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Direct action of anisodamine on T cells or monocytes prepared from human PBMCs. (A) Human peripheral blood T cells (5 10 5 cells) were stimulated with anti-CD3 and anti-CD28 antibodies in the presence or the absence of anisodamine for 48 h. The culture supernatants were assayed for cytokine levels by ELISA. The concentrations of anisodamine added were as follows: open bars, none; shaded bars, 25 g/ml; solid bars, 50 g/ml. (B) Reconstruction experiments were performed with isolated human peripheral blood T cells and monocytes. The compositions of the cells were as follows: open bars, T cells plus monocytes; shaded bars, T cells plus monocytes pretreated with anisodamine; solid bars, T cells pretreated with anisodamine plus monocytes. The mixed cells were stimulated with TSST-1 (10 ng/ml) for 48 h, and the culture supernatants were assayed for cytokines by ELISA.
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Toxic shock syndrome toxin 1 (TSST-1), produced by Staphylococcus aureus (including methicillin-resistant S. aureus), is a superantigenic toxin responsible for toxic shock syndrome as well as neonatal TSS-like exanthematous disease. TSST-1 exhibits its deleterious effects by leading to the abnormal proliferation of, e.g., Vbeta2+ T cells and overpr...
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... peripheral blood T cells were iso- lated and stimulated with anti-CD3 and anti-CD28 antibodies for 48 h in the presence or the absence of anisodamine. Stim- ulation with the antibodies in the absence of anisodamine caused a marked induction of TNF-, IL-2, and IFN-; and the simultaneous addition of anisodamine significantly decreased the responses (Fig. 3A). The rates of inhibition by anisodamine at 25 g/ml (or at 50 g/ml) were 37.9% (51.7%) for TNF-, 67.3% (80.4%) for IL-2, and 70.0% (77.8%) for IFN-. The inhibitory levels observed were comparable to the TSST-1- stimulated responses in human ...
Context 2
... reconstruction experiments were performed. For this, isolated T cells or isolated monocytes were separately pre- treated with anisodamine (50 g/ml), washed, and then mixed together for experiments with TSST-1 (Fig. 3B). When only T cells were pretreated with anisodamine and then mixed, the rates of inhibition were 59% for TNF-, 98% for IL-2, and 39% for IFN-, while when only monocytes were pretreated with anisodamine and then mixed, the rates were 77.2% for TNF-, 75% for IL-2, and 51.3% for ...
Citations
... Interestingly, anisodamine is an alkaloid produced by a Chinese herb that reduces the TSST-1 concentration in serum and the risk of toxic shock syndrome [71]. Anisodamine is an immunomodulator that inhibits the expression of cytokines such as tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), interleukin 8 (IL-8), interleukin 2 (IL-2), and interferon gamma (IFN-γ) expression in a dose-dependent manner, which may eventually reduce the effects of the cytokine storm induced during the toxic shock syndrome [71,72]. ...
... Interestingly, anisodamine is an alkaloid produced by a Chinese herb that reduces the TSST-1 concentration in serum and the risk of toxic shock syndrome [71]. Anisodamine is an immunomodulator that inhibits the expression of cytokines such as tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), interleukin 8 (IL-8), interleukin 2 (IL-2), and interferon gamma (IFN-γ) expression in a dose-dependent manner, which may eventually reduce the effects of the cytokine storm induced during the toxic shock syndrome [71,72]. [64,98,99] Moreover, phenolic compounds (in particular, many flavonoids) could be used to control the hemolytic activity and secretion of some SEs (Table 1). ...
Staphylococcal infections are a widespread cause of disease in humans. In particular, S. aureus is a major causative agent of infection in clinical medicine. In addition, these bacteria can produce a high number of staphylococcal enterotoxins (SE) that may cause food intoxications. Apart from S. aureus, many coagulase-negative Staphylococcus spp. could be the source of food contamination. Thus, there is an active research work focused on developing novel preventative interventions based on food supplements to reduce the impact of staphylococcal food poisoning. Interestingly, many plant-derived compounds, such as polyphenols, flavonoids, or terpenoids, show significant antimicrobial activity against staphylococci, and therefore these compounds could be crucial to reduce the incidence of food intoxication in humans. Here, we reviewed the most promising strategies developed to prevent staphylococcal food poisoning.
