Metabolic syndrome is defined as a set of coexisting metabolic disorders that increase an individual’s likelihood of developing type 2 diabetes, cardiovascular disease and stroke. Medicinal plants, some of which have been used for thousands of years, serve as an excellent source of bioactive compounds for the treatment of metabolic syndrome because they contain a wide range of phytochemicals with diverse metabolic effects. In order for botanicals to be effectively used against metabolic syndrome, however, botanical preparations must be characterized and standardized through the identification of their active compounds and respective modes of action, followed by validation in controlled clinical trials with clearly defined endpoints. This review assesses examples of commonly known and partially characterized botanicals to describe specific considerations for the phytochemical, preclinical and clinical characterization of botanicals associated with metabolic syndrome.
Botanical; cardiovascular disease; diabetes; hypertension; insulin resistance; phytochemical; obesity
The present study demonstrated that defatted soybean flour (DSF) can sorb polyphenols from blueberry and cranberry juices while separating them from sugars. Depending on DSF concentration and juice dilution, the concentration of blueberry anthocyanins and total polyphenols sorbed to DSF ranged from 2 – 22 mg/g and 10 – 95 mg/g, respectively while the concentration of anthocyanins and proanthocyanidins in cranberry polyphenol-enriched DSF ranged from 2.5 – 17 mg/g and 21 – 101 mg/g, respectively. Blueberry polyphenols present in one serving of fresh blueberries (73g) were delivered in just 1.4 g of blueberry polyphenol-enriched DSF. Similarly, one gram of cranberry polyphenol-enriched DSF delivered the amount of proanthocyanidins available in three 240 ml servings of cranberry juice cocktail. The concentration of blueberry anthocyanins and total polyphenols eluted from DSF remained constant after 22 weeks of incubation at 37°C, demonstrating the high stability of the polyphenol-DSF matrix. LC-MS analysis of eluates confirmed DSF retained major cranberry and blueberry polyphenols remained intact. Blueberry polyphenol-enriched DSF exhibited significant hypoglycemic activities in C57bl/6J mice, and cranberry polyphenol-enriched DSF showed anti-microbial and anti-UTI activities in vitro, confirming its efficacy. The described sorption process provides a means to create protein-rich food ingredients containing concentrated plant bioactives without excess sugars, fats and water that can be incorporated in a variety of scientifically validated functional foods and dietary supplements.
polyphenols; anthocyanins; proanthocyanidins; soybean flour; nutrition; diabetes; antibacterial
Two different strategies for investigating the likely fate, after ingestion, of natural, bioactive berry constituents (anthocyanins and other non-nutritive flavonoids) are compared. A model of the human gastrointestinal tract (TIM-1) which mimicked the biological environment from the point of swallowing and ingestion through the duodenum, jejunum, and ileum (but not the colon) was used to monitor the stability and bioaccessibility of anthocyanins from both maqui berry and wild blueberry. TIM-1 revealed that most anthocyanins were bioaccessible between the second and third hour after intake. Alternatively, biolabeled anthocyanins and other flavonoids generated in vitro from berry and grape cell cultures were administered to in vivo (rodent) models, allowing measurement and tracking of the absorption and transport of berry constituents and clearance through the urinary tract and colon. The advantages and limitations of the alternative strategies are considered.
bioavailability; bioaccessibility; radiolabeling; artificial gastrointestinal tract
Plant extracts continue to represent an untapped source of renewable therapeutic compounds for the treatment and prevention of illnesses including chronic metabolic disorders. With the increase in worldwide obesity and its related morbidities, the need for identifying safe and effective treatments is also rising. As such, use of primary human adipose-derived stem cells represents a physiologically relevant cell system to screen for bioactive agents in the prevention and treatment of obesity and its related complications. By using these cells in a primary screen, the risk and cost of identifying artifacts due to interspecies variation and immortalized cell lines is eliminated. We demonstrate that these cells can be formatted into 384-well high throughput screens to rapidly identify botanical extracts that affect lipogenesis and lipolysis. Additionally, counterscreening with human primary stem cells from distinct adipose depots can be routinely performed to identify tissue specific responses. In our study, over 500 botanical extracts were screened and 16 (2.7%) were found to affect lipogenesis and 4 (0.7%) affected lipolysis.
