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.

Stroke Repair via Biomimicry of the Subventricular Zone

“…In addition, oxygen plasma treatment preserves the chitosan microstructure in nerve conduit models, confirming improvement in behavior and functional recovery (Cheng et al, 2007). Chitosan nanoparticles loaded with acetyl-11-keto-β-boswellic acid, a resin extract which may control inflammatory responses, demonstrate a neuroprotective effect in a MCAO rat model, reducing infarct volume and cell death (Ding et al, 2016). In addition, the encapsulation of ESC derived ECs into a chitosan-based hydrogel loaded with VEGF microtubes presents minimal cytotoxicity in vivo and high cell survival, inducing neovascularization in hind limb ischemia mouse models (Lee et al, 2015).…”

Aqueous and Ethanolic Extracts of Boswellia serrata Protect Against Focal Cerebral Ischemia and Reperfusion Injury in Rats

“…Recently, Ding et al . () showed that nanoformulation of AKBA leads to enhanced protection of AKBA against cerebral ischemic insult by improving antioxidant defence (SOD and glutathione peroxidase) and diminishing inflammation (TNF‐α and IL‐1β), as well as the improvement activation of the nuclear factor erythroid‐2‐related factor 2/heme oxygenase‐1 pathway and inhibition of inflammatory protein expressions (NF‐kB and 5‐lipoxygenase). Sayed and El Sayed () showed that co‐administration of AKBA and celecoxib reversed the behavioural and molecular changes caused by lipopolysaccharide‐induced cognitive dysfunction in mice.…”

“…An in vitro study also revealed that beta-boswellic acid could significantly enhance neurite outgrowth and branching of primary cells of hippocampal tissue in rats (Karima et al, 2010). Recently, Ding et al (2016) showed that nanoformulation of AKBA leads to enhanced protection of AKBA against cerebral ischemic 1964 F. FOROUZANFAR ET AL.…”

Chromatographic methods used for characterization of boswellic acids

“…Trapezoidal rule was used for the estimation of the area under plasma concentration time. 48 further studied anti-inflammatory activity in the form of herbal gel for management of gout. The physicochemical properties of drug were evaluated on the basis of solubility, UV, FTIR, HPLC and DSC.…”