Identification of Metabolites in Plasma and Urine of Uruguayan Propolis-Treated Rats

Laboratory of Functional Food Science and COE Program in the 21st Century, School of Food and Nutritional Sciences, University of Shizuoka, 52-1 Yada, Shizuoka 422-8526, Japan.
Journal of Agricultural and Food Chemistry (Impact Factor: 2.91). 06/2004; 52(10):3083-8. DOI: 10.1021/jf0353234
Source: PubMed


Propolis is a resinous substance collected by honeybees from various plant sources. It is extensively used in food and beverages to improve health and prevent diseases such as heart disease, diabetes, and cancer. To investigate the absorption and metabolism of the components in propolis, in the present study, we administered ethanol extracts of Uruguayan propolis (poplar type propolis) orally to rats and analyzed their plasma and urine by high-performance liquid chromatography with photodiode array and mass spectrometric detection. After deconjugation of the components by beta-glucuronidase/sulfatase treatment of the specimen, pinobanksin 5-methyl ether, pinobanksin, kaempferol, chrysin, pinocembrin, and galangin were detected in plasma of rats orally administered propolis. These compounds were detected also in urine after beta-glucuronidase/sulfatase treatment. Furthermore, pinobanksin 5-methyl ether, pinobanksin, chrysin, pinocembrin, and galangin were present in the urine also in free form. These results suggest that flavonoids in propolis are metabolized and circulate in the body after oral administration of propolis.

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    • "That is, introducing the genes for biosynthesis of pinocembrin could increase natural crop resistance to herbivory, and/or produce high-yielding cultivars as a source of natural botanical insecticides. Pinocembrin can be extracted from numerous plants or from propolis (Kumazawa et al. 2004), and can be synthesized easily using established methods because of its molecular simplicity. Compared with commercial synthetic insecticides, pinocembrin may represent a more environmentally friendly insecticide, and its potential availability makes it a useful alternative. "
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    ABSTRACT: Flavonoids function in many aspects of plant–insect interactions, but the responses of insects to these compounds vary greatly. In this study, we determined the effects of two widely distributed flavonoids, pinocembrin and quercetin, on the feeding behavior, survival, and development of the fall armyworm Spodoptera frugiperda J.E. (Smith) (Lepidoptera: Noctuidae). In a choice test, S. frugiperda larvae strongly rejected leaves treated with pinocembrin at concentrations of 10, 50, or 100 μg/cm2. Larvae fed normally on leaves treated with quercetin at 10 and 50 μg/cm2, but showed 57 % deterrence when fed on leaves treated with 100 μg/cm2 quercetin. At concentrations of 0.01–1 µg/cm2, pinocembrin and quercetin functioned as phagostimulants for S. frugiperda. In a multiple-choice experiment, S. frugiperda larvae preferred to consume untreated leaves or those treated with 0.1 µg/cm2 pinocembrin, but rejected leaves treated with 5–50 µg/cm2 pinocembrin. In a no-choice feeding experiment, larvae fed on leaves treated with 5 and 50 μg/cm2 pinocembrin consumed less than those fed on leaves treated with 0.1 and 1 μg/cm2 pinocembrin or untreated leaves. Pinocembrin at 1–50 μg/cm2 negatively affected larval weight and survival, thus showing a toxic effect. In contrast, leaf consumption and larval weight were not significantly affected by quercetin at 0.1, 1, 5, and 50 μg/cm2, and mortality rates only slightly increased. Because of its dual activity, pinocembrin could be used for insect control in a stimulo-deterrent diversionary strategy: the same compound could promote both stimulate (low doses) and deter insect activity (high doses).
    Journal of Pest Science 01/2015; DOI:10.1007/s10340-014-0641-z · 2.64 Impact Factor
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    • "It has been extracted as a pure compound from propolis, and subsequently pinocembrin was synthesized and approved by the State Food and Drug Administration (SFDA) of China for stroke clinical trials in 2008. This compound is well metabolized and can circulate in the body after oral administration [20]. In particular, it is able to pass through the blood-brain barrier (BBB) in a passive transport process partly conducted by P-glycoprotein [21]. "
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    ABSTRACT: Background It is known that amyloid-β peptide (Aβ) plays a pivotal role in the pathogenesis of Alzheimer's disease (AD). Interaction between Aβ and the receptor for advanced glycation end products (RAGE) has been implicated in neuronal degeneration associated with this disease. Pinocembrin, a flavonoid abundant in propolis, has been reported to possess numerous biological activities beneficial to health. Our previous studies have demonstrated that pinocembrin has neuroprotective effects on ischemic and vascular dementia in animal models. It has been approved by the State Food and Drug Administration of China for clinical use in stroke patients. Against this background, we investigated the effects of pinocembrin on cognitive function and neuronal protection against Aβ-induced toxicity and explored its potential mechanism. Methods Mice received an intracerebroventricular fusion of Aβ25-35. Pinocembrin was administrated orally at 20 mg/kg/day and 40 mg/kg/day for 8 days. Behavioral performance, cerebral cortex neuropil ultrastructure, neuronal degeneration and RAGE expression were assessed. Further, a RAGE-overexpressing cell model and an AD cell model were used for investigating the mechanisms of pinocembrin. The mechanisms underlying the efficacy of pinocembrin were conducted on target action, mitochondrial function and potential signal transduction using fluorescence-based multiparametric technologies on a high-content analysis platform. Results Our results showed that oral administration of pinocembrin improved cognitive function, preserved the ultrastructural neuropil and decreased neurodegeneration of the cerebral cortex in Aβ25-35-treated mice. Pinocembrin did not have a significant effect on inhibiting Aβ1-42 production and scavenging intracellular reactive oxygen species (ROS). However, pinocembrin significantly inhibited the upregulation of RAGE transcripts and protein expression both in vivo and in vitro, and also markedly depressed the activation of p38 mitogen-activated protein kinase (MAPK)-MAPKAP kinase-2 (MK2)-heat shock protein 27 (HSP27) and stress-activated protein kinase (SAPK)/c-Jun N-terminal kinase (JNK)-c-Jun pathways and the downstream nuclear factor κB (NFκB) inflammatory response subsequent to Aβ-RAGE interaction. In addition, pinocembrin significantly alleviated mitochondrial dysfunction through improving mitochondrial membrane potential and inhibiting mitochondrial oxidative stress, and regulated mitochondrion-mediated apoptosis by restoration of B cell lymphoma 2 (Bcl-2) and cytochrome c and inactivation of caspase 3 and caspase 9. Conclusions Pinocembrin was shown to infer cognitive improvement and neuronal protection in AD models. The mechanisms of action of the compound were illustrated on RAGE-dependent transduction inhibition and mitochondrion protection. It appears to be a promising candidate for the prevention and therapy of AD.
    BMC Medicine 09/2012; 10(1):105. DOI:10.1186/1741-7015-10-105 · 7.25 Impact Factor
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    • "ompounds ( Fig . 4 ) . PIN is one of the major components of propolis . Collected from various natural plant sources , propolis is a resinous substance exten - sively eaten to improve health and to prevent diseases such as heart disease , diabetes , and cancer both as a dietary sup - plement and in applications within the pharmaceutical industry ( Kumazawa et al . , 2004 ) . Recently , much attention has been paid to PIN because of its benefits for human health due to anti - inflammatory , antioxidant , anti - thrombotic , antimicrobial , anti - allergic , hepatoprotective , anti - viral , cancer chemopreven - tive , and anti - asthmatic activities ( Hwang et al . , 2003 ; Sala et al . , 2003 ) . Howeve"
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    ABSTRACT: The increased expression and cross-linking activity of tissue transglutaminase (tTG) have been demonstrated in acute liver injury and fibrosis. We focused on the molecular mechanisms that contribute to ethanol-induced tTG expression and investigated the efficacy of propolis components in preventing both the tTG expression in vitro and fibrogenesis in vivo. We demonstrate herein that both ERK1/2 and PI3K/Akt pathways can regulate the effects of ethanol on NF-kappaB-dependent transcription and these signaling pathways may be involved in activation of ethanol-mediated tTG expression. We also found that administration of pinocembrin (PIN), one of the major components of propolis, inhibited tTG activation and significantly prevented the development of thioacetamide (TAA)-induced liver cirrhosis. The present study suggests that tTG may be an important member of the cascade of factors necessary for ethanol-induced liver fibrogenesis and PIN could serve as an anti-fibrogenic agent.
    Toxicology 05/2008; 246(2-3):148-57. DOI:10.1016/j.tox.2008.01.009 · 3.62 Impact Factor
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