Adipogenesis; Adipose-derived Stem Cells; Botanical Extracts; Lipogenesis; Lipolysis; Subcutaneous; Visceral
Ethanolic extracts of diploid Artemisia dracunculus L. (wild tarragon) from populations in the U.S., and polyploid tarragon from a variety of sources, were screened for the anti-diabetic compounds davidigenin; sakuranetin; 2′,4′-dihydroxy-4-methoxydihydrochalcone; 4,5-di-O-caffeoylquinic acid; 5-O-caffeoylquinic acid and 6-demethoxycapillarisin using LC-MS. Only decaploid plants contained all six target compounds and were the only plants that contained davidigenin and 2,4-dihydroxy-4-methoxydihydrochalcone. These results exhibit the importance of germplasm selection and provenance when studying plants for medicinal activity. Relying only on the “right species” for consistent medicinal activities may not be sufficient, as intraspecific variation may be highly significant.
Artemisia dracunculus; wild tarragon; polyploidy; germplasm; diabetes; sakuranetin
Defatted soybean flour (DSF) can efficiently sorb, concentrate, and stabilize polyphenols, but not sugars, from Concord grape juice, to yield grape polyphenol-enriched DSF. Sorption of grape polyphenols to DSF particles was dependent on the ratio of DSF and grape juice concentrate used, but not time of mixing or pH. Depending on ratios of starting materials, 1 g of grape polyphenol-enriched DSF contained 1.6–10.4 mg of anthocyanins, 7.5–93.1 mg of proanthocyanidins, and 20.5–144.5 mg of total polyphenols. LC-MS analysis of grape juice samples before and after addition and removal of DSF and eluate from grape polyphenol-enriched DSF confirmed that a broad range of grape compounds were sorbed to the DSF matrix. Finally, grape polyphenol-enriched DSF was able to significantly lower blood glucose levels in hyperglycemic C57BL/6J mice. The data indicate that grape polyphenol-enriched DSF can provide a high-protein, low-sugar ingredient for delivery of concentrated grape polyphenolics.
Concord grape juice; defatted soy flour; anthocyanins; proanthocyanidins; polyphenols; hypoglycemic; diabetes
Brassinosteroids are plant-derived polyhydroxylated derivatives of 5α-cholestane, structurally similar to cholesterol-derived animal steroid hormones and insect ecdysteroids. In this study, we synthesized a set of brassinosteroid analogues of a natural brassinosteroid (22S,23S)-homobrassinolide (HB, 1) including (22S,23S)-homocastasterone (2), (22S,23S)-3α-fluoro-homobrasinolide (3), (22S,23S)-3α-fluoro-homocastasterone (4), (22S,23S)-7v-aza-homobrassinolide (5), (22S,23S)-6-aza-homobrassinolide (6), and studied their anabolic efficacy in the L6 rat skeletal muscle cells in comparison to other synthetic and naturally occurring brassinosteroids (22R,23R)-homobrassinolide (7), (22S,23S)-epibrassinolide (8), and (22R,23R)-epibrassinolide (9). Presence of the 6-keto group in the B ring and stereochemistry of 22α,23α-vicinal hydroxyl groups in the side chain were critical for the anabolic activity, possibly due to higher cytotoxicity of the 22β, 23β-hydroxylated brassinosteroids. All anabolic brassinosteroids tested in this study selectively activated PI3K/Akt signaling pathway as evident by increased Akt phosphorylation in vitro. Plant brassinosteroids and their synthetic derivatives may offer a novel therapeutic strategy for promoting growth, repair, and maintenance of skeletal muscles.
brassinosteroid; protein synthesis; protein degradation; anabolic steroids; muscle mass; muscle loss
Aim of the study
The objective of this study was to isolate and characterize the active constituents of the traditionally used antimalarial plant Liriodendron tulipifera by antiplasmodial-assay guided fractionation.
