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  • 1
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    Phytochemical characterization of Tabernanthe iboga root bark and its effects on dysfunctional metabolism and cognitive performance in high-fat-fed C57BL/6J mice
    International Society for Nutraceuticals & Functional Foods (ISNFF) ; 2018
    In:  Journal of Food Bioactives Vol. 3 ( 2018-09-30), p. 111-123
    Details
    In: Journal of Food Bioactives, International Society for Nutraceuticals & Functional Foods (ISNFF), Vol. 3 ( 2018-09-30), p. 111-123
    Abstract: Preparations of the root bark of Tabernanthe iboga have long been used in Central and West African traditional medicine to combat fatigue, as a neuro-stimulant in rituals, and for treatment of diabetes. The principal alkaloid of T. iboga, ibogaine, has attracted attention in many countries around the world for providing relief for opioid craving in drug addicts. Using a plant metabolomics approach, we detected five phenolic compounds, including 3-O-caffeoylquinic acid, and 30 alkaloids, seven of which were previously reported from T. iboga root bark. Following a report that iboga extracts contain insulinotropic agents, we aimed to determine the potential alleviating effects of the water extract of iboga root bark on high-fat diet (HFD)-induced hyperglycemia as well as its effects on cognitive function in male C57BL/6J mice. Feeding a HFD to mice for 10 weeks produced manifestations of metabolic syndrome such as increased body weight and increased plasma levels of glucose, triacylglycerols, total cholesterol, LDL-cholesterol, insulin, leptin, and pro-inflammatory mediators (IL-6, MCP-1, ICAM-1), as compared to mice fed a low-fat diet (LFD). Supplementation of HFD with iboga extract at ibogaine doses of 0.83 (low) and 2.07 (high) mg/kg/day did not improve these HFD-induced metabolic effects except for a reduction of plasma MCP-1 in the low dose group, indicative of an anti-inflammatory effect. When the HFD mice were tested in the water maze, the high-dose iboga extract caused hippocampus-dependent impairments in spatial learning and memory, as compared to mice receiving only a HFD.
    Type of Medium: Online Resource
    ISSN: 2637-8779 , 2637-8752
    URL: Article
    DOI: 10.31665/JFB.2018.3154
    Language: Unknown
    Publisher: International Society for Nutraceuticals & Functional Foods (ISNFF)
    Publication Date: 2018
    detail.hit.zdb_id: 3005768-1
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  • 2
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    DataSheet1.docx
    Frontiers Media SA ; 2024
    In:  Frontiers in Aging Vol. 5 ( 2024-5-6)
    Details
    In: Frontiers in Aging, Frontiers Media SA, Vol. 5 ( 2024-5-6)
    Abstract: Background: A water extract (CAW) of the Ayurvedic plant Centella asiatica administered in drinking water has been shown to improve cognitive deficits in mouse models of aging and neurodegenerative diseases. Here the effects of CAW administered in drinking water or the diet on cognition, measures of anxiety and depression-like behavior in healthy aged mice are compared. Methods: Three- and eighteen-month-old male and female C57BL6 mice were administered rodent AIN-93M diet containing CAW (0, 0.2, 0.5 or 1% w/w) to provide 0, 200 mg/kg/d, 500 mg/kg/d or 1,000 mg/kg/d CAW for a total of 5 weeks. An additional group of eighteen-month-old mice were treated with CAW (10 mg/mL) in their drinking water CAW for a total of 5 weeks to deliver the same exposure of CAW as the highest dietary dose (1,000 mg/kg/d). CAW doses delivered were calculated based on food and water consumption measured in previous experiments. In the fourth and fifth weeks, mice underwent behavioral testing of cognition, anxiety and depression (n = 12 of each sex per treatment group in each test). Results: Aged mice of both sexes showed cognitive deficits relative to young mice while only female aged mice showed increased anxiety compared to the young female mice and no differences in depression were observed between the different ages. CAW (1,000 mg/kg/d) in the drinking water improved deficits in aged mice in learning, executive function and recognition memory in both sexes and attenuated the increased measures of anxiety observed in the aged female mice. However, CAW in the diet only improved executive function in aged mice at the highest dose (1,000 mg/kg/d) in both sexes and did so less robustly than when given in the water. There were no effects of CAW on depression-like behavior in aged animals regardless of whether it was administered in the diet or the water. Conclusions: These results suggest that CAW can ameliorate age-related changes in measures of anxiety and cognition and that the mode of administration is important for the effects of CAW on resilience to these age-related changes.
