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1.
Biofactors ; 49(3): 584-599, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36785888

RESUMO

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.


Assuntos
Garcinia , Animais , Garcinia/química , Índia , Garcinia cambogia/química , Antioxidantes/farmacologia , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Compostos Fitoquímicos/farmacologia
2.
Nutrients ; 13(8)2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34445005

RESUMO

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.


Assuntos
Nível de Alerta/efeitos dos fármacos , Ondas Encefálicas/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Estimulantes do Sistema Nervoso Central/farmacologia , Eletroencefalografia , Garcinia cambogia , Extratos Vegetais/farmacologia , Animais , Fármacos Antiobesidade/farmacologia , Encéfalo/fisiologia , Cafeína/farmacologia , Estimulantes do Sistema Nervoso Central/isolamento & purificação , Frutas , Garcinia cambogia/química , Hipnóticos e Sedativos/farmacologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Pentobarbital/farmacologia , Extratos Vegetais/isolamento & purificação , Sono/efeitos dos fármacos
3.
Food Funct ; 12(14): 6432-6441, 2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34075995

RESUMO

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).


Assuntos
Anti-Inflamatórios/farmacologia , Benzofenonas/farmacologia , Frutas/química , Garcinia cambogia/química , Animais , Anti-Inflamatórios/química , Benzofenonas/química , Sobrevivência Celular/efeitos dos fármacos , Dicroísmo Circular/métodos , Lipopolissacarídeos/farmacologia , Espectroscopia de Ressonância Magnética/métodos , Camundongos , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase/metabolismo , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Células RAW 264.7 , Espectrometria de Massas por Ionização por Electrospray/métodos
4.
J Cell Physiol ; 236(3): 1822-1839, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32716094

RESUMO

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.


Assuntos
Adipogenia , Garcinia cambogia/química , Mitose , Proteínas Quinases S6 Ribossômicas 90-kDa/antagonistas & inibidores , Fator de Transcrição STAT3/antagonistas & inibidores , 1-Metil-3-Isobutilxantina/farmacologia , Células 3T3-L1 , Adipócitos/citologia , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Adipogenia/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Proliferação de Células/efeitos dos fármacos , Células Clonais , Dexametasona/farmacologia , Insulina/farmacologia , Camundongos , Mitose/efeitos dos fármacos , Modelos Biológicos , Fosforilação/efeitos dos fármacos , Transporte Proteico/efeitos dos fármacos , Proteínas Quinases S6 Ribossômicas 90-kDa/metabolismo , Fator de Transcrição STAT3/metabolismo
5.
Oncol Rep ; 44(4): 1747-1757, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32945501

RESUMO

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.


Assuntos
Glicogênio Sintase Quinase 3 beta/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamento farmacológico , Xantonas/farmacologia , beta Catenina/genética , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Garcinia cambogia/química , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Medicina Tradicional Chinesa/métodos , Fosforilação/efeitos dos fármacos , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patologia , Via de Sinalização Wnt/efeitos dos fármacos
6.
Eur Rev Med Pharmacol Sci ; 24(11): 6434-6445, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32572941

RESUMO

OBJECTIVE: Kidney stone formers have a high rate of stone recurrence after kidney stone removal surgery and there is no effective medication for treatment. Hydroxycitric acid (HCA), which is the major component of Garcinia cambogia extract, can dissolve calcium oxalate crystals in vitro, suggesting that Garcinia cambogia could be used to treat calcium oxalate kidney stone. In this study, we used the Drosophila kidney disease model to evaluate the effect of Garcinia cambogia on the prevention and removal of calcium oxalate stones in vivo. MATERIALS AND METHODS: Flies were reared in fly food containing different concentrations of GCE for one week. The effect of GCE on preventing the formation of calcium oxalate stone was examined. WT and v-ATPase gene RNAi knockdown flies were reared in fly food with 0.3% NaOx for one week, then fed different concentrations of GCE for one week. The effect of GCE on the removal of calcium oxalate stone was examined. RESULTS: Garcinia cambogia extract dissolves calcium oxalate crystals from Malpighian tubules in both genetic and non-genetic Drosophila kidney stone models compared to citric acid. Hydroxycitric acid also directly dissolves calcium oxalate crystals in Drosophila Malpighian tubules ex vivo. CONCLUSIONS: Garcinia cambogia extract removes calcium oxalate kidney stones from Drosophila Malpighian tubules via directly dissolving calcium oxalate stones by HCA. Our study strongly suggests that clinical-grade Garcinia cambogia extract could be used to treat patients with nephrolithiasis in the future.


