Artemisinin and curcumin show an additive interaction in killing Plasmodium falciparum in culture. In vivo, 3 oral doses of curcumin following a single injection of ␣,-arteether to Plasmodium berghei-infected mice are able to prevent recrudescence due to ␣,-arteether monotherapy and ensure almost 100% survival of the animals.Artemisinin derivative-based combination therapy (ACT) has been advocated as the therapy of choice to handle widespread drug resistance in Plasmodium falciparum malaria, at the same time preventing recrudescence due to artemisinin monotherapy. However, most of the combinations are less than ideal because of side effects, pharmacokinetic mismatch, and cost (8,15). Studies in this laboratory have shown that curcumin isolated from the roots of Curcuma longa (turmeric) has antimalarial activity in P. falciparum culture and in Plasmodium berghei-infected mice (10). In this study, we propose a novel artemisinin-curcumin therapy to treat malaria.Artemisinin and curcumin (98% curcuminoid content) were purchased from Sigma Chemicals, Bangalore, India. ␣,-Arteether (EMAL, a synthetic derivative of artemisinin) developed by Central Drug Research Institute, Lucknow, India, was a kind gift from IPCA Laboratories Ltd., Mumbai, India. [ 3 H]hypoxanthine was purchased from PerkinElmer, Singapore.The P. falciparum FCK strain, a local chloroquine-resistant isolate, was cultured in human O-positive washed erythrocytes using standard protocols (14). Parasites were synchronized using 5% (wt/vol) D-sorbitol, and the cultures were pooled and the parasites released from the erythrocyte with 0.15% (wt/vol) saponin (3) for further processing. The 50% inhibitory concentrations (IC 50 s) for artemisinin and curcumin were determined in P. falciparum cultures by measuring [3 H]hypoxanthine uptake into the parasite as a measure of viability (2). Fractional inhibitory concentrations (FIC) were calculated using the formulawhere A C and B C are the concentrations of A and B in the combination associated with a particular level of effect, e.g., IC 60 , and A E and B E are the concentrations of A and B when used singly to produce the same level of effect, on the basis that a simple additive interaction should lead to a value of 1 (7). FIC were derived from graphs drawn using GraphPad Prism 4.Means Ϯ standard deviations and Student's t test were analyzed using Microsoft Excel. For in vivo studies, Swiss mice (25 to 28 g) were injected intraperitoneally with P. berghei-infected mouse blood (60 to 70% parasitemia) on day 0, such that the animals developed high parasitemia and died in about 5 to 8 days. The artemisinin derivative ␣,-arteether was injected intramuscularly at different doses on day 1. This was followed by oral feeding of curcumin in dimethyl sulfoxide on days 1, 2, and 3 (100 mg/kg of body weight). The mice were observed for external symptoms and mortality when the drugs were given alone or in combination. Blood from the tail vein was analyzed on different days for parasitemia using Giemsa to stain the slides.De...
Among the primary brain tumors, glioblastoma is the most common and severe. Glioblastoma have poor prognosis because of their highly diffusive growth pattern and invasion into surrounding brain tissue. Human glioblastoma cells overexpress interleukin-1β (IL-1β) and also the levels of IL-1β in U87MG glioma cells are significantly higher than in U373, T98G, A172 glioma cell lines. Malignant tumors are characterized by unlimited proliferation, migration and invasion. This study examines the effect of IL-1β microenvironment on proliferation, migration and invasion in human glioma cell line U87MG that expresses wild-type p53 protein, and U251MG which expresses mutant p53. Proliferation was investigated by MTT assay, migration by wound-healing migration assay and invasion by in vitro transwell Matrigel invasion assay. An IL-1β microenvironment significantly increased migration and invasion of both wild-type and mutant p53 expressing glioma cells, but significantly increased proliferation only in U87MG glioma cells. These effects were inhibited by IL-1 receptor antagonist (IL-1Ra), thus giving evidence that an IL-1β milieu promotes glioma cell migration, invasion, and proliferation.
Benign and malignant prostatic growths are associated with an increase in sialoconjugates (e.g. prostate-specific antigen (PSA)) in blood. Oxidative stress plays a crucial role in pathogenesis of various malignancies. The objective of this study was to evaluate oxidative stress parameters and protein-bound sialic acid level in sera of prostatic tumor cases and to asses for any association between them. Sera samples were collected and estimated for carbonylation of proteins, lipid peroxidation products, PSA and protein-bound sialic acid from 10 patients in each group with prostatic carcinoma (Ca prostate) and benign prostatic hyperplasia (BPH) along with 10 healthy male subjects of similar age group as control. In carcinoma prostate cases, lipid peroxides, protein carbonyls, protein-bound sialic acid and PSA were significantly increased compared to BPH and controls. There was significant association between oxidative stress parameters (lipid peroxide and protein carbonyl) and sialoconjugates (PSA and protein-bound sialic acid). In BPH cases, serum lipid peroxides and protein-bound sialic acid were significantly higher in comparison to controls and protein carbonyls were correlated with protein-bound sialic acid. ROC curve for sialic acid showed that it can be used as a marker to differentiate carcinoma prostate from benign growth of prostate at a cutoff level of 11.38 lg/mg protein with a sensitivity of 100% and specificity of 80%. We conclude that oxidative stress might be associated with the degree of sialylation of protein and graded changes in these parameters possibly unveil the pathogenic demarcation from benign to malignant condition of prostate.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.