TY - JOUR
T1 - Nanocurcumin is superior to native curcumin in preventing degenerative changes in Experimental Cerebral Malaria
AU - Dende, Chaitanya
AU - Meena, Jairam
AU - Nagarajan, Perumal
AU - Nagaraj, Viswanathan Arun
AU - Panda, Amulya Kumar
AU - Padmanaban, Govindarajan
N1 - Funding Information:
G.P. was supported by Centre of Excellence grant by the Department of Biotechnology, Government of India (BT0i/10/MPB/DT/2010 and BT/PR13760/COE/34/42/2015). G.P. is a NASI-Platinum Jubilee Senior Scientist. A.K.P. was supported by the core grant of the National Institute of Immunology (NII), New Delhi and project grant (BT/PR2426/NNT/289/531/2011) received from the Department of Biotechnology, Government of India. Thanks are due to Dr P.N. Rangarajan for support.
Publisher Copyright:
© 2017 The Author(s).
PY - 2017/12/1
Y1 - 2017/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41598-017-10672-9
DO - 10.1038/s41598-017-10672-9
M3 - Article
C2 - 28855623
AN - SCOPUS:85028616916
SN - 2045-2322
VL - 7
JO - Scientific reports
JF - Scientific reports
IS - 1
M1 - 10062
ER -