Assuntos
Oxalato de Cálcio/química , Citratos/farmacologia , Garcinia cambogia/química , Cálculos Renais/tratamento farmacológico , Túbulos Renais/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Oxalato de Cálcio/isolamento & purificação , Citratos/química , Citratos/isolamento & purificação , Cristalização , Modelos Animais de Doenças , Drosophila , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação
7.
Int J Mol Sci ; 20(20)2019 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-31614647

RESUMO

BACKGROUND: Age-related macular degeneration (AMD) is the leading cause of blindness and can be classified into two types called atrophic AMD (dry AMD) and neovascular AMD (wet AMD). Dry AMD is characterized by cellular degeneration of the retinal pigment epithelium, choriocapillaris, and photoreceptors. Wet AMD is characterized by the invasion of abnormal vessels from the choroid. Although anti-vascular endothelial growth factor (VEGF) therapy has a potent therapeutic effect against the disease, there is a possibility of chorio-retinal atrophy and adverse systemic events due to long-term robust VEGF antagonism. We focused on hypoxia-inducible factor (HIF) regulation of VEGF transcription, and report the suppressive effects of HIF inhibition against ocular phenotypes in animal models. Many of the known HIF inhibitors are categorized as anti-cancer drugs, and their systemic side effects are cause for concern in clinical use. In this study, we explored food ingredients that have HIF inhibitory effects and verified their effects in an animal model of AMD. METHODS: Food ingredients were screened using a luciferase assay. C57BL6/J mice were administered the Garcinia cambogia extract (Garcinia extract) and hydroxycitric acid (HCA). Choroidal neovascularization (CNV) was induced by laser irradiation. RESULTS: Garcinia extract and HCA showed inhibitory effects on HIF in the luciferase assay. The laser CNV model mice showed significant reduction of CNV volume by administering Garcinia extract and HCA. Conclusions: Garcinia extract and HCA showed therapeutic effects in a murine AMD model.


Assuntos
Citratos/administração & dosagem , Garcinia cambogia/química , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Degeneração Macular/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Animais , Citratos/química , Citratos/farmacologia , Modelos Animais de Doenças , Regulação para Baixo , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Terapia com Luz de Baixa Intensidade/efeitos adversos , Degeneração Macular/etiologia , Degeneração Macular/genética , Masculino , Camundongos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Resultado do Tratamento
8.
Food Chem Toxicol ; 128: 61-67, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30940594

RESUMO

Garcinia cambogia supplements are widely used for weight loss. Knowing that epilepsy patients are at greater risk of developing overweight/obesity, the investigation of herb-drug interactions involving antiepileptic drugs of narrow therapeutic index is fully justified. This work was planned to assess potential pharmacokinetic-based interactions between G. cambogia extract and lamotrigine (LTG) through two independent pharmacokinetic studies. In the first study (co-administration study), rats were orally co-administered with a single-dose of G. cambogia extract (821 mg/kg) and LTG (10 mg/kg). In the second study (pre-treatment study), rats were orally pre-treated for 14 days with G. cambogia extract (821 mg/kg/day), being LTG administered (10 mg/kg) on the 15th day. Rats of the control groups received water instead of the extract. Following LTG administration, blood samples were collected until 96 h post-dose, and plasma LTG concentrations were determined and submitted to a non-compartmental analysis. Globally, no statistically significant effects were identified in the co-administration study of G. cambogia extract and LTG. In the 14-day pre-treatment study, a statistically significant decrease in the rate of systemic exposure to LTG and an increase of apparent volume of distribution were found. Even so, a minor or no clinical impact is expected from the administration of G. cambogia dietary supplements and LTG.


