Mangostanin, a Xanthone Derived from Garcinia mangostana Fruit, Exerts Protective and Reparative Effects on Oxidative Damage in Human Keratinocytes

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.

Heterotypic signaling of cancer-associated fibroblasts in shaping the cancer cell drug resistance

“…An earlier study has reported that FRA regulates TGF-β signaling in fibrotic liver disease [168] , which hints therapeutic potential of FRA in treating cancer, as both are characterized by the accumulation of myofibroblasts. A recent report demonstrated that FRA-loaded nanoparticle inhibits the CAF phenotype by impeding TGF-β signaling in PDAC [169] . Mangostin (MG) is a xanthone and exhibits several medicinal properties such as antibacterial, antifungal, antioxidant, anti-inflammatory, anticancer, and cardioprotective effects [170] .…”

“…A recent report demonstrated that FRA-loaded nanoparticle inhibits the CAF phenotype by impeding TGF-β signaling in PDAC [ 169 ] . Mangostin (MG) is a xanthone and exhibits several medicinal properties such as antibacterial, antifungal, antioxidant, anti-inflammatory, anticancer, and cardioprotective effects [ 170 ] . Studies have demonstrated that MG displays antitumor activities by inducing apoptosis and inhibiting angiogenesis, ECM modification, and EMT [ 171 ] .…”

Phytochemical Profile and Anticancer Activity from Medicinal Plants Against Melanoma Skin Cancer: A Review

“…In this case, the xanthone derivative in the form of alpha-mangostin (αM) is the main component (Maligan et al, 2019). The seeds and pericarp are mainly used empirically, including for treating gastrointestinal and urinary tract infections, laxatives, anti-fever agents, and treatment of insomnia (Abate et al, 2022). It has an activity as an antitumor, anti-inflammatory, and antioxidant.…”

Anti-Acanthamoeba activity of a semi-synthetic mangostin derivative and its ability in removal of Acanthamoeba triangularis WU19001 on contact lens

“…It has been used as a medicinal plant ( Nauman & Johnson, 2022 ). Mangosteen pericarp (MP) is an important source of bioactive xanthones, which has remarkable antioxidant, anti-inflammatory, immunomodulatory, antiviral, antifungal, antibacterial, and anticancer activities ( Abate et al, 2022 ; Nauman & Johnson, 2022 ). In literature, G. mangostana extract and α-mangostin have previously shown anti- Acanthamoeba activity and anti-adhesion properties against Acanthamoeba triangularis ( Sangkanu et al, 2021 ; Sangkanu et al, 2022 ).…”