Sublingual AKBA Exerts Antidepressant Effects in the Aβ-Treated Mouse Model.

Maria Grazia Morgese,Matteo Francavilla,Maria Bove,Paolo Tucci,Luigia Trabace,Stefania Schiavone,Anna Laura Colia,Stefania Dimonte,Matteo Bevilacqua

doi:10.3390/biom11050686

Abstract

The 3-O-acetyl-11-keto-β-boswellic acid (AKBA) is the most active compound of Boswellia serrata proposed for treating neurodegenerative disorders, including Alzheimer’s disease (AD), characterized in its early phase by alteration in mood. Accordingly, we have previously demonstrated that an intracerebroventricular injection of soluble amyloid beta 1-42 (Aβ) peptide evokes a depressive-like phenotype in rats. We tested the protective effects of AKBA in the mouse model of an Aβ-induced depressive-like phenotype. We evaluated the depressive-like behavior by using the tail suspension test (TST) and the splash test (ST). Behavioral analyses were accompanied by neurochemical quantifications, such as glutamate (GLU), kynurenine (KYN) and monoamines, and by biochemical measurements, such as glial fibrillary acid protein (GFAP), CD11b and nuclear factor kappa B (NF-kB), in mice prefrontal cortex (PFC) and hippocampus (HIPP). AKBA prevented the depressive-like behaviors induced by Aβ administration, since we recorded a reduction in latency to initiate self-care and total time spent to perform self-care in the ST and reduced time of immobility in the TST. Likewise, the increase in GLU and KYN levels in PFC and HIPP induced by the peptide injection were reverted by AKBA administration, as well as the displayed increase in levels of GFAP and NF-kB in both PFC and HIPP, but not in CD11b. Therefore, AKBA might represent a food supplement suitable as an adjuvant for therapy of depression in early-stage AD.

Highlights

In order to evaluate if acetyl-11-keto-β-boswellic acid (AKBA) was able to cross the blood brain barrier we quantified cerebral and plasmatic AKBA levels at 5, 15, and 30 min after its sublingual or intranasal administration
Such an endpoint was significantly different from the 30 min one only for sublingual administration
We showed the protective effect of sublingual administration of AKBA on the depressive-like profile induced by the icv injection of Aβ in mice

Summary

Introduction

The genus Boswellia, comprising about 20 species, has been studied as a new candidate for neurodegenerative disorders, including Alzheimer’s disease (AD) [2] In keeping with this hypothesis, it has been reported that AKBA holds antioxidant and anti-inflammatory properties and recently it has been tested as a disease-modifying therapeutic potential drug for AD by using a transgenic animal model [3]. In this light, it has been shown that this compound was able to reverse cognitive impairments and to decrease cerebral amyloid beta (Aβ) production and plaque burden in APPswe/PS1dE9, an AD genetic model. AKBA seems to have anti-amyloidogenic action [2] and has been shown

Methods

Results

Discussion

Conclusion