- 1. Tanshinone I Activates the Nrf2-Dependent Antioxidant Response and Protects Against As(III)-Induced Lung Inflammation In Vitro and In Vivo.
Abstract Aims: The NF-E2 p45-related factor 2 (Nrf2) signaling pathway regulates the cellular antioxidant response and activation of Nrf2 has recently been shown to limit tissue damage from exposure to environmental toxicants, including As(III). In an attempt to identify improved molecular agents for systemic protection against environmental insults, we have focused on the identification of novel medicinal plant-derived Nrf2 activators. Results: Tanshinones [tanshinone I (T-I), tanshinone IIA, dihydrotanshinone, cryptotanshinone], phenanthrenequinone-based redox therapeutics derived from the medicinal herb Salvia miltiorrhiza, have been tested as experimental therapeutics for Nrf2-dependent cytoprotection. Using a dual luciferase reporter assay overexpressing wild-type or mutant Kelch-like ECH-associated protein-1 (Keap1), we demonstrate that T-I is a potent Keap1-C151-dependent Nrf2 activator that stabilizes Nrf2 by hindering its ubiquitination. In human bronchial epithelial cells exposed to As(III), T-I displays pronounced cytoprotective activity with upregulation of Nrf2-orchestrated gene expression. In Nrf2 wild-type mice, systemic administration of T-I attenuates As(III) induced inflammatory lung damage, a protective effect not observed in Nrf2 knockout mice. Innovation: Tanshinones have been identified as a novel class of Nrf2-inducers for antioxidant tissue protection in an in vivo As(III) inhalation model, that is relevant to low doses of environmental exposure. Conclusion: T-I represents a prototype Nrf2-activator that displays cytoprotective activity upon systemic administration targeting lung damage originating from environmental insults. T-I based Nrf2-directed systemic intervention may provide therapeutic benefit in protecting other organs against environmental insults. Antioxid. Redox Signal. 00, 000-000....(more)
Tao S, et al. Antioxid Redox Signal 2013 Mar 21.
Related Products: Cryptotanshinone
- 2. Qualitative and quantitative analysis of the major constituents in Chinese medicinal preparation Dan-Lou tablet by ultra high performance liquid chromatography/diode-array detector/quadrupole time-of-flight tandem mass spectrometry.
A rapid ultra high performance liquid chromatography/diode-array detector/quadrupole time-of-flight tandem mass spectrometry (UPLC-DAD-QTOF) method and a ultra high performance liquid chromatography coupled with diode-array detector (UPLC-DAD) method were developed for qualitative and quantitative analyses of the major chemical constituents in Dan-Lou tablet. Sixty-eight compounds including flavonoids, phenolic acids, tanshinones, protostane triterpenoids, lactones, and paeoniflorins were unambiguously or tentatively identified by comparing their retention times and accurate mass measurement in 40min with references or literature data. Among them, 19 compounds: gallic acid, danshensu, 5-hydroxymethyl-2-furaldehyde, 3'-hydroxy puerarin, puerarin, 3'-methoxy puerarin, mirificin, daidzin, paeoniflorin, calycosin-7-O-β-D-glucoside, naringin, genistin, rosmarinic acid, salvianolic acid B, salvianolic acid A, formononetin, calycosin, cryptotanshinone and tanshinone IIA were further quantified in 30min as marker substances. It was found that the calibration curves for all analytes showed good linearity (R(2)>0.9997) within the test ranges. The overall limits of detection (LODs) and limits of quantification (LOQs) were 0.0073-0.34μg/mL and 0.022-1.04μg/mL, respectively. The relative standard deviations (RSDs) for intra- and inter-day precisions were below 1.90% and 2.85%, respectively. The results of repeatability were less than 2.74%. The sample was stable for at least 48h. The mean recovery rates ranged from 95.5% to 105% with the relative standard deviations (RSDs) less than 2.96%. The results showed that the developed quantitative method was linear, sensitive, and precise for quality control of Dan-Lou tablet....(more)
Dong J, et al. J Pharm Biomed Anal 2013 Jun;80:50-62.
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- 3. Anticancer activity in human multiple myeloma U266 cells: synergy between cryptotanshinone and arsenic trioxide.
Arsenic trioxide (As2O3) has been recently established as one of the most effective drugs for the treatment of patients with acute promyelocytic leukemia. However, it has exhibited to be less efficient for the non-promyelocytic leukaemia or other types of malignant tumors. The purpose of the present study was to explore new therapeutic strategies based on As2O3 for human multiple myeloma. Here, we first report cryptotanshinone (CPT) and As2O3 synergy for enhanced cytotoxicity in human multiple myeloma U266 cells. In particular, the apoptosis related proteins (e.g., cleaved poly (ADP-ribose) polymerase (PARP), caspase-3 and -9) were significantly increased by the combination treatment (iAs<sup>III</sup> + CPT), whereas, the expression of survival proteins such as Bcl-2 and survivin was suppressed, suggesting that the induction of apoptosis through mitochondrial-mediated apoptotic pathway. In addition, there were no appreciable effects observed in cells after exposure to either As2O3 or CPT alone. In order to better understand the molecular mechanism, we further determined the phosphorylation of STAT3, JNK, ERK and p38. Interestingly, phosphorylation of JNK and p38 were remarkably induced by combination treatment, and no significant inhibition of STAT3 or ERK was observed. In addition, induction of apoptosis in human multiple myeloma cells was partially abrogated only by pretreatment with JNK inhibitor and not by p38 inhibitor, suggesting that JNK pathway may play an important role in induction of apoptosis by the combination of iAs<sup>III</sup> and CPT. Further studies are needed to evaluate this synergistic anticancer effect in vivo. In the near future, this new approach might be used clinically for multiple myeloma (MM) treatment....(more)
Liu P, et al. Metallomics 2013 Mar 26.
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- 4. Tanshinone IIA and Cryptotanshinone Prevent Mitochondrial Dysfunction in Hypoxia-Induced H9c2 Cells: Association to Mitochondrial ROS, Intracellular Nitric Oxide, and Calcium Levels.
The protective actions of tanshinones on hypoxia-induced cell damages have been reported, although the mechanisms have not been fully elucidated. Given the importance of nitric oxide (NO) and reactive oxygen species (ROS) in regulation of cell functions, the present study investigated the effects of two major tanshinones, Tanshinone IIA (TIIA) and cryptotanshinone (CT), on hypoxia-induced myocardial cell injury and its relationships with intracellular NO and ROS, calcium, and ATP levels in H9c2 cells. Chronic hypoxia significantly reduced cell viability which accompanied with LDH release, increase in mitochondrial ROS, intracellular NO and calcium levels, decrease in superoxide dismutase (SOD) activity, and cellular ATP contents. TIIA and CT significantly prevented cell injury by increasing cell viability and decreasing LDH release. The protective effects of tanshinones were associated with reduced mitochondrial superoxide production and enhanced mitochondrial SOD activity. Tanshinones significantly reduced intracellular NO and Ca(2+) levels. ATP levels were also restored by TIIA. These findings suggest that the cytoprotective actions of tanshinones may involve regulation of intracellular NO, Ca(2+), ATP productions, mitochondrial superoxide production, and SOD activity, which contribute to their actions against hypoxia injuries....(more)
Jin HJ, et al. Evid Based Complement Alternat Med 2013;2013:610694.