Assuntos
Anticonvulsivantes/farmacocinética , Garcinia cambogia/química , Interações Ervas-Drogas , Lamotrigina/farmacocinética , Extratos Vegetais/farmacologia , Animais , Anticonvulsivantes/administração & dosagem , Anticonvulsivantes/sangue , Área Sob a Curva , Peso Corporal/efeitos dos fármacos , Suplementos Nutricionais , Meia-Vida , Lamotrigina/administração & dosagem , Lamotrigina/sangue , Masculino , Extratos Vegetais/administração & dosagem , Ratos Wistar
9.
J Agric Food Chem ; 67(11): 3188-3197, 2019 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-30827101

RESUMO

(-)-Hydroxycitric acid (HCA) inhibits the deposition of fat in animals and humans, while the molecular mechanism is still unclear. The present study investigated the effect and mechanism of (-)-HCA's regulation of lipid, glucose, and energy metabolism in broiler chickens. The current results showed that (-)-HCA decreased the accumulation of lipid droplets and triglyceride content by reducing fatty acid synthase protein level and enhancing phosphorylation of acetyl-CoA carboxylase protein level. (-)-HCA accelerated carbohydrate aerobic metabolisms by increasing the activities of phosphofructokinase-1, pyruvate dehydrogenase, succinate dehydrogenase, and malate dehydrogenase. Furthermore, (-)-HCA increased adiponectin receptor 1 mRNA level and enhanced phospho-AMPKα, peroxisome proliferator-activated receptor gamma coactivator-1α, nuclear respiratory factor-1, and mitochondrial transcription factor A protein levels in broiler chickens. These data indicated that (-)-HCA reduced lipid droplet accumulation, improved glucose catabolism, and accelerated energy metabolism in broiler chickens, possibly via activation of adiponectin-AMPK signaling pathway. These results revealed the biochemical mechanism of (-)-HCA-mediated fat accumulation and the prevention of metabolic disorder-related diseases in broiler chickens.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Adiponectina/metabolismo , Galinhas/metabolismo , Citratos/metabolismo , Metabolismo Energético/efeitos dos fármacos , Garcinia cambogia/química , Gotículas Lipídicas/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Extratos Vegetais/metabolismo , Proteínas Quinases Ativadas por AMP/genética , Adiponectina/genética , Ração Animal/análise , Animais , Galinhas/genética , Garcinia cambogia/metabolismo , Receptores de Adiponectina/genética , Receptores de Adiponectina/metabolismo , Transdução de Sinais/efeitos dos fármacos , Triglicerídeos/metabolismo
10.
J Pharm Pract ; 32(1): 99-102, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28982303

RESUMO

Garcinia cambogia is a Southeast Asian fruit becoming increasingly popular as a weight management supplement. Hydroxycitric acid (HCA) is the primary active ingredient which demonstrates serotonergic- and muscarinic-enhancing properties via inhibition of selective serotonin reuptake and acetylcholinesterase. We report a young adult female with no history of bipolar disorder who developed mania and psychosis approximately 1 week following initiation of G cambogia and the Cleanse and Detox™ dietary supplement manufactured by Apex Vitality Health. She presented with a predominantly expansive mood, psychomotor agitation, disorganized and pressured speech, flight of ideas, grandiosity, delusions, and auditory hallucinations. Following discontinuation of G cambogia and the initiation of lithium and quetiapine, the patient experienced rapid and progressive mood stabilization and was discharged after 8 days. Seven previous case reports associating (hypo)mania and/or psychosis with G cambogia consumption have been published. The chronology of mania and/or psychosis onset may appear between 1 and 8 weeks following initiation of G cambogia. Psychiatric symptoms have resolved with G cambogia discontinuation in some instances and may not require chronic pharmacotherapy. Our report should encourage further research and case reports regarding this adverse event and the reconciliation of complete herbal supplement use at clinic visits and hospital admissions.


