The effects of Garcinia cambogia (hydroxycitric acid) on lipid profile: A systematic review and meta-analysis of randomized controlled trials.

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.

Garcinia gummi-gutta: Phytochemicals and pharmacological applications.

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.

Arousal-Inducing Effect of Garcinia cambogia Peel Extract in Pentobarbital-Induced Sleep Test and Electroencephalographic Analysis.

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.

Polyisoprenylated benzophenone derivatives from Garcinia cambogia and their anti-inflammatory activities.

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).

Garcinia cambogia suppresses adipogenesis in 3T3-L1 cells by inhibiting p90RSK and Stat3 activation during mitotic clonal expansion.

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.

Gambogic acid inhibits proliferation and induces apoptosis of human acute T­cell leukemia cells by inducing autophagy and downregulating ß­catenin signaling pathway: Mechanisms underlying the effect of Gambogic acid on T­ALL cells.

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.

Clinical-grade Garcinia cambogia extract dissolves calcium oxalate crystals in Drosophila kidney stone models.

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.

Therapeutic Effect of Garcinia cambogia Extract and Hydroxycitric Acid Inhibiting Hypoxia-Inducible Factor in a Murine Model of Age-Related Macular Degeneration.

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.

Short-term effects of Garcinia cambogia extract on the pharmacokinetics of lamotrigine given as a single-dose in Wistar rats.

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.

(-)-Hydroxycitric Acid Suppresses Lipid Droplet Accumulation and Accelerates Energy Metabolism via Activation of the Adiponectin-AMPK Signaling Pathway in Broiler Chickens.

(-)-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.

Possible Garcinia cambogia-Induced Mania With Psychosis: A Case Report.

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.

Determination of macro, micro, trace essential, and toxic elements in Garcinia cambogia fruit and its anti-obesity commercial products.

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.

Metabolomics reveals the mechanism of (-)-hydroxycitric acid promotion of protein synthesis and inhibition of fatty acid synthesis in broiler chickens.

(-)-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.

Binding of hydroxycitrate to human ATP-citrate lyase.

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.

Inhibitory Effects of Garcinia cambogia Extract on CYP2B6 Enzyme Activity.

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.

Identification and quantification of adulteration in Garcinia cambogia commercial products by chromatographic and spectrometric methods.

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.

(-)-Hydroxycitric Acid Nourishes Protein Synthesis via Altering Metabolic Directions of Amino Acids in Male Rats.

(-)-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.

New Dietary Supplements for Obesity: What We Currently Know.

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.

Systematic analysis of O-methyltransferase gene family and identification of potential members involved in the formation of O-methylated flavonoids in Citrus.

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.