Anthocyanins encapsulated by PLGA@PEG nanoparticles potentially improved its free radical scavenging capabilities via p38/JNK pathway against Aβ1-42-induced oxidative stress.
BACKGROUND
In order to increase the bioavailability of hydrophilic unstable drugs like anthocyanins, we employed a polymer-based nanoparticles approach due to its unique properties such as high stability, improved bioavailability and high water-soluble drug loading efficiency. Anthocyanins constitute a subfamily of flavonoids that possess anti-oxidative, anti-inflammatory and neuroprotective properties. However, anthocyanins are unstable because their phenolic hydroxyl groups are easily oxidized into quinones, causing a reduced biological activity. To overcome this drawback and improve the free radical scavenging capabilities of anthocyanins, in the current study we for the first time encapsulated the anthocyanins in biodegradable nanoparticle formulation based on poly (lactide-co-glycolide) (PLGA) and a stabilizer polyethylene glycol (PEG)-2000. The biological activity and neuroprotective effect of anthocyanin loaded nanoparticles (An-NPs) were investigated in SH-SY5Y cell lines.


RESULTS
Morphological examination under transmission electron microscopy (TEM) showed the formation of smooth spherically shaped nanoparticles. The average particle size and zeta potential of An-NPs were in the range of 120-165 nm and -12 mV respectively, with a low polydispersity index (0.4) and displayed a biphasic release profile in vitro. Anthocyanins encapsulation in PLGA@PEG nanoparticles (NPs) did not destroy its inherent properties and exhibit more potent neuroprotective properties. An-NPs were nontoxic to SH-SY5Y cells and increased their cell viability against Aβ1-42by its free radical scavenging characteristics and abrogated ROS generation via the p38-MAPK/JNK pathways accompanied by induction of endogenous nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1). Comparative to native bulk anthocyanins, An-NPs effectively attenuated Alzheimer's markers like APP (amyloid precursor protein), BACE-1 (beta-site amyloid precursor protein cleaving enzyme 1), neuroinflammatory markers such as p-NF-kB (phospho-nuclear factor kappa B), TNF-α (tumor necrosis factor) and iNOS (inducible nitric oxide synthase) and neuroapoptotic markers including Bax, Bcl2, and Caspase-3 protein expressions accompanied by neurodegeneration against Aβ1-42in SH-SY5Y cell lines.


CONCLUSIONS
Overall, this data not only confirmed the therapeutic potential of anthocyanins in reducing AD pathology but also offer an effective way to improve the efficiency of anthocyanins through the use of nanodrug delivery systems.
Department of Biology and Applied Life Science (BK 21), College of Natural Sciences Gyeongsang National University, Jinju, 660-701, South Korea.
Faiz Ul
FU
Amin
Department of Biology and Applied Life Science (BK 21), College of Natural Sciences Gyeongsang National University, Jinju, 660-701, South Korea.
Shahid Ali
SA
Shah
Department of Biology and Applied Life Science (BK 21), College of Natural Sciences Gyeongsang National University, Jinju, 660-701, South Korea.
Haroon
H
Badshah
Department of Biology and Applied Life Science (BK 21), College of Natural Sciences Gyeongsang National University, Jinju, 660-701, South Korea.
Mehtab
M
Khan
Department of Biology and Applied Life Science (BK 21), College of Natural Sciences Gyeongsang National University, Jinju, 660-701, South Korea. mokim@gnu.ac.kr.
Myeong Ok
MO
Kim
D000544:Alzheimer Disease / Q000517:prevention & control; D016229:Amyloid beta-Peptides / Q000494:pharmacology; D000872:Anthocyanins / Q000494:pharmacology*; D001682:Biological Availability; D018929:Cell Culture Techniques; D002460:Cell Line; D002470:Cell Survival; D016503:Drug Delivery Systems; D065546:Drug Liberation; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry*; D020935:MAP Kinase Signaling System; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry*; D018696:Neuroprotective Agents / Q000494:pharmacology; D018384:Oxidative Stress; D010316:Particle Size; D010446:Peptide Fragments / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer
D016229:Amyloid beta-Peptides; D000872:Anthocyanins; D016166:Free Radical Scavengers; D018696:Neuroprotective Agents; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols; C000595210:polyethylene glycol 2000
Alzheimer’s disease; Anthocyanins; Neuroprotection; Oxidative stress; PLGA@PEG-nanoparticles