Related Products: Cryptotanshinone
- 5. Conical coils counter-current chromatography for preparative isolation and purification of tanshinones from Salvia miltiorrhiza Bunge.
Modern counter-current chromatography (CCC) originated from the helical coil planet centrifuge. Recently, spiral coils were found to possess higher separation efficiency in both the retention of stationary phase and solutes resolution than other CCC coils like the helical and toroidal coils used on type-J CCC and cross-axis CCC. In this work, we built a novel conical coil CCC for the preparative isolation and purification of tanshinones from Salvia miltiorrhiza Bunge. The conical coils were wound on three identical upright tapered holders in head-to-tail and left-handed direction and connected in series. Compared with helical and spiral coil CCC, conical coil CCC not only placed CCC column in a two-dimensional centrifugal field, but also provided a potential centrifugal force gradient both in axial and radial directions. The extra centrifugal gradient made mobile phase move faster and enabled CCC much higher retention of stationary phase and better resolution. As a result, higher efficiency has been obtained with the solvent system of hexane-ethyl acetate-methanol-water (HEMWat) with the volume ratio of 5:5:7:3 by using conical coil CCC apparatus. Four tanshinones, including cryptotanshinone (1), tanshinone I (2), 1,2-dihydrotanshinquinone (3) and tanshinone IIA (4), were well resolved from 500mg to 1g crude samples with high purity. Furthermore, the conical coil CCC can make a much higher solid phase retention, which makes it to be a powerful separation tool with high throughput. This is the first report about conical coil CCC for separation of tanshinones and it may also be an important advancement for natural products isolation....(more)
Liang J, et al. J Chromatogr A 2013 May 3;1288:35-9.
Related Products: Cryptotanshinone
- 6. PF2401-SF, standardized fraction of Salvia miltiorrhiza shows anti-inflammatory activity in macrophages and acute arthritis in vivo.
Standardization of processing methods for herbs is as important as authentication to maintain their quality and ensure their safe use. We had previously prepared a standardized and purified Salvia miltiorrhiza Bunge extract, PF2401-SF, and showed that it protects against liver injury in vivo, at a greater potency than an ethanol extract. PF2401-SF was enriched with tanshinone I (11.5%), tanshinone IIA (41.0%), and cryptotanshinone (19.1%). In this study, we investigated potential anti-inflammatory effects of PF2401-SF in vitro and in vivo. We demonstrated that PF2401-SF shows anti-inflammatory potency on lipopolysaccharide (LPS)-induced nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression in RAW 264.7 cells. A mechanistic study indicated that PF2401-SF induced heme oxygenase (HO)-1 expression through extracellular signal-regulated kinases (ERK1/2) phosphorylation. Moreover, we also evaluated that PF2401-SF significantly reduced inflammation on carrageenan- or dextran-induced acute arthritis in rats. Our results suggest that PF2401-SF may be a potential candidate for the treatment of various inflammatory diseases....(more)
Jiang WY, et al. Int Immunopharmacol 2013 Apr 10.
Related Products: Cryptotanshinone
- 7. A novel inhibitor, 16-hydroxy-cleroda-3,13-dien-16,15-olide, blocks the autophosphorylation site of focal adhesion kinase (Y397) by molecular docking.
BACKGROUND:
Focal adhesion kinase (FAK) is a nonreceptor protein tyrosine plays an important role in a number of cell signaling pathways, including cell migration, proliferation, and cell survival. This study was aimed to identify novel and specific inhibitors from natural compounds via molecular docking of FAK (Y397).
METHODS:
The 3D structure of FAK (PDB ID: 2AL6) was used for docking 109 natural compounds. Based on high affinity and energy interaction, four of ten candidate compounds, 16-hydroxy-cleroda-3,13-dien-16,15-olide (HCD), curcumin, quercetin, and catechin hydrate, were hit, and the inhibitory activity against FAK was validated in these compounds in C6 glioma and N18 neuroblastoma cell lines.
RESULTS:
HCD showed a potential effect on cell viability by MTT assay and cell arrest in the G0-G1 phase, and a TUNEL assay confirmed further apoptosis. Treatment with HCD decreased anti-apoptotic proteins and increased pro-apoptotic proteins. Atomic force microscopy data depicted that the formation of filopodia on the intracellular surface decreased in treated cells compared with the control. Zymography showed that HCD inhibited the activity of MMP-2 and MMP-9. The protein levels of FAK, pFAK, Rac1 and Cdc42, which are the key regulators for the formation of filopodia, were decreased. Additionally, HCD regulated the expression of epithelial mesenchymal transition proteins.
CONCLUSIONS:
HCD effectively interacted at the autophosphorylation site of FAK and interaction analysis indicated an H-bond with the Arg 86 and Arg 125 residues.
GENERAL SIGNIFICANCE:
This study suggests that HCD could be a potential inhibitor of FAK and could be used for anti-tumorigenesis and anti-metastasis treatments.
Copyright © 2013. Published by Elsevier B.V....(more)
Varadharajan T, et al. Biochim Biophys Acta 2013 Apr 26.
Related Products: Curcumin
- 8. Curcumin Acts as a Pro-Oxidant Inducing Apoptosis Via JNKs in the Isolated Perfused Rana ridibunda Heart.
Amphibians are known to better tolerate and endure adverse environmental conditions such as redox imbalances conferred by reactive oxygen species (ROS), compared to mammals. Interestingly, the exact adaptation strategies and signaling mechanisms mediating these effects have not been fully elucidated. Therefore, in the present study, we probed into the molecular response of the isolated perfused Rana ridibunda heart to curcumin, in the context of mitogen-activated protein kinases (MAPKs) phosphorylation patterns and apoptotic markers occurrence. In particular, this polyphenol was found to exert a pro-oxidant effect in our model and to significantly upregulate p38-MAPK and JNKs phosphorylation (thus activation). The early apoptosis observed, substantiated by poly(ADP-ribose) polymerase (PARP) cleavage, was established to be JNKs- and ROS-mediated, while no involvement of p38-MAPK was detected. Subsequently, the pro-oxidative activity of curcumin was confirmed to mimic H2 O2 . Furthermore, NADPH oxidase as well as Na<sup>+</sup> /K<sup>+</sup> -ATPase were found to mediate JNKs phosphorylation as well as PARP proteolytic cleavage. Curcumin exerts pleiotropic actions, both beneficial and detrimental and is currently the subject of intense scientific research. Being a low-molecular-weight antioxidant, it is intriguing to investigate curcumin's role in redox homeostasis in the amphibian heart, under conditions that apparently favor its pro-oxidative properties. Comparative studies of its multifaceted role in different species may contribute to the clarification of the signaling mechanisms it triggers and the terminal physiological response it confers. Collectively, this is to our knowledge, the first time that the signal transduction pathways stimulated by curcumin have been assessed in a non-mammalian species. J. Exp. Zool. 9999A: XX-XX, 2013. © 2013 Wiley Periodicals, Inc....(more)
Aggeli IK, et al. J Exp Zool A Ecol Genet Physiol 2013 Apr 29.
