells. GA also had antileukemic activity, at least in part, through the downregulation of the Wnt/ßcatenin signaling pathway.