α-glucosidase inhibitory potential of endophytic Colletotrichum fructicola of Cinnamomum tamala.

Despite the antidiabetic significance of Cinnamomum tamala (Buch.-Ham.) T.Nees & C.H.Eberm., its endophytic fungal community remains largely unexplored. This study presents the first comprehensive investigation on endophytic fungal diversity of C. tamala, identifying fungi from 17 distinct genera colonizing its leaf, bark, and stem tissues. Moreover, this is the first report evaluating the α-glucosidase inhibitory potential of its endophytic fungi. A novel, cost-effective, and high-throughput qualitative spot assay was developed for preliminary screening. Among 87 fungal isolates screened, 32.2% exhibited α-glucosidase inhibitory activity, with isolate #2-4CTChP2-6 demonstrating the highest inhibition (IC₅₀- 55.2 µg/mL). Morphological and multi-locus phylogenetic analysis identified this isolate as Colletotrichum fructicola. This is the first report of α-glucosidase inhibitory activity by C. fructicola from C. tamala. Optimization of culture conditions using a two-phase sequential approach: one-variable-at-a-time (OVAT) followed by Response Surface Methodology (RSM), enhanced activity by 1.27-fold, lowering the IC₅₀ to 43.6 µg/mL. These findings position C. tamala-associated endophytes, particularly C. fructicola, as a promising microbial source of α-glucosidase inhibitors with potential relevance in the management of postprandial hyperglycemia.