Related Products: Curcumin
- 9. p300-Mediated Histone Acetylation is Essential for the Regulation of GATA4 and MEF2C by BMP2 in H9c2 Cells.
Histone acetylase (HAT) p300 plays an important role in the regulation of cardiac gene expression. During cardiac development, bone morphogenetic protein (BMP)-2 induces the expression of cardiac transcription factors. However, the underlying molecular mechanism(s) is not clear. In the present study, we tested the hypothesis that p300-mediated histone acetylation was essential for the regulation of cardiac transcription factors by BMP2. Cultured rat H9c2 embryonic cardiac myocytes (H9c2 cells) were transfected with recombinant adenoviruses expressing human BMP2 (AdBMP2) with or without curcumin, a specific p300-HAT inhibitor. Quantitative real-time RT-PCR analysis showed that curcumin substantially inhibited both AdBMP2-induced and basal expression levels of cardiac transcription factors GATA4 and MEF2C, but not Tbx5. Similarly, chromatin immunoprecipitation (ChIP) analysis showed that curcumin inhibited both AdBMP2-induced and basal histone H3 acetylation levels in the promoter regions of GATA4 and MEF2C, but not of Tbx5. In addition, curcumin selectively suppressed AdBMP2-induced expression of HAT p300, but not HAT GCN5 in H9c2 cells. The data indicated that inhibition of histone H3 acetylation with curcumin diminished BMP2-induced expression of GATA4 and MEF2C, suggesting that p300-mediated histone acetylation was essential for the regulation of GATA4 and MEF2C by BMP2 in H9c2 cells....(more)
Zheng M, et al. Cardiovasc Toxicol 2013 Apr 30.
Related Products: Curcumin
- 10. Role of curcumin in systemic and oral health: An overview.
Various modalities of treatment are available for different dental diseases, but the major drawback of these conventional drug therapies is the numerous side effects associated with their use. This has led to renewed interest in the discovery of novel anti-infective natural compounds derived from plants. Plants have been the major source of medicine since the time immemorial. Turmeric has been attributed a number of medicinal properties in the traditional system of medicine. The objective of this article is to review the efficacy of turmeric herb in maintenance of oral health, in particular, and overall health, in general. Turmeric, a rhizome of Curcuma longa, is a herb known for its medicinal properties and is a more acceptable and viable option for a common man. It has proven properties like anti-inflammatory, antioxidant, antimicrobial, hepatoprotective, immunostimulant, antiseptic, and antimutagenic. Due to these properties, it is quite useful in dentistry as well. It has a role in the treatment of periodontal diseases and oral cancers. Turmeric can also be used as a pit and fissure sealant, mouth wash, and subgingival irrigant in different preparations. It can also be used as a component in local drug delivery system in gel form....(more)
Nagpal M, et al. J Nat Sci Biol Med 2013 Jan;4(1):3-7.
Related Products: Curcumin
- 11. Microbial Transformation of Curcumin to Its Derivatives with a Novel Pichia kudriavzevii ZJPH0802 Strain.
Curcumin, a polyphenolic compound, has shown a wide range of pharmacological activities and has been widely used as a food additive. However, the clinical use of curcumin is limited to some extent because of its poor water solubility and low bioavailability. To overcome these problems, many approaches have been attempted and structural modification of curcumin by microbial transformation has been proven to be an alternative. In this study, we isolated a novel yeast strain Pichia kudriavzevii ZJPH0802 from a soil sample, which is capable of converting curcumin to its derivatives. The transformed products by this strain were evaluated by HPLC, (+) electrospray ionization (ESI)-MS<sup>n</sup>, and <sup>1</sup>H nuclear magnetic resonance methods. Compared with controls, two new peaks of the transformed broth appeared at retention times of 26 min (I) and 62 min (II) by HPLC analysis. The two transformed products were then further identified by (+) ESI-MS<sup>n</sup>. The spectrum showed that compound I had an accurate [M+H+NH3]<sup>+</sup> ion at m/z 392, [M+H]<sup>+</sup> ion at m/z 375, [M+H-H2O]<sup>+</sup> ion at m/z 357, and (+) ESI-MS<sup>3</sup> spectrum showed that ion at m/z 357 could further form fragment ions at m/z 339, 177, and 163; compound II had an accurate [M+H]<sup>+</sup> ion at m/z 373, [M+H-H2O]<sup>+</sup> ion at m/z 355, and (+) ESI-MS<sup>3</sup> spectrum showed that ion at m/z 355 could further form fragment ions at m/z 219, 179, 177, 163, and 137. These two transformed products thereby were confirmed as hexahydrocurcumin (I) and tetrahydrocurcumin (II)....(more)
Zhang W, et al. Appl Biochem Biotechnol 2013 May 1.
Related Products: Curcumin
- 12. Curcumin acts via transient receptor potential vanilloid-1 receptors to inhibit gut nociception and reverses visceral hyperalgesia.
BACKGROUND:
An antinociceptive effect has been reported for curcumin in animal models and in humans, but the molecular mechanisms of curcumin's effect remain undefined. In this study, we explored the possibility that curcumin inhibit visceral nociception via antagonizing the transient receptor potential vanilloid-1 (TRPV1) receptor.
METHODS:
The effects of curcumin were explored using two experimental models: viscero-motor response (VMR) to colorectal distension (CRD) in rats and jejunal afferent firing in the ex vivo mouse jejunum preparations [TRPV1 knockout (KO) and wild-type mice, naive and trinitrobenzene sulfonic acid (TNBS)-treated Kunming mice]. In addition, capsaicin-induced calcium transients and whole-cell currents were examined in acutely dissociated dorsal root ganglia (DRG) neurons.
KEY RESULTS:
In the anesthetized rat, curcumin (4 mg kg<sup>-1</sup> min<sup>-1</sup> for 3 min) caused a marked and rapidly reversible inhibition of CRD-induced VMRs. In the mouse jejunum, the mesenteric afferent nerve response to ramp distension was attenuated by curcumin (3, 10 μmol L<sup>-1</sup> ), an effect that was significantly reduced in TRPV1 KO mice compared with wild-type (WT) controls. Moreover, in WT mice, curcumin (1-30 μmol L<sup>-1</sup> ) was found to inhibit the afferent responses to capsaicin in a concentration-dependent manner. Trinitrobenzene sulfonic acid-induced hypersensitivity of jejunal afferents was also attenuated by curcumin. Curcumin potently inhibited capsaicin-induced rise in intracellular calcium and inward currents in mouse or rat DRG neurons.
CONCLUSIONS & INFERENCES:
Our results provide strong evidence that curcumin inhibit visceral nociception via antagonizing TRPV1 and may be a promising lead for the treatment of functional gastrointestinal diseases.
© 2013 John Wiley & Sons Ltd....(more)
Zhi L, et al. Neurogastroenterol Motil 2013 May 3.
Related Products: Curcumin
- 13. Simultaneously screening four epidermal growth factor receptor antagonists from Curcuma longa via cell membrane chromatography online coupled with high performance liquid chromatography/mass spectrometry.
