Neurodegenerative diseases are characterized by a progressive process of degeneration and neuronal death in the nervous system, with neuroinflammation being one of the main factors contributing to the progression of these diseases. Aristotelia chilensis (Maqui) is a native tree of Chile used in the Mapuche folk medicine for wounds and digestive treatment. It produces edible black berries with the highest antioxidant capacity among berries, and the Mapuche people used it for producing an alcoholic beverage. The leaves of Maqui contain indole alkaloids with different pharmacological properties that suggest neuroprotective effects. Here, the isolation and chemical characterization of a new alkaloid, named 9-hydroxyaristoquinolone, and the evaluation of its anti-inflammatory activity in the microglial cell line HMC-3, treated with LPS, are reported. 9-Hydroxyaristoquinolone protects microglia from LPS-induced morphological changes at concentrations as low as 1 mu M, with a reduction in IKB alpha-P levels and inhibition of the NF-kappa B pathway, which was assessed by THP-1 NF-kappa B dual cell reporter and Western blot in HMC-3 cells. In silico studies suggest that 9-hydroxyaristoquinolone does not induce hepatotoxicity or genotoxicity and exhibits BBB permeability.