Materials and methods
Bark and leaves were extracted with solvents of increasing polarity. Fractions were generated using flash chromatography, counter current chromatography and preparative HPLC and subjected to in vitro antiplasmodial and cytotoxicity assays. Active fractions were subjected to further fractionation until pure compounds were isolated, for which the IC50 values were calculated.
Results and discussion
Six known aporphine alkaloids, asimilobine (1), norushinsunine (2), norglaucine (3), liriodenine (4), anonaine (5) and oxoglaucine (6) were found to be responsible for the antiplasmodial activity of the bark. Leaves yielded two known sesquiterpene lactones, peroxyferolide (7) and lipiferolide (8) with antiplasmodial activity. The antiplasmodial activity of (2) (IC50 = 29.6 μg/ml), (3) (IC50 = 22.0 μg/ml), (6) (IC50= 9.1 μg/mL), (7) (IC50 = 6.2 μg/ml) and (8) (IC50 = 1.8 μg/ml) are reported for the first time.
This work supports the historical use of Liriodendron tulipifera as an antimalarial remedy of the United States and characterizes its antiplasmodial constituents.
Antimalarial; Aporphine alkaloids; Sesquiterpene lactones; Liriodendron tulipifera L.; Magnoliaceae; Cytotoxicity
To investigate the mechanisms underlying the satiety-promoting effects of a novel protease inhibitors concentrate derived from potato (PPIC).
Acute and prolonged effects of oral PPIC administration (100 mg/kg per day) on food intake, body weight, and gastric emptying were evaluated in healthy rats. Parameters of body weight, food intake, plasma glucose, insulin, and cholecystokinin (CCK) were measured. Duodenal proteolytic activity and CCK expression were determined in tissue extracts. Intestinal STC-1 cell culture model was used to investigate the direct effect of PPIC on CCK transcript level and secretion.
Acute oral administration of PPIC reduced immediate food intake during the first two hours following the treatment, delayed gastric emptying, and decreased proteolytic activity in the duodenum. Repeated oral ingestion of PPIC reduced weight gain in male rats and significantly elevated the plasma CCK levels. Although duodenal mucosal CCK mRNA levels increased in response to PPIC administration, the concentrate failed to elevate CCK expression or release in STC-1 cells. The 14-day ascending dose range study (33 to 266 mg/kg PPIC per day) showed no adverse side effects associated with PPIC administration.
These findings provided evidence that PPIC is effective in reducing food intake and body weight gain in healthy rats when administered orally by increasing circulating CCK levels through a trypsin-dependent mechanism.
satiety; body weight; cholecystokinin; protease inhibitors; potato
An ethanolic extract of Artemisia dracunculus L. (PMI-5011) was shown to be hypoglycemic in animal models for Type 2 diabetes and contain at least 6 bioactive compounds responsible for its anti-diabetic properties. To evaluate the bioavailability of the active compounds, high fat dietary induced obese C57BL/6J male mice were gavaged with PMI-5011 at 500 mg/kg body weight, after 4 h of food restriction. Blood plasma samples (200 uL) were obtained after ingestion, and the concentrations of the active compound in the blood sera were measured by electrospray LC-MS and determined to be maximal 4–6 h after gavage. Formulations of the extract with bioenhancers/solubilizers were evaluated in vivo for hypoglycemic activity and their effect on the abundance of active compounds in blood sera. At doses of 50–500 mg/kg/day, the hypoglycemic activity of the extract was enhanced 3–5 fold with the bioenhancer Labrasol, making it comparable to the activity of the anti-diabetic drug metformin. When combined with Labrasol, one of the active compounds, 2′, 4′-dihydroxy-4-methoxydihydrochalcone, was at least as effective as metformin at doses of 200–300 mg/kg/day. Therefore, bioenhancing agents like Labrasol can be used with multi-component botanical therapeutics such as PMI-5011 to increase their efficacy and/or to reduce the effective dose.