The epidermal growth factor receptors are significant targets for screening active compounds. In this work, an analytical method was established for rapid screening, separation and identification epidermal growth factor receptors antagonists from Curcuma longa. Human embryonic kidney 293 cells with steadily high expression epidermal growth factor receptors were used to prepare the cell membrane stationary phase in cell membrane chromatography model for screening active compounds. Separation and identification of the retention chromatographic peaks was achieved by the high performance liquid chromatography/mass spectrometry. The acting sites, docking extents and inhibitory effects of the active compounds were also demonstrated. The screening result found that ar-turmerone, curcumin, demethoxycurcumin and bisdemethoxycurcumin from Curcuma longa could be active components in a similar manner to gefitinib. Biological trials showed that all of four compounds can inhibit epidermal growth factor receptors protein secretion and cell growth in a dose-dependent manner, down regulate phosphorylation of epidermal growth factor receptors. This analytical method demonstrated fast and effective characteristics for screening, separation and identification active compounds from complex system and should be useful for drug discovery with natural medicinal herbs. This article is protected by copyright. All rights reserved....(more)
Sun M, et al. J Sep Sci 2013 May 3.
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- 14. Molecular changes induced by the curcumin analogue D6 in human melanoma cells.
BACKGROUND:
In a previous report, we described the in vitro and in vivo antiproliferative and proapoptotic activity of a hydroxylated biphenyl (D6), a structural analogue of curcumin, on malignant melanoma and neuroblastoma tumours. In this paper, we investigated the molecular changes induced by such a compound, underlying cell growth arrest and apoptosis in melanoma cells.
RESULTS:
To shed light on the mechanisms of action of D6, we firstly demonstrated its quick cellular uptake and subsequent block of cell cycle in G2/M phase transition. A gene expression profile analysis of D6-treated melanoma cells and fibroblasts was then carried out on high density microarrays, to assess gene expression changes induced by this compound. The expression profile study evidenced both an induction of stress response pathways and a modulation of cell growth regulation mechanisms. In particular, our data suggest that the antiproliferative and proapoptotic activities of D6 in melanoma could be partially driven by up-regulation of the p53 signalling pathways as well as by down-regulation of the PI3K/Akt and NF-kB pathways. Modulation of gene expression due to D6 treatment was verified by western blot analysis for single proteins of interest, confirming the results from the gene expression profile analysis.
CONCLUSIONS:
Our findings contribute to the understanding of the mechanisms of action of D6, through a comprehensive description of the molecular changes induced by this compound at the gene expression level, in agreement with its the previously reported anti-tumour effects on melanoma cells....(more)
Rozzo C, et al. Mol Cancer 2013 May 4;12(1):37.
Related Products: Curcumin
- 15. Natural polyphenols in the management of major depression.
Introduction: Natural polyphenols, the non-essential micronutrients, found in array of plant products, are known to affect various physiological and biochemical functions in the body. Studies have shown the protective effect of these polyphenols in different neurological and mental disorders. These polyphenols modulate monoaminergic neurotransmission in the brain and thus possess antidepressant-like activity at least in animal models of depression. Areas covered: The present review discusses the use of these natural polyphenols in the treatment of major depression. The review article discusses the antidepressant potential of some important polyphenols such as amentoflavone, apigenin, chlorogenic acid, curcumin, ferulic acid, hesperidin, rutin, quercetin, naringenin, resveratrol, ellagic acid, nobiletin and proanthocyanidins. The mechanism of action of these polyphenols in the treatment of major depression is also discussed in detail. Expert opinion: There is an exciting prospect in the discovery of natural polyphenols as therapeutic agents in the treatment of major depression....(more)
Pathak L, et al. Expert Opin Investig Drugs 2013 May 6.
Related Products: Curcumin
- 16. The possible roles of vitamin D and curcumin in treating gonorrhea.
Drug-resistant gonorrhea, Neisseria gonorrhoeae (N. gonorrhoeae), is an emerging concern, especially because the risk of bladder cancer is associated with this infection. N. gonorrhoeae suppresses T-helper 1(Th1) and Th2 responses and enhances Th17 responses via a mechanism involving transforming growth factor-beta (TGF-β) and regulatory T cells. Blockade of TGF-β alleviates the suppression of specific anti-gonococcal responses and allows Th1 and Th2 responses to emerge with concomitant boosting of immune memory and protective immunity. Gonorrhea activates nuclear factor kappaB (NF-kappaB), which plays a critical role in signal-transduction pathways involved in inflammation. The innate immune system can eventually clear gonorrhea. Vitamin D is emerging as a potential, powerful, anti-microbial agent with these effects: it supports the innate immune system in combating bacterial infections; it decreases levels of TGF-β and NF-kappaB activation; and it induces production of LL-37 (cathelicidin), which has antimicrobial and antiendotoxin properties. In addition, via an independent vitamin D receptor pathway, curcumin also induces LL-37 production, inhibiting N. gonorrhoeae-induced NF-kappaB signaling and inducing autophagy. Therefore, vitamin D and curcumin taken together may be useful in combating both normal and drug-resistant gonorrhea. Moreover, the possible synergy between these two agents in improving outcomes is worthy of additional investigation....(more)
Youssef DA, et al. Med Hypotheses 2013 Apr 30.
Related Products: Curcumin
- 17. [Isolation and analysis of a new phytoecdysteroid from Cyanotis arachnoidea C. B. Clarke].
Cyanotis arachnoidea is a plant with plenty of phytoecdysteroid. To study the active compound in it, a new phytoecdysteroid with 5alpha-cholesta skeleton, was isolated from the whole plant of Cyanotis arachnoidea C. B. Clarke by using various chromatographic methods (alumina column chromatography, silica gel column chromatography, octadecyl silane (ODS) column chromatography, thin layer chromatography (TLC) and high performance liquid chromatography (HPLC)). Its structure was analyzed on the basis of 1D and 2D nuclear magnetic resonances (NMR), electrospray ionization mass spectrometry (ESI-MS) methods. It is a compound with structure of 3beta,14alpha, 14alpha,20R,22R,25-hexahydroxy-5alpha-cholest-7-en-6-one, which is a rare phytoecdysteroid with 5alpha-H....(more)
Tan C, et al. Se Pu 2011 Sep;29(9):937-41. Chinese.
Related Products: Cyanotis Vaga extract
- 18. Multilocus analysis of honeyeaters (Aves: Meliphagidae) highlights spatio-temporal heterogeneity in the influence of biogeographic barriers in the Australian monsoonal zone.
Multilocus studies in phylogenetics and comparative phylogeography have the power to explore a broader spectrum of evolutionary questions than either discipline has alone. To examine the origins of sympatry in a group of closely related birds of mostly mesic eucalypt woodlands in Australia, we reconstructed the relationships among species of Entomyzon and Melithreptus honeyeaters (Aves: Passeriformes: Meliphagidae) using a mitochondrial marker, ND2, and six non-coding nuclear loci (total 4719 base pairs). By sampling across the geographical range of each species, we studied not only their phylogenetic relationships to each other but also the spatial distribution of their genetic diversity. We tested several biogeographic hypotheses concerning the role of Pleistocene environmental change in Australia. Phylogenetic gene trees support the current understanding of E. cyanotis as the sister to Melithreptus. Non-monophyly of M. lunatus in Australia's southern temperate woodlands highlights the need for a revision of systematics within Melithreptus. Phylogeographic analysis of the three northern species in Australia's monsoon tropics, M. gularis, M. albogularis and E. cyanotis, suggests that the roles of the Carpentarian and Torresian Barriers in shaping geographic structure in each of the species have been more complex and temporally dynamic than earlier morphology-based arguments of vicariance had suggested. We discuss their roles as ecological filters as well as barriers....(more)
Toon A, et al. Mol Ecol 2010 Jul;19(14):2980-94.
