Abstract
Curcumin has many pharmacological activities despite its poor bioavailability and in vivo stability. Here, we show that a nanoformulated curcumin (PLGA-curcumin) has better therapeutic index than native curcumin in preventing the onset of neurological symptoms and delaying the death of mice in experimental cerebral malaria. Oral PLGA-curcumin was at least as effective as native curcumin at a 15-fold lower concentration in preventing the breakdown of blood-brain barrier and inhibition of brain mRNAs for inflammatory cytokines, chemokine receptor CXCR3 and its ligand CXCL10, with an increase in the anti-inflammatory cytokine IL-10. This was also reflected in serum cytokine and chemokine levels. At equivalent concentrations, a single oral dose of PLGA-curcumin was more effective in inhibiting serum IFNγ levels and enhancing IL-10 levels than native curcumin. Even at low concentrations, PLGA-curcumin was superior to native curcumin in inhibiting the sequestration of parasitized-RBCs and CD8+ T cells in the brain. A single oral dose of 5 mg PLGA-curcumin containing 350 μg of curcumin resulted in 3–4 fold higher concentration and prolonged presence of curcumin in the brain than that obtained with 5 mg of native curcumin, indicating better bioavailability of PLGA-curcumin. PLGA-curcumin has potential as an adjunct drug to treat human cerebral malaria.
Highlights
Curcumin from turmeric plant Curcuma longa and its derivatives known as curcuminoids have been recognized to be effective in experimental studies for a very large number of diseases with an large number of diverse molecular targets[1, 2]
We have recently shown that native curcumin alone is effective in counteracting the neurological symptoms and
The results indicated that PLGA-curcumin nanoparticles have the potential to be used as adjunct therapy for treating Human cerebral malaria (HCM)
Summary
Curcumin (diferuloylmethane) from turmeric plant Curcuma longa and its derivatives known as curcuminoids have been recognized to be effective in experimental studies for a very large number of diseases with an large number of diverse molecular targets[1, 2]. It has been suggested that nanocurcumin represents a promising therapeutic advancement over native curcumin[8] It is in this context that we want to report our results obtained with curcumin nanoparticles prepared using poly(lactide-co-glycolide) (PLGA) in comparison with native curcumin to treat experimental cerebral malaria (ECM). It was observed that PLGA-curcumin was as effective as native curcumin at a 15-fold lower concentration in counteracting the neurological symptoms and inflammation parameters, and in preventing the breakdown of BBB. It was more effective than native curcumin in preventing the sequestration of lymphocytes and pRBCs in brain.
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