220 research outputs found
Phytochemical composition and antioxidant activity of Lavandula dentate extracts
Le but de ce travail consiste à étudier la composition des huiles essentielles et des polyphénols des racines, des tiges et des feuilles de la Lavande dentée et d’évaluer leurs potentialités antioxydantes. L’analyse et la quantification des huiles essentielles a montré que les feuilles sont les plus riches en huiles essentielles (0.89 mg/g MS) suivies par les tiges (0.68 mg/g MS) et enfin les racines (0,23 mg/g MS). Le constituant majeur de l’HE des racines est: le β-ocimène. D’autre part, le limonène représente le composé majeur de l’HE des tiges. Quant à l’HE des feuilles, elle est dominée par le camphre. D’autre part, nos résultats ont montré que les organes de la lavande montrent des teneurs en polyphénols totaux élevées et variables selon l’organe étudié. En effet, les extraits des racines sont caractérisés par le contenu le plus élevé en polyphénols. D’autre part, l’étude de l’activité antioxydante des extraits des différents organes a indiqué que les extraits de la racine sont particulièrement les plus actifs et que leur analyse par RP-HPLC a montré que ces derniers sont riches essentiellement en acide rosmarinique. Finalement, les extraits de la Lavande dentée et particulièrement ceux de la racine peuvent être considérés comme des sources alternatives d’antioxydants naturels puissants qui peuvent être utilisés en industrie agroalimentaire et pharmaceutique.In this study, Lavandula dentata organs (roots, stems and leaves) were investigated for their essential oils, total phenolics, flavonoids contents and antioxidant activities. Essential oil yields were 0.22% in roots, 0.68 % in stems and 0.89 % in flowers. Major components of the oils were β-ocimene, limonene and 1,8 cineol in roots, stems and leaves and flowers, respectively. In all organs, total phenolics content ranged from 42.57 to 16.17 mg gallic acid equivalents per gram of dry weight (mg GAE/g DW).The antioxidant activities of Lavandula dentata extracts obtained from the three organs were assessed using two tests (DPPH and reducing power). The root extract was strongly effective as DPPH radical scavenger and reducing agent. Thus, the identification of individual target polyphenolic compounds of roots was performed by RP-HPLC. The major phenolic compound detected in roots was rosmarinic acid. This activity was high enough for the plant to be a new and natural source of strongly antioxidant substances for use as natural additives in food and pharmaceutical industry
Concurrent regulation of LKB1 and CaMKK2 in the activation of AMPK in castrate-resistant prostate cancer by a well-defined polyherbal mixture with anticancer properties
Abstract
Background
Zyflamend, a blend of herbal extracts, effectively inhibits tumor growth using preclinical models of castrate-resistant prostate cancer mediated in part by 5′-adenosine monophosphate-activated protein kinase (AMPK), a master energy sensor of the cell. Clinically, treatment with Zyflamend and/or metformin (activators of AMPK) had benefits in castrate-resistant prostate cancer patients who no longer responded to treatment. Two predominant upstream kinases are known to activate AMPK: liver kinase B1 (LKB1), a tumor suppressor, and calcium-calmodulin kinase kinase-2 (CaMKK2), a tumor promotor over-expressed in many cancers. The objective was to interrogate how Zyflamend activates AMPK by determining the roles of LKB1 and CaMKK2.
Methods
AMPK activation was determined in CWR22Rv1 cells treated with a variety of inhibitors of LKB1 and CaMKK2 in the presence and absence of Zyflamend, and in LKB1-null HeLa cells that constitutively express CaMKK2, following transfection with wild type LKB1 or catalytically-dead mutants. Upstream regulation by Zyflamend of LKB1 and CaMKK2 was investigated targeting protein kinase C-zeta (PKCζ) and death-associated protein kinase (DAPK), respectively.