Related Products: Cyanotis Vaga extract
- 19. Ecdysteroids from Cyanotis longifolia Benth. (Commelinaceae).
Cyanotis longifolia Benth. (Commelinaceae) contains ecdysteroids, which are highly concentrated in the roots and flowers, whereas leaves contain only very low amounts and stems intermediate amounts. 20-Hydroxyecdysone is the major component found in all tissues, but roots also contain large amounts of 20-hydroxyecdysone 3-acetate and ajugasterone C. A preparative experiment has shown that roots contain a complex ecdysteroid mixture, and the analysis of minor components has allowed the isolation of several already known ecdysteroids (polypodine B, 2-deoxy-20,26-dihydroxyecdysone, isovitexirone, poststerone) together with five new (ajugasterone C 3-acetate, 5beta-hydroxy-poststerone, poststerone 2-acetate, 14(15)-dehydro-poststerone 2-acetate, 24-epi-atrotosterone A [=24-methyl-ajugasterone C]) ecdysteroids that have been fully characterized. A preliminary investigation of 55 species belonging to 15 different genera of the Commelinaceae has shown that several of them contain significant concentrations of ecdysteroids, among which some previously uninvestigated ones appear to be very promising sources of ecdysteroids.
(c) 2009 Wiley Periodicals, Inc....(more)
Crouzet S, et al. Arch Insect Biochem Physiol 2009 Dec;72(4):194-209.
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- 20. CC4, a dimer of cytisine, is a selective partial agonist at α4β2/α6β2 nAChR with improved selectivity for tobacco smoking cessation.
BACKGROUND AND PURPOSE:
Many of the addictive and rewarding effects of nicotine are due to its actions on the neuronal nicotinic ACh receptor (nAChR) subtypes expressed in dopaminergic mesocorticolimbic cells. The partial agonists, cytisine and varenicline, are helpful smoking cessation aids. These drugs have a number of side effects that limit their usefulness. The aim of this study was to investigate the preclinical pharmacology of the cytisine dimer1,2-bisN-cytisinylethane (CC4).
EXPERIMENTAL APPROACH:
The effects of CC4 on nAChRs were investigated using in vitro assays and animal behaviours.
KEY RESULTS:
When electrophysiologically tested using heterologously expressed human subtypes, CC4 was less efficacious than cytisine on neuronal α4β2, α3β4, α7 and muscle-type receptors, and had no effect on 5-hydroxytryptamine3 receptors. Acting through α4β2 and α6β2 nAChRs, CC4 is a partial agonist of nAChR-mediated striatal dopamine release and, when co-incubated with nicotine, prevented nicotine's maximal effect on this response. In addition, it had low affinity for, and was less efficacious than nicotine and cytisine on the α3β4 and α7-nAChR subtypes. Like cytisine and nicotine, CC4-induced conditioned place preference (CPP), and its self-administration shows an inverted-U dose-response curve. Pretreatment with non-reinforcing doses of CC4 significantly reduced nicotine-induced self-administration and CPP without affecting motor functions.
CONCLUSION AND IMPLICATIONS:
Our in vitro and in vivo findings reveal that CC4 selectively reduces behaviours associated with nicotine addiction consistent with the partial agonist selectivity of CC4 for β2-nAChRs. The results support the possible development of CC4 or its derivatives as a promising drug for tobacco smoking cessation.
© 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society....(more)
Sala M, et al. Br J Pharmacol 2013 Feb;168(4):835-49.
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- 21. Cytisine confers neuronal protection against excitotoxic injury by down-regulating GluN2B-containing NMDA receptors.
Cytisine (CYT), one of the principal bioactive components derived from the seeds of Cytisus laborinum L, has been widely used for central nervous system (CNS) diseases treatment. The present study investigated the protective effect of CYT on cultured cortical neural injury induced by N-methyl-d-aspartate (NMDA). Our data showed that CYT conferred protective effect against loss of cellular viability induced by brief exposure to 200 μM NMDA in a concentration-dependent manner. CYT significantly inhibited the neuronal apoptosis induced by NMDA exposure by reversing intracellular Ca(2+) overload and balancing Bcl-2 and Bax expression levels. Furthermore, CYT significantly reversed the up-regulation of GluN2B-containing NMDA receptors by exposure to NMDA, but it did not affect the level of GluN2A-containing NMDA receptors. These findings suggest that CYT protects cortical neurons, at least partially, by inhibiting the level of GluN2B-containing NMDA receptors and regulating Bcl-2 family....(more)
Li YJ, et al. Neurotoxicology 2013 Jan;34:219-25.
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- 22. Modulation of α7 nicotinic acetylcholine receptor and fibrillar amyloid-β interactions in Alzheimer's disease brain.
The nicotinic receptors (nAChRs), which play a critical role in cognitive function, are impaired early in the course of Alzheimer's disease (AD). We have previously demonstrated that amyloid-β (Aβ) assemblies bind to α7 nAChRs and form complexes in AD brain, suggesting that this cooperative process may contribute to disruption of synaptic function in AD. In the current study, we further characterized the interaction between different nAChR subtypes and fibrillar Aβ by binding assays in postmortem brain from AD and control cases using a wide range of drugs with different molecular targets, including selective nAChR subtype agonists, and the amyloid ligand Pittsburgh compound B (PIB) that binds with high (nanomolar) affinity to fibrillar Aβ. The α7 nAChR agonists varenicline and JN403, but not the α4β2 nAChR agonist cytisine, increased the 3H-PIB binding in autopsy tissue homogenates from AD and control frontal cortex. This effect was blocked in the presence of the α7 nAChR antagonists methyllycaconitine, α-bungarotoxin, and mecamylamine, but not by the α4β2 nAChR antagonist dihydro-β-erythroidine. Increases in (3)H-PIB binding evoked by varenicline and JN403 were also prevented by pre-incubation with another amyloid ligand, BF-227. The acetylcholinesterase inhibitor and allosteric nAChR modulator galantamine as well as the N-methyl-d-aspartate receptor blocker memantine did not significantly alter (3)H-PIB binding levels in AD brain. The present findings further support a specific interaction between fibrillar Aβ and α7 nAChRs in the brain, suggesting that treatment with α7 nAChR stimulatory drugs can modulate Aβ/α7 nAChR pathogenic signaling mechanisms in AD brain....(more)
Ni R, et al. J Alzheimers Dis 2013;33(3):841-51.
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- 23. Nicotinic α4β2 receptor imaging agents. Part IV. Synthesis and biological evaluation of 3-(2-(S)-3,4-dehydropyrrolinyl methoxy)-5-(3'-¹?F-fluoropropyl)pyridine (¹?F-Nifrolene) using PET.
