bisdemethoxycurcumin and Hemolysis

The present study deals with the toxicity assessment of NBDMCA in vitro using red cell model and in vivo using rat model. Hemolysis was used as toxicity index in red blood cells. Different concentrations of NBDMCA viz., 20, 40, 60, 80, 100μg/ml in PBS were incubated with the red blood cells of rat. NBDMCA was found to induce less than 3% hemolysis in intact erythrocytes which was far lesser than the accepted threshold of 5%. Hematological cum biochemical parameters along with histopathological analysis and hemolysis were used as toxicity indices in rats. Whole blood of the NBDMCA-treated rats and control rats were analyzed for hematological parameters: erythrocyte count, leukocyte count, leukocyte differential count, hemoglobin, hematocrit, mean cell volume (MCV), mean corpuscular hemoglobin (MCH) using fully automated hematology analyzer. All hematological parameters analyzed were within the normal values in both the groups. Plasma samples were analyzed for biochemical parameters including glucose, blood urea nitrogen (BUN), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), creatinine (Cre), albumin (Alb), total protein (TP), calcium (Ca) and phosphorus (P) using fully automated biochemistry analyzer. Invariably, all the biochemical parameters are significantly similar in both the groups. Gross examination of vital organs like lung, heart, kidney, spleen and brain reveals no detectable abnormalities in NBDMCA-treated animals. Internal organs like heart, brain, lung, liver, spleen and kidneys of the experimental animals were collected and fixed in 10% formalin, processed in vacuum infiltration tissue processor, embedded with paraffin wax and sectioned at approximately 5μm thick, stained with hematoxylin and eosin. The sections were examined and imaged through light microscopy. NBDMCA did not produce any significant changes in the histoarchitecture of all the organs studied. Heart, aorta, brain, lung, liver, kidney and spleen showed normal pathology report. The histopathological data correlated with the biochemical results indicating normal hepatocellular and nephrotic function. Our investigation clearly revealed that NBDMCA is hemocompatible in vitro and also safe to vital organs in vivo. We conclude that NBDMCA is non-toxic and safe and can be promoted as an ideal therapeutic tool for human use.

Topics: Administration, Intravenous; Animals; Cells, Cultured; Curcumin; Diarylheptanoids; Erythrocyte Count; Erythrocyte Indices; Erythrocytes; Hemolysis; Leukocyte Count; Male; Nanoparticles; Rats, Wistar

Curcuminoids are poorly water-soluble compounds with promising antimalarial activity. To overcome some of the drawbacks of curcuminoids, we explored the potential of liposomes for the intravenous delivery of curcuminoids in a model of mouse malaria. The curcuminoids-loaded liposomes were formulated from phosphatidylcholine (soy PC) by the thin-film hydration method. Antimalarial activity of curcuminoids-loaded liposomes alone and in combination with α/β arteether when administered intravenously, was evaluated in Plasmodium berghei infected mice. Animals treated with curcuminoids-loaded liposomes showed lower parasitemia and higher survival when compared to control group (no treatment). Importantly, the combination therapy of curcuminoids-loaded liposomes (40 mg/kg body wt) along with α/β arteether (30 mg/kg body wt) was able to not only cure infected mice but also prevented recrudescence. These data suggest that curcuminoids-loaded liposomes may show promise as a formulation for anti-malarial therapy.

Topics: Animals; Antimalarials; Artemisinins; Curcuma; Curcumin; Diarylheptanoids; Disease Models, Animal; Hemolysis; Humans; Liposomes; Malaria; Mice; Phytotherapy; Plant Extracts; Plant Roots; Plasmodium berghei; Polyphenols

The antioxidant activities of curcumin, its natural demethoxy derivatives (demethoxycurcumin, Dmc and bisdemethoxycurcumin, Bdmc) and metabolite hydrogenated derivatives (tetrahydrocurcumin, THC; hexahydrocurcumin, HHC; octahydrocurcumin; OHC) were comparatively studied using 2,2-diphenyl-1-picrylhydrazyl (DDPH) radical, 2,2'-azobis(2-amidinopropane)dihydrochloride (AAPH) induced linoleic oxidation and AAPH induced red blood cell hemolysis assays. Hydrogenated derivatives of curcumin exhibited stronger DPPH scavenging activity compared to curcumin and a reference antioxidant, trolox. The scavenging activity significantly decreased in the order THC>HHC=OHC>trolox>curcumin>Dmc>>>Bdmc. Stronger antioxidant activities toward lipid peroxidation and red blood cell hemolysis were also demonstrated in the hydrogenated derivatives. By the model of AAPH induced linoleic oxidation, the stoichiometric number of peroxyl radical that can be trapped per molecule (n) of hydrogenated derivatives were 3.4, 3.8 and 3.1 for THC, HHC and OHC, respectively. The number (n) of curcumin and Dmc were 2.7 and 2.0, respectively, which are comparable to trolox, while it was 1.4 for Bdmc. The inhibition of AAPH induced red blood cell hemolysis significantly decreased in the order OHC>THC=HHC>trolox>curcumin=Dmc. Results in all models demonstrated the lower antioxidant activity of the demethoxy derivatives, suggesting the ortho-methoxyphenolic groups of curcumin are involved in antioxidant activities. On the other hand, hydrogenation at conjugated double bonds of the central seven carbon chain and beta diketone of curcumin to THC, HHC and OHC remarkably enhance antioxidant activity.

Topics: Amidines; Antioxidants; Biphenyl Compounds; Chromans; Curcumin; Diarylheptanoids; Erythrocyte Membrane; Free Radical Scavengers; Free Radicals; Hemolysis; Humans; Hydrogenation; In Vitro Techniques; Linoleic Acid; Lipid Peroxidation; Molecular Structure; Oxidants; Picrates; Structure-Activity Relationship; Time Factors