Mangosteen (Garcinia mangostana) Pericarp and Leaf Tinctures Inhibit LPS-Induced Pro-Inflammatory Responses in Macrophages and Activate Nrf2

<b>Background/Objectives</b>: Xanthones from the tropical fruit mangosteen (<i>Garcinia mangostana</i>) have been reported to modulate oxidative stress and inflammatory responses. This work explored the anti-inflammatory potential of mangosteen in the form of tinctures. <b>Methods</b>: Tinctures were prepared from the pericarp and leaves, characterized for their major constituents, and evaluated for their in vitro, anti-inflammatory and antioxidant potential. <b>Results</b>: HPLC analysis revealed eight major isoprenylated xanthones whose concentrations increased with an increasing alcohol percentage. α-Mangostin and γ-mangostin, two major xanthones present in the tinctures, were stable for 12 weeks at room and elevated (40 °C) temperatures, indicating stability of the tincture. In vitro luciferase reporter assays using HepG2-ARE revealed an alcohol concentration-dependent activation of Nrf2 by pericarp and leaf tinctures. The tinctures inhibited lipopolysaccharide (LPS)-induced production of nitric oxide (NO) and reactive oxygen species (ROS) in RAW264.7 cells. Garcinone C (GarC) and garcinone D (GarD) caused significant inhibition of LPS-induced NO production and iNOS expression. GarC and GarD also induced nuclear translocation of Nrf2 and upregulated heme oxygenase 1 (HO-1), NAD(P)H quinone dehydrogenase 1 (NQO1), and glutathione S-transferase Pi 1 (GSTP1) in RAW264.7 cells. <b>Conclusions</b>: Taken together, mangosteen tinctures are a significant source of prenylated xanthones with anti-inflammatory and antioxidant potential.