Imaging agents for nicotinic α4β2 receptors in the brain have been under way for studying various CNS disorders. Previous studies from our laboratories have reported the successful development of agonist, ¹F-nifene. In attempts to develop potential antagonists, ¹F-nifrolidine and ¹F-nifzetidine were previously reported. Further optimization of these fluoropropyl derivatives has now been carried out resulting in 3-(2-(S)-3,4-dehydropyrrolinylmethoxy)-5-(3'-Fluoropropyl)pyridine (nifrolene) as a new high affinity agent for nicotinic α4β2 receptors. Nifrolene in rat brain homogenate assays--labeled with ³H-cytisine--exhibited a binding affinity of 0.36 nM. The fluorine-18 analog, ¹F-nifrolene, was synthesized in approximately 10%-20% yield and specific activity was estimated to be >2000 Ci/mmol. Rat brain slices indicated selective binding to anterior thalamic nuclei, thalamus, subiculum, striata, cortex and other regions consistent with α4β2 receptor distribution. This selective binding was displaced >90% by 300 μM nicotine. Thalamus to cerebellum ratio (>10) was the highest for ¹F-nifrolene with several other regions showing selective binding. In vivo rat PET studies exhibited rapid uptake of ¹F-nifrolene in the brain with specific retention in the thalamus and other brain regions while clearing out from the cerebellum. Thalamus to cerebellum ratio value in the rat was >4. Administration of nicotine caused a rapid decline in the thalamic ¹F-nifrolene suggesting reversible binding to nicotinic receptors. PET imaging studies of ¹F-nifrolene in anesthetized rhesus monkey revealed highest binding in the thalamus followed by regions of the lateral cingulated and temporal cortex. Cerebellum showed the least binding. Thalamus to cerebellum ratio in the monkey brain was >3 at 120 min. These ratios of ¹F-nifrolene are higher than measured for ¹F-nifrolidine and ¹F-nifzetidine. ¹F-Nifrolene thus shows promise as a new PET imaging agent for α4β2 nAChR....(more)
Pichika R, et al. Nucl Med Biol 2013 Jan;40(1):117-25.
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- 24. Molecular determinants of subtype-selective efficacies of cytisine and the novel compound NS3861 at heteromeric nicotinic acetylcholine receptors.
Deciphering which specific agonist-receptor interactions affect efficacy levels is of high importance, because this will ultimately aid in designing selective drugs. The novel compound NS3861 and cytisine are agonists of nicotinic acetylcholine receptors (nAChRs) and both bind with high affinity to heteromeric α3β4 and α4β2 nAChRs. However, initial data revealed that the activation patterns of the two compounds show very distinct maximal efficacy readouts at various heteromeric nAChRs. To investigate the molecular determinants behind these observations, we performed in-depth patch clamp electrophysiological measurements of efficacy levels at heteromeric combinations of α3- and α4-, with β2- and β4-subunits, and various chimeric constructs thereof. Compared with cytisine, which selectively activates receptors containing β4- but not β2-subunits, NS3861 displays the opposite β-subunit preference and a complete lack of activation at α4-containing receptors. The maximal efficacy of NS3861 appeared solely dependent on the nature of the ligand-binding domain, whereas efficacy of cytisine was additionally affected by the nature of the β-subunit transmembrane domain. Molecular docking to nAChR subtype homology models suggests agonist specific interactions to two different residues on the complementary subunits as responsible for the β-subunit preference of both compounds. Furthermore, a principal subunit serine to threonine substitution may explain the lack of NS3861 activation at α4-containing receptors. In conclusion, our results are consistent with a hypothesis where agonist interactions with the principal subunit (α) primarily determine binding affinity, whereas interactions with key amino acids at the complementary subunit (β) affect agonist efficacy....(more)
Harpsøe K, et al. J Biol Chem 2013 Jan 25;288(4):2559-70.
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- 25. Study on noncovalent complexes of alkaloids with DNA duplex using electrospray ionization mass spectrometry.
RATIONALE:
DNA is an important molecular target in modern medicine research. Some DNA-binding ligands have been used to treat numerous diseases. Therefore, understanding the interactions of different ligands with DNA and looking for new DNA agents are necessary to develop new drugs.
METHODS:
Electrospray ionization mass spectrometry (ESI-MS) in the negative ion mode was used to screen the noncovalent complexes between 11 alkaloids with double helix oligonucleotides at molar ratios 1:1 to 1:4. The relative binding affinities based on the fraction of bound DNA and sequence selectivities of alkaloids towards the duplex were also investigated by ESI-MS. Moreover, tandem mass spectrometry of 5-charged complex ions was used to try to determine DNA-binding modes.
RESULTS:
Six alkaloids showed complexation with the selected DNA duplex, i.e., berberine, coptisine, peimine, aconitine, oxysophoridine and cytisine. They showed their binding affinities with d(AACTCCCGGCACAC/GTGTGCCGGGAGTT) in the order of berberine > coptisine > peimine > aconitine, oxysophoridine > cytosine; additional experiments involving collision energy proved this result. Sequence selectivities were not apparent for coptisine, peimine, aconitine and oxysophoridine with four DNA duplexes. The complexes containing berberine and coptisine underwent the predominant loss of the G base. However, for complexes containing the other four alkaloids, they dissociated via the loss of neutral drug. The results confirmed that they may have different binding modes.
CONCLUSIONS:
According to experiment data and structural information, the binding mode of individual drugs with DNA was speculated. It was noted that the bindings of alkaloids peimine, aconitine and oxysophoridine with DNA are discovered firstly. This may give a clue to design duplex-binding ligands and be helpful for understanding biological activities of these alkaloids.
Copyright © 2012 John Wiley & Sons, Ltd....(more)
Ma L, et al. Rapid Commun Mass Spectrom 2013 Jan 15;27(1):51-8.
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- 26. Patterns of nicotinic receptor antagonism II: Cardiovascular effects in rats.
BACKGROUND:
Tobacco cessation pharmacotherapies currently are limited to nicotine itself, the partial nicotine agonists varenicline and cytisine, and the antidepressant bupropion. Compared with agonists, nicotinic antagonists such as the noncompetitive, nonselective compound mecamylamine, and the competitive, α4β2-preferring antagonist dihydro-β-erythroidine (DHβE) may be a novel approach to the treatment of tobacco smoking as both are effective antagonists of nicotine's central effects. Considering nicotinic acetylcholine receptors mediate critical peripheral effects of acetylcholine, such as cardiovascular effects, it is important to study how nicotinic antagonists would alter the cardiovascular system and the cardiovascular changes induced by nicotine.
METHODS:
The effects of several nicotinic agonists and antagonists on blood pressure and heart rate were measured in conscious, unrestrained rats following parenteral administration using a telemetry system.
RESULTS:
Nicotine and other nicotinic receptor agonists (epibatidine, varenicline, and cytisine) produced similar increases in blood pressure, whereas their effects on heart rate were biphasic. The cardiovascular changes were attenuated by the nonselective nicotine antagonist, mecamylamine, but the peripherally restricted antagonist hexamethonium blocked only the agonist-induced changes in blood pressure. The α7-preferring antagonist, MLA, and the α4β2-preferring antagonist, DHβE, were much less effective in blocking the agonist-induced cardiovascular changes, indicating that nicotine's cardiovascular effects, are due to activation at autonomic ganglia involving nicotinic receptor subtypes other than α4, α7, or β2.