Wild berries are integral dietary components for Alaska Native tribes and a rich source of polyphenolic metabolites that can ameliorate metabolic disorders such as obesity and diabetes. In this study, five species of wild Alaskan berries (Vaccinium ovalifolium, V. uliginosum, Rubus chamaemorus, R. spectabilis, and Empetrum nigrum) were screened for bioactivity through a community-participatory research method involving three geographically-distinct tribal communities. Compositional analysis by HPLC and LC-MS2 revealed substantial site-specific variation in anthocyanins (0.01-4.39 mg/g-FW) and proanthocyanidins (0.74-6.25 mg/g-FW), and identified A-type proanthocyanidin polymers. R. spectabilis increased expression levels of preadipocyte-factor-1 (182%), and proanthocyanidin-enriched fractions from other species reduced lipid accumulation in 3T3-L1 adipocytes. Selected extracts reduced serum glucose levels in C57bl/6j mice by up to 45%. Local observations provided robust insights into effects of climatic fluctuations on berry abundance and quality, and preliminary site-specific compositional and bioactivity differences were noted, suggesting the need to monitor this Alaska Native resource as climate shifts impact the region.
Anthocyanins; proanthocyanidins; Vaccinium ovalifolium; Vaccinium uliginosum; Rubus spectabilis; Rubus chamaemorus; Empetrum nigrum; Traditional Ecological Knowledge; pref-1; adipocytes; diabetes; obesity; metabolic syndrome
Traditional Chinese Medicines (TCM) are rapidly gaining attention in the West as sources of new drugs, dietary supplements and functional foods. However, lack of consistent manufacturing practices and quality standards, fear of adulteration, and perceived deficiencies in scientific validation of efficacy and safety impede worldwide acceptance of TCM. In addition, Western pharmaceutical industries and regulatory agencies are partial toward single ingredient drugs based on synthetic molecules, and skeptical of natural product mixtures. This review concentrates on three examples of TCM-derived pharmaceuticals and functional foods that have, despite these usual obstacles, risen to wide acceptance in the West based on their remarkable performance in recent scientific investigations. They are: Sweet wormwood (Artemisia annua), the source of artemisinin, which is the currently preferred single compound anti-malarial drug widely used in combination therapies and recently approved by US FDA; Thunder god vine (Tripterygium wilfordii) which is being developed as a botanical drug for rheumatoid arthritis; and green tea (Camellia sinensis) which is used as a functional beverage and a component of dietary supplements.
Artemisia annua; artemisinin; Camellia sinensis; (−)-epigallocatechin-3-gallate (EGCG); functional foods; nutraceuticals; traditional Chinese medicine (TCM); tripdiolide; Tripterygium wilfordii; triptolide
Plants have been used as a source of medicine throughout history and continue to serve as the basis for many pharmaceuticals used today. Although the modern pharmaceutical industry was born from botanical medicine, synthetic approaches to drug discovery have become standard. However, this modern approach has led to a decline in new drug development in recent years and a growing market for botanical therapeutics that are currently available as dietary supplements, drugs, or botanical drugs. Most botanical therapeutics are derived from medicinal plants that have been cultivated for increased yields of bioactive components. The phytochemical composition of many plants has changed over time, with domestication of agricultural crops resulting in the enhanced content of some bioactive compounds and diminished content of others. Plants continue to serve as a valuable source of therapeutic compounds because of their vast biosynthetic capacity. A primary advantage of botanicals is their complex composition consisting of collections of related compounds having multiple activities that interact for a greater total activity.
