BackgroundBiofilms contribute to the pathogenesis of many forms of Staphylococcus aureus infection. Treatment of these infections is complicated by intrinsic resistance to conventional antibiotics, thus creating an urgent need for strategies that can be used for the prevention and treatment of biofilm-associated infections.Methodology/Principal FindingsThis study demonstrates that a botanical natural product composition (220D-F2) rich in ellagic acid and its derivatives can limit S. aureus biofilm formation to a degree that can be correlated with increased antibiotic susceptibility. The source of this composition is Rubus ulmifolius Schott. (Rosaceae), a plant used in complementary and alternative medicine in southern Italy for the treatment of skin and soft tissue infections. All S. aureus clonal lineages tested exhibited a reduced capacity to form a biofilm at 220D-F2 concentrations ranging from 50–200 µg/mL, which were well below the concentrations required to limit bacterial growth (530–1040 µg/mL). This limitation was therapeutically relevant in that inclusion of 220D-F2 resulted in enhanced susceptibility to the functionally-distinct antibiotics daptomycin, clindamycin and oxacillin. Testing with kidney and liver cell lines also demonstrated a lack of host cell cytotoxicity at concentrations of 220D-F2 required to achieve these effects.Conclusions/SignificanceThese results demonstrate that extract 220D-F2 from the root of Rubus ulmifolius can be used to inhibit S. aureus biofilm formation to a degree that can be correlated with increased antibiotic susceptibility without toxic effects on normal mammalian cells. Hence, 220D-F2 is a strong candidate for development as a botanical drug for use in the prevention and treatment of S. aureus biofilm-associated infections.
At the present time, scientists place a great deal of effort worldwide trying to improve the therapeutic potential of metal complexes of curcumin and curcuminoids. Herein, the synthesis of four homoleptic metal complexes with diacetylcurcumin (DAC), using a ligand designed to prevent the interaction of phenolic groups, rendering metal complexes through the β-diketone functionality, is reported. Due to their physiological relevance, we used bivalent magnesium, zinc, copper, and manganese for complexation with DAC. The resulting products were characterized by ultraviolet-visible (UV-Vis), fluorescence spectroscopy, infrared spectroscopy (IR), liquid and solid-state nuclear magnetic resonance (NMR), electron paramagnetic resonance (EPR), magnetic moment, mass spectrometry (MS), single crystal, and powder X-ray diffraction (SCXRD and PXRD). Crystallization was achieved in dimethylsulfoxide (DMSO) or N,N-dimethylformamide (DMF) as triclinic systems with space group P-1, showing the metal bound to the β-diketone function, while the 1H-NMR confirmed the preference of the enolic form of the ligand. Single crystal data demonstrated a 1:2 metal:ligand ratio. The inhibition of lipid peroxidation was evaluated using the thiobarbituric acid reactive substance assay (TBARS). All four metal complexes (Mg, Zn, Cu, and Mn) exhibited good antioxidant effect (IC50 = 2.03 ± 0.27, 1.58 ± 0.07, 1.58 ± 0.15 and 1.24 ± 0.10 μM respectively) compared with butylated hydroxytoluene (BHT) and α-tocopherol. The cytotoxic activity in human cancer cell lines against colon adenocarcinoma (HCT-15), mammary adenocarcinoma (MCF-7), and lung adenocarcinoma (SKLU-1) was found comparable ((DAC)2Mg), or ca. 2-fold higher ((DAC)2Zn) than cisplatin. The acute toxicity assays indicate class 5 toxicity, according to the Organization for Economic Co-operation and Development (OECD) guidelines at doses of 3 g/kg for all complexes. No mortality or changes in the behavior of animals in any of the treated groups was observed. A therapeutic potential can be envisaged from the relevant cytotoxic activity upon human cancer cell lines in vitro and the undetected in vivo acute toxicity of these compounds.
Urolithiasis is a multifaceted process, progressing from urine supersaturation to the formation of mature renal calculi. Calcium oxalate, the main component of kidney stones, has toxicological effects on renal epithelial cells. Some medicinal plants have shown pharmacological effects against renal lithiasis, such as Selaginella lepidophylla (Hook. et Grev) Spring, a plant empirically used in Mexico for its diuretic and antilithiasic activity. The plant was identified and ground, and a chloroform extract (CE) was obtained. Urolithiasis was induced in Wistar female rats by administration of ethylene glycol and ammonium chloride for 21 days. Urolithiasis rats were treated with the CE (50 mg/kg) for 21 days. Osmolality, creatinine, sodium and potassium concentrations were measured in blood and urine. Glomerular filtration rate (GFR), and electrolytic and water balances were calculated. Urinary oxalic acid concentration was measured. Apoptosis, lipoperoxidation, ROS and p-amino hippuric acid were determined in cortical tissue. Urolithiasis rats showed a decrease of urinary flow, GFR, electrolytic balance, renal tubular secretion and ATP concentration and increase of urinary oxalic acid, lipoperoxidation, oxidative stress and apoptosis in cortical tissue. After treatment with the CE, urinary flow rate, GFR and renal tubular secretion levels were recovered; on the other hand, serum creatinine and urinary oxalic acid decreased on day 21. CE of Selaginella lepidophylla prevented the damage caused by lithiasic process by improving the active secretion in the proximal tubules, counteracting the ROS and lipoperoxidation effects by oxalate and decreased the OAT3 expression on kidney.
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