Results
Zyflamend’s activation of AMPK appears to be LKB1 dependent, while simultaneously inhibiting CaMKK2 activity. Zyflamend failed to rescue the activation of AMPK in the presence of pharmacological and molecular inhibitors of LKB1, an effect not observed in the presence of inhibitors of CaMKK2. Using LKB1-null and catalytically-dead LKB1-transfected HeLa cells that constitutively express CaMKK2, ionomycin (activator of CaMKK2) increased phosphorylation of AMPK, but Zyflamend only had an effect in cells transfected with wild type LKB1. Zyflamend appears to inhibit CaMKK2 by DAPK-mediated phosphorylation of CaMKK2 at Ser511, an effect prevented by a DAPK inhibitor. Alternatively, Zyflamend mediates LKB1 activation via increased phosphorylation of PKCζ, where it induced translocation of PKCζ and LKB1 to their respective active compartments in HeLa cells following treatment. Altering the catalytic activity of LKB1 did not alter this translocation.
Discussion
Zyflamend’s activation of AMPK is mediated by LKB1, possibly via PKCζ, but independent of CaMKK2 by a mechanism that appears to involve DAPK.
Conclusions
Therefore, this is the first evidence that natural products simultaneously and antithetically regulate upstream kinases, known to be involved in cancer, via the activation of AMPK.https://deepblue.lib.umich.edu/bitstream/2027.42/144515/1/12906_2018_Article_2255.pd
Antioxidant and antimicrobial phenolic compounds from extracts of cultivated and wild-grown Tunisian Ruta chalepensis
The antioxidant and antibacterial activities of phenolic compounds from cultivated and wild Tunisian Ruta chalepensis L. leaves, stems, and flowers were assessed. The leaves and the flowers exhibited high but similar total polyphenol, flavonoid, and tannin content. Moreover, two organs showed strong, although not significantly different, total antioxidant activity, 2,2-diphenyl-1-picrylhydrazyl scavenging ability, and reducing power. Investigation of the phenolic composition showed that vanillic acid and coumarin were the major compounds in the two organs, with higher percentages in the cultivated organs than in the spontaneous organs. Furthermore, R. chalepensis extracts showed marked antibacterial properties against human pathogen strains, and the activity was organ- and origin-dependent. Spontaneous stems had the strongest activity against Pseudomonas aeruginosa. From these results, it was concluded that domestication of Ruta did not significantly affect its chemical composition and consequently the possibility of using R. chalpensis organs as a potential source of natural antioxidants and as an antimicrobial agent in the food industry
Zn treatment effects on biological potential of fennel bulbs as affected by in vitro digestion process
Zn treatment effects on the stability of polyphenols, MDA (malondialdehyde) content, antioxidant and lipoxygenase inhibition activities of two varieties of fennel bulbs were studied by using an in vitro gastrointestinal digestion model. Likewise, the effect of Zn on viability cells of E. coli was also performed. The results revealed that high amounts of total phenolic and flavonoid compounds were released during the digestion process, especially after the intestinal phase. Additionally, the antioxidant and lipoxygenase inhibitory activity were affected by the gastrointestinal digestion process and seems to be correlated with total phenol contents. On the other hand, the viability of E. coli was not affected by the activity of our tested bulbs during passage through the artificial digestion model, but the treated bulbs activity contribute relatively to the inhibition growth of bacteria. The survival of E. coli in fennel bulbs was challenged with simulated gastrointestinal fluids and the results showed that the E. coli strains, despite having experienced a viability reduction at the intestinal phase, were able to overcome the exposure to the gastrointestinal synthetic fluids. This E. coli ability reinforces the need for good hygienic measures to assure safe fresh produce, even for those that are rich in antibacterial compounds.info:eu-repo/semantics/publishedVersio
Modulation of Cellular Hsp72 Levels in Undifferentiated and Neuron-Like SH-SY5Y Cells Determines Resistance to Staurosporine-Induced Apoptosis
