The active fraction and/or compounds of Calendula officinalis responsible for wound healing are not known yet. In this work we studied the molecular target of C. officinalis hydroethanol extract (CEE) and its active fraction (water fraction of hydroethanol extract, WCEE) on primary human dermal fibroblasts (HDF). In vivo, CEE or WCEE were topically applied on excisional wounds of BALB/c mice and the rate of wound contraction and immunohistological studies were carried out. We found that CEE and only its WCEE significantly stimulated the proliferation as well as the migration of HDF cells. Also they up-regulate the expression of connective tissue growth factor (CTGF) and α-smooth muscle actin (α-SMA) in vitro. In vivo, CEE or WCEE treated mice groups showed faster wound healing and increased expression of CTGF and α-SMA compared to placebo control group. The increased expression of both the proteins during granulation phase of wound repair demonstrated the potential role of C. officinalis in wound healing. In addition, HPLC-ESI MS analysis of the active water fraction revealed the presence of two major compounds, rutin and quercetin-3-O-glucoside. Thus, our results showed that C. officinalis potentiated wound healing by stimulating the expression of CTGF and α-SMA and further we identified active compounds. Copyright © 2016 John Wiley & Sons, Ltd.

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An acetate-bridged binuclear Cu((II)) complex of the antiparasitic drug ornidazole was synthesized and characterized by different techniques. Single crystal X-ray diffraction revealed that the complex had a paddle wheel structure. Enzymatic assay experiments performed under anaerobic conditions on ornidazole and its Cu((II))-complex using xanthine oxidase as a model nitro-reductase showed that complex formation is able to cause a significant decrease in the reduction of the nitro group on the imidazole ring. Reduction products of 5-nitroimidazoles interact with DNA, causing destruction of the double helical structure and strands, leading to the inhibition of protein synthesis. Although not directly coordinated to the metal center, such a decrease in the generation of nitro radical anion through complex formation would result in decreased cytotoxicity of the complex, which could be a disadvantage from the standpoint of drug efficacy. For this reason, other aspects associated with the drug action of 5-nitroimidazoles, such as DNA binding, were studied. Experiments using cyclic voltammetry revealed that the binding of the complex was almost comparable to ornidazole. Bactericidal activity of ornidazole and the complex was studied on two separate bacterial strains, showing that the complex was comparable to ornidazole. Nitro radical anions are known to adversely affect the central nervous system, and this study showed that the Cu((II)) complex has the ability to decrease the generation of NO2˙(-) to an extent that struck the correct balance for beneficial activity, as cytotoxicity due to ornidazole was not affected.

Synthesis, characterization, enzyme assay, DNA binding and antimicrobial activity of a monomeric complex of CuII with tinidazole: significance of the controlled formation of the nitro radical anion.

A Cu(ii) complex of tinidazole is more radiosensitizing than it in radiation-induced damage of nucleic acids, calf thymus DNA and DNA in MCF-7 breast cancer cells. NO2˙− was modulated to strike a balance between efficacy and toxic side effects.