TY  - JOUR
T1  - Neuroprotective Role of Microbial Biotransformed Metabolites of Sinapic Acid on Repetitive Traumatic Brain Injury in Rats
A1  - Samir M. Osman
A1  - Hesham S. M. Soliman
A1  - Fadila M. Hamed
A1  - Diaa A. Marrez
A1  - Amira A. El-Gazar
A1  - Ahmed S. Alazzouni
A1  - Tamer Nasr
A1  - Haitham A. Ibrahim
JF  - Pharmacophore
JO  - Pharmacophore
SN  - 2229-5402
Y1  - 2022
VL  - 13
IS  - 5
DO  - 10.51847/1Rj6v3EGdU
SP  - 112
EP  - 126
N2  - 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-3β 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-a 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.
UR  - https://pharmacophorejournal.com/article/neuroprotective-role-of-microbial-biotransformed-metabolites-of-sinapic-acid-on-repetitive-traumatic-w1ofnp6llt7zhka
ER  -