Abstract

The fruit of Garcinia mangostana (mangosteen) is known in ancient traditional Asian medicine for its antioxidant, anti-inflammatory, immunomodulatory and anticancer activities. These effects are mainly due to the action of polyphenols known as xanthones, which are contained in the pericarp of the fruit. In recent years, there has been a growing interest from pharmaceutical companies in formulating new topicals based on mangosteen full extracts to prevent skin aging. However, the molecules responsible for these effects and the mechanisms involved have not been investigated so far. Here, the arils and shells of Garcinia mangostana were extracted with chloroform and methanol, and the extracts were further purified to yield 12 xanthone derivatives. Their effects were evaluated using in vitro cultures of human epidermal keratinocytes. After confirming the absence of cytotoxicity, we evaluated the antioxidant potential of these compounds, identifying mangostanin as capable of both protecting and restoring oxidative damage induced by H2O2. We showed how mangostanin, by reducing the generation of intracellular reactive oxygen species (ROS), prevents the activation of AKT (protein kinase B), ERK (extracellular signal-regulated kinase), p53, and other cellular pathways underlying cell damage and apoptosis activation. In conclusion, our study is the first to demonstrate that mangostanin is effective in protecting the skin from the action of free radicals, thus preventing skin aging, confirming a potential toward its development in the nutraceutical and cosmeceutical fields.

Highlights

  • Introduction iationsGarcinia mangostana L. is an evergreen tropical tree native to SoutheastAsia belonging to the Clusiaceae or Guttiferae family [1]

  • The chloroform extract of mangosteen shells submitted to purification by HPLC-UV allowed the isolation of mangostanol (6), garcinone D (7), γ-mangostin (8), gudraxanthone (9), 8-deoxygartanin

  • reactive oxygen species (ROS), and for this reason, we investigated the expression of proteins, such as epidermal growth factor receptor EGFR, protein kinase B (AKT), extracellular regulated protein kinase (ERK), p38 mitogen-activated protein kinases (p38 MAPK), p53, and signaling pathways which are implicated in the control of cell response to external damage induced by

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Summary

Introduction

(mangosteen) is an evergreen tropical tree native to Southeast. Asia belonging to the Clusiaceae or Guttiferae family [1]. It is renowned as the “queen of the fruits” due to the delicious taste of the fruits as well as for its use in traditional medicine [2]. In Southeast Asia, the seeds and peels have been used as infusions and decoctions for the treatment of gastrointestinal and urinary tract infections and as a laxative, anti-fever agent, and an insomnia treatment [2,3]. Various components have been found to be responsible for the pharmacological properties of mangosteen, such as saccharides, flavonoids, phenolic acids, and, most importantly, xanthones.

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