CONCLUSIONS:
The data indicate that the cardiovascular effects of nicotine and nicotine-like agents are mediated through receptor mechanisms that are distinct from those that mediate the central effects of nicotine.
Copyright © 2013 Elsevier Ireland Ltd. All rights reserved....(more)
Jutkiewicz EM, et al. Drug Alcohol Depend 2013 Jan 17.
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- 27. Nicotine-morphine interactions at α4β2, α7 and α3(?) nicotinic acetylcholine receptors.
Nicotine and opioids share several behavioral and rewarding properties. Although both opioids and nicotine have their own specific mechanism of action, there is empirical and experimental evidence of interactions between these drugs. We studied receptor-level interactions of nicotine and morphine at α4β2, α7 and α3() nicotinic acetylcholine receptors. [(3)H]epibatidine displacement was used to determine if morphine binds competitively to nicotinic acetylcholine receptors. Functional interactions of morphine and nicotine were studied with calcium fluorometry and (86)Rb(+) efflux assays. Morphine displaced [(3)H]epibatidine from nicotinic agonist binding sites in all cell lines studied. The Ki values for morphine were 13.2μM in SH-EP1-hα4β2 cells, 0.16μM and 126μM in SH-SY5Y cells and 43.7μM in SH-EP1-hα7 cells. In SH-EP1-hα4β2 cells expressing α4β2 nicotinic acetylcholine receptors, morphine acted as a partial agonist of (86)Rb(+) efflux comparable to cytisine (with EC50 values of 53.3μM for morphine and 5.38μM for cytisine). The effect of morphine was attenuated concentration-dependently by the nicotinic antagonist mecamylamine. In the SH-SY5Y cell line expressing several subtypes of nicotinic acetylcholine receptors morphine had an inhibitory effect on nicotine induced (86)Rb(+) ion efflux mediated by α3() nicotinic acetylcholine receptors. These results suggest that morphine acts as a partial agonist at α4β2 nicotinic acetylcholine receptors and as a weak antagonist at α3() nicotinic acetylcholine receptors....(more)
Talka R, et al. Eur J Pharmacol 2013 Feb 15;701(1-3):57-64.
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- 28. Varenicline and cytisine: two nicotinic acetylcholine receptor ligands reduce ethanol intake in University of Chile bibulous rats.
RATIONALE:
Neuronal nicotinic acetylcholine receptors (nAChRs) are pharmacological targets that have recently been implicated in the reinforcing effects of many drugs of abuse, including ethanol. Varenicline and cytisine are nAChR partial agonists in clinical use as smoking cessation aids. However, their efficacies to reduce alcohol consumption have not been fully studied.
OBJECTIVES:
This study aims to compare the effects of varenicline and cytisine on ethanol consumption by rats bred for many generations as high ethanol drinkers (UChB).
RESULTS:
Repeated dosing (0.5 or 1.0 mg/kg/day i.p.) of varenicline or cytisine, for three consecutive days, to male UChB rats pre-exposed to 10 % (v/v) ethanol and water 24 h/day for 4 weeks, significantly reduced alcohol intake and preference of ethanol over water during 1- and 24-h ethanol access periods. This effect was specific for ethanol intake and was not observed for 0.2 % saccharin or water consumption. Varenicline appears to be more effective than cytisine, probably due to its more favorable pharmacokinetic and pharmacodynamic properties. Long-term use of both nAChRs ligands for more than 8-10 days induced tolerance to their effects on ethanol consumption.
CONCLUSIONS:
This preclinical study in UChB rats demonstrated that both varenicline and cytisine reduce alcohol intake, with varenicline producing a greater and longer-lasting reduction than cytisine. However, dose adjustment will have to be considered as a possible way to counter tolerance arising after continued use....(more)
Sotomayor-Zárate R, et al. Psychopharmacology (Berl) 2013 May;227(2):287-98.
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- 29. Efficacy of cytisine in helping smokers quit: systematic review and meta-analysis.
BACKGROUND:
A recent rigorous study has shown that cytisine, a low-cost drug, is effective for smoking cessation. A number of earlier studies exist, mostly from former communist countries where cytisine has been used since the 1960s. The key question now is whether there is sufficient evidence to warrant licensing cytisine or whether more work is needed. A systematic review was undertaken to assess the efficacy of cytisine in smoking cessation.
METHODS:
The Cochrane Library, CINAHL, Embase, Medline and PsycINFO databases were searched for relevant data. Data from controlled trials were entered into two separate meta-analyses. The first considered the strictest definition of outcome and longest follow-up from all available studies and the second pooled outcomes from studies with biochemically validated abstinence and follow-up of 6 months or longer.
RESULTS:
Eight controlled trials were identified. Seven trials provided extractable data and, when pooled (first meta-analysis), produced a risk ratio (RR) of 1.57 (95% CI 1.42 to 1.74). Data from two high-quality studies (second meta-analysis) produced a pooled RR of 3.29 (95% CI 1.84 to 5.90). Patients on cytisine reported more gastrointestinal symptoms than patients on placebo (RR=1.76, 95% CI 1.28 to 2.42). There was no difference in overall reports of adverse events and no specific safety concerns emerged.
CONCLUSIONS:
Cytisine is an effective treatment for smoking cessation with efficacy comparable to that of other currently licensed treatments. Given its low cost and potential for public health benefit, expedited licensing of cytisine for smoking cessation is warranted....(more)
Hajek P, et al. Thorax 2013 Feb 12.
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- 30. 4,4,6a,6b,11,12,14b-Heptamethyl-16-oxo-1,2,3,4,4a,5,6,6a,6b,7,8,9,10,11,12,12a,14a,14b-octa-deca-hydro-12b,8a-(epoxy-methano)-picen-3-yl acetate.
The title compound, C32H48O4, which was extracted from the bark of Rhododendron arboreum, consists of five fused rings to which an acetate and seven methyl groups are attached. The A, D and E rings adopt chair conformations, the B ring is in a distorted chair and the C ring is in a half-chair conformation. The five-membered ring formed by the lactone group, which bridges from the A/B to the B/C ring junctions, is an approximate envelope with the C atom of the methyne group as the flap [displacement from the other four atoms = 0.753(2)Å]. There are no identified directional inter-actions in the crystal structure....(more)
Nisar M, et al. Acta Crystallogr Sect E Struct Rep Online 2013 Mar 23;69(Pt 4):o573.
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- 31. Investigation of effects of farrerol on suppression of murine T lymphocyte activation in vitro and in vivo.
Farrerol, a new type of 2,3-dihydro-flavonoid, has been isolated from the leaves of Rhododendron dauricum L. In the present study, we found that farrerol exerted potent immunosuppressive effects on murine T cells both in vitro and in vivo. In vitro, farrerol markedly suppressed concanavalin A (ConA)-induced lymphocyte proliferation, Th1 and Th2 cytokine production, cluster of differentiation 4-positive (CD4<sup>+</sup>) T cell populations, and the ratio of CD4<sup>+</sup>/cluster of differentiation 8-positive (CD8<sup>+</sup>) T cells. Moreover, farrerol significantly inhibited the T cell-mediated delayed-type hypersensitivity (DTH) reaction in vivo. In addition, we investigated signal transduction mechanisms to determine how farrerol's effects by Western blotting. The data revealed that farrerol could downregulate the activation of the nuclear factor κB (NF-B) and nuclear factor of activated T cells 2 (NFAT2) signal transduction pathways. These findings suggested that farrerol has potential effects on the regulation of the immune system and could be developed as a practicable immunosuppressive compound.
