Boswellia serrata suppress fipronil-induced neuronal necrosis and neurobehavioral alterations via promoted inhibition of oxidative/inflammatory/apoptotic pathways

Abstract

Boswellic acid (BA) is a pentacyclic terpenoid derived from the gum-resin of Boswellia serrate. It is known for its strong antioxidant, anti-inflammatory, and anticancer properties. It has improved spatial learning and provides neuroprotection against trimethyltin-induced memory impairment. The aim of this study is to evaluate the possible neuroprotective activity of B. serrata extract (BSE) containing BA against fipronil (FPN)-induced neurobehavioral toxicity in Wister male albino rats. Sixty male rats were allocated equally into six groups. The first group served as control; the second and third groups received BSE at two different oral doses (250 or 500 mg/kg body weight [BW], respectively). The fourth group was orally intoxicated with FPN (20 mg/kg BW), whereas the fifth and sixth groups served as preventive groups and co-treated with FPN (20 mg/kg BW) and BSE (250 or 500 mg/kg BW, respectively). The experiment was conducted over 8 weeks period. Results revealed that co-treatment with BSE led to significant (p > 0.05) dose-dependent reduction in malondialdehyde (MDA), nitric oxide (NO), interleukin-6 (IL6), tumor necrosis factors-alpha (TNF-α), nuclear factor Kappa-B (NF-κB), Cyclooxegenase-2 (COX-2), prostaglandin E2 (PGE2), serotonin, and acetylcholine (ACh). Conversely, significant (p > 0.05) up regulation of catalase (CAT), glutathione peroxidase (GSH-Px), gamma-aminobutyric acid (GABA), and acetylcholine esterase (AChE) has reported in BSE-co-treated groups. In addition, significant (p > 0.05) promotion in neurobehaviours, histopathologic imaging of the cerebral, cerebellar, and hippocampal regions, and immunohistochemical expression of caspase-3 and glial fibrillary acidic protein (GFAP) were also reported in the BSE-treated groups in a dose-dependent manner. In conclusion, BSE (500 mg/kg BW) is a natural, promising neuroprotective agent that can mitigate FPN-induced neurobehavioral toxicity via the suppression of oxidative, inflammatory, and apoptotic pathways and relieve neuronal necrosis and astrogliosis.