    Type of Medium: Online Resource
    ISSN: 2673-6217
    URL: Article
    URL: Article
    DOI: 10.3389/fragi.2024.1357922
    DOI: 10.3389/fragi.2024.1357922.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2024
    detail.hit.zdb_id: 3076785-4
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  • 3
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    Table1.xlsx
    Frontiers Media SA ; 2022
    In:  Frontiers in Pharmacology Vol. 13 ( 2022-10-3)
    Details
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 13 ( 2022-10-3)
    Abstract: Consumption of a high fat diet (HFD) is linked to metabolic syndrome and cognitive impairments. This is exacerbated in age-related cognitive decline (ACD) and in individuals with a genetic risk for Alzheimer’s disease (AD). Apolipoprotein E (apoE) is involved in cholesterol metabolism. In humans, there are three major isoforms, E2, E3, and E4. Compared to E3, E4 increases ACD and AD risk and vulnerability to the deleterious cognitive effects of a HFD. The plant compound Xanthohumol (XN) had beneficial effects on cognition and metabolism in C57BL/6J wild-type (WT) male mice put on a HFD at 9 weeks of age for 13 weeks. As the effects of XN in the context of a HFD in older WT, E3, and E4 female and male mice are not known, in the current study male and female WT, E3, and E4 mice were fed a HFD alone or a HFD containing 0.07% XN for 10 or 19 weeks, starting at 6 months of age, prior to the beginning of behavioral and cognitive testing. XN showed sex- and ApoE isoform-dependent effects on cognitive performance. XN-treated E4 and WT, but not E3, mice had higher glucose transporter protein levels in the hippocampus and cortex than HFD-treated mice. E3 and E4 mice had higher glucose transporter protein levels in the hippocampus and lower glucose transporter protein levels in the cortex than WT mice. In the standard experiment, regardless of XN treatment, E4 mice had nearly double as high ceramide and sphingomyelin levels than E3 mice and male mice had higher level of glycosylated ceramide than female mice. When the differential effects of HFD in E3 and E4 males were assessed, the arginine and proline metabolism pathway was affected. In the extended exposure experiment, in E3 males XN treatment affected the arginine and proline metabolism and the glycine, serine, and threonine metabolism. Myristic acid levels were decreased in XN-treated E3 males but not E3 females. These data support the therapeutic potential for XN to ameliorate HFD-induced cognitive impairments and highlight the importance of considering sex and ApoE isoform in determining who might most benefit from this dietary supplement.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fphar.2022.954980
    DOI: 10.3389/fphar.2022.954980.s001
    DOI: 10.3389/fphar.2022.954980.s002
    DOI: 10.3389/fphar.2022.954980.s003
    DOI: 10.3389/fphar.2022.954980.s004
    DOI: 10.3389/fphar.2022.954980.s005
    DOI: 10.3389/fphar.2022.954980.s006
    DOI: 10.3389/fphar.2022.954980.s007
    DOI: 10.3389/fphar.2022.954980.s008
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2587355-6
    SSG: 15,3
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  • 4
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    datasheet1.docx
    Frontiers Media SA ; 2021
    In:  Frontiers in Pharmacology Vol. 12 ( 2021-4-20)
    Details
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 12 ( 2021-4-20)
    Abstract: The farnesoid X receptor (FXR) plays a critical role in the regulation of lipid and bile acid (BA) homeostasis. Hepatic FXR loss results in lipid and BA accumulation, and progression from hepatic steatosis to nonalcoholic steatohepatitis (NASH). This study aimed to evaluate the effects of xanthohumol (XN), a hop-derived compound mitigating metabolic syndrome, on liver damage induced by diet and FXR deficiency in mice. Wild-type (WT) and liver-specific FXR-null mice (FXR Liver−/− ) were fed a high-fat diet (HFD) containing XN or the vehicle formation followed by histological characterization, lipid, BA and gene profiling. HFD supplemented with XN resulted in amelioration of hepatic steatosis and decreased BA concentrations in FXR Liver−/− mice, the effect being stronger in male mice. XN induced the constitutive androstane receptor (CAR), pregnane X receptor (PXR) and glucocorticoid receptor (GR) gene expression in the liver of FXR Liver−/− mice. These findings suggest that activation of BA detoxification pathways represents the predominant mechanism for controlling hydrophobic BA concentrations in FXR Liver−/− mice. Collectively, these data indicated sex-dependent relationship between FXR, lipids and BAs, and suggest that XN ameliorates HFD-induced liver dysfunction via FXR-dependent and independent signaling.