Assuntos
Transtorno Bipolar/etiologia , Suplementos Nutricionais/efeitos adversos , Garcinia cambogia/efeitos adversos , Transtornos Psicóticos/etiologia , Transtorno Bipolar/tratamento farmacológico , Feminino , Frutas , Garcinia cambogia/química , Humanos , Transtornos Psicóticos/tratamento farmacológico , Fatores de Tempo , Adulto Jovem
11.
J Sci Food Agric ; 99(5): 2455-2462, 2019 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-30367475

RESUMO

BACKGROUND: Garcinia (Clusiaceae) species are traditionally used as flavoring agents in curries and to cure several human health complications. This study investigated 31 macro, micro, and trace elements in microwave-assisted digested samples of Garcinia cambogia fruit and its anti-obesity commercial products by inductively coupled plasma-optical emission spectroscopy (ICP-OES) and inductively coupled plasma-mass spectrometric (ICP-MS) techniques. The methods were also validated using the coefficient of determination (R2 ), limits of detection and quantification (LOD, LOQ), precision (CV%), analysis of certified reference materials, spiking recovery experiments, and participation in an accredited laboratory proficiency test organized by Food Analysis Performance Assessment Scheme (FAPAS). RESULTS: Quality assurance confirmed that the methods were efficient and in accordance with criteria set by the Association of Official Analytical Chemists (AOAC). In the elemental analysis, the analyzed macro, micro, and trace essential elements were present in appreciable concentrations, which could meet the human nutritional requirements. Traces of toxic elements were within safe limits. CONCLUSION: From the results of the current study, the fruit and its commercial products could be considered potential sources of mineral elements without posing any threats to consumers. © 2018 Society of Chemical Industry.


Assuntos
Fármacos Antiobesidade/química , Garcinia cambogia/química , Extratos Vegetais/química , Oligoelementos/química , Fármacos Antiobesidade/economia , Fármacos Antiobesidade/toxicidade , Frutas/química , Garcinia cambogia/toxicidade , Limite de Detecção , Espectrometria de Massas , Extratos Vegetais/economia , Extratos Vegetais/toxicidade , Oligoelementos/economia
12.
Animal ; 12(4): 774-783, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28877777

RESUMO

(-)-Hydroxycitric acid (HCA), a major component of Garcinia cambogia extracts, has been shown to suppress BW gain and fat accumulation in animals and humans. However, the mechanism remains unknown. In this study, gas chromatography-mass spectrometry was used to analyse serum metabolites, and principal component analysis and partial least-squares-discriminant analysis models were generated to analyse serum metabolite changes in broiler chickens after the administration of (-)-HCA at 0, 1000, 2000 and 3000 mg/kg diets for 28 days. Metabolites showing significant changes were screened by 'variable importance in the projection' plots. The results showed that 20 metabolites in the 1000 mg/kg (-)-HCA treatment group and 16 metabolites in 3000 mg/kg (-)-HCA treatment group were significantly altered. Metabolites pathway enrichment analysis indicated that these metabolites were mainly associated with metabolism of amino acids, protein synthesis, citric acid cycle, and uric acid and fatty acid synthesis. The data indicated that (-)-HCA promoted protein synthesis by regulating the metabolic directions of amino acids. At the same time, (-)-HCA treatment inhibited fatty acid synthesis by promoting the citric acid cycle, resulting in reduced cytosolic acetyl-CoA content in broiler chickens. The present study identified global changes in metabolites and analysed the main canonical metabolic pathways in broiler chickens supplemented with (-)-HCA. These results will deepen our understanding of the mechanism of (-)-HCA's effects in animals.


Assuntos
Galinhas/metabolismo , Citratos/farmacologia , Suplementos Nutricionais , Ácidos Graxos/biossíntese , Metabolômica , Adipogenia , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Animais , Citratos/química , Dieta/veterinária , Relação Dose-Resposta a Droga , Garcinia cambogia/química , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Extratos Vegetais/farmacologia , Biossíntese de Proteínas
13.
Acta Crystallogr D Struct Biol ; 73(Pt 8): 660-671, 2017 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-28777081