An alcoholic extract of Artemisia dracunculus L (PMI 5011) has been shown to decrease glucose and improve insulin levels in animal models, suggesting an ability to enhance insulin sensitivity. We sought to assess the cellular mechanism by which this botanical affects carbohydrate metabolism in primary human skeletal muscle culture. We measured basal and insulin-stimulated glucose uptake, glycogen accumulation, phosphoinositide 3 (PI-3) kinase activity, and Akt phosphorylation in primary skeletal muscle culture from subjects with type 2 diabetes mellitus incubated with or without various concentrations of PMI 5011. We also analyzed the abundance of insulin receptor signaling proteins, for example, IRS-1, IRS-2, and PI-3 kinase. Glucose uptake was significantly increased in the presence of increasing concentrations of PMI 5011. In addition, glycogen accumulation, observed to be decreased with increasing free fatty acid levels, was partially restored with PMI 5011. PMI 5011 treatment did not appear to significantly affect protein abundance for IRS-1, IRS-2, PI-3 kinase, Akt, insulin receptor, or Glut-4. However, PMI 5011 significantly decreased levels of a specific protein tyrosine phosphatase, that is, PTP1B. Time course studies confirmed that protein abundance of PTP1B decreases in the presence of PMI 5011. The cellular mechanism of action to explain the effects by which an alcoholic extract of A dracunculus L improves carbohydrate metabolism on a clinical level may be secondary to enhancing insulin receptor signaling and modulating levels of a specific protein tyrosine phosphatase, that is, PTP1B.
Blueberry fruits are known as a rich source of anthocyanin components. In this study we demonstrate that anthocyanins from blueberry have the potency to alleviate symptoms of hyperglycemia in diabetic C57b1/6J mice. The anti-diabetic activity of different anthocyanin-related extracts was evaluated using the pharmaceutically acceptable self-microemulsifying drug delivery system; Labrasol. Treatment by gavage (500 mg/kg body wt) with a phenolic-rich extract and an anthocyanin-enriched fraction formulated with Labrasol lowered elevated blood glucose levels by 33 and 51%, respectively. The hypoglycemic activities of these formulae were comparable to that of the known anti-diabetic drug metformin (Baily and Day, 2004; 27% at 300 mg/kg). The extracts were not significantly hypoglycemic when administered without Labrasol, demonstrating its bio-enhancing effect, most likely due to increasing the bioavailability of the administered preparations. The phenolic-rich extract contained 287.0 ± 9.7 mg/g anthocyanins, while the anthocyanin-enriched fraction contained 595 ± 20.0 mg/g (cyanidin-3-glucoside equivalents), as measured by HPLC and pH differential analysis methods. The greater hypoglycemic activity of the anthocyanin-enriched fraction compared to the initial phenolic-rich extract suggested that the activity was due to the anthocyanin components. Treatment by gavage (300 mg/kg) with the pure anthocyanins, delphinidin-3-O-glucoside and malvidin-3-O- glucoside, formulated with Labrasol, showed that malvidin-3-O- glucoside was significantly hypoglycemic while delphinidin-3-O-glucoside was not.
Blueberry; Vaccinium angustifolium; Anthocyanins; Malvidin; Diabetes; Hyperglycemia; Hypoglycemia; Labrasol
Phenethylisothiocyanate (PEITC) is produced by Brassica food plants. PEO is a PEITC Essential Oil containing >95% natural PEITC. PEITC is known to produce various health benefits but its effect in alleviation of ulcerative colitis signs is unknown.
In two efficacy studies (acute and chronic) oral administration of PEO was effective at remitting acute and chronic signs of ulcerative colitis (UC) in mice. Disease activity, histology and biochemical characteristics were measured in the treated animals and were compared with appropriate controls. PEO treatment significantly improved body weights and stool consistency as well as decreased intestinal bleeding. PEO treatment also reduced mucosal inflammation, depletion of goblet cells and infiltration of inflammatory cells. Attenuation of proinflammatory interleukin1β production was observed in the colons of PEO-treated animals. Expression analyses were also carried out for immune function related genes, transcription factors and cytokines in lipopolysaccharide-activated mouse macrophage cells. PEO likely affects an intricate network of immune signaling genes including a novel concentration dependent reduction of total cellular Signal Transducer and Activator of Transcription 1 (STAT1) as well as nuclear phosphorylated-STAT1 (activated form of STAT1). A PEO-concentration dependent decrease of mRNA of C-X-C motif ligand 10 (a STAT1 responsive chemokine) and Interleukin 6 were also observed.