Copyright © 2013. Published by Elsevier B.V....(more)
Xiong Y, et al. Int Immunopharmacol 2013 Apr 22.
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- 32. Ecosystem Function in Appalachian Headwater Streams during an Active Invasion by the Hemlock Woolly Adelgid.
Forested ecosystems in the southeastern United States are currently undergoing an invasion by the hemlock woolly adelgid (HWA). Previous studies in this area have shown changes to forest structure, decreases in canopy cover, increases in organic matter, and changes to nutrient cycling on the forest floor and soil. Here, we were interested in how the effects of canopy loss and nutrient leakage from terrestrial areas would translate into functional changes in streams draining affected watersheds. We addressed these questions in HWA-infested watersheds at the Coweeta Hydrologic Laboratory in North Carolina. Specifically, we measured stream metabolism (gross primary production and ecosystem respiration) and nitrogen uptake from 2008 to 2011 in five streams across the Coweeta basin. Over the course of our study, we found no change to in-stream nutrient concentrations. While canopy cover decreased annually in these watersheds, this change in light penetration did not translate to higher rates of in-stream primary production during the summer months of our study. We found a trend towards greater heterotrophy within our watersheds, where in-stream respiration accounted for a much larger component of net ecosystem production than GPP. Additionally, increases in rhododendron cover may counteract changes in light and nutrient availability that occurred with hemlock loss. The variability in our metabolic and uptake parameters suggests an actively-infested ecosystem in transition between steady states....(more)
Northington RM, et al. PLoS One 2013 Apr 22;8(4):e61171.
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- 33. Historical connectivity, contemporary isolation and local adaptation in a widespread but discontinuously distributed species endemic to Taiwan, Rhododendron oldhamii (Ericaceae).
Elucidation of the evolutionary processes that constrain or facilitate adaptive divergence is a central goal in evolutionary biology, especially in non-model organisms. We tested whether changes in dynamics of gene flow (historical vs contemporary) caused population isolation and examined local adaptation in response to environmental selective forces in fragmented Rhododendron oldhamii populations. Variation in 26 expressed sequence tag-simple sequence repeat loci from 18 populations in Taiwan was investigated by examining patterns of genetic diversity, inbreeding, geographic structure, recent bottlenecks, and historical and contemporary gene flow. Selection associated with environmental variables was also examined. Bayesian clustering analysis revealed four regional population groups of north, central, south and southeast with significant genetic differentiation. Historical bottlenecks beginning 9168-13,092 years ago and ending 1584-3504 years ago were revealed by estimates using approximate Bayesian computation for all four regional samples analyzed. Recent migration within and across geographic regions was limited. However, major dispersal sources were found within geographic regions. Altitudinal clines of allelic frequencies of environmentally associated positively selected outliers were found, indicating adaptive divergence. Our results point to a transition from historical population connectivity toward contemporary population isolation and divergence on a regional scale. Spatial and temporal dispersal differences may have resulted in regional population divergence and local adaptation associated with environmental variables, which may have played roles as selective forces at a regional scale.Heredity advance online publication, 17 April 2013; doi:10.1038/hdy.2013.31....(more)
Hsieh YC, et al. Heredity (Edinb) 2013 Apr 17.
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- 34. Epidemiology of intoxication of domestic animals by plants in Europe.
This review focuses on some of the most important poisonous plants in Europe and provides an overview of the poisoning episodes that have occurred in European countries. Poisoning of livestock and companion animals by plants is a relatively common occurrence. In Europe livestock and horses are commonly poisoned by Datura stramonium (Jimson weed), Senecio spp. (ragworts and groundsels), Quercus spp. (oak), Taxus baccata (European yew), Nerium oleander (oleander), Pteridium aquilinum (bracken fern), Robinia pseudoacacia (black locust) and Rhododendron spp. (rhododendrons and azaleas). Poisoning may occur when the fresh plant is ingested in pasture or when it contaminates hay or silage. In pets, the greatest majority of plant poisonings are the result of ingestion of house or garden plants, such as Cycas revoluta (Sago palm), Ricinus communis (castor bean), Allium spp., Euphorbia pulcherrima (poinsettia), Lilium spp., Convallaria majalis (Lily of the valley), Pyracantha spp. (firethorn), Rhododendron spp. (rhododendrons and azaleas), Melia azedarach (Chinaberry tree), Taxus baccata (European yew) and Nerium oleander (oleander).
Copyright © 2013 Elsevier Ltd. All rights reserved....(more)
Cortinovis C, et al. Vet J 2013 Apr 6.
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- 35. A novel system for in situ determination of heat tolerance of plants: first results on alpine dwarf shrubs.
BACKGROUND:
Heat stress and heat damage to plants gain globally increasing importance for crop production and plant survival in endangered habitats. Therefore the knowledge of heat tolerance of plants is of great interest. As many heat tolerance measurement procedures require detachment of plants and protocols expose samples to various heat temperatures in darkness, the ecological relevance of such results may be doubted. To overcome these constraints we designed a novel field compatible Heat Tolerance Testing System (HTTS) that opens the opportunity to induce controlled heat stress on plants in situ under full natural solar irradiation. Subsequently, heat tolerance can be evaluated by a variety of standard viability assays like the electrolyte leakage test, chlorophyll fluorescence measurements and visual assessment methods. Furthermore, recuperation can be studied under natural environmental conditions which is impossible when detached plant material is used. First results obtained on three alpine dwarf - shrubs are presented.
RESULTS:
When heat tolerance of Vaccinium gaultherioides Bigelow was tested with the HTTS in situ, the visual assessment of leaves showed 50% heat injury (LT50) at 48.3°C, while on detached leaves where heat exposure took place in small heat chambers this already happened at 45.8°C. Natural solar irradiation being applied during heat exposure in the HTTS had significantly protective effects: In Loiseleuria procumbens L. (Desv.), if heat exposure (in situ) took place in darkness, leaf heat tolerance was 50.6°C. In contrast, when heat exposure was conducted under full natural solar irradiation heat tolerance was increased to 53.1°C. In Rhododendron ferrugineum L. heat tolerance of leaves was 42.5°C if the exposure took place ex situ and in darkness, while it was significantly increased to 45.8°C when this happened in situ under natural solar irradiation.
CONCLUSIONS:
The results obtained with the HTTS tested in the field indicate a mitigating effect of natural solar irradiation during heat exposure. Commonly used laboratory based measurement procedures expose samples in darkness and seem to underestimate leaf heat tolerance. Avoidance of detachment by the use of the HTTS allows studying heat tolerance and recuperation processes in the presence of interacting external abiotic, biotic and genetic factors under field conditions. The investigation of combined effects of heat exposure under full solar irradiation, of recuperation and repair processes but also of possible damage amplification into the results with the HTTS appears to be particularly useful as it allows determining heat tolerance of plants with a considerably high ecological significance....(more)
Buchner O, et al. Plant Methods 2013 Mar 14;9(1):7.
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