Macrophages In Concentration-dependent Manner Research Articles

Chemical composition and antioxidant, antibacterial and antiproliferative activities of Macrolobium latifolium Vogel (Fabaceae) stem bark

Macrolobium latifolium Vogel belongs to the Fabaceae family and ethnopharmacological investigations have shown that some species from this family have been popularly used for treatment of chronic diseases. M. latifolium is widely distributed in semi-arid Bahia (Brazil) but reports on its biological activity and chemical composition are absent. In this context, our aim was to evaluate the preliminary chemical constitution and biological activity of M. latifolium stem bark. Overall, ethyl acetate fraction of M. latifolium stem bark (EAFML) was the most effective in reducing DPPH• (2,2-diphenyl-1-picrylhydrazyl radical) and ABTS•+ (2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid cation radical) radicals in vitro (IC50 = 8.4 and 4.6 μg/mL, respectively) and protecting H2O2-exposed Raw 264.7 macrophages against cell death. Similarly, EAFML enhanced the heme oxygenase activity of Raw 264.7 macrophages in concentration-dependent manner, suggesting the involvement of Nrf2 pathway. EAFML demonstrated the highest antibacterial activity on Staphylococcus aureus (MIC = MBC = 250 µg/mL), Staphylococcus epidermidis (MIC = 50 µg/mL and MBC = 100 µg/mL), Klebsiella pneumoniae (MIC = MBC = 100 µg/mL), and Proteus mirabilis (MIC = MBC = 100 µg/mL) when compared among other fractions. In addition, proliferation of HepG2 (human hepatocellular carcinoma), MCF7 (human breast carcinoma), and HCT116 (human colon carcinoma) tumor cells were significantly reduced by EAFML (IC50 = 26.4, 19.9, and 22.1 μg/mL, respectively), with no evidence of toxicity against non-tumor cells (MCR5, human fibroblast) and Raw 264.7 macrophages. Classical phytochemical assays and UPLC-MS/MS analysis revealed the presence of quercetin-type flavonols and oleanane-type triterpenoids in the EAFML, which may be related to its biological activities. In conclusion, this study demonstrated the variety of biological properties of M. latifolium stem bark, indicating its therapeutic potential as source of molecules for treatment of oxidative and infectious disorders, as well as cancer.

Immunomodulation of Inflammatory Markers in Activated Macrophages by Leaf Extracts of Gingko Biloba

Much recent attention has been given to traditional medicines and natural products with potential and promising anti-inflammatory properties. Leaf extract of Ginkgo biloba GbE-761, possesses several clinical beneficial effects and is now used in a broad spectrum of pharmacological actions. However, mechanisms associated with its anti-inflammatory effect are not very much clear. Previously we established that GbE-761 exerts a neuroprotective effect against ischemic brain injury through an anti-apoptotic mechanism. In this study we investigated the anti-inflammatory effect of GbE-761 in LPS-activated murine macrophage. Our results demonstrate that GbE-761 potently inhibited LPS-induced NO and PGE2 production and these observations were consistent with the inhibition in the protein and mRNA expression levels of inducible iNOS and COX-2 enzymes in a dose dependent manner. Not only this, GbE-761 attenuated the production of pro-inflammatory cytokines like IL-1 , IL-6 and TNFin LPS-activated murine macrophages in concentration dependent manner. In addition we reported inhibition in the protein and mRNA expression levels of IL-1 , IL-6 and TNF. Furthermore, GbE-761 inhibited the NFB activation induced by LPS. Together these results suggest that anti-inflammatory properties of GbE-761 extract might be the results of inhibition of iNOS and COX-2 by upregulating anti-oxidative enzymes and inhibition of pro-inflammatory cytokines (IL-1 , IL-6 and TNF) expression through the down-regulation of NF-kB activation in murine macrophages.

Interaction of Mycobacterium avium complex with human macrophages: roles of membrane receptors and serum proteins

Invasive, disease-associated members of the Mycobacterium avium complex are facultative intracellular pathogens of mammalian macrophages. The mechanism(s) by which M. avium is ingested by mononuclear phagocytes is unknown. We examined the role of membrane receptors on macrophages as well as the role of opsonic components of the serum (complement, fibronectin, C-reactive protein and fibrinogen in the attachment and ingestion of M. avium by human monocyte-derived macrophages. Preincubation of serum with antibodies against C3 and fibronectin, in contrast to preincubation of serum with antibodies against complement-reactive protein and fibrinogen, significantly reduced the binding of M. avium to macrophages in concentration-dependent manner (57 to 93% and 35 to 61% inhibition by anti-C3 and anti-fibronectin antibody, respectively, in a concentration range of 25 to 100 micrograms/ml). We also observed that incubation of macrophages with OKM1 anti-complement receptor type 3 (CR3) antibody in the presence of serum decreased the binding of M. avium to macrophages by 86% +/- 6%, while the same antibody inhibited binding by 63% +/- 7% in the absence of serum. In contrast, incubation of macrophages with anti-LFA-1, anti-p 150.95, anti-CR1, or anti-Mac-1 had no effect on the ability of M. avium to bind to the cell. In addition, incubation of macrophages with alpha-methyl-D-mannoside was also associated with decreased attachment of M. avium to macrophages. These results provide evidence for the role of three macrophage receptors (CR3, fibronectin, and mannosyl-fucosyl receptors) in the uptake of M. avium by human macrophages.