PEO might be a promising candidate to develop as a treatment for ulcerative colitis patients. The disease attenuation by PEO is likely associated with suppression of activation of STAT1 transcription and inhibition of pro-inflammatory cytokines.
Triptolide is a diterpene triepoxide from the Chinese medicinal plant Tripterygium wilfordii Hook F., with known anti-inflammatory, immunosuppressive and anti-cancer properties.
Here we report the expression profile of immune signaling genes modulated by triptolide in LPS induced mouse macrophages. In an array study triptolide treatment modulated expression of 22.5% of one hundred and ninety five immune signaling genes that included Toll-like receptors (TLRs). TLRs elicit immune responses through their coupling with intracellular adaptor molecules, MyD88 and TRIF. Although it is known that triptolide inhibits NFκB activation and other signaling pathways downstream of TLRs, involvement of TLR cascade in triptolide activity was not reported. In this study, we show that triptolide suppresses expression of proinflammatory downstream effectors induced specifically by different TLR agonists. Also, the suppressive effect of triptolide on TLR-induced NFκB activation was observed when either MyD88 or TRIF was knocked out, confirming that both MyD88 and TRIF mediated NFκB activation may be inhibited by triptolide. Within the TLR cascade triptolide downregulates TLR4 and TRIF proteins.
This study reveals involvement of TLR signaling in triptolide activity and further increases understanding of how triptolide activity may downregulate NFκB activation during inflammatory conditions.
Artemisia species are a rich source of herbal remedies with antioxidant and anti-inflammatory properties. We evaluated PMI-5011, an ethanolic extract of Artemisia dracunculus L., on neuropathy in high-sfat diet-fed mice, a model of prediabetes and obesity developing oxidative stress and proinflammatory changes in peripheral nervous system. C57Bl6/J mice fed high-fat diet for 16 weeks developed obesity, moderate nonfasting hyperglycemia, nerve conduction deficit, thermal and mechanical hypoalgesia, and tactile allodynia. They displayed 12/15-lipoxygenase overexpression, 12(S)-hydroxyeicosatetraenoic acid accumulation, and nitrosative stress in peripheral nerve and spinal cord. PMI-5011 (500 mgkg−1d−1, 7 weeks) normalized glycemia, alleviated nerve conduction slowing and sensory neuropathy, and reduced 12/15-lipoxygenase upregulation and nitrated protein expression in peripheral nervous system. PMI-5011, a safe and nontoxic botanical extract, may find use in treatment of neuropathic changes at the earliest stage of disease.
Four wild berry species, Amelanchier alnifolia, Viburnum trilobum, Prunus virginiana, and Shepherdia argentea, all integral to the traditional subsistence diet of Native American tribal communities, were evaluated to elucidate phytochemical composition and bioactive properties related to performance and human health. Biological activity was screened using a range of bioassays that assessed the potential for these little-known dietary berries to affect diabetic microvascular complications, hyperglycemia, pro-inflammatory gene expression, and metabolic syndrome symptoms. Non-polar constituents from berries, including carotenoids, were potent inhibitors of aldose reductase (an enzyme involved in the etiology of diabetic microvascular complications) whereas the polar constituents, mainly phenolic acids, anthocyanins, and proanthocyanidins, were hypoglycemic agents and strong inhibitors of IL-1β and COX-2 gene expression. Berry samples also showed the ability to modulate lipid metabolism and energy expenditure in a manner consistent with improving metabolic syndrome. The results demonstrate that these berries traditionally consumed by tribal cultures contain a rich array of phytochemicals that have the capacity to promote health and protect against chronic diseases, such as diabetes.
