Bioactive metabolites and antidiabetic activity of Cannabis sativa-derived endophytic fungi

Cannabis sativa L. (Cannabaceae) has long been valued in traditional medicine, including Ayurveda, for managing disorders such as diabetes, cancer, and kidney diseases. Although the plant itself is known to influence glucose metabolism, the therapeutic potential of its associated endophytic fungi remains underexplored. In this study, 56 fungal isolates were obtained from different tissues of C. sativa and evaluated for antidiabetic activity. Two isolates, identified by ITS1/4 rDNA sequencing as Aspergillus micronesiensis and Nodulisporium verrucosum, exhibited strong inhibitory effects on α-amylase, α-glucosidase, DPP-IV, and lipase (IC₅₀ < 100 µg/mL). Their ethyl acetate extracts demonstrated low cytotoxicity, enhanced cell viability, and significantly promoted insulin secretion in MIN6 pancreatic β-cells. GC–MS analysis revealed bioactive metabolites, including 2,4-di-tert-butylphenol, 7,9-di-tert-butyl-1-oxaspiro(4,5)deca-6,9-diene-2,8-dione, 2-methylcinnamic acid, and tetraneurin-A, which are reported to possess antidiabetic potential. FTIR further confirmed the presence of functional groups corresponding to these compounds. Together, these findings highlight C. sativa-derived endophytic fungi as promising sources of novel antidiabetic agents, bridging traditional knowledge with modern drug discovery.