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

## TL;DR

Mangosteen tinctures reduce inflammation and oxidative stress in cells, likely due to their xanthone content.

## Contribution

This study demonstrates that mangosteen tinctures inhibit pro-inflammatory responses and activate antioxidant pathways in macrophages.

## Key findings

- Mangosteen tinctures inhibited LPS-induced nitric oxide and reactive oxygen species in RAW264.7 cells.
- Xanthones in tinctures activated Nrf2 and upregulated antioxidant enzymes like HO-1 and NQO1.
- GarC and GarD significantly reduced iNOS expression and induced Nrf2 nuclear translocation.

## Abstract

Background/Objectives: Xanthones from the tropical fruit mangosteen (Garcinia mangostana) have been reported to modulate oxidative stress and inflammatory responses. This work explored the anti-inflammatory potential of mangosteen in the form of tinctures. Methods: Tinctures were prepared from the pericarp and leaves, characterized for their major constituents, and evaluated for their in vitro, anti-inflammatory and antioxidant potential. Results: 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. Conclusions: Taken together, mangosteen tinctures are a significant source of prenylated xanthones with anti-inflammatory and antioxidant potential.