RESUMO

Hydroxycitrate from the fruit of Garcinia cambogia [i.e. (2S,3S)-2-hydroxycitrate] is the best-known inhibitor of ATP-citrate lyase. Well diffracting crystals showing how the inhibitor binds to human ATP-citrate lyase were grown by modifying the protein. The protein was modified by introducing cleavage sites for Tobacco etch virus protease on either side of a disordered linker. The protein crystallized consisted of residues 2-425-ENLYFQ and S-488-810 of human ATP-citrate lyase. (2S,3S)-2-Hydroxycitrate binds in the same orientation as citrate, but the citrate-binding domain (residues 248-421) adopts a different orientation with respect to the rest of the protein (residues 4-247, 490-746 and 748-809) from that previously seen. For the first time, electron density was evident for the loop that contains His760, which is phosphorylated as part of the catalytic mechanism. The pro-S carboxylate of (2S,3S)-2-hydroxycitrate is available to accept a phosphoryl group from His760. However, when co-crystals were grown with ATP and magnesium ions as well as either the inhibitor or citrate, Mg2+-ADP was bound and His760 was phosphorylated. The phosphoryl group was not transferred to the organic acid. This led to the interpretation that the active site is trapped in an open conformation. The strategy of designing cleavage sites to remove disordered residues could be useful in determining the crystal structures of other proteins.


Assuntos
ATP Citrato (pro-S)-Liase/química , ATP Citrato (pro-S)-Liase/metabolismo , Citratos/metabolismo , Sítios de Ligação , Domínio Catalítico , Citratos/química , Cristalografia por Raios X , Frutas/química , Frutas/metabolismo , Garcinia cambogia/química , Garcinia cambogia/metabolismo , Humanos , Magnésio/química , Magnésio/metabolismo , Simulação de Acoplamento Molecular , Ligação Proteica , Domínios Proteicos
14.
Planta Med ; 83(11): 895-900, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28288493

RESUMO

This study assessed the inhibitory effects of Garcinia cambogia extract on the cytochrome P450 enzymes in vitro. G. cambogia extract was incubated with cytochrome P450 isozyme-specific substrates in human liver microsomes and recombinant CYP2B6 isozyme, and the formation of the marker metabolites was measured to investigate the inhibitory potential on cytochrome P450 enzyme activities. The results showed that G. cambogia extract has significant inhibitory effects on CYP2B6 activity in a concentration-dependent manner. Furthermore, the inhibition was potentiated following preincubation with NADPH, indicating that G. cambogia extract is a time-dependent inhibitor of CYP2B6. Meanwhile, hydroxycitric acid, the major bioactive ingredient of G. cambogia extract, did not exhibit significant inhibition effects on cytochrome P450 enzyme activities. G. cambogia extract could modulate the pharmacokinetics of CYP2B6 substrate drugs and lead to interactions with those drugs. Therefore, caution may be required with respect to concomitant intake of dietary supplements containing G. cambogia extract with CYP2B6 substrates.


Assuntos
Inibidores do Citocromo P-450 CYP2B6/isolamento & purificação , Garcinia cambogia/química , Microssomos Hepáticos/efeitos dos fármacos , Extratos Vegetais/farmacologia , Citocromo P-450 CYP2B6/metabolismo , Inibidores do Citocromo P-450 CYP2B6/farmacologia , Humanos , Técnicas In Vitro , Microssomos Hepáticos/enzimologia , Plantas Medicinais/química
15.
Artigo em Inglês | MEDLINE | ID: mdl-27702395

RESUMO

Species of genus Garcinia are rich sources of bioactive constituents with antimicrobial, anticancer, anti-inflammatory, hepatoprotective and anti-HIV activities. Commercial products of Garcinia cambogia are used as anti-obesity drugs with increasing market demand. Because of the high price of its products, it can be adulterated with similar lower-priced species. This study was designed to develop and validate an accurate and efficient method for the detection of any adulteration (G. indica) in G. cambogia products. For this purpose, high performance liquid chromatography (HPLC) was used to analyse the ethanolic fruit rind extracts of G. cambogia and G. indica, their formulations of 0.5, 1, 2, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90 and 95% G. indica with G. cambogia, and 11 G. cambogia commercial products. The analytical methods were validated by quality assurance parameters of linearity, sensitivity, precision and accuracy. Two marker peaks were detected in G. indica fruit extract, whereas G. cambogia did not show these peaks. The detected peaks were identified as anthocyanins; cyanidin-3-O-sambubioside and cyanidin-3-O-glucoside. In the study to determine the effect of pH and temperature on the stability of its anthocyanin content, HPLC analysis of G. indica extract showed the highest content at pH 1 and 50°C. Using two different mobile phases, the limits of detection (LOD) for cyanidin-3-O-sambubioside and cyanidin-3-O-glucoside were 0.036 and 0.059, and 0.022 and 0.033 mg kg-1, respectively. Furthermore, the inter-day precision (< 3.2%) confirmed that the applied analytical method fulfils the required criteria of Association of Official Analytical Chemists (AOAC). From this study, it was found that the HPLC method used for the detection of adulteration in G. cambogia products is rapid and accurate.


