Pistacia lentiscus L. var. Chia is an endemic tree cultivated in the Southern part of Chios Greek Island. Chios mastiha, the aromatic resin secreted from this tree, has been used as traditional remedy since ancient times to cure many peptic system diseases and as a nutritional agent. Nowadays, Chios mastiha has been widely investigated for its biological activities and its chemical composition. A major part of Chios mastiha’s bioactive compounds are triterpenoids, which are proposed to interfere with glucocorticoid receptor (GR) signaling, acting as selective GR agonists. In this study a specific “neutral fraction” of Chios mastiha resin, a portion devoid of acidic triterpenoids, was investigated regarding its biological potential and chemical composition. The study aimed to determine if the neutral triterpenoids, the non-carboxylic ones, within this fraction drive Chios mastiha’s interference with GR signaling and whether it exhibits anti-inflammatory, apoptotic, and potential antilipidemic activities. The phytochemical characterization of this specific resin portion, applying 1H NMR and HPLC-QTOF-MS/MS analysis, identified novel unidentified Chios mastiha’s phenolic components (apigenin, astragalin, diosmetin, flavidin, genistein), a complex mixture of fatty acids (palmitic, stearic, oleic), non-carboxylic triterpenoids (lupeol, β-amyrin, keto-oleanolic aldehyde), and a trace of terpenoids. Biological assessment of DEX-induced GR transcriptional activation revealed that neutral triterpenoid fractions only minimally contribute to GR transcriptional activation while positively regulating GR and its target, phosphoenolpyruvate carboxykinase (PEPCK), protein levels. Additionally, negative regulation of the peroxisome proliferator-activated receptor alpha (PPARα) protein levels as well as inhibition of the TNFα-induced NF-κΒ activity and reduction in the p65 subunit of NF-κΒ protein levels, were observed, indicating potential antilipidemic and anti-inflammatory Chios mastiha’s neutral fraction activities, which were attributed to its composition in triterpenoids, fatty acids, and novel phenolic compounds. Moreover, mitochondrial-dependent induction of apoptosis accompanied by reduction in cell viability was observed in lupeol, β-amyrin, and fatty acids-enriched fractions. The plethora of bioactive compounds associated with a variety of Chios mastiha’s neutral fraction render Chios mastiha a valuable food additive and nutritional agent.
Kalousi et al. (2026) studied this question.