Neuroprotective compound Quercetin from endophytic fungus, Nigrospora oryzae isolated from Tinospora cordifolia

Abstract

Alzheimer’s disease (AD) is considered as one of the most prevalent neurodegenerative disorder. Dementia is one of the core symptom of AD. Tinospora cordifolia exhibits neuroprotective activity. Moreover, endophytic mycobiota of Tinospora cordifolia possesses antigout, anticancer and antioxidant properties. Therefore, the present study investigated the therapeutic effects of endophytic fungi obtained from medicinal plant, Tinospora cordifolia in an experimental animal model of dementia. In vitro acetylcholinesterase (AChE) inhibitory and anti-oxidant assays revealed that GL15 showed significant effect which was equivalent to reference drugs. GL15 (5 mg/kg; i.p.) attenuated the SCO-induced loss in spatial recognition memory in Y-maze and PAT. The SCO-induced modulation in cholinergic pathway was ameliorated by GL15 (5 mg/kg) in hippocampus, resulting in decrease in acetylcholinesterase activity. GL15 (5 mg/kg) restored the cytoarchitecture of hippocampus. Subsequently, the effect of GL15 (5 mg/kg) on AChE-mediated mechanism in pathophysiological condition of dementia was evaluated. GL15 (5 mg/kg) showed the significant decrease in expression of AChE activity. These results were comparable with donepezil. These observations emphasize the fact GL15 may show improvement in cognitive impairments in animals through AChE-mediated mechanism. GL15 could be a potential therapeutic option in the management of AD. Column chromatography was run to obtain various fractions of GL15 and fraction 3 of GL15 showed 87.1% percentage AChE inhibition. UV absorbance of fraction 3 of GL15 was identical to that of quercetin. In FTIR of fraction 3, percentage transmittance vs wave numbers showed spectrum which was analogous to quercetin. Positive ionization mode of ESI-MS showed the m/z value of 303.22 which was similar to that of quercetin. Based upon the various techniques of characterization, it may be concluded that quercetin is present in fraction 3 of GL15. Endophytic fungus GL15 was identified through microscopic and molecular techniques and it was observed that GL15 showed showed septate hyphae and spore morphology similar to Nigrospora oryzae. Molecular identification confirmed that GL15 was N. oryzae as phylogenetic tree showed clustering of GL15 with Nigrospora oryzae.