<i>Piper auritum</i> (Kunth) Fungal Endophytes: A Source of Metabolites to Inhibit the Formation of Advanced Glycation End Products

Excessive accumulation of advanced glycation end products (AGEs) is implicated in the development of non-communicable diseases like diabetes, neurodegeneration, and cancer, among others. Inhibition of AGEs formation represents a promising therapeutic alternative for management of these diseases. This study explores 12 fungal endophytes from Piper auritum (Kunth) as sources of inhibitors of AGEs formation (in vitro). Extracts from Neopestalotiopsis and Diaporthe exhibited the strongest activity, reducing AGEs formation more than 60%. Chemical profiling of these extracts was performed by untargeted and phenolics-targeted approaches using ultra-high performance liquid chromatography coupled to mass spectrometry (UPLC-high resolution mass spectrometry [HRMS] and UPLC-MS/MS, respectively). A total of 41 and 36 compounds were identified in Diaporthe and Neopestalotiopsis extracts, respectively. Seven phenolic compounds were identified in the targeted approach and evaluated for their inhibitory effects on AGEs and fructosamine formation. Gentisic acid displayed the strongest inhibition on fluorescent AGEs formation, followed by sinapic acid, whereas secoisolariciresinol, detected in Neopestalotiopsis extracts, was the most effective inhibitor of fructosamine formation. Additionally, several coumarins, xanthones, and terpenoids are suggested as bioactive candidates due to their structural similarity to known anti-AGEs compounds. We conclude that Neopestalotiopsis and Diaporthe endophytes from P. auritum harbor promising and yet underexplored anti-AGEs compounds with potential biomedical relevance.