Increased expression of Hsp72 accompanies differentiation of human neuroblastoma SH-SY5Y cells to neuron-like cells. By modulating cellular levels of Hsp72, we demonstrate here its anti-apoptotic activity both in undifferentiated and neuron-like cells. Thermal preconditioning (43°C for 30 min) induced Hsp72, leading to cellular protection against apoptosis induced by a subsequent treatment with staurosporine. Preconditioned staurosporine-treated cells displayed decreased Bax recruitment to mitochondria and subsequent activation, as well as reduced cytochrome c redistribution from mitochondria. The data are consistent with Hsp72 blocking apoptosis upstream of Bax recruitment to mitochondria. Neuron-like cells (with elevated Hsp72) were more resistant to staurosporine by all measured indices of apoptotic signaling. Use of stable transfectants ectopically expressing moderately elevated levels of Hsp72 revealed that such cells in the undifferentiated state showed enhanced resistance to staurosporine-induced apoptosis, which was even more robust after differentiation to neuron-like cells. Overall, the protective effects of differentiation, thermal preconditioning and ectopic Hsp72 expression were additive. The strong inverse correlation between cellular Hsp72 levels and susceptibility to apoptosis support the notion that Hsp72 acts as a significant neuroprotective factor, enabling post-mitotic neurons to withstand potentially lethal stress that induces apoptosis
Oral manifestations of thrombocytopaenia
The appearance in the mouth of haemorrhagic petechiae, ecchymoses or blood blisters
with spontaneous bleeding is suggestive of a haemorrhagic disorder that may be caused either by
functional impairment of platelets or of blood vessel walls, by an abnormal decrease in the number
of circulating platelets (thrombocytopaenia), or by defects in the blood clotting mechanism. Thrombocytopaenia
from decreased production or increased destruction of platelets may be caused by
multiple factors including immune mediated mechanisms, drugs or infections.
A diagnosis of thrombocytopaenic purpura can be made when any other disease entity that might
be causing the purpura is excluded on the basis of the medical history, the physical examination, a
complete blood count and a peripheral blood smear.
In this paper, we outline the clinical features of oral thrombocytopaenic purpura and briefly discuss
some aspects of its aetiopathogenesis and treatment
Temporal Dynamics and Impact of Climate Factors on the Incidence of Zoonotic Cutaneous Leishmaniasis in Central Tunisia
Old world cutaneous leishmaniasis is a vector-borne disease occurring in rural areas of developing countries. The main reservoirs are the rodents Psammomys obesus and Meriones shawi. Zoonotic Leishmania transmission cycle is maintained in the burrows of rodents where the sand fly Phlebotomus papatasi finds the ideal environment and source of blood meals. In the present study we showed seasonality of the incidence of disease during the same cycle with an inter-epidemic period ranging from 4 to 7 years. We evaluated the impact of climate variables (rainfall, humidity and temperature) on the incidence of zoonotic cutaneous leishmaniais in central Tunisia. We confirmed that the risk of disease is mainly influenced by the humidity related to the months of July to September during the same season and mean rainfall lagged by 12 to 14 months
Regulation of Brown Fat Adipogenesis by Protein Tyrosine Phosphatase 1B
Protein-tyrosine phosphatase 1B (PTP1B) is a physiological regulator of insulin signaling and energy balance, but its role in brown fat adipogenesis requires additional investigation.To precisely determine the role of PTP1B in adipogenesis, we established preadipocyte cell lines from wild type and PTP1B knockout (KO) mice. In addition, we reconstituted KO cells with wild type, substrate-trapping (D/A) and sumoylation-resistant (K/R) PTP1B mutants, then characterized differentiation and signaling in these cells. KO, D/A- and WT-reconstituted cells fully differentiated into mature adipocytes with KO and D/A cells exhibiting a trend for enhanced differentiation. In contrast, K/R cells exhibited marked attenuation in differentiation and lipid accumulation compared with WT cells. Expression of adipogenic markers PPARγ, C/EBPα, C/EBPδ, and PGC1α mirrored the differentiation pattern. In addition, the differentiation deficit in K/R cells could be reversed completely by the PPARγ activator troglitazone. PTP1B deficiency enhanced insulin receptor (IR) and insulin receptor substrate 1 (IRS1) tyrosyl phosphorylation, while K/R cells exhibited attenuated insulin-induced IR and IRS1 phosphorylation and glucose uptake compared with WT cells. In addition, substrate-trapping studies revealed that IRS1 is a substrate for PTP1B in brown adipocytes. Moreover, KO, D/A and K/R cells exhibited elevated AMPK and ACC phosphorylation compared with WT cells.These data indicate that PTP1B is a modulator of brown fat adipogenesis and suggest that adipocyte differentiation requires regulated expression of PTP1B
Simian Immunodeficiency Virus Infection of Chimpanzees (Pan troglodytes) Shares Features of Both Pathogenic and Non-pathogenic Lentiviral Infections.