... TSST-1 is another important toxin belonging to the category of staphylococcal superantigens and is primarily responsible for toxic shock syndrome development, by triggering a massive release of proinflammatory cytokines producing an overwhelming inflammatory response (Nakagawa et al., 2005;Xu and McCormick, 2012). In a rabbit model of infective endocarditis and sepsis, comparing different lineages of S. aureus, even though no difference in lethality was observed among investigated clones, strains carrying tst gene caused lethal sepsis (King et al., 2016). ...
Methicillin-resistant Staphylococcus aureus (MRSA) remains an important cause of nosocomial and community-associated infections due to its ability to produce toxins and evade host’s immune responses. The aim of the present study was to investigate the association of monocytes immune response in terms of cytokines produced after inoculation with different MRSA clones. Thirty-one clinical MRSA strains were selected on the basis of clonal types, accessory gene regulator (agr) groups and toxin genes carriage. Isolates were identified as S. aureus by Gram stain, catalase, coagulase production and PCR for nuc gene. The presence of mecA, lukS/lukF-PV (Panton-Valentine Leukocidin) and tst (Toxic Shock Syndrome Toxin-1) genes, as well as, the determination of agr groups was performed by PCR. Clonality was investigated by means of multi-locus sequence typing (MLST). Peripheral blood mononuclear cells were stimulated with live bacterial cells for 45 min at a ratio of 1:10. Cells were incubated for 10 h and supernatants were collected. The levels of Tumor Necrosis Factor alpha (TNFa), IL-1b, IL-8, IL-6, IL-12p40, IL-10, interferon-gamma (IFN-γ) and IL-2, were measured by Human Cytokine Multiplex Immunoassay kit. Thirteen strains were tst and 12 lukS/lukF-PV-positive. Seven strains belonged to ST80 and ST225, five to ST30 and ST239, while the remaining seven isolates were grouped together as “other.” Strains belonging to ST80 induced statistically lower levels of TNFa, IL-1b, IL-8, IL-6, IL-10, IFN-γ, and IL-2. PVL-positive strains classified into ST80 clone induced statistically lower concentrations of most cytokines as compared to PVL-positive strains belonging to other clones, tst-positive strains and toxin-negative ones. Strains of agr3 group belonging to ST80 induced statistically lower concentrations of most tested cytokines as compared to agr3 strains not-belonging to ST80, agr2 or agr1. This low induction of immune response by MRSA ST80 cannot be attributed to the presence of neither lukS/lukF-PV nor agr3.
... violaceum and P. aeruginosa). Among them, 22 compounds presented varying levels of QSI activity, including the monoterpenes α-phellandrene (287), p-cimene (288), thymol, carvacol, geraniol (296), menthone (299), linalool (293), camphene (307), and camphor (308) and the sesquiterpenes farnesol (318), nerolidol (320), and nerol (321). The performance of α-terpineol (291) was emphasized as violacein inhibitor, similarly to thujone (292) and citral (293), which were shown to be pyocyanin inhibitiors. ...
... Among them, 22 compounds presented varying levels of QSI activity, including the monoterpenes α-phellandrene (287), p-cimene (288), thymol, carvacol, geraniol (296), menthone (299), linalool (293), camphene (307), and camphor (308) and the sesquiterpenes farnesol (318), nerolidol (320), and nerol (321). The performance of α-terpineol (291) was emphasized as violacein inhibitor, similarly to thujone (292) and citral (293), which were shown to be pyocyanin inhibitiors. Interestingly, it was observed that the (+)-enantiomers of some monoterpenes increased violacein and pyocyanin production, while their levorotary analogues (−) carvone (297), (−) limonene (302), and (−) borneol (309) inhibited their production. ...
... Menthol (300) strongly interfered with QS-regulated virulence factors of P. aeruginosa, as observed in a concentration-dependent decrease in swarming motility. 100 Several monoterpenes were evaluated by Echeverrigaray and co-workers, 269 including α-terpineol (291), citral (293), citronellol (294), citronellal (295), geraniol (296), pulegone (298), terpinene-4-ol (303), and 1,8-cineol (304), concerning inhibition of P. mirabilis motility. Of all the compounds evaluated, these eight monoterpenes that effectively inhibited swarming are oxygenated, indicating the importance of the hydroxyl group for P. mirabilis swarming inhibition. ...
