Inhibition of cellular immune responses by in experimental models

Ganguly, Tanmoy

doi:10.1078/0944-7113-00055

Cited by 60 publications

(26 citation statements)

References 20 publications

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“…These alkaloids were also shown to have anti-inflammatory, antiasthmatic, and antianaphylactic properties with consequences of altered immunological status in vivo (Gopalakrishnan et al, 1979(Gopalakrishnan et al, , 1980Raina and Raina, 1980;Ganguly and Sainis, 2001;Staerk et al, 2002). Although adenyl cyclase was stimulated in asthmatic patients' peripheral leukocytes treated with tylophorine (Raina and Raina, 1980), the molecular mechanisms of actions of these phenanthroindolizidine alkaloids for aforementioned functions are not clear as yet.…”

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confidence: 99%

Anti-Inflammatory Mechanisms of Phenanthroindolizidine Alkaloids

Yang¹,

Chen²,

Wu³

et al. 2005

Mol Pharmacol

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The molecular mechanisms for the anti-inflammatory activity of phenanthroindolizidine alkaloids were examined in an in vitro system mimicking acute inflammation by studying the suppression of lipopolysaccharide (LPS)/interferon-␥ (IFN␥)-induced nitric oxide production in RAW264.7 cells. Two of the phenanthroindolizidine alkaloids, NSTP0G01 (tylophorine) and NSTP0G07 (ficuseptine-A), exhibited potent suppression of nitric oxide production and did not show significant cytotoxicity to the LPS/IFN␥-stimulated RAW264.7 cells, in contrast to their respective cytotoxic effects on cancer cells. Tylophorine was studied further to investigate the responsible mechanisms. It was found to inhibit the induced protein levels of tumor necrosis factor-␣, inducible nitric-oxide synthase (iNOS), and cyclooxygenase (COX)-II. It also inhibited the activation of murine iNOS and COX-II promoter activity. However, of the two common responsive elements of iNOS and COX-II promoters, nuclear factor-B (NF-B) and adaptor protein (AP)1, only AP1 activation was inhibited by tylophorine in the LPS/IFN␥-stimulated RAW264.7 cells. Further studies showed that the tylophorine enhanced the phosphorylation of Akt and thus decreased the expression and phosphorylation levels of c-Jun protein, thereby causing the subsequent inhibition of AP1 activity. Furthermore, the tylophorine was able to block mitogen-activated protein/extracellular signal-regulated kinase kinase 1 activity and its downstream signaling activation of NF-B and AP1. Thus, NSTP0G01 exerts its anti-inflammatory effects by inhibiting expression of the proinflammatory factors and related signaling pathways.Phenanthroindolizidine alkaloids are a small group of compounds well known for their profound cytotoxic activity (Pettit et al., 1984;Abe et al., 1998;Staerk et al., 2000Staerk et al., , 2002 and thus have been exploited as potential therapeutic leads for anticancer agents (Staerk et al., 2002). These alkaloids were also shown to have anti-inflammatory, antiasthmatic, and antianaphylactic properties with consequences of altered immunological status in vivo (Gopalakrishnan et al., 1979(Gopalakrishnan et al., , 1980Raina and Raina, 1980;Ganguly and Sainis, 2001;Staerk et al., 2002). Although adenyl cyclase was stimulated in asthmatic patients' peripheral leukocytes treated with tylophorine (Raina and Raina, 1980), the molecular mechanisms of actions of these phenanthroindolizidine alkaloids for aforementioned functions are not clear as yet. Moreover, the analysis and knowledge of the structure-activity relationships of the phenanthroindolizidine alkaloids with their biological function are also scarce.Inflammation is a central feature of many pathological conditions and is mediated by a variety of soluble factors and cellular signaling events. For example, NF-B-dependent gene expression plays an important role in inflammatory responses and increases the expression of genes encoding cytokines and receptors involved in proinflammatory enzymes such as iNOS and COX-II (Giuliani et al....

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confidence: 99%

Anti-Inflammatory Mechanisms of Phenanthroindolizidine Alkaloids

Yang¹,

Chen²,

Wu³

et al. 2005

Mol Pharmacol

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“…Alkaloids were one of the phytochemical compounds identified in this study. Most common biological properties of alkaloids are toxic against cells of foreign organisms, anti-inflammatory, anti-asthmatic, and anti-anaphylactic properties (Ganguly and Sainis, 2001;Staerk et al, 2002) and may be responsible for the observed activity.…”

Section: Discussionmentioning

confidence: 99%

Bioactivity of Hydnora africana on selected bacterial pathogens: Preliminary phytochemical screening

Nethathe¹,

Ndip²

2011

Afr. J. Microbiol. Res.

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Medicinal plants contain a variety of chemical substances with important therapeutic properties that can be utilized in the treatment of human diseases. Hydonora africana is used in folklore remedies for the treatment of diarrhoea, dysentery, kidney and bladder complaints among other ailments; hence we assessed the in vitro antimicrobial activity of this plant against three bacterial species (Helicobacter pylori ATCC 43526, Helicobacter pylori PE 252C, Staphylococcus aureus NCTC 6571 and Aeromonas hydrophila ATCC 35654). The agar well diffusion method was used to determine the susceptibility of bacterial strains to crude extracts of the plant. The minimum inhibitory concentration (MIC 50 ) and minimum bactericidal concentration (MBC) of the active crude extracts were determined by the microdilution test. Ciprofloxacin (0.0125 mg/mL) was used as positive control. The presence of phytochemicals was also assessed using standard methods. Results were analyzed statistically by the one-way ANOVA test. Hydnora africana demonstrated antimicrobial activity against all the organisms with a mean zone diameter of inhibition ranging from 0 to 22 mm. The MIC 50 of the extracts ranged from 0.078 to 2.5 mg/mL and MBC ranged from 0.78 to 25 mg/mL. Phytochemical assay revealed the presence of alkaloids, tannins, flavonoids, saponins and steroids in the extracts. It is concluded that H. africana may contain compounds with therapeutic activity.

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“…Li et al (2003) reported that tannins have remarkable activity in cancer prevention and anticancer, this suggests that date fruit could be a possible source of important bioactive molecules for the treatment and prevention of cancer. Alkaloids known for their toxicity against cells of foreign organisms was also observed in the date fruit (Ganguly and Sainis, 2001). Saponins, a well reported antimicrobial compound was also recorded.…”

Section: Antifungal Screeningmentioning

confidence: 99%