title: Enhanced Neuroprotection of Acetyl-11-Keto-β-Boswellic Acid (AKBA)-Loaded O-Carboxymethyl Chitosan Nanoparticles Through Antioxidant and Anti-Inflammatory Pathways.
abstract: Acetyl-11-keto-β-boswellic acid (AKBA), a main active constituent from Boswellia serrata resin, is a novel candidate for therapy of cerebral ischemia-reperfusion (I/R) injury. Nevertheless, its poor solubility in aqueous solvent, bioavailability, and rapid clearance limit its curative efficacy. To enhance its potency, in our study, AKBA-loaded o-carboxymethyl chitosan nanoparticle (AKBA-NP) delivery system was synthesized. The transmission electron microscopy and transmission electron microscope images of AKBA-NPs suggested that particle size was 132 ± 18 nm, and particles were spherical in shape with smooth morphology. In pharmacokinetics study, AKBA-NPs apparently increases the area under the curve of plasma concentration-time and prolonged half-life compared with AKBA. The tissue distribution study confirmed that AKBA-NPs had a better brain delivery efficacy in comparison with AKBA. The results from our pharmacodynamic studies showed that AKBA-NPs possess better neuroprotection compared with AKBA in primary neurons with oxygen-glucose deprivation (OGD) model and in animals with middle cerebral artery occlusion (MCAO) model. Additionally, AKBA-NPs modulate antioxidant and anti-inflammatory pathways more effectively than AKBA by increasing nuclear erythroid 2-related factor 2 and heme oxygenase-1 expression, and by decreasing nuclear factor-kappa B and 5-lipoxygenase expression. Collectively, our results suggest that AKBA-NPs serve as a potent delivery vehicle for AKBA in cerebral ischemic therapy.
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Department of Pharmaceutical Analysis, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Youbei
authors.initials: Y
authors.lastname: Qiao
authors.affiliation: Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Huinan
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Yikai
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Ge
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China. liyuwenzs@gmail.com.
authors.forename: Yuwen
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China. adwen-2004@hotmail.com.
authors.forename: Aidong
authors.initials: A
authors.lastname: Wen
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000378:metabolism*; D000975:Antioxidants / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D048271:Chitosan / Q000031:analogs & derivatives* / Q000737:chemistry; D004195:Disease Models, Animal; D005947:Glucose / Q000172:deficiency; D005979:Glutathione Peroxidase / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy / Q000473:pathology; D053583:Interleukin-1beta / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D000066829:Neuroprotection / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D010100:Oxygen; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism; D014018:Tissue Distribution / Q000187:drug effects; D014315:Triterpenes / Q000493:pharmacokinetics / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D053583:Interleukin-1beta; D018696:Neuroprotective Agents; C504164:O-carboxymethylchitosan; D014315:Triterpenes; D014409:Tumor Necrosis Factor-alpha; C094432:acetyl-11-ketoboswellic acid; D048271:Chitosan; D007770:L-Lactate Dehydrogenase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005947:Glucose; D010100:Oxygen
keywords: Boswellic acid; Cerebral ischemia; Nanoparticle; Neuroprotective effects; Pharmacokinetics