Decreased antimicrobial efficiency has become a global public health issue. The paucity of new antibacterial drugs is evident, and the arsenal against infectious diseases needs to be improved urgently. The selection of plants as a source of prototype compounds is appropriate, since plant species naturally produce a wide range of secondary metabolites that act as a chemical line of defense against microorganisms in the environment. Although traditional approaches to combat microbial infections remain effective, targeting microbial virulence rather than survival seems to be an exciting strategy, since the modulation of virulence factors might lead to a milder evolutionary pressure for the development of resistance. Additionally, anti-infective chemotherapies may be successfully achieved by combining antivirulence and conventional antimicrobials, extending the lifespan of these drugs. This review presents an updated discussion of natural compounds isolated from plants with chemically characterized structures and activity against the major bacterial virulence factors: quorum sensing, bacterial biofilms, bacterial motility, bacterial toxins, bacterial pigments, bacterial enzymes, and bacterial surfactants. Moreover, a critical analysis of the most promising virulence factors is presented, highlighting their potential as targets to attenuate bacterial virulence. The ongoing progress in the field of antivirulence therapy may therefore help to translate this promising concept into real intervention strategies in clinical areas.
... Anisodamine was found to protect animals from toxic shock induced by the Staphylococcus aureus Toxic Shock Syndrome Toxin-1 (TSST-1) (Nakagawa et al., 2005), and Shiga Toxin Type -2 . In both studies, the protective effect involved down-regulation of proinflammatory cytokines like TNFα and others, and in the case of TSST-1 the effect was mediated by inhibition of NFκB activation (Nakagawa et al., 2005). ...
... Anisodamine was found to protect animals from toxic shock induced by the Staphylococcus aureus Toxic Shock Syndrome Toxin-1 (TSST-1) (Nakagawa et al., 2005), and Shiga Toxin Type -2 . In both studies, the protective effect involved down-regulation of proinflammatory cytokines like TNFα and others, and in the case of TSST-1 the effect was mediated by inhibition of NFκB activation (Nakagawa et al., 2005). ...
In cases of organophosphate poisoning patients are treated with a combination of antidotes. Beside these poison-directed antidotes, supportive treatment like supplemental oxygen and ventilation, as well as other modalities may be needed due to the wide range of toxic effects. Anisodamine is a belladonna alkaloid, and like other drugs from this family is non subtype-selective muscarinic, and a nicotinic cholinergic antagonist, which has been employed in traditional Chinese medicine. As a muscarinic antagonist, it displays similar pharmacological effects as atropine and scopolamine. Anisodamine is less potent than atropine and scopolamine, but also less toxic. Current in vitro and animal model studies demonstrate protective effects of anisodamine in a variety of diseases. Organophosphate poisoning involves not only the central and peripheral nervous systems, but also the cardiac and respiratory systems, as well as activation of inflammatory processes and oxidative stress. Therefore, the anticholinergic and additional activities of anisodamine seem to be relevant and justify its consideration as an addition to the existing medical countermeasures. More research is needed, as the current results on the role of anisodamine in the management of organophosphate poisoning are little. Here we review the beneficial effects of anisodamine on processes relevant to organophosphate poisoning.
... Histopathological observation showed haemorrhages in the pericardium as well as in between the myocardial bundles in focal manner in group of rats irradiated with acute high dose gamma irradiation, and ANI treatment markedly improved haemorrhages in the pericardium but there were hyalinization and granular degeneration in the myocardium. The protective effects of anisodamine may also be associated with activating super oxide dismutase (SOD) in the tissues, decreasing the level of malondialdehyde (MDA), inhibiting expression of endothelin and inhibiting apoptosis of cells (Nakagawa et al., 2005). Recently, some studies have shown that anisodamine could enhance spontaneous vasomotion of microvessels, increase the velocity of blood flow, and reduce the permeability of microvasculature, which is beneficial for improving microcirculation (Wang Yan-bo, et al., 2012). ...
Radiation-induced heart disease is becoming an increasing concern for patients and clinicians alike as the use of radiation therapy for the treatment of certain malignancies increases. Anisodamine (ANI) is a naturally occurring atropine derivative, first isolated in China it has capability of improving the microcirculatory flow, ANI has been reported to work as an anti-shock medicine to treat burn shock, septic shock, So the object of this study is to investigate the beneficial therapeutic effects of anisodamine on the complications occurred to heart after exposure to ionizing radiation.