Assuntos
Fármacos Antiobesidade/análise , Contaminação de Alimentos/análise , Garcinia cambogia/química , Cromatografia Líquida de Alta Pressão , Frutas/química , Espectrometria de Massas por Ionização por Electrospray
16.
Phytother Res ; 30(8): 1316-29, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27145492

RESUMO

(-)-Hydroxycitric acid (HCA), a major active ingredient of Garcinia Cambogia extracts, had shown to suppress body weight gain and fat accumulation in animals and humans. While, the underlying mechanism of (-)-HCA has not fully understood. Thus, this study was aimed to investigate the effects of long-term supplement with (-)-HCA on body weight gain and variances of amino acid content in rats. Results showed that (-)-HCA treatment reduced body weight gain and increased feed conversion ratio in rats. The content of hepatic glycogen, muscle glycogen, and serum T4 , T3 , insulin, and Leptin were increased in (-)-HCA treatment groups. Protein content in liver and muscle were significantly increased in (-)-HCA treatment groups. Amino acid profile analysis indicated that most of amino acid contents in serum and liver, especially aromatic amino acid and branched amino acid, were higher in (-)-HCA treatment groups. However, most of the amino acid contents in muscle, especially aromatic amino acid and branched amino acid, were reduced in (-)-HCA treatment groups. These results indicated that (-)-HCA treatment could reduce body weight gain through promoting energy expenditure via regulation of thyroid hormone levels. In addition, (-)-HCA treatment could promote protein synthesis by altering the metabolic directions of amino acids. Copyright © 2016 John Wiley & Sons, Ltd.


Assuntos
Peso Corporal/efeitos dos fármacos , Citratos/química , Garcinia cambogia/química , Extratos Vegetais/farmacologia , Biossíntese de Proteínas/efeitos dos fármacos , Aminoácidos , Animais , Humanos , Masculino , Ratos
17.
Curr Obes Rep ; 5(2): 262-70, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27053066

RESUMO

Obesity and its associated cardiometabolic alterations currently are considered an epidemic; thus, their treatment is of major importance. The cornerstone for such treatment involves therapeutic lifestyle changes; however, the vast majority of cases fail and/or significant weight loss is maintained only in the short term because of lack of compliance. The popularity of dietary supplements for weight management has increased, and a wide variety of these products are available over the counter. However, the existing scientific evidence is insufficient to recommend their safe use. Hence, the purpose of this article is to review the clinical effects, proposed mechanism of action, and safety profile of some of the new dietary supplements, including white bean extract, Garcinia cambogia, bitter orange, Hoodia gordonii, forskolin, green coffee, glucomannan, ß-glucans, chitosan, guar gum, and raspberry ketones.


Assuntos
Fármacos Antiobesidade/uso terapêutico , Depressores do Apetite/uso terapêutico , Terapias Complementares , Suplementos Nutricionais , Obesidade/dietoterapia , Redução de Peso/efeitos dos fármacos , Citrus/química , Garcinia cambogia/química , Humanos , Obesidade/prevenção & controle , Fitoterapia , Extratos Vegetais , Resultado do Tratamento
18.
Gene ; 575(2 Pt 2): 458-472, 2016 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-26407870

