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Biomedical subjects

M Djavad Mossalayi

Publications and source records attributed to M Djavad Mossalayi.

6 recordsLinked to original sources
PubMed2006

Therapeutic and preventive properties of quercetin in experimental arthritis correlate with decreased macrophage inflammatory mediators.

Pentahydroxyflavone dihydrate, quercetin (QU) is one of common flavonols biosynthesized by plants and has been suggested to modulate inflammatory responses in various models. In the present study, we investigated in vivo effects of oral or intra-cutaneous QU in chronic rat adjuvant-induced arthritis (AA). Growth delay and arthritic scores were evaluated daily after AA induction in Lewis rats. Oral administration of QU (5 x 160 mg/kg) to arthritic rats resulted in a clear decrease of clinical signs compared to untreated controls. Intra-cutaneous injections of lower doses (5 x 60 mg/kg) of QU gave similar anti-arthritic effects, while 5 x 30 mg/kg concentrations were inefficient in this respect. Finally, injection of relatively low QU doses (5 x 30 mg/kg) prior to AA induction significantly reduced arthritis signs. As QU was suggested to inhibit macrophage-derived cytokines and nitric oxide (NO), we then analyzed macrophage response ex vivo. Anti-arthritic effects of QU correlated with significant decrease of inflammatory mediators produced by peritoneal macrophages, ex vivo and in vitro. These data indicate that QU is a potential anti-inflammatory therapeutic and preventive agent targeting the inflammatory response of macrophages.

Administration, Oral↗
PubMed2006

Nitric oxide involvement in the anti-tumor effect of mistletoe (Viscum album L.) extracts Iscador on human macrophages.

Lectins from different types of mistletoe (Viscum album, VA) have cytotoxic and immunomodulatory properties that may be relevant in the inhibition of tumor growth. The mechanism of this anti-tumoral activity remains unknown, although recent investigations point out the induction of anti-tumoral cytotoxic T cell activation. In this study therapeutically available mistletoe extracts (Iscador) prepared from Quercus (VA-Q), apple (Malus, VA-M) or pine (Pinus, VA-P) were used to investigate their capacity to induce tumor regression through the modulation of another T helper-1 (Th-1)-mediated anti-tumoral activity: the activation of macrophages. Macrophages are essential targets for both pro- or anti-inflammatory drugs and constitute an essential member of the anti-tumoral immune response. Freshly isolated human monocyte-derived macrophages are activated and various VA extracts are directly incorporated to cultures to assay their properties on the inflammatory and/or tumor cytotoxic responses. The data indicate that immunomodulatory activities of VA extracts differ according to their origin. VA-M and VA-P were able to increase anti-tumoral activity of activated human macrophages, with a possible role for nitric oxide in this effect.

Antineoplastic Agents, Phytogenic↗
PubMed2004

Long-acting beta2-adrenergic formoterol and salmeterol induce the apoptosis of B-chronic lymphocytic leukaemia cells.

B-cell chronic lymphocytic leukaemia (B-CLL) is a neoplastic disorder characterized by defective apoptosis, cell accumulation in G0/G1, and high expression of BCL2 oncogene. Intracellular cyclic adenosine monophosphate (cAMP) accumulation increases the chemosensitivity of B-CLL cells in vitro and in vivo. In the present study, we investigated the effects of beta2-adrenergic compounds, well known cAMP-inducing drugs, on the in vitro survival of leukaemia cells. In contrast to the short-acting beta2-mimetic (beta2Mim) salbutamol, a consistent pro-apoptotic effect was observed with the long-acting beta2Mim salmeterol and formoterol. Normal B cells isolated from control donors were totally resistant to the above molecules. These compounds also increased chlorambucil- and fludarabine-induced death of B-CLL cells. Blockade of beta-adrenergic receptor signalling or cAMP did not alter B-CLL apoptosis with beta2 Mimagents. Leukaemia cell apoptosis by beta2Mim correlated with an increase in calcium influx, decreased bcl-2 protein and mRNA levels, increase in BAX gene expression and a marked rise in BCL2/BAX mRNA ratios. Interleukin-4, a cytokine that increases bcl-2 expression in B-CLL cells, rescued leukaemia cell from apoptosis with beta2Mim. These data show that long-acting beta2-adrenergic agents promote apoptotic leukaemia cell death through an adrenoreceptor- and cAMP-independent, Ca2+-dependent mechanism.

Adrenergic beta-Agonists↗
PubMed2004

Quercetin induces apoptosis of Trypanosoma brucei gambiense and decreases the proinflammatory response of human macrophages.

In addition to parasite spread, the severity of disease observed in cases of human African trypanosomiasis (HAT), or sleeping sickness, is associated with increased levels of inflammatory mediators, including tumor necrosis factor (TNF)-alpha and nitric oxide derivatives. In the present study, quercetin (3,3',4',5,7-pentahydroxyflavone), a potent immunomodulating flavonoid, was shown to directly induce the death of Trypanosoma brucei gambiense, the causative agent of HAT, without affecting normal human cell viability. Quercetin directly promoted T. b. gambiense death by apoptosis as shown by Annexin V binding. In addition to microbicidal activity, quercetin induced dose-dependent decreases in the levels of TNF-alpha and nitric oxide produced by activated human macrophages. These results highlight the potential use of quercetin as an antimicrobial and anti-inflammatory agent for the treatment of African trypanomiasis.

Animals↗
PubMed2002

Resveratrol inhibits the growth and induces the apoptosis of both normal and leukemic hematopoietic cells.

It is often postulated that trans-3,4',5-trihydroxystilbene (resveratrol, RES) exhibits cell growth regulatory and chemopreventive activities. However, mechanisms by which this polyphenol inhibits tumor cell growth, and its therapeutic potential are poorly understood. Using various human leukemia cells, we have first defined the anti-tumoral doses of this compound. RES inhibited the proliferation and induced the apoptosis of all tested lymphoid and myeloid leukemia cells with IC(50) = 5-43 microM. Prior to apoptosis, RES-induced caspase activity in a dose-dependent manner and cell cycle arrest in G(2)/M-phase, correlating with a significant accumulation of cyclins A and B. Leukemia cell death with RES required both caspase-dependent and -independent proteases, as it was significantly inhibited by simultaneous addition of Z-VAD-FMK and leupeptin to these cultures. While RES did not affect non-activated normal lymphocytes, this agent decreased the growth and induced the apoptosis of cycling normal human peripheral blood lymphocytes at lower concentrations (IC(50) <8 microM) than those required for most leukemia cells. RES also induced the apoptosis of early normal human CD34(+) cells and decreased the number of colonies generated by these precursor cells in a dose-dependent manner (IC(50) = 60 microM). Together, the data point to the complexity of RES-mediated signaling pathways and revealed the high anti-proliferative and proapoptotic activities of RES in normal cycling hemopoietic cells.

Apoptosis↗