In vitro and in vivo anti-inflammatory active copper(II)-lawsone complexes

Abstract

We report in vitro and in vivo anti-inflammatory activities of a series of copper(II)-lawsone complexes of the general composition [Cu(Law)2(LN)x(H2O)(2-x)]·yH2O; where HLaw = 2-hydroxy-1,4-naphthoquinone, x = 1 when LN = pyridine (1) and 2-aminopyridine (3) and x = 2 when LN = imidazole (2), 3-aminopyridine (4), 4-aminopyridine (5), 3-hydroxypyridine (6), and 3,5-dimethylpyrazole (7). The compounds were thoroughly characterized by physical techniques, including single crystal X-ray analysis of complex 2. Some of the complexes showed the ability to suppress significantly the activation of nuclear factor κB (NF-κB) both by lipopolysaccharide (LPS) and TNF-alpha (complexes 3–7 at 100 nM level) in the similar manner as the reference drug prednisone (at 1 μM level). On the other hand, all the complexes 1–7 decreased significantly the levels of the secreted TNF-alpha after the LPS activation of THP-1 cells, thus showing the anti-inflammatory potential via both NF-κB moderation and by other mechanisms, such as influence on TNF-alpha transcription and/or translation and/or secretion. In addition, a strong intracellular pro-oxidative effect of all the complexes has been found at 100 nM dose in vitro. The ability to suppress the inflammatory response, caused by the subcutaneous application of λ-carrageenan, has been determined by in vivo testing in hind-paw edema model on rats. The most active complexes 1–3 (applied in a dose corresponding to 40 μmol Cu/kg), diminished the formation of edema simalarly as the reference drug indomethacine (applied in 10 mg/kg dose). The overall effect of the complexes, dominantly 1–3, shows similarity to anti-inflammatory drug benoxaprofen, known to induce intracellular pro-oxidative effects.

Copper(II) Complexes Containing Natural Flavonoid Pomiferin Show Considerable In Vitro Cytotoxicity and Anti-inflammatory Effects

“…Pomiferin itself did not increase the amount of ROS in both experiments. Similar behaviour was also observed previously for heteroleptic copper(II) complexes containing 1,4-naphthoquinone derivative lawson [54].…”

“…The relative cell viability of floating monocytes THP-1 were determined after 24 h incubation in a serum-free medium with compounds 1 – 5 dissolved in N , N -dimethylformamide (DMF) at increasing concentrations (20–0.125 µM) by the cell proliferation reagent WST-1 (Roche, Basel, Switzerland) according to the manufacturer’s manual, as we described previously [ 54 ]. The IC 50 values were calculated from resultant viability curves by four-parameter logistic (4PL) analysis.…”

Ethnopharmacological survey of medicinal plants with hallucinogenic effect and plants used against pain, inflammatory diseases, diabetes and urinary lithiasis in Zagora “Morocco”.

“…An experimental study realized by Ait El Cadi et al demonstrated that ethanolic and aqueous extracts of Z. gaetulum L reduce inflammation in edema induced by carrageenan [44]. In another hand, Liou et al confirmed anti-inflammatory activity of two components (lawsochylin 1 and lawsonaphthoate A) from L. inermis these molecules inhibit superoxide anion generation in inflammation process [45]. Plants that were identified as having hallucinogenic effects belong to three species, namely, H. muticus L., D. stramonium L., and M. fragrans L. These results are in accordance with the well-established result of toxicological studies showing hallucination symptoms appearing following ingestion of high doses of H. muticus and D. stramonium L. [46,47].…”

Investigation of Anti-Inflammatory Potential of N-Arylcinnamamide Derivatives

“…The activity of NF-κB transcription factors was evaluated on THP1-Blue™ NF-κB cells as described previously [50,51]. Briefly, cells were transferred into serum-free RPMI 1640 medium as was delineated above in Section 3.4.…”

“…To differentiate THP1-Blue™ NF-κB monocytes into macrophages, the cells were stimulated with phorbol myristate acetate (PMA) at the final concentration of 50 ng/mL, as was described previously [51,52]. Cells were seeded into 8-well cell culture glass slide (SPL, Korea) at the concentration of 500,000 cells/mL, 150,000 cells per well.…”