Acetylcholinesterase inhibiting withanolides from Curvularia pseudobrachyspora, an endophytic fungus of Withania somnifera (L.) Dunal.

Alzheimer's disease is the most prominent neurological illness, and the present investigation sets out to determine the impact of bioactive substances from endophytic fungi on acetylcholinesterase (AChE) inhibition. Medicinal plant Withania somnifera (L.) Dunal was used to isolate endophytic fungi, and WSE42 (out of 49 isolates) exhibited higher AChE inhibition (78.57%) and free radical scavenging activity (82.47%) in its methanolic crude extract. WSE42 was identified as Curvularia pseudobrachyspora (accession number-PP837926), and among all the fractions collected by column chromatography, two fractions (F3 and F4) exhibited potential for AChE inhibition with IC50 of 17.99 µg/ml and 19.91 µg/ml, respectively. These two fractions were found to show IC50 values in the range of 36-44 µg/ml for antioxidant potential. Structural elucidation studies revealed the compound to be 2,3-dihydrowithaferin A (F3) and withanolide Z (F4). Thus, this study ascertained the potential of withanolides as AChE inhibitors and antioxidant molecules that can play a key role in the management of Alzheimer's disease.