RESUMO

The O-methylation of various secondary metabolites is mainly catalyzed by S-adenosyl-l-methionine (SAM)-dependent O-methyltransferase (OMT) proteins that are encoded by the O-methyltransferase gene family. Citrus fruits are a rich source of O-methylated flavonoids that have a broad spectrum of biological activities, including anti-inflammatory, anticarcinogenic, and antiatherogenic properties. However, little is known about this gene family and its members that are involved in the O-methylation of flavonoids and their regulation in Citrus. In this study, 58 OMT genes were identified from the entire Citrus sinensis genome and compared with those from 3 other representative dicot plants. A comprehensive analysis was performed, including functional/substrate predictions, identification of chromosomal locations, phylogenetic relationships, gene structures, and conserved motifs. Distribution mapping revealed that the 58 OMT genes were unevenly distributed on the 9 citrus chromosomes. Phylogenetic analysis of 164 OMT proteins from C.sinensis, Arabidopsis thaliana, Populus trichocarpa, and Vitis vinifera showed that these proteins were categorized into group I (COMT subfamily) and group II (CCoAOMT subfamily), which were further divided into 10 and 2 subgroups, respectively. Finally, digital gene expression and quantitative real-time polymerase chain reaction analyses revealed that citrus OMT genes had distinct temporal and spatial expression patterns in different tissues and developmental stages. Interestingly, 18 and 11 of the 27 genes predicted to be involved in O-methylation of flavonoids had higher expression in the peel and pulp during fruit development, respectively. The citrus OMT gene family identified in this study might help in the selection of appropriate candidate genes and facilitate functional studies in Citrus.


Assuntos
Citrus sinensis/enzimologia , Flavonoides/biossíntese , Proteína O-Metiltransferase/classificação , Proteína O-Metiltransferase/genética , Citrus sinensis/química , Citrus sinensis/genética , Flavonoides/química , Garcinia cambogia/química , Regulação da Expressão Gênica no Desenvolvimento , Regulação Enzimológica da Expressão Gênica , Genoma de Planta , Metilação , Família Multigênica , Especificidade de Órgãos , Filogenia , Proteínas de Plantas/classificação , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Proteína O-Metiltransferase/metabolismo
20.
Fitoterapia ; 102: 134-48, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25732350

RESUMO

The fruit rind of Garcinia gummi-gutta, commonly known as Garcinia cambogia (syn.), is extensively used traditionally as a flavourant in fish curries due to its sharp sour taste. Additional ethnobotanical uses include its use as a digestive and a traditional remedy to treat bowel complaints, intestinal parasites and rheumatism. This small fruit, reminiscent of a pumpkin in appearance, is currently most popularly used and widely advertised as a weight-loss supplement. Studies have shown that the extracts as well as (-)-hydroxycitric acid (HCA), a main organic acid component of the fruit rind, exhibited anti-obesity activity including reduced food intake and body fat gain by regulating the serotonin levels related to satiety, increased fat oxidation and decreased de novo lipogenesis. HCA is a potent inhibitor of adenosine triphosphate-citrate lyase, a catalyst for the conversion process of citrate to acetyl-coenzyme A, which plays a key role in fatty acid, cholesterol and triglycerides syntheses. The crude extract or constituents from the plant also exerted hypolipidaemic, antidiabetic, anti-inflammatory, anticancer, anthelmintic, anticholinesterase and hepatoprotective activities in in vitro and in vivo models. Phytochemical studies of various plant parts revealed the presence of mainly xanthones (e.g. carbogiol) and benzophenones (e.g. garcinol) together with organic acids (e.g. HCA) and amino acids (e.g. gamma aminobutyric acid). Currently, a large number of G. cambogia/HCA dietary supplements for weight management are being sold although the possible toxicity associated with the regular use of these supplements has raised concerns. In most cases, complaints have been related to multicomponent formulations and at this stage G. cambogia has not been confirmed as the potentially toxic culprit. This review presents a scientific overview of G. cambogia with reference to relevant botanical aspects, ethnobotanical uses, phytochemistry and biological activity as well as toxicity.


Assuntos
Citratos/farmacologia , Garcinia cambogia/química , Extratos Vegetais/farmacologia , Animais , Fármacos Antiobesidade/farmacologia , Peso Corporal/efeitos dos fármacos , Suplementos Nutricionais , Etnobotânica , Feminino , Frutas/química , Masculino , Extratos Vegetais/química , Extratos Vegetais/toxicidade
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