Forty female Wistar rats, weighing 150 ±21 g were randomly divided into four groups: group I (normal control group), group II (control group administrated ANI 2mg/kg), group III: (irradiated group with 5 Gy γ irradiation single dose) and group IV (irradiated group with 5 Gy γ irradiation single dose and treated with ANI 2mg/kg) drugs were given i.p. to the experimental groups daily for 15 days after irradiation and saline was given i.p. to the control group. The results of the present study showed benefit effects of the anticholinergic anisodamine, administration of ANI remarkably reduced the plasma concentrations of cholesterol, triglycerides (TG), and increased high density lipoproteins (HDL) as compared with group of rats exposed to γ irradiation. It also reduced malondialdehyde (MDA) content, myeloperoxidase (MPO) activity, and enhanced superoxide dismutase (SOD) activity in heart tissues of treated group as compared with irradiated group, and significantly decreased (p< 0.05) the concentration of tumor necrosis factor alpha (TNF-α) and intercellular adhesion molecule 1 (ICAM) in heart tissues of the treated group with ANI as compared with irradiated group. Also the results revealed up-regulation in monocyte chemotactic protein-1 (MCP-1) and copeptine genes in group of rats exposed to ionizing radiation, anisodamine alleviated the inflammatory damage by significantly reducing the expressions of these genes as indicated in the treated group.
Histopathological observation showed haemorrhages in the pericardium as well as in between the myocardial bundles in focal manner in group of rats irradiated with acute dose gamma irradiation, and ANI treatment markedly improved haemorrhages in the pericardium but there were hyalinization and granular degeneration in the myocardium.
These results indicated that ANI has the benefit effects on heart damage resulting from exposure to gamma irradiation.
... synergistically cause death in doses that cannot lead to Our study focused on the formation of the nervous any death when applied alone [26]. centers, investigating the effects of LPS in different doses ...
Lipopolysaccharide (LPS) also known as endotoxin, is a component of the Gram-negative bacteria cell wall which is a mitogen and activate B-cells, causing the release of inflammatory cytokines such as IL-1 and 2 Tumor Necrosis Factor-(TNF-) that followed by stimulation of immune system. Stimulation of immune system and the effects of these toxins are more intense and serious in uterus and during the formation of the nervous center. Nowadays, it has been demonstrated that some of the complications of nervous system diseases, even in old ages and behavioral disorders as well as diseases such as Parkinson are directly related to fetal conflict with infectious factors. Some studies also have investigated the embryonic loss of neurons due to bacterial toxins in infected mothers. In this study, the effects of Salmonella typhimurium LPS on the formation of nerve centers and behavior of NIH mice race were examined. Salmonella typhimurium LPS were extracted by hot phenol extraction method and then was injected intraperitoneally (IP) to different groups of mice at 30, 60 and 120 µg/Kg of body weight doses. After prove of onset mice pregnancy, LPS was injected to different groups of mice at the eighth and tenth day of pregnancy. After parturition, offspring's anxiety as a physiological behavior and intake of food and water tests were carried out. The results showed that maternal LPS injection could cause behavioral changes in offspring.
... • The Chinese herbal extract anisodamine inhibited the S. aureus toxin in human blood mononuclear cells [148]. ...
There is a need to develop food-compatible conditions to alter the structures of fungal, bacterial, and plant toxins, thus transforming toxins to nontoxic molecules. The term 'chemical genetics' has been used to describe this approach. This overview attempts to survey and consolidate the widely scattered literature on the inhibition by natural compounds and plant extracts of the biological (toxicological) activity of the following food-related toxins: aflatoxin B1, fumonisins, and ochratoxin A produced by fungi; cholera toxin produced by Vibrio cholerae bacteria; Shiga toxins produced by E. coli bacteria; staphylococcal enterotoxins produced by Staphylococcus aureus bacteria; ricin produced by seeds of the castor plant Ricinus communis; and the glycoalkaloid α-chaconine synthesized in potato tubers and leaves. The reduction of biological activity has been achieved by one or more of the following approaches: inhibition of the release of the toxin into the environment, especially food; an alteration of the structural integrity of the toxin molecules; changes in the optimum microenvironment, especially pH, for toxin activity; and protection against adverse effects of the toxins in cells, animals, and humans (chemoprevention). The results show that food-compatible and safe compounds with anti-toxin properties can be used to reduce the toxic potential of these toxins. Practical applications and research needs are suggested that may further facilitate reducing the toxic burden of the diet. Researchers are challenged to (a) apply the available methods without adversely affecting the nutritional quality, safety, and sensory attributes of animal feed and human food and (b) educate food producers and processors and the public about available approaches to mitigating the undesirable effects of natural toxins that may present in the diet.
