Neuroprotective Role of Microbial Biotransformed Metabolites of Sinapic Acid on Repetitive Traumatic Brain Injury in Rats

Abstract

Sinapic acid biotransformation was studied and screened using eleven fungal cultures. Penicillium chermesinum AUMC 275, Aspergillus ochraceus AUMC 11328, and Paecilomyces variotii AUMC 5618 showed positive results in the production of metabolites. Sinapic acid biotransformation resulted in the production of gallic acid after 10 days incubation with P. chermesinum, protocatechuic acid after 7 days with A. ochraceus, and ferulic acid after 5 days with P. variotii. The investigated compounds' anti-inflammatory efficacy results, as well as the suggested binding mechanism, affinity, preferred orientation of each docking pose, and binding free energy with the GSK-3 beta enzyme, were predicted using molecular modeling. The predicted interaction energies for the examined chemicals agreed with the experimental findings. Moreover, we evaluated the neuroprotective potential of the obtained metabolites using the mild repetitive traumatic brain injury (mRTBI) model. Animals were exposed to 5 repetitive hits once per day by weight drop device and were divided into 6 groups (control, mTBI, mRTBI-10, mRTBI-10+Fa, mRTBI-10+PCA, mRTBI-10+GA). All the treatments decreased cortical contents of Tau protein (dementia marker), inflammatory markers (TNF-alpha and il-6), and signaling molecules such as GSK3B and DKK-1. Furthermore, the histological findings added another neuroprotective potential of obtained metabolites where marked improvements and ameliorative effect on the histoarchtexture of the hippocampus and mild changes in the hippocampus layers by GA, PCA, and FA, respectively. All these effects were mirrored in behavior outcomes, and a significant enhancement in animal behavior was observed. We concluded that GA, PCA, and FA have therapeutic potential for preventing TBI-induced brain injury. Copyright (c) 2013 - All Rights Reserved - Pharmacophore