title: Curcumin micelles improve mitochondrial function in neuronal PC12 cells and brains of NMRI mice - Impact on bioavailability.
abstract: Curcumin, a polyphenolic compound abundant in the rhizome of Curcuma longa, has been reported to have various beneficial biological and pharmacological activities. Recent research revealed that curcumin might be valuable in the prevention and therapy of numerous disorders including neurodegenerative diseases like Alzheimer's disease. Due to its low absorption and quick elimination from the body, curcumin bioavailability is rather low which poses major problems for the use of curcumin as a therapeutic agent. There are several approaches to ameliorate curcumin bioavailability after oral administration, amongst them simultaneous administration with secondary plant compounds, micronization and micellation. We examined bioavailability in vivo in NMRI mice and the effects of native curcumin and a newly developed curcumin micelles formulation on mitochondrial function in vitro in PC12 cells and ex vivo in isolated mouse brain mitochondria. We found that curcumin micelles improved bioavailability of native curcumin around 10- to 40-fold in plasma and brain of mice. Incubation with native curcumin and curcumin micelles prevented isolated mouse brain mitochondria from swelling, indicating less mitochondrial permeability transition pore (mPTP) opening and prevention of injury. Curcumin micelles proved to be more efficient in preventing mitochondrial swelling in isolated mouse brain mitochondria and protecting PC12 cells from nitrosative stress than native curcumin. Due to their improved effectivity, curcumin micelles might be a suitable formulation for the prevention of mitochondrial dysfunction in brain aging and neurodegeneration.
authors.affiliation: Department of Pharmacology, Biozentrum Niederursel, Goethe University, Max-von-Laue-Str. 9, 60438 Frankfurt, Germany. Electronic address: hagl@em.uni-frankfurt.de.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Hagl
authors.affiliation: Institute of Biological Chemistry and Nutrition, University of Hohenheim, Garbenstr. 28, 70599 Stuttgart, Germany.
authors.forename: Alexa
authors.initials: A
authors.lastname: Kocher
authors.affiliation: Institute of Biological Chemistry and Nutrition, University of Hohenheim, Garbenstr. 28, 70599 Stuttgart, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Schiborr
authors.affiliation: Department of Pharmacology, Biozentrum Niederursel, Goethe University, Max-von-Laue-Str. 9, 60438 Frankfurt, Germany.
authors.forename: Natalie
authors.initials: N
authors.lastname: Kolesova
authors.affiliation: Institute of Biological Chemistry and Nutrition, University of Hohenheim, Garbenstr. 28, 70599 Stuttgart, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Frank
authors.affiliation: Department of Pharmacology, Biozentrum Niederursel, Goethe University, Max-von-Laue-Str. 9, 60438 Frankfurt, Germany.
authors.forename: Gunter P
authors.initials: GP
authors.lastname: Eckert
mesh_terms: D000818:Animals; D001682:Biological Availability; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003474:Curcumin / Q000008:administration & dosage / Q000378:metabolism*; D016503:Drug Delivery Systems / Q000639:trends; D005260:Female; D051379:Mice; D008823:Micelles; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D016716:PC12 Cells; D051381:Rats
chemical_list: D008823:Micelles; D003474:Curcumin
keywords: Bioavailability; Curcumin; Micelles; Mitochondrial function; NMRI mice; PC12 cells