... Mononuclear cells were also isolated by density gradient centrifugation. Monocytes were further purified from mononuclear cells, as described previously ( Nakagawa et al., 2005). After incubation in a human serum-coated dish, nonadherent cells (including lymphocytes) were washed away, and monocytes were recovered as adherent cells. ...
... Human monocytic leukemia THP-1 cells (American Type Culture Collection, Manassas, VA) were maintained as described previously ( Nakagawa et al., 2005) and differentiated to monocyte-like cells (called mTHP-1 cells) by incubation with 10 ng mL À1 PMA in RPMI1640 containing 10% FBS, 100 unit mL À1 penicillin G, and 100 lg mL À1 streptomycin (Gibco) at 37 °C overnight. After washing, adherent cells (mTHP-1 cells) were recovered and used for the following experiments. ...
The mechanisms for the cytotoxicity of staphylococcal Panton-Valentine leukocidin (PVL), a pore-forming toxin consisting of LukS-PV and LukF-PV, in human immune cells are still unclear. Because LukS-PV binds to ganglioside GM1, a constituent of detergent-resistant membrane microdomains (DRMs) of the plasma membrane, the role of DRMs in PVL cytotoxicity was examined in human polymorphonuclear neutrophils (PMNs), monocytes, HL-60 cells, and THP-1 cells. PVL binding capacities in HL-60 and THP-1 cells were higher than those in PMNs and monocytes; however, the PVL concentration to obtain more than 80% cell lysis in HL-60 cells was 10 times higher than that in PMNs and PVL even at such concentration induced < 10% cell lysis in THP-1 cells. After incubation of PMNs with LukS-PV, more than 90% of LukS-PV bound to the detergent-soluble membranes. Subsequent incubation with LukF-PV at 4 °C induced the accumulation of more than 70% of PVL components and 170- to 220-kDa complex formation in DRMs in an actin-independent manner. However, only 30% of PVL was found, and complex formation was under detectable level in DRMs in HL-60 cells. PVL did not accumulate in DRMs in THP-1 cells. Our observations strongly indicate that PVL accumulation in DRMs is essential for PVL cytotoxicity.
... Nakagawa et al. were able to block TSST-1-induced production of cytokines in PBMC using anisodamine (20 μg/ml), a naturally occurring tropane alkoid that has been used in Chinese herbal medicines. Anisodamine (50 mg/kg via intraperitoneal injection) was able to protect mice from TSST-1-induced lethality[164].Watson et al. used epigallocatechin gallate (100 μM); a component of green tea, to inhibit SEB-induced cytokines from PBMC[153]. Several studies have used pyrrolidine dithiocarbamate, sodium pyrithione, N-acetyl-L-cysteine, and curcumin to inhibit SEA-, SEB-, and TSST-1-induced cytokine production from PBMCs[156,165]. ...
Objective This subject was designed to investigate effects of anisodamine on the expressions of tumor necrosis factor-alpha (TNF-alpha) and cycloxygenase 2 (COX-2) in a rabbit model of infusion phlebitis and to analyze the preventative and treatment mechanisms of anisodamine in experimental infusion phlebitis. Method The rabbits were randomly assigned to the control group, the model group, the magnesium sulfate group and the anisodamine group. Expressions of TNF-alpha and COX-2 were determined and contrasted with the control group treated with normal saline by histopathology, immunohistochemistry, reverse transcription polymerase chain reaction, and western blotting assay, respectively. Results Obvious pathohistological changes were observed and the model group showed the highest expressions of TNF-alpha and COX-2 in the four groups (P<0.01). On the contrary, anisodamine alleviated the inflammatory damage by significantly reducing the expressions of TNF-alpha and COX-2 compared with the model group (P<0.01). There was no difference in the expressions of TNF-alpha and COX-2 between the magnesium sulfate group and the anisodamine group (P>0.05). Conclusion Anisodamine alleviates the inflammatory damages by significantly reducing the expressions of TNF-alpha and COX-2, and shows significant protective effects in the animal model of infusion phlebitis. [Zhang Zhenxiang, Zhang Qiushi, Wang Peng, Pan Xue, Zhao Qingxia, Wang Xiaokai. Effects of anisodamine on the expressions of tumor necrosis factor-alpha and cycloxygenase 2 in experimental infusion phlebitis. Life Sci J 2012; 9(2): 533-539]. (ISSN: 1097-8135). http://www.lifesciencesite.com. 80