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    URL: Article
    URL: Article
    DOI: 10.3389/fphar.2021.643857
    DOI: 10.3389/fphar.2021.643857.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2587355-6
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  • 5
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    Image1.JPEG
    Frontiers Media SA ; 2021
    In:  Frontiers in Pharmacology Vol. 12 ( 2021-12-16)
    Details
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 12 ( 2021-12-16)
    Abstract: Centella asiatica is an herb used in Ayurvedic and traditional Chinese medicine for its beneficial effects on brain health and cognition. Our group has previously shown that a water extract of Centella asiatica (CAW) elicits cognitive-enhancing effects in animal models of aging and Alzheimer’s disease, including a dose-related effect of CAW on memory in the 5xFAD mouse model of ß -amyloid accumulation. Here, we endeavor to elucidate the mechanisms underlying the effects of CAW in the brain by conducting a metabolomic analysis of cortical tissue from 5xFAD mice treated with increasing concentrations of CAW. Tissue was collected from 8-month-old male and female 5xFAD mice and their wild-type littermates treated with CAW (0, 200, 500, or 1,000 mg/kg/d) dissolved in their drinking water for 5 weeks. High-performance liquid chromatography coupled to high-resolution mass spectrometry analysis was performed and relative levels of 120 annotated metabolites were assessed in the treatment groups. Metabolomic analysis revealed sex differences in the effect of the 5xFAD genotype on metabolite levels compared to wild-type mice, and variations in the metabolomic response to CAW depending on sex, genotype, and CAW dose. In at least three of the four treated groups (5xFAD or wild-type, male or female), CAW (500 mg/kg/d) significantly altered metabolic pathways related to purine metabolism, nicotinate and nicotinamide metabolism, and glycerophospholipid metabolism. The results are in line with some of our previous findings regarding specific mechanisms of action of CAW (e.g., improving mitochondrial function, reducing oxidative stress, and increasing synaptic density). Furthermore, these findings provide new information about additional, potential mechanisms for the cognitive-enhancing effect of CAW, including upregulation of nicotinamide adenine dinucleotide in the brain and modulation of brain-derived neurotrophic factor. These metabolic pathways have been implicated in the pathophysiology of Alzheimer’s disease, highlighting the therapeutic potential of CAW in this neurodegenerative disease.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fphar.2021.788312
    DOI: 10.3389/fphar.2021.788312.s001
    DOI: 10.3389/fphar.2021.788312.s002
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2587355-6
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  • 6
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    Caffeoylquinic Acids in Centella asiatica Protect against Amyloid-β Toxicity
    IOS Press ; 2014
    In:  Journal of Alzheimer's Disease Vol. 40, No. 2 ( 2014-03-31), p. 359-373
    Details
    In: Journal of Alzheimer's Disease, IOS Press, Vol. 40, No. 2 ( 2014-03-31), p. 359-373
    Type of Medium: Online Resource
    ISSN: 1875-8908 , 1387-2877
    URL: Article
    DOI: 10.3233/JAD-131913
    Language: Unknown
    Publisher: IOS Press
    Publication Date: 2014
    detail.hit.zdb_id: 2070772-1
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  • 7