The virus-host relationship in simian immunodeficiency virus (SIV) infected chimpanzees is thought to be different from that found in other SIV infected African primates. However, studies of captive SIVcpz infected chimpanzees are limited. Previously, the natural SIVcpz infection of one chimpanzee, and the experimental infection of six chimpanzees was reported, with limited follow-up. Here, we present a long-term study of these seven animals, with a retrospective re-examination of the early stages of infection. The only clinical signs consistent with AIDS or AIDS associated disease was thrombocytopenia in two cases, associated with the development of anti-platelet antibodies. However, compared to uninfected and HIV-1 infected animals, SIVcpz infected animals had significantly lower levels of peripheral blood CD4+ T-cells. Despite this, levels of T-cell activation in chronic infection were not significantly elevated. In addition, while plasma levels of β2 microglobulin, neopterin and soluble TNF-related apoptosis inducing ligand (sTRAIL) were elevated in acute infection, these markers returned to near-normal levels in chronic infection, reminiscent of immune activation patterns in 'natural host' species. Furthermore, plasma soluble CD14 was not elevated in chronic infection. However, examination of the secondary lymphoid environment revealed persistent changes to the lymphoid structure, including follicular hyperplasia in SIVcpz infected animals. In addition, both SIV and HIV-1 infected chimpanzees showed increased levels of deposition of collagen and increased levels of Mx1 expression in the T-cell zones of the lymph node. The outcome of SIVcpz infection of captive chimpanzees therefore shares features of both non-pathogenic and pathogenic lentivirus infections.This work was supported by the Biotechnology and Biological Sciences Research Council and by the Wellcome Trust.This is the final version of the article. It first appeared from PLOS via http://dx.doi.org/10.1371/journal.ppat.100514
First report of naturally infected Sergentomyia minuta with Leishmania major in Tunisia
International audienceBackground: Many sand fly species are implicated in the transmission cycle of Leishmania parasites around the world. Incriminating new sand flies species, as vectors of Leishmania is crucial to understanding the parasite-vector transmission cycle in different areas in Tunisia and surrounding countries. Findings: Seventy-four unfed females belonging to the genera Sergentomyia and Phlebotomus were collected in South Tunisia between June and November 2014, using sticky papers. PCR-RFLP (Restriction Fragment Length Polymorphism) analysis of the internal transcribed spacer 1 (ITS1) was used for Leishmania parasites detection and identification. Leishmania (L.) major (Yakimoff & Shokkor, 1914) was identified within two Sergentomyia (S.) minuta (Rondani, 1843) and one Phlebotomus papatasi (Scopoli, 1786). Conclusion: This is the first report of L. major identified from S. minuta in Tunisia. This novel finding enhances the understanding of the transmission cycle of L. major parasites of cutaneous leishmaniasis in an endemic area in South Tunisia
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