Amelanchier alnifolia; Viburnum trilobum; Prunus virginiana; Shepherdia argentea; diabetes; inflammation; energy expenditure
The ethyl acetate extract of the aerial parts of Ajuga turkestanica afforded 6 neo-clerodane diterpenes, including two novel compounds, 14, 15-dihydroajugachin B (1) and 14-hydro-15-methoxyajugachin B (2), in addition to the known diterpenoids chamaepitin (3), ajugachin B (4), ajugapitin (5) and lupulin A (6). Structures were established through exhaustive NMR spectroscopic analysis and chemical transformation in the case of 1. The full 1H and 13C NMR assignment of the C-15 R and S configurations of 14-hydro-15-methoxyajugachin B and chamaepitin were elucidated.
Ajuga turkestanica; Labiatae; neo-clerodane diterpenes; 14, 15-dihydroajugachin B; 14-hydro-15-methoxyajugachin B
There are many similarities between research on combinatorial chemistry and natural products and research on dietary supplements and botanicals in the NIH Botanical Research Centers. The technologies in the centers are similar to those used by other NIH-sponsored investigators. All centers rigorously examine the authenticity of botanical dietary supplements and determine the composition and concentrations of the phytochemicals therein, most often by liquid chromatography–mass spectrometry. Several of the centers specialize in fractionation and high-throughput evaluation to identify the individual bioactive agent or a combination of agents. Some centers are using DNA microarray analyses to determine the effects of botanicals on gene transcription with the goal of uncovering the important biochemical pathways they regulate. Other centers focus on bioavailability and uptake, distribution, metabolism, and excretion of the phytochemicals as for all xenobiotics. Because phytochemicals are often complex molecules, synthesis of isotopically labeled forms is carried out by plant cells in culture, followed by careful fractionation. These labeled phytochemicals allow the use of accelerator mass spectrometry to trace the tissue distribution of 14C-labeled proanthocyanidins in animal models of disease. State-of-the-art proteomics and mass spectrometry are also used to identify proteins in selected tissues whose expression and posttranslational modification are influenced by botanicals and dietary supplements. In summary, the skills needed to carry out botanical centers’ research are extensive and may exceed those practiced by most NIH investigators.
activity-guided fractionation; bioavailability; isotopic labeling of phytochemicals in plant cell culture; DNA microarray analysis; 2D-gel electrophoresis; peptide mass fingerprinting; tandem mass spectrometry
Quercetin, a polyphenolic compound and a major bioflavonoid in the human diet, has anti-inflammatory properties and has been postulated to enhance energy expenditure (EE). We sought to determine whether quercetin alters body weight, body composition, EE, and circulating markers of inflammation. At 6 weeks (W) of age, 2 cohorts of C57BL/6J mice (N = 80) were placed on one of 2 diets for 3W or 8W: (1) high fat (HF) (45% kcal fat) or (2) high fat + quercetin (HF + Q) (45% kcal fat + 0.8% quercetin). Quercetin concentrations in the diet and plasma were evaluated using mass spectrometry. Body weight, composition (nuclear magnetic resonance), and food consumption were measured weekly. Energy expenditure was measured by indirect calorimetry at 3 and 8W, and inflammatory markers were measured in plasma obtained at 8W. The presence of quercetin in the HF diet did not alter food consumption over time in the HF + Q group and did not differ from the HF group at any time point. However, circulating plasma quercetin concentrations declined between 3 and 8W. At 3W, EE was higher during both day and night phases (P < .0001) in the HF + Q group compared with the HF group; but this difference was not detected at 8W and did not translate into significant differences between the HF + Q and HF groups with respect to body weight or body composition. During the night phase, concentrations of the inflammatory markers (interferon-γ, interleukin-1α, and interleukin-4) were significantly lower when compared with HF treatment group (P < .05). Dietary supplementation with quercetin produces transient (3W) increases in EE that are not detected after 8W on the diet. A corresponding decrease in circulating quercetin between 3 and 8W suggests that metabolic adaptation may have diminished the impact of quercetin's early effect on EE and diminished its overall effect on nutrient partitioning and adiposity. However, quercetin at the levels provided was effective in reducing circulating markers of inflammation observed in animals on an HF diet at 8W.