Ferula L. Plant Extracts and Dose-Dependent Activity of Natural Sesquiterpene Ferutinin: From Antioxidant Potential to Cytotoxic Effects

• Published in: Molecules (Basel, Switzerland) Switzerland), 2020-12, Vol.25 (23), p.5768
• Main Authors: Macrì, Roberta, Musolino, Vincenzo, Gliozzi, Micaela, Carresi, Cristina, Maiuolo, Jessica, Nucera, Saverio, Scicchitano, Miriam, Bosco, Francesca, Scarano, Federica, Ruga, Stefano, Zito, Maria Caterina, Guarnieri, Lorenza, Bombardelli, Ezio, Mollace, Vincenzo
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; antioxidant and anti-inflammatory potential; Antioxidants; Antioxidants - chemistry; Antioxidants - pharmacology; Antioxidants - therapeutic use; Apiaceae; Apoptosis - drug effects; Benzoates - chemistry; Benzoates - pharmacology; Benzoates - therapeutic use; Bioactive compounds; Bridged Bicyclo Compounds - chemistry; Bridged Bicyclo Compounds - pharmacology; Bridged Bicyclo Compounds - therapeutic use; Cancer; Cell death; Cell Line, Tumor; Cycloheptanes - chemistry; Cycloheptanes - pharmacology; Cycloheptanes - therapeutic use; Cytotoxicity; Data acquisition; Diabetes; Dose-Response Relationship, Drug; Electron Transport - drug effects; Estrogens; Ferula; Ferula - chemistry; Ferula communis; Ferula L; ferutinin; Flavonoids; Hormone Replacement Therapy; Humans; Inflammation; ionophoric property; Kinases; Medical treatment; Mitochondria; Mitochondria - drug effects; Mitochondria - metabolism; mitochondrial dysfunction; Molecular modelling; Nitric Oxide - metabolism; Phytochemicals - chemistry; Phytochemicals - pharmacology; phytoestrogenic activity; Phytoestrogens - chemistry; Phytoestrogens - pharmacