- 1. Evolution in medicinal chemistry of E-ring-modified Camptothecin analogs as anticancer agents.
Camptothecin (CPT), a natural topoisomerase (Topo) I inhibitor, exhibits powerful antineoplastic activity against colorectal, breast, lung and ovarian cancers. However, the poor solubility and the inherent instability of the lactone E-ring in physiological pH resulted in low therapeutic efficacy and severe toxicity. In the past several decades' substantial progress toward understanding its pharmacology, lots of analogs have been prepared to overcome its drawbacks. The review provides a detailed discussion of the evolution in medicinal chemistry of CPT analogs with modification of the E-ring lactone....(more)
Huang Q, et al. Eur J Med Chem 2013 Mar 21;63C:746-757.
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- 2. Isolation and characterization of endophytic fungi from Camptotheca acuminata.
In this study, a total of 161 endophytic fungal isolates from Camptotheca acuminata were obtained and classified to 16 taxa according to morphological and molecular analysis. These taxa were composed of 2 frequent genera (Botryosphaeria and Fusarium) and 14 infrequent groups such as Xylaria, Diaporthe, Rhizopus, Epicoccum, and Preussia, demonstrating that fungal endophytes in C. acuminata were highly abundant and diverse. Antimicrobial activity screening using filter-paper diffusion method showed that 47.6 % of the tested isolates had antimicrobial activity against at least one of the test microorganisms. Screening of fungal endophyte-derived camptothecin analogues by TLC and LC-MS/MS<sup>3</sup> demonstrated that a strain Botryosphaeria dothidea, X-4 could produce 9-methoxycamptothecin (9-MCPT) when cultured in Sabouraud's dextrose broth for 12 days under shake flask and bench-scale fermention conditions. This work showed that the fungal endophytes from C. acuminata could be an alternative source for the production of 9-MCPT and other natural antimicrobial compounds....(more)
Ding X, et al. World J Microbiol Biotechnol 2013 Apr 12.
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- 3. Synthesis, metabolite analysis, and in vivo evaluation of [<sup>11</sup>C]irinotecan as a novel positron emission tomography (PET) probe.
INTRODUCTION:
Irinotecan is a semisynthetic derivative of camptothecin that exerts potent antitumor activity by inhibiting topoisomerase I. Despite much research into the complex pharmacokinetic profile and pharmacodynamic effects of irinotecan, unpredictable and severe side effects are still commonly observed. In this study, we synthesized [<sup>11</sup>C]irinotecan as a positron emission tomography (PET) probe, performed the metabolite analysis, and evaluated the biodistribution and kinetics of [<sup>11</sup>C]irinotecan using small animal PET.
METHODS:
[<sup>11</sup>C]Irinotecan was synthesized by two routes using [<sup>11</sup>C]phosgene and [<sup>11</sup>C]carbon dioxide fixation. Metabolites in the plasma of mice following injection of [<sup>11</sup>C] irinotecan were investigated using a combination of column-switching high-performance liquid chromatography (HPLC) and on-line solid-phase extraction (SPE). Whole-body PET studies were conducted in wild-type mice and P-glycoprotein and breast cancer resistance protein (Pgp/Bcrp) knockout mice.
RESULTS:
[<sup>11</sup>C]Irinotecan was successfully synthesized by the two abovementioned routes. Decay-corrected radiochemical yields based on [<sup>11</sup>C]carbon dioxide using [<sup>11</sup>C]phosgene and [<sup>11</sup>C]carbon dioxide fixation were 8.8±2.0% (n=8) and 16.9±2.9 % (n=5), respectively. Metabolite analysis of the plasma of mice following injection of [<sup>11</sup>C]irinotecan was successfully performed using the column-switching HPLC and on-line SPE combination resulting in greater than 87 % recovery of radioactivity from HPLC. In the PET study in mice, the radioactivity levels in the brain, liver, and small intestine were slightly increased by inhibition of the Pgp/Bcrp function for more than 30min after [<sup>11</sup>C]irinotecan injection. This result demonstrated that in vivo behavior of [<sup>11</sup>C] irinotecan and radioactive metabolites are influenced by the Pgp/Bcrp function.
CONCLUSION:
PET studies using [<sup>11</sup>C]irinotecan combined with metabolite analysis may be a useful tool for evaluating irinotecan pharmacokinetics and toxicity.
Copyright © 2013 Elsevier Inc. All rights reserved....(more)
Kawamura K, et al. Nucl Med Biol 2013 Apr 11.
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- 4. 3EZ,20Ac-ingenol, a catalytic inhibitor of topoisomerases, downregulates p-Akt and induces DSBs and apoptosis of DT40 cells.
We have previously reported that many ingenol compounds derived from Euphorbia kansui exhibit topoisomerase (topo) II inhibitory activity. Of these compounds, 3EZ,20Ac-ingenol inhibited topo I activity. Camptothecin, which inhibits the religation activity of topo I without interfering with the binding of topo I to DNA and induces topo I-mediated DNA cleavage, was used as a positive control. In this study, we found that 3EZ,20Ac-ingenol did not hamper the binding of topo I to DNA in the same manner as camptothecin but affected the inhibition of cleavage of one DNA strand. 3EZ,20Ac-ingenol inhibited cell proliferation by blocking cell cycle progression in the G2/M phase. To define the mechanism of inhibition of DT40 cell proliferation, the change in Akt activity was observed because Akt activity is regulated in response to DNA damage. Western blot analysis revealed that 3EZ,20Ac-ingenol downregulated the expression of p-Akt, and apoptosis was detected by the presence of DNA double-strand breaks and caspase 3 activation....(more)
Fukuda Y, et al. Arch Pharm Res 2013 Apr 18.
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- 5. An electrophoretic mobility shift assay identifies a mechanistically unique inhibitor of protein sumoylation.
The dynamic, posttranslational modification of proteins with a small ubiquitin-like modifier (SUMO) tag has been recognized as an important cellular regulatory mechanism relevant to a number of cancers as well as normal embryonic development. As part of a program aimed toward the identification of inhibitors of SUMO-conjugating enzymes, we developed a microfluidic electrophoretic mobility shift assay to monitor sumoylation events in real time. We disclose herein the use of this assay to identify a cell-permeable compound capable of blocking the transfer of SUMO-1 from the E2 enzyme Ubc9 to the substrate. We screened a small collection of compounds and identified an oxygenated flavonoid derivative that inhibits sumoylation in vitro. Next, we carried out an in-depth mechanistic analysis that ruled out many common false-positive mechanisms such as aggregation or alkylation. Furthermore, we report that this flavonoid inhibits a single step in the sumoylation cascade: the transfer of SUMO from the E2 enzyme (Ubc9) thioester conjugate to the substrate. In addition to having a unique mechanism of action, this inhibitor has a discrete structure-activity relationship uncharacteristic of a promiscuous inhibitor. Cell-based studies showed that the flavonoid inhibits the sumoylation of topoisomerase-I in response to camptothecin treatment in two different breast cancer cell lines, while isomeric analogs are inactive. Importantly, this compound blocks sumoylation while not affecting ubiquitylation in cells. This work identifies a point of entry for pharmacologic inhibition of the sumoylation cascade and may serve as the basis for continued study of additional pharmacophores that modulate SUMO-conjugating enzymes such as Ubc9....(more)
Kim YS, et al. Chem Biol 2013 Apr 18;20(4):604-13.
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- 6. Protein Phosphatases but not Reactive Oxygen Species Play Functional Role in Acute Amphetamine-Mediated Dopamine Release.
Drug abuse-induced neurodegeneration can be triggered by elevated production of reactive oxygen species (ROS). Involvement of oxidative stress in acute amphetamine (AMPH)-mediated dopamine (DA) release, however, has not been completely understood yet. In order to elucidate the dopaminergic response of PC12 cells to a single dose of 10 μM AMPH, ROS production was measured as related to the extracellular DA level. Due to the spontaneous oxidation of peroxide-sensitive fluorophore 2',7'-dichlorofluorescin diacetate (DCFH-DA) to 2',7'-dichlorofluorescein (DCF), the increase in fluorescence could not be unambiguously attributed to AMPH-triggered ROS production. Based on Amplex Red fluorescence, no ROS production was detected after acute AMPH application. Our data strongly suggest that ROS development was not the main triggering factor for immediate DA release after acute AMPH treatment. On the other hand, AMPH-induced elevation of DA levels in rat brain striatal slices was quenched by the water soluble antioxidant, N-acetylcysteine (NAC) at 10 mM. In this study, we also investigated the contribution of protein phosphatases to the AMPH-induced rat brain striatal dopaminergic response. The experimental protocol, double AMPH challenge was applied for screening the effect of NAC and cantharidin on AMPH-mediated DA release. Here we show that AMPH-mediated DA release increased nearly twofold in striatal rat brain slices pretreated for 30 min with 1000 μM cantharidin, a selective PP1 and PP2A inhibitor. These findings prove the lack of ROS inhibitory action on protein phosphatase activity in acute AMPH-mediated DA efflux....(more)
Paszti-Gere E, et al. Cell Biochem Biophys 2013 Apr 30.
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- 7. Pharmacological properties of blister beetles (Coleoptera: Meloidae) promoted their integration into the cultural heritage of native rural Spain as inferred by vernacular names diversity, traditions, and mitochondrial DNA.
ETHNOPHARMACOLOGICAL RELEVANCE:
Beetles of the family Meloidae (blister beetles) are often reported in pharmacological literature because of their content of cantharidin. Cantharidin has a long history in human medicine and was commonly applied in the 19th and the early 20th centuries, although its use has been progressively abandoned since then. Contrary to most, even common, large species of Coleoptera, blister beetles of the genera Berberomeloe, Physomeloe and to a lesser extent Meloe, are usually recognized and often incorporated into local folk taxonomy by inhabitants of rural areas in Spain.
AIM OF THE STUDY:
To demonstrate the role that pharmacological properties of blister beetles must have played in their integration in the culture of early Iberian human societies, but also in the preservation of their identity until today, a rare case for Spanish insects. To achieve this purpose we document the diversity of vernacular names applied in rural areas of Spain, and we determine, using molecular data, the antiquity of the presence of two species of the better-known blister beetle in rural Spain, Berberomeloe majalis and Berberomeloe insignis.
MATERIALS AND METHODS:
We try to document the extent of traditional knowledge of meloid beetles in rural areas by interviewing about 120 people from villages in central and southern Spain. We also use mitochondrial DNA sequences (Cytochrome Oxidase I and 16SrRNA) obtained from several populations of two species of the better known blister beetle in rural Spain, Berberomeloe majalis and Berberomeloe insignis, to determine whether these beetles were already present in the Iberian Peninsula when earlier ancient cultures were developing.
RESULTS:
Our results show that, based on mitochondrial DNA, blister beetles of the genus Berberomeloe were present in the Iberian Peninsula long before humans arrived, so ancient Iberian cultures were in contact with the same beetle species occurring now in rural areas. On the other hand, people interviewed in rural communities provided us with more than 28 different vernacular names, a few short songs incorporated to local folklore, and some therapeutic uses.
CONCLUSIONS:
Current knowledge of blister beetles of the family Meloidae in rural Spain was likely developed as a consequence of their pharmacological properties; we hypothesize this knowledge was inherited from ancient pre-Christian Iberian native cultures as part of their traditional therapeutic traditions. It is possible then, that current vernacular names and traditional songs are the only remnants of an ancient knowledge of pharmacological uses of meloid beetles, verbally transmitted from the ancestral cultures to modern day rural Spain. Our work suggests that this legacy, part of the European Cultural Heritage, is disappearing fast, in parallel to the loss of traditional agricultural techniques.
Copyright © 2013 Elsevier Ireland Ltd. All rights reserved....(more)
Percino-Daniel N, et al. J Ethnopharmacol 2013 Mar 26.
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- 8. Cantharidin Impedes Activity of Glutathione S-Transferase in the Midgut of Helicoverpa armigera Hübner.
Previous investigations have implicated glutathione S-transferases (GSTs) as one of the major reasons for insecticide resistance. Therefore, effectiveness of new candidate compounds depends on their ability to inhibit GSTs to prevent metabolic detoxification by insects. Cantharidin, a terpenoid compound of insect origin, has been developed as a bio-pesticide in China, and proves highly toxic to a wide range of insects, especially lepidopteran. In the present study, we test cantharidin as a model compound for its toxicity, effects on the mRNA transcription of a model Helicoverpa armigera glutathione S-transferase gene (HaGST) and also for its putative inhibitory effect on the catalytic activity of GSTs, both in vivo and in vitro in Helicoverpa armigera, employing molecular and biochemical methods. Bioassay results showed that cantharidin was highly toxic to H. armigera. Real-time qPCR showed down-regulation of the HaGST at the mRNA transcript ranging from 2.5 to 12.5 folds while biochemical assays showed in vivo inhibition of GSTs in midgut and in vitro inhibition of rHaGST. Binding of cantharidin to HaGST was rationalized by homology and molecular docking simulations using a model GST (1PN9) as a template structure. Molecular docking simulations also confirmed accurate docking of the cantharidin molecule to the active site of HaGST impeding its catalytic activity....(more)
Khan RA, et al. Int J Mol Sci 2013 Mar 8;14(3):5482-500.
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- 9. Anti-metastatic effect of cantharidin in A549 human lung cancer cells.
Cancer metastasis is represented by migration and invasion of cancer cells. Cancer cells invade into the blood or lymphatic vessels and this leads to the spread of cancer into the organs in distant sites. For cancer cells to migrate, extracellular matrix (ECM) must be degraded. Cantharidin, a compound derived from blister beetles, is known for its anti-cancer effect in several cancer cells. Here we report that cantharidin inhibits migration and invasion of A549 human lung cancer cell. We found that cantharidin inhibits activation of phosphatidylinositol 3-kinase/Akt signaling pathway. This leads to the selective attenuation of one of the gelatinases, matrix metalloproteinase 2, which can degrade components of ECM, and inhibits migration and invasion of A549 human lung cancer cell....(more)
Kim YM, et al. Arch Pharm Res 2013 Apr;36(4):479-84.
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- 10. Suppressions of Migration and Invasion by Cantharidin in TSGH-8301 Human Bladder Carcinoma Cells through the Inhibitions of Matrix Metalloproteinase-2/-9 Signaling.
Cancer metastasis becomes an initial cause of cancer death in human population. In many cancers, it has been shown that the high levels of matrix metalloproteinase (MMP)-2 and/or MMP-9 are associated with the invasive phenotypes of cancer cells. In this study, we investigated the effects of cantharidin, a derivative of blister beetles which is one of the traditional Chinese medicines, on the adhesion, migration, and invasion of human bladder cancer TSGH-8301 cells. Cantharidin effectively suppressed TSGH-8301 cell adhesion, migration, and invasion in a concentration-dependent manner. Results from Western blotting, RT-PCR, and gelatin zymography assays indicated that cantharidin blocked the protein levels, gene expression (mRNA), and activities of MMP-2 and -9 in TSGH-8301 cells. Cantharidin also significantly suppressed the protein expressions of p-p38 and p-JNK1/2 in TSGH-8301 cells. Taken together, cantharidin was suggested to present antimetastatic potential via suppressing the levels of MMP-2 and MMP-9 expression that might be mediated by targeting the p38 and JNK1/2 MAPKs pathway in TSGH-8301 human bladder cancer cells....(more)
Huang YP, et al. Evid Based Complement Alternat Med 2013;2013:190281.
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- 11. Lethal and sublethal effects of cantharidin on the life history traits and population parameters of Helicoverpa armigera (Hübner) (Lepidoptera: Noctuidae).
BACKGROUND:
The cotton bollworm, Helicoverpa armigera (Hübner), is a serious and cosmopolitan pest of many economic crops. Its control has not been adequate owing to its resistance to many groups of insecticides. Toxicity of cantharidin on armyworm and diamondback moth has already been reported. However, its toxicity on H. armigera has not been investigated previously. In this study, lethal and sublethal effects of cantharidin on H. armigera under laboratory conditions are reported.
RESULTS:
Results showed gross abnormalities in the population parameters of H. armigera, ranging from larvae to adults. Reduction in larval weight and wing malformation were observed in the cantharidin-treated population cohort, and higher mortality at the larval, pupal and adult stages was observed in cantharidin-treated H. armigera compared with the control. Moreover, almost 5 times less fecundity was recorded in the treated population cohort. Fertility was also severely affected, and reduction in all population parameters was observed.
CONCLUSION:
Cantharidin caused larval mortality and other serious abnormalities in H. armigera population parameters, and therefore may have positive implications for pest management decision-making process. More interestingly, the experiment revealed that cantharidin in sublethal dose mimicked insect growth regulator insecticides. Furthermore, cantharidin could be used as a precursor compound for the synthesis of new analogues and compounds to replace ineffective older compounds. © 2013 Society of Chemical Industry.
© 2013 Society of Chemical Industry....(more)
Khan RA, et al. Pest Manag Sci 2013 Feb 19.
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- 12. Exploiting Protein Phosphatase Inhibitors Based on Cantharidin Analogues for Cancer Drug Discovery.
Cantharidin (CTD), a natural toxin, can inhibit a variety of tumor cell lines, especially hepatocellular carcinoma cells. It is a strong inhibitor of protein phosphatase type 1 (PP1) and type 2A (PP2A). Because of the cytotoxicity, the clinical application of CDT is limited. Here, we review the structure-activity relationships of CDT analogues, including norcantharidin (NCTD), cantharimides and related derivatives of CTDs, which have more powerful antitumor activity but less cytotoxicity than CDT itself. Important advances in the design of the CTD-based inhibitors achieved recently are outlined here in order to establish principles for synthesis, screening, and the applications of promising anti-cancer drug candidates. In addition, efforts to ameliorate the intrinsic cytotoxicity through the use of drug carriers are also discussed. It is conceivable that rational design of the protein phosphatase inhibitors based on cantharidin analogues can be facilitated by studies of mechanism of the protein-inhibitor interactions and the related structural biology in the future....(more)
Deng L, et al. Mini Rev Med Chem 2013 Jan 31.
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- 13. Norcantharidin inhibits tumor angiogenesis via blocking VEGFR2/MEK/ERK signaling pathways.
Norcantharidin (NCTD), the demethylated form of Cantharidin, a reagent isolated from blister beetles, has been shown to be an anti-tumor agent capable of inhibiting proliferation as well as inducing apoptosis in many cancer cell lines. However, little is known about the effect of NCTD in tumor angiogenesis. In this study, we demonstrated that NCTD inhibited vascular endothelial growth factor (VEGF)-induced cell proliferation, migration, invasion, and capillary tube formation of primary human umbilical vein endothelial cells (HUVECs) in a dose-dependent manner. Furthermore, we showed NCTD inhibited tumor growth and angiogenesis of colon cancer cells (LOVO) in vivo. We then mechanistically described that NCTD specifically abrogated the phosphorylation/activation of vascular endothelial growth factor receptor-2 (VEGFR2)/MEK/ERK pathway kinases, with little effect on the phosphorylation of p38 MAPK and Akt, and on Cox-2 expression. In summary, our results indicate that NCTD is a potential inhibitor of tumor angiogenesis by blocking VEGFR2/MEK/ERK signaling.
© 2013 Japanese Cancer Association....(more)
Zhang L, et al. Cancer Sci 2013 May;104(5):604-10.
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- 14. Changes in Glutathione, Oxidative Stress, Mitochondrial Membrane Potential in Apoptosis Involving the Anticancer Activity Of Cantharidin Isolated From Red-Headed Blister Beetles, Epicauta Hirticornis.
The present work describes the anticancer activity of cantharidin isolated from red-headed blister beetles, Epicauta hirticornis and its possible mode of action involving induction of apoptosis, oxidative stress and decrease in glutathione against murine ascites Dalton's lymphoma. The structure of isolated compound was confirmed as cantharidin by X-ray diffraction method. Cantharidin treatment showed potent anticancer activity with an increase in life span (~ 87%) of tumor-bearing mice. Cantharidin treatment induced apoptosis in Dalton's lymphoma cells and also caused an oxidative stress due to generation of reactive oxygen species (ROS) and an increase in lipid peroxidation. The observed canthardin-mediated decrease in glutathione and glutathione related enzymes activities in the tumor cells may weaken the cellular antioxidant system. Moreover, cantharidin treatment also caused a significant decrease in mitochondrial cytochrome c and simultaneous increase in cytosolic cytochrome c which ultimately facilitates activation of caspase 9 and 3 to augment mitochondrial apoptotic pathway causing cancer cell death. Based on the present findings, it may be suggested that cantharidin-mediated anticancer activity could be due to decrease in the protective ability of cancer cells by ROS and subsequent activation of effecter caspases leading to apoptotic cell death....(more)
Verma AK, et al. Anticancer Agents Med Chem 2013 Jan 2.
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- 15. Oral bioavailability of cantharidin-loaded solid lipid nanoparticles.
BACKGROUND:
The clinical application of cantharidin (CA) is limited by its insolubility, toxicity and short half-life in circulation. This study aims to achieve a steady and sustained blood concentration-time profile, using solid lipid nanoparticles (SLNs) as a drug carrier.
METHODS:
CA-SLNs were prepared by a film dispersion-ultrasonication method. The physiochemical properties were studied by transmission electron microscopy. In vitro release and in vivo evaluation of CA-SLNs were studied by GC and GC-MS, while a comparison of the pharmacokinetic properties between CA-SLNs and free CA was performed in rats.
RESULTS:
The mean size, drug content and encapsulation yield of CA-SLNs were 121 nm, 13.28 ± 0.12% and 93.83 ± 0.45%, respectively. The results show that CA-SLNs had a sustained release profile without a burst effect, a higher bioavailability than free CA after oral administration, and that the relative bioavailability of CA-SLNs to free CA was 250.8%.
CONCLUSION:
CA-SLNs could improve the solubility and oral bioavailability of CA....(more)
Dang YJ, et al. Chin Med 2013 Jan 8;8(1):1.
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- 16. Paradoxic effects of propofol on visceral pain induced by various TRPV1 agonists.
Intraperitoneal injection of propofol inhibits subsequent acetic acid-induced writhing response in mice. Propofol increases the sensitivity of dorsal root ganglion neurons to capsaicin through transient receptor potential ankyrin subtype-1 (TRPA1) and protein kinase Cε (PKCε)-mediated phosphorylation of transient receptor potential vanilloid subtype-1 (TRPV1). Intraperitoneal co-injection of propofol may increase visceral nociception induced by TRPV1 agonists via sensitization of TRPV1. Therefore, we investigated the effects of intraperitoneal co-injection of propofol on nociception induced by acetic acid and capsaicin. The number of writhing movements induced by acetic acid or nociception time by capsaicin with or without propofol were counted. Neonatal capsaicin-treated mice were also used to demonstrate the role of TRPV1 in the effects of propofol on nociception, induced by TRPV1 agonists. Co-injection of propofol resulted in a pronociceptive effect on the writhing response induced by acetic acid, while the same dose of propofol ameliorated the response to capsaicin. The writhing response to intraperitoneal acetic acid was sharply inhibited following neonatal treatment with capsaicin. Co-injection with propofol reduced the number of writhing movements induced by acetic acid in neonatal capsaicin-treated mice. These results suggest that propofol binds to TRPV1 at the capsaicin-binding pocket....(more)
Ji W, et al. Exp Ther Med 2013 Apr;5(4):1259-1263.
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- 17. Phα1β toxin prevents capsaicin-induced nociceptive behavior and mechanical hypersensitivity without acting on TRPV1 channels.
Phα1β toxin is a peptide purified from the venom of the armed spider Phoneutria nigriventer, with markedly antinociceptive action in models of acute and persistent pain in rats. Similarly to ziconotide, its analgesic action is related to inhibition of high voltage activated calcium channels with more selectivity for N-type. In this study we evaluated the effect of Phα1β when injected peripherally or intrathecally in a rat model of spontaneous pain induced by capsaicin. We also investigated the effect of Phα1β on Ca<sup>2+</sup> transients in cultured dorsal root ganglia (DRG) neurons and HEK293 cells expressing the TRPV1 receptor. Intraplantar or intrathecal administered Phα1β reduced both nocifensive behavior and mechanical hypersensitivity induced by capsaicin similarly to that observed with SB366791, a specific TRPV1 antagonist. Peripheral nifedipine and mibefradil did also decrease nociceptive behavior induced by intraplantar capsaicin. In contrast, ω-conotoxin MVIIA (a selective N-type Ca<sup>2+</sup> channel blocker) was effective only when administered intrathecally. Phα1β, MVIIA and SB366791 inhibited, with similar potency, the capsaicin-induced Ca<sup>2+</sup> transients in DRG neurons. The simultaneous administration of Phα1β and SB366791 inhibited the capsaicin-induced Ca<sup>2+</sup> transients that were additive suggesting that they act through different targets. Moreover, Phα1β did not inhibit capsaicin-activated currents in patch-clamp recordings of HEK293 cells that expressed TRPV1 receptors. Our results show that Phα1β may be effective as a therapeutic strategy for pain and this effect is not related to the inhibition of TRPV1 receptors....(more)
Castro-Junior CJ, et al. Neuropharmacology 2013 Apr 15;71C:237-246.
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- 18. Eight weeks of supplementation with a multi-ingredient weight loss product enhances body composition, reduces hip and waist girth, and increases energy levels in overweight men and women.
BACKGROUND:
Numerous natural products are marketed and sold claiming to decrease body weight and fat, but few undergo finished product-specific research demonstrating their safety and efficacy.
OBJECTIVE:
To determine the safety and efficacy of a multi-ingredient supplement containing primarily raspberry ketone, caffeine, capsaicin, garlic, ginger and Citrus aurantium (Prograde Metabolism™ [METABO]) as an adjunct to an eight-week weight loss program.
METHODS:
Using a randomized, placebo-controlled, double-blind design, 70 obese but otherwise healthy subjects were randomly assigned to METABO or a placebo and underwent 8 weeks of daily supplementation, a calorie restricted diet, and exercise training. Subjects were tested for changes in body composition, serum adipocytokines (adiponectin, resistin, leptin, TNF-α, IL-6) and markers of health including heart rate and blood pressure.
RESULTS:
Of the 45 subjects who completed the study, significant differences were observed in: body weight (METABO -2.0% vs. placebo -0.5%, P < 0.01), fat mass (METABO -7.8 vs. placebo -2.8%, P < 0.001), lean mass (METABO +3.4% vs. placebo +0.8%, P < 0.03), waist girth (METABO -2.0% vs. placebo -0.2%, P < 0.0007), hip girth (METABO -1.7% vs. placebo -0.4%, P < 0.003), and energy levels per anchored visual analogue scale (VAS) (METABO +29.3% vs. placebo +5.1%, P < 0.04). During the first 4 weeks, effects/trends for maintaining elevated serum leptin (P < 0.03) and decreased serum resistin (P < 0.08) in the METABO group vs. placebo were also observed. No changes in systemic hemodynamics, clinical blood chemistries, adverse events, or dietary intake were noted between groups.
CONCLUSIONS:
METABO administration is a safe and effective adjunct to an eight-week diet and exercise weight loss program by augmenting improvements in body composition, waist and hip girth. Adherence to the eight-week weight loss program also led to beneficial changes in body fat in placebo. Ongoing studies to confirm these results and clarify the mechanisms (i.e., biochemical and neuroendocrine mediators) by which METABO exerts the observed salutary effects are being conducted....(more)
Lopez HL, et al. J Int Soc Sports Nutr 2013 Apr 19;10(1):22.
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- 19. Evaluation of mechanisms involved in the antinociception of the ethanol extract from the inner bark of Caesalpinia pyramidalis in mice.
ETHNOPHARMACOLOGICAL RELEVANCE:
Caesalpinia pyramidalis Tul. (Fabaceae) is an endemic tree of the Northeast region of Brazil, mainly in the Caatinga region. More commonly, inner bark or flowers are traditionally used to treat many painful and inflammatory processes. A common use of this plant is made by macerating a handful of its stem bark in a liter of wine or sugarcane brandy. It is drunk against stomachache, dysenteries, and diarrheas.
MATERIALS AND METHODS:
The ethanol extract of Caesalpinia pyramidalis inner bark was used in mice via oral route, at the doses of 10, 30, and 100mg/kg, in behavioral models of nociception and investigates some of the mechanisms underlying this effect.
RESULTS:
The ethanol extract (30 and 100mg/kg, P<0.001), given orally, produced dose dependent inhibition of acetic acid-induced visceral pain. The ethanol extract also caused significant and dose-dependent inhibition of capsaicin-(100mg/kg, P<0.001) and glutamate-(10, 30, and 100mg/kg, P<0.01) induced pain. The antinociception caused by the ethanol extract (30mg/kg) in the abdominal constriction test was significantly attenuated (P<0.001) by intraperitoneal treatment of mice with l-arginine (600mg/kg).
CONCLUSIONS:
Collectively, the present results suggest that the ethanol extract of Caesalpinia pyramidalis produced dose-related antinociception in several models of pain through mechanisms that involved both glutamatergic system and/or the l-arginine-nitric oxide pathway, supporting the folkloric usage of the plant to treat various painful processes.
Copyright © 2013. Published by Elsevier Ireland Ltd....(more)
Santos CA, et al. J Ethnopharmacol 2013 Apr 17.
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- 20. Artemin-GFRα3 interactions partially contribute to acute inflammatory hypersensitivity.
The expression of artemin (ARTN), a glial cell line-derived neurotrophic factor (GDNF) family ligand, increases in pre-clinical models of nociception and recent evidence suggests this growth factor may play a causative role in inflammatory pain mechanisms. The aim of this study was to demonstrate functional inhibition of ARTN with monoclonal antibodies and to determine whether ARTN neutralisation could reverse inflammatory pain in mice. We show that monoclonal antibodies with high affinity to ARTN, completely inhibit ARTN-induced Ret and ERK activation in a human neuroblastoma cell line, and block capsaicin-induced CGRP secretion from primary rat DRG cultures. In addition, administration of anti-ARTN antibodies to mice provides a transient, partial reversal (41%) of FCA-induced mechanical hypersensitivity. Anti-ARTN antibodies had no effect on hypersensitivity in response to partial nerve ligation in mice. These data suggest that ARTN-GFRα3 interactions partially mediate early stage nociceptive signalling following an inflammatory insult....(more)
Thornton P, et al. Neurosci Lett 2013 Apr 19.
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- 21. Capsaicin Regulates the NF-κB Pathway in Salivary Gland Inflammation.
Salivary gland epithelial cells (SGEC) release several cytokines that play important roles in the inflammatory process. In this study, we examined whether capsaicin can modulate cytokine release in SGEC. After cells were stimulated with polyinosinic-polycytidylic acid [poly(I:C)] or lipopolysaccharide (LPS), mRNA transcript and protein levels were detected by reverse-transcriptase-polymerase chain-reaction (RT-PCR), real-time PCR, and enzyme-linked immunosorbent assay (ELISA). These findings demonstrated that the increases in TNFα and IL-6 mRNA transcripts were highest at 3 hrs and 1 hr after incubation with poly(I:C) and LPS, respectively. Pre-treatment of the cells with 10 μµ capsaicin, however, significantly inhibited mRNA transcripts and its protein levels. The simultaneous application of 10 μµ capsazepine with capsaicin did not block the inhibitory effect of capsaicin. Furthermore, the inhibitory effect of capsaicin was also shown in primary cultured cells from TRPV1<sup>-/-</sup> mice. We found that both poly(I:C) and LPS induced IκB-α degradation and phosphorylation, which resulted in NF-κB activation, and capsaicin inhibited this NF-κB pathway. These results demonstrate that SGEC release pro-inflammatory cytokines mediated by TLR, and capsaicin inhibits this process through the NF-κB pathway. This study suggests that capsaicin could potentially alleviate inflammation in salivary glands....(more)
Shin YH, et al. J Dent Res 2013 Apr 19.
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- 22. Dietary capsaicin prevents nonalcoholic fatty liver disease through transient receptor potential vanilloid 1-mediated peroxisome proliferator-activated receptor δ activation.
Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic lipid deposition and coincides often with cardiometabolic diseases. Several dietary factors attenuate NAFLD. Here, we report beneficial effects of chronic dietary capsaicin intake on NAFLD which is mediated by the transient receptor potential vanilloid 1 (TRPV1) activation. The results showed that TRPV1 activation by capsaicin reduced free fatty acids (FFAs) induced the intracellular lipid droplets in HepG2 cells and prevented fatty liver in vivo. Chronic dietary capsaicin promoted lipolysis by increasing hepatic phosphorylated hormone-sensitive lipase (phospho-HSL), carnitine palmitoyltransferase 1 (CPT1), and peroxisome proliferator-activated receptor δ (PPARδ) in wild-type (WT) mice. This effect was absent in TRPV1<sup>-/-</sup> mice. Dietary capsaicin did not affect lipogenesis, as indicated by the detection of hepatic fatty acid synthase (FAS), sterol regulatory element-binding protein-1 (SREBP-1), PPARα, and liver X receptor (LXR) in mice. Importantly, TRPV1 causes PPARδ activation which significantly increased the expression of autophagy-related proteins, such as light chain 3 (LC3)II, Beclin1, Atg5, and Atg7 in HepG2 cells. In the in vivo study, TRPV1 activation by dietary capsaicin enhanced hepatic PPARδ and autophagy-related proteins and reduced hepatic enzymes and inflammatory factor in WT but not TRPV1<sup>-/-</sup> mice. TRPV1 activation by dietary capsaicin prevents NAFLD through PPARδ-dependent autophagy enhancement in mice. Dietary capsaicin may represent a beneficial intervention in populations at high risk for NAFLD....(more)
Li Q, et al. Pflugers Arch 2013 Apr 21.
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- 23. TRPV1-mediated UCP2 upregulation ameliorates hyperglycemia-induced endothelial dysfunction.
BACKGROUND:
Diabetic cardiovascular complications are characterised by oxidative stress-induced endothelial dysfunction. Uncoupling protein 2 (UCP2) is a regulator of mitochondrial reactive oxygen species (ROS) generation and can antagonise oxidative stress, but approaches that enhance the activity of UCP2 to inhibit ROS are scarce. Our previous studies show that activation of transient receptor potential vanilloid 1 (TRPV1) by capsaicin can prevent cardiometabolic disorders. In this study, we conducted experiments in vitro and in vivo to investigate the effect of capsaicin treatment on endothelial UCP2 and oxidative stress. We hypothesised that TRPV1 activation by capsaicin attenuates hyperglycemia-induced endothelial dysfunction through a UCP2-mediated antioxidant effect.
METHODS:
TRPV1-/-, UCP2 -/- and db/db mice, as well as matched wild type (WT) control mice, were included in this study. Some mice were subjected to dietary capsaicin for 14 weeks. Arteries isolated from mice and endothelial cells were cultured. Endothelial function was examined, and immunohistological and molecular analyses were performed.
RESULTS:
Under high-glucose conditions, TRPV1 expression and protein kinase A (PKA) phosphorylation were found to be decreased in the cultured endothelial cells, and the effects of high-glucose on these molecules were reversed by the administration of capsaicin. Furthermore, high-glucose exposure increased ROS production and reduced nitric oxide (NO) levels both in endothelial cells and in arteries that were evaluated respectively by dihydroethidium (DHE) and DAF-2 DA fluorescence. Capsaicin administration decreased the production of ROS, restored high-glucose-induced endothelial dysfunction through the activation of TRPV1 and acted in a UCP2-dependent manner in vivo. Administration of dietary capsaicin for 14 weeks increased the levels of PKA phosphorylation and UCP2 expression, ameliorated the vascular oxidative stress and increased NO levels observed in diabetic mice. Prolonged dietary administration of capsaicin promoted endothelium-dependent relaxation in diabetic mice. However, the beneficial effect of capsaicin on vasorelaxation was absent in the aortas of UCP2 -/- mice exposed to high-glucose levels.
CONCLUSION:
TRPV1 activation by capsaicin might protect against hyperglycemia-induced endothelial dysfunction through a mechanism involving the PKA/UCP2 pathway....(more)
Sun J, et al. Cardiovasc Diabetol 2013 Apr 22;12:69.
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- 24. Inhibitory effects of Capsicum annuum L. water extracts on lipoprotein lipase activity in 3T3-L1 cells.
Obesity, an intractable metabolic disease, currently has no medical treatment without side effects, so studies have been actively carried out to find natural compounds that have anti-obesity activity with minimum side effects. In this study, the anti-obesity effects of water extracts of seven Capsicum annuum L. varieties being Putgochu (Pca), Oyee gochu (Oca), Kwari putgochu (Kca), Green pepper (Gca), Yellow paprika (Yca), Red paprika (Rca) and Cheongyang gochu (Cca), were examined through the evaluation of lipoprotein lipase (LPL) mRNA expression level in 3T3-L1 cells (mouse pre-adipocytes). After capsaicin elimination by chloroform defatting, freeze-dried powder of Cca was treated to 3T3-L1 cells and anti-obesity effects were examined by determining the LPL mRNA level using the RT-PCR method. Of the primary fractions, only proven fractions underwent secondary and tertiary refractionating to determine anti-obesity effects. From seven different Capsicum annuum L., there was a significant decrease of the LPL mRNA expression level of 50.9% in Cca treatment compared to the control group. A significant decrease of the LPL mRNA expression level was shown in primary fractions (Fr) 5 (36.2% decrease) and 6 (30.5% decrease) of the Cca water extracts. Due to the impurities checked by UPLC chromatography, Fr 5 and 6 were refractionated to determine the LPL mRNA expression level. Treatment of Fr 6-6 (35.8% decrease) and Fr 5-6 (35.3% decrease) showed a significant decrease in the LPL mRNA expression level. When analyzed using UPLC, major compounds of Fr 6-6 and Fr 5-6 were very similar. Subsequently, we refractionated Fr 6-6 and Fr 5-6 to isolate the major peak for structure elucidation. Treatment of Fr 5-6-1 (26.6% decrease) and Fr 6-6-1 (29.7% decrease) showed a significant decrease in the LPL mRNA expression level. Consequently, the fractions may have a possibility to ameliorate obesity through the decrease of the LPL mRNA expression level....(more)
Baek J, et al. Nutr Res Pract 2013 Apr;7(2):96-102.
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- 25. Relative Contributions of the Thalamus and the Paraventricular Nucleus of the Hypothalamus to the Cardiac Sympathetic Afferent Reflex.
The cardiac sympathetic afferent reflex (CSAR) is induced by stimulating the cardiac sympathetic afferents which evokes increases in sympathetic outflow and arterial pressure. In the present study, we attempted to identify the contribution of thalamic and hypothalamic nuclei involved in the CSAR. First, we observed that there was an increase in the number of c-fos labeled cells in the paraventricular nucleus (PVN) (190 ± 18 vs. 101±15; P<0.05), the paraventricular nucleus of the thalamus (PVT) (239 ± 23 vs.151 ± 15; P<0.05) and in the mediodorsal thalamic nucleus (MD) (92 ± 9 vs. 63 ± 6; P<0.05) following epicardial application of bradykinin (BK) compared to the control group (P<0.05). Second, using extracellular single-unit recording, we found 25% of spontaneously active neurons in the thalamus were stimulated by epicardial application of BK or capsaicin in intact rats. However, 24% of spontaneously active neurons in the thalamus were still stimulated by epicardial application of BK or capsaicin despite vagotomy and sinoaortic denervation. None of the neurons in the thalamus responded to baroreflex changes in arterial pressure, induced by I.V. injection of phenylephrine or sodium nitroprusside. The CSAR was inhibited by microinjection of muscimol or lidocaine into the PVN. However it was not inhibited or blocked by microinjection muscimol or lidocaine into the thalamus. Taken together, these data suggest that the thalamus while activated is not critical for autonomic adjustments in response to activation of the CSAR. On the other hand, the PVN is critically involved in the central pathway of the CSAR....(more)
Xu B, et al. Am J Physiol Regul Integr Comp Physiol 2013 Apr 24.
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- 26. Antibacterial activity of Capsicum annuum extract and synthetic capsaicinoid derivatives against Streptococcus mutans.
The inhibitory effects of the ethyl acetate extract and capsaicin (1) and dihydrocapsaicin (2) isolated from fruits of Capsicum annuum chili pepper type, and synthetic capsaicinoid derivatives (N-(4-hydroxyphenylethyl)decamide (3), (E)-N-(4-hydroxy-3-methoxybenzyl)-3,7-dimethylocta- 2,6-dienamide (4), 4-hydroxy-3-methoxy-N-((E)-3, 7-dimethylocta-2,6-dienyl)benzamide (5) andN-(4-hydroxy- 3-methoxybenzyl)decamide (6) at different concentrations were evaluated against Streptococcus mutans. The minimum inhibitory concentration at which the ethyl acetate extract prevented the growth of S. mutans was 2.5 mg/mL; those of the isolated compounds 1 and 2 were 1.25 μg/mL, while 3 was 5.0 μg/mL, and 4, 5 and 6 were 2.5 μg/mL, respectively....(more)
Santos MM, et al. J Nat Med 2012 Apr;66(2):354-6.
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- 27. Reverse phase chromatographic behaviour of major components in Capsicum Annuum extract.
BACKGROUND:
The purpose of the study is to develop a suitable analytical method in order to establish appropriate conditions for isolation and assay of the dominant compounds in extracts of Capsicum annuum.
RESULTS:
The studies are performed with standard substances to establish the HPLC conditions for complete separation of capsaicin and dihydrocapsaicin, the two major components of interest. Because of their prevalent apolar features, reverse phase chromatographic version was approached. Systematic studies on different eluents revealed the 65% methanol-35% water mixture as a proper mobile phase providing a complete separation of the components according to analytical claims.
CONCLUSIONS:
The results may be of interest to develop a specific analytical procedure with advanced specificity for quantitative assay of capsaicin and dihydrocapsaicin in pharmaceutical products and in foods....(more)
Butnariu M, et al. Chem Cent J 2012 Dec 4;6(1):146.
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- 28. The antioxidant activity and polyphenolic contents of different plant seeds extracts.
Different plant seeds extracts of Citrus sinensis, Hordeum sativum, Triticum sativum, Canna indica, Citrullus vulgaris and Capsicum annuum were evaluated for their antioxidant activity by the following methods: 2,2-diphenyl-1-pycril-hydrazyl (DPPH) radical scavenging, reducing power, RBCs hemolysis and linoleic acid oxidation, a long with the determination of total phenolic and flavonoids contents. All the methanolic extracts showed high antioxidant activity and have high contents of phenolic and flavonoid. The Canna indica extract exhibited strong antioxidant as a reducing power and as DPPH radical-scavenging (3.61 absorbance, 87.12%, respectively), while the Hordeum sativum extract exhibited highest inhibitory effect on RBCs hemolysis (59.55%) and the Capsicum annuum extract has highest inhibitory effect on linoleic acid peroxidation (65.06%)....(more)
Atrooz OM. Pak J Biol Sci 2009 Aug 1;12(15):1063-8.
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- 29. Final report on the safety assessment of capsicum annuum extract, capsicum annuum fruit extract, capsicum annuum resin, capsicum annuum fruit powder, capsicum frutescens fruit, capsicum frutescens fruit extract, capsicum frutescens resin, and capsaicin.
Capsicum-derived ingredients function as skin-conditioning agents--miscellaneous, external analgesics, flavoring agents, or fragrance components in cosmetics. These ingredients are used in 19 cosmetic products at concentrations as high as 5%. Cosmetic-grade material may be extracted using hexane, ethanol, or vegetable oil and contain the full range of phytocompounds that are found in the Capsicum annuum or Capsicum frutescens plant (aka red chiles), including Capsaicin. Aflatoxin and N-nitroso compounds (N-nitrosodimethylamine and N-nitrosopyrrolidine) have been detected as contaminants. The ultraviolet (UV) absorption spectrum for Capsicum Annuum Fruit Extract indicates a small peak at approximately 275 nm, and a gradual increase in absorbance, beginning at approximately 400 nm. Capsicum and paprika are generally recognized as safe by the U.S. Food and Drug Administration for use in food. Hexane, chloroform, and ethyl acetate extracts of Capsicum Frutescens Fruit at 200 mg/kg resulted in death of all mice. In a short-term inhalation toxicity study using rats, no difference was found between vehicle control and a 7% Capsicum Oleoresin solution. In a 4-week feeding study, red chilli (Capsicum annuum) in the diet at concentrations up to 10% was relatively nontoxic in groups of male mice. In an 8-week feeding study using rats, intestinal exfoliation, cytoplasmic fatty vacuolation and centrilobular necrosis of hepatocytes, and aggregation of lymphocytes in the portal areas were seen at 10% Capsicum Frutescens Fruit, but not 2%. Rats fed 0.5 g/kg day-1 crude Capsicum Fruit Extract for 60 days exhibited no significant gross pathology at necropsy, but slight hyperemia of the liver and reddening of the gastric mucosa were observed. Weanling rats fed basal diets supplemented with whole red pepper at concentrations up to 5.0% for up to 8 weeks had no pathology of the large intestines, livers, and kidneys, but destruction of the taste buds and keratinization and erosion of the gastrointestinal (GI) tract were noted in groups fed 0.5% to 5.0% red pepper. The results of 9-and 12-month extension of this study showed normal large intestines and kidneys. In rabbits fed Capsicum Annuum Powder at 5 mg/kg day-1 in the diet daily for 12 months damage to the liver and spleen was noted. A rabbit skin irritation test of Capsicum Annuum Fruit Extract at concentrations ranging from 0.1% to 1.0% produced no irritation, but Capsicum Frutescens Fruit Extract induced concentration-dependent (at 25 to 500 microg/ml) cytotoxicity in a human buccal mucosa fibroblast cell line. An ethanol extract of red chili was mutagenic in Salmonella typhimurium TA98, but not in TA100, or in Escherichia coli. Other genotoxicity assays gave a similar pattern of mixed results. Adenocarcinoma of the abdomen was observed in 7/20 mice fed 100 mg red chilies per day for 12 months; no tumors were seen in control animals. Neoplastic changes in the liver and intestinal tumors were observed in rats fed red chili powder at 80 mg/kg day-1 for 30 days, intestinal and colon tumors were seen in rats fed red chili powder and 1,2-dimethyl hydrazine, but no tumors were observed in controls. In another study in rats, however, red chile pepper in the diet at the same dose decreased the number of tumors seen with 1,2-dimethylhydrazine. Other feeding studies evaluated the effect of red chili peppers on the incidence of stomach tumors produced by N-methyl-N'-nitro-N-nitrosoguanidine, finding that red pepper had a promoting effect. Capsicum Frutescens Fruit Extract promoted the carcinogenic effect of methyl(acetoxymethyl)nitrosamine (carcinogen) or benzene hexachloride (hepatocarcinogen) in inbred male and female Balb/c mice dosed orally (tongue application). Clinical findings include symptoms of cough, sneezing, and runny nose in chili factory workers. Human respiratory responses to Capsicum Oleoresin spray include burning of the throat, wheezing, dry cough, shortness of breath, gagging, gasping...(more)
[No authors listed] Int J Toxicol 2007;26 Suppl 1:3-106. Review.
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- 30. Catabolism of (+)-Catechin and (-)-Epicatechin by Rat Intestinal Microbiota.
Catabolism of (+)-catechin (+C) and (-)-epicatechin (EC) by rat intestinal microbiota was examined in vitro. +C and EC metabolites isolated were identified by LC-MS and NMR analyses. As a result, 4-hydroxy-5-(3-hydroxyphenyl)valeric acid (C-5 and EC-5), 4-oxo-5-(3, 4-dihydorxyphenyl)valeric acid (EC-7), 4-oxo-5-(3-hydorxyphenyl)valeric acid (EC-8), and 1-(4-hydroxyphenyl)-3-(2, 4, 6-trihydroxyphenyl)propan-2-ol (EC-13) were identified as new metabolites of +C or EC. From the measurement of optical rotation, each of +C and EC metabolites possessing the same chemical structure and chiral carbon was inferred to have enantiomeric relationship to each other and to maintain the configurations at 3 position of the original catechins. On the basis of these findings together with previous information, the proposed metabolic pathway of +C and EC by rat intestinal microbiota was updated....(more)
Takagaki A, et al. J Agric Food Chem 2013 Apr 26.
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- 31. Systematic identification and quantification of tetracyclic monoterpenoid oxindole alkaloids in Uncaria rhynchophylla and their fragmentations in Q-TOF-MS spectra.
Uncaria rhynchophylla (UR) is a species of Uncaria that is distributed mainly in China and Japan. In this study, the chemical constituents, including alkaloids, flavonoids, and quinic acids, in UR have been systematically identified and quantified by a developed method of high-performance liquid chromatography coupled with diode-array detection and quadrupole time-of-flight mass spectrometry (Q-TOF-MS). Tetracyclic monoterpenoid oxindole alkaloids (TMOAs) are characteristic compounds in this herb, and their fragmentations in Q-TOF-MS have been investigated. Diagnostic fragmentation ions (DFIs) were first delineated for isorhynchophylline-type (7S, C20-ethyl) and corynoxeine-type (7R, C20-vinyl) TMOAs, and these were used for identification of these alkaloids in UR. In this study, a total of 29 compounds, comprising 18 alkaloids, six flavonoids, and five quinic acids, were identified. Among them, there are four novel TMOAs, named as 22-O-β-glucopyranosyl isorhynchophyllic acid (10), 22-O-β-glucopyranosyl rhynchophyllic acid (11), 9-hydroxy isocorynoxeine (16), and 9-hydroxy corynoxeine (20), which have not been reported previously. Furthermore, eight marker compounds, namely chlorogenic acid (3), catechin (8), epicatechin (9), isocorynoxeine (24), rhynchophylline (25), isorhynchophylline (27), vincoside lactam (28), and corynoxeine (29), have been simultaneously quantified. The developed method has been validated and successfully applied to analyze three samples of UR from Jiangxi Province. The contents of the marker compounds have been detected and compared....(more)
Xie S, et al. J Pharm Biomed Anal 2013 Apr 2;81-82C:56-64.
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- 32. The Effect of the Aerial Part of Lindera akoensis on Lipopolysaccharides (LPS)-Induced Nitric Oxide Production in RAW264.7 Cells.
Four new secondary metabolites, 3α-((E)-Dodec-1-enyl)-4β-hydroxy-5β-methyldihydrofuran-2-one (1), linderinol (6), 4'-O-methylkaempferol 3-O-α-L-(4''-E-p-coumaroyl)rhamnoside (11) and kaempferol 3-O-α-L-(4''-Z-p-coumaroyl)rhamnoside (12) with eleven known compounds-3-epilistenolide D1 (2), 3-epilistenolide D2 (3), (3Z,4α,5β)-3-(dodec-11-ynylidene)-4-hydroxy-5-methylbutanolide (4), (3E,4β,5β)-3-(dodec-11-ynylidene)-4-hydroxy-5-methylbutanolide (5), matairesinol (7), syringaresinol (8), (+)-pinoresinol (9), salicifoliol (10), 4''-p-coumaroylafzelin (13), catechin (14) and epicatechin (15)-were first isolated from the aerial part of Lindera akoensis. Their structures were determined by detailed analysis of 1D- and 2D-NMR spectroscopic data. All of the compounds isolated from Lindera akoensis showed that in vitro anti-inflammatory activity decreases the LPS-stimulated production of nitric oxide (NO) in RAW 264.7 cell, with IC50 values of 4.1-413.8 µM....(more)
Yang CP, et al. Int J Mol Sci 2013 Apr 26;14(5):9168-81.
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- 33. Phenolic Constituents, Antioxidant and Preliminary Antimycoplasmic Activities of Leaf Skin and Flowers of Aloe vera (L.) Burm. f. (syn. A. barbadensis Mill.) from the Canary Islands (Spain).
The methanol extracts of leaf skins and flowers of Aloe vera from the Canary Islands were analyzed for their phenolic profiles and screened for their antioxidant and antimycoplasmic activities. The use of reversed phase high performance liquid chromatography (RP-HPLC) allowed the identification of 18 phenolic constituents. Leaf skin extracts were characterized by the abundance of catechin, sinapic acid and quercitrin. Gentisic acid, epicatechin and quercitrin were the most prominent phenolic compounds of the flowers. The in vitro antioxidant activities determined by using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) and ferric antioxidant reducing power (FRAP) assays revealed that both extracts exhibited antioxidant activity, being the leaf skin extract the most active fraction. The leaf skin extract was also found to be active against the microbial strains tested. Therefore, A. vera extracts from leaf skin and flowers can be considered as good natural antioxidant sources....(more)
López A, et al. Molecules 2013 Apr 26;18(5):4942-54.
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- 34. Catechins in Dietary Supplements and Hepatotoxicity.
BACKGROUND:
Many herbal dietary supplements (HDS) contain green tea extract (GTE) and its component catechins, although their presence may not always be indicated on the product label.
PURPOSE:
Because GTE and catechins have been implicated in human hepatotoxicity in several case reports, our objective was to determine whether catechins were present in HDS that were implicated in hepatotoxicity, even if not identified among the labeled ingredients, and whether these compounds could be associated with liver injury.
METHODS:
We assayed 97 HDS implicated in human hepatotoxicity for catechins.
RESULTS:
We found that 29 of 73 HDS (39.7 %) that did not identify GTE or any of its component catechins on their label contained catechins. Among patients with confirmed hepatotoxicity, there was no statistically significant association between the presence of catechin or the dose consumed and liver injury causality score, severity, or pattern of liver injury. Catechin levels tended to be highest in products used for weight loss, although catechin concentrations were low in most products.
CONCLUSIONS:
Many HDS commonly contain catechins that are implicated in hepatotoxicity, although their presence may not be indicated on the product label. Although our results did not establish an association between GTE or catechins with hepatotoxicity, they highlight some of the many complexities and uncertainties that surround the attribution of drug-induced liver injury (DILI) to HDS....(more)
Navarro VJ, et al. Dig Dis Sci 2013 Apr 27.
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- 35. First regiocontrolled synthesis of procyanidin B<sub>6</sub>, a catechin dimer with rare connectivity: a halo-capping strategy for formation of 4,6-interflavan bonds.
The first regiocontrolled synthesis of procyanidin B6, a dimer with a rare 4,6-interflavan linkage, is described. Regioselective linking was achieved by the halo-capping strategy followed by removal of all the benzyl protecting groups and the halo-caps by one-pot hydrogenolysis....(more)
Watanabe G, et al. Chem Commun (Camb) 2013 Apr 29.
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