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    Data_Sheet_3.docx
    Frontiers Media SA ; 2021
    In:  Frontiers in Cardiovascular Medicine Vol. 8 ( 2021-4-21)
    Details
    In: Frontiers in Cardiovascular Medicine, Frontiers Media SA, Vol. 8 ( 2021-4-21)
    Abstract: Background: While oxylipins have been linked to coronary artery disease (CAD), little is known about their diagnostic and prognostic potential. Objective: We tested whether plasma concentration of specific oxylipins may discriminate among number of diseased coronary arteries and predict median 5-year outcomes in symptomatic adults. Methods: Using a combination of high-performance liquid chromatography (HPLC) and quantitative tandem mass spectrometry, we conducted a targeted analysis of 39 oxylipins in plasma samples of 23 asymptomatic adults with low CAD risk and 74 symptomatic adults (≥70% stenosis), aged 38–87 from the Greater Portland, Oregon area. Concentrations of 22 oxylipins were above the lower limit of quantification in & gt;98% of adults and were compared, individually and in groups based on precursors and biosynthetic pathways, in symptomatic adults to number of diseased coronary arteries [(1) n = 31; (2) n = 23; (3) n = 20], and outcomes during a median 5-year follow-up (no surgery: n = 7; coronary stent placement: n = 24; coronary artery bypass graft surgery: n = 26; death: n = 7). Results: Plasma levels of six quantified oxylipins decreased with the number of diseased arteries; a panel of five oxylipins diagnosed three diseased arteries with 100% sensitivity and 70% specificity. Concentrations of five oxylipins were lower and one oxylipin was higher with survival; a panel of two oxylipins predicted survival during follow-up with 86% sensitivity and 91% specificity. Conclusions: Quantification of plasma oxylipins may assist in CAD diagnosis and prognosis in combination with standard risk assessment tools.
    Type of Medium: Online Resource
    ISSN: 2297-055X
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fcvm.2021.645786
    DOI: 10.3389/fcvm.2021.645786.s001
    DOI: 10.3389/fcvm.2021.645786.s002
    DOI: 10.3389/fcvm.2021.645786.s003
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2781496-8
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  • 8
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    Label-Free Proteomics Assisted by Affinity Enrichment for Elucidating the Chemical Reactivity of the Liver Mitochondrial Proteome toward Adduction by the Lipid Electrophile 4-hydroxy-2-nonenal (HNE)
    Frontiers Media SA ; 2016
    In:  Frontiers in Chemistry Vol. 4 ( 2016-03-03)
    Details
    In: Frontiers in Chemistry, Frontiers Media SA, Vol. 4 ( 2016-03-03)
    Type of Medium: Online Resource
    ISSN: 2296-2646
    URL: Article
    DOI: 10.3389/fchem.2016.00002
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2016
    detail.hit.zdb_id: 2711776-5
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  • 9
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    Integrated Identification and Quantification of Cyanobacterial Toxins from Pacific Northwest Freshwaters by Liquid Chromatography and High-resolution Mass Spectrometry
    Sociedad Quimica de Mexico, A.C. ; 2018
    In:  Journal of the Mexican Chemical Society Vol. 62, No. 2 ( 2018-06-06)
    Details
    In: Journal of the Mexican Chemical Society, Sociedad Quimica de Mexico, A.C., Vol. 62, No. 2 ( 2018-06-06)
    Abstract: 〈 p class="PlaceholderText1" 〉 The occurrence of harmful algal blooms in nutrient-rich freshwater bodies has increased world-wide, including in the Pacific Northwest. Some cyanobacterial genera have the potential to produce secondary metabolites that are highly toxic to humans, livestock and wildlife. Reliable methods for the detection of cyanobacterial toxins with high specificity and low limits of detection are in high demand. Here we test a relatively new hybrid high resolution accurate mass quadrupole time-of-flight mass spectrometry platform (TripleTOF) for the analysis of cyanobacterial toxins in freshwater samples. We developed a new method that allows the quantitative analysis of four commonly observed microcystin congeners (LR, LA, YR, and RR) and anatoxin-a in a 6-min LC run without solid-phase enrichment. Limits of detection for the microcystin congeners (LR, LA, YR, and RR) and anatoxin-a were & lt;5 ng/L (200-fold lower than the guideline value of 1 µg/L as maximum allowable concentration of MC-LR in drinking water). The method was applied for screening freshwaters in the Pacific Northwest during the bloom and post-bloom periods. The use of high resolution mass spectrometry and concomitant high sensitivity detection of specific fragment ions with high mass accuracy provides an integrated approach for the simultaneous identification and quantification of cyanobacterial toxins. The method is sensitive enough for detecting the toxins in single 〈 em 〉 Microcystis 〈 /em 〉 colonies. 〈 /p 〉
    Type of Medium: Online Resource
    ISSN: 2594-0317 , 1870-249X
    URL: Article
    DOI: 10.29356/jmcs.v62i2.386
    Language: Unknown
    Publisher: Sociedad Quimica de Mexico, A.C.
    Publication Date: 2018
    detail.hit.zdb_id: 2210387-9
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  • 10
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    Data_Sheet_1.PDF
    Frontiers Media SA ; 2022
    In:  Frontiers in Nutrition Vol. 8 ( 2022-1-14)
    Details
    In: Frontiers in Nutrition, Frontiers Media SA, Vol. 8 ( 2022-1-14)
    Abstract: Botanical products are frequently sold as dietary supplements and their use by the public is increasing in popularity. However, scientific evaluation of their medicinal benefits presents unique challenges due to their chemical complexity, inherent variability, and the involvement of multiple active components and biological targets. Translation away from preclinical models, and developing an optimized, reproducible botanical product for use in clinical trials, presents particular challenges for phytotherapeutic agents compared to single chemical entities. Common deficiencies noted in clinical trials of botanical products include limited characterization of the product tested, inadequate placebo control, and lack of rationale for the type of product tested, dose used, outcome measures or even the study population. Our group has focused on the botanical Centella asiatica due to its reputation for enhancing cognition in Eastern traditional medicine systems. Our preclinical studies on a Centella asiatica water extract (CAW) and its bioactive components strongly support its potential as a phytotherapeutic agent for cognitive decline in aging and Alzheimer's disease through influences on antioxidant response, mitochondrial activity, and synaptic density. Here we describe our robust, scientific approach toward developing a rational phytotherapeutic product based on Centella asiatica for human investigation, addressing multiple factors to optimize its valid clinical evaluation. Specific aspects covered include approaches to identifying an optimal dose range for clinical assessment, design and composition of a dosage form and matching placebo, sourcing appropriate botanical raw material for product manufacture (including the evaluation of active compounds and contaminants), and up-scaling of laboratory extraction methods to available current Good Manufacturing Practice (cGMP) certified industrial facilities. We also address the process of obtaining regulatory approvals to proceed with clinical trials. Our study highlights the complexity of translational research on botanicals and the importance of identifying active compounds and developing sound analytical and bioanalytical methods for their determination in botanical materials and biological samples. Recent Phase I pharmacokinetic studies of our Centella asiatica product in humans (NCT03929250, NCT03937908) have highlighted additional challenges associated with designing botanical bioavailability studies, including specific dietary considerations that need to be considered.
    Type of Medium: Online Resource
    ISSN: 2296-861X
    URL: Article
    URL: Article
    DOI: 10.3389/fnut.2021.799137
    DOI: 10.3389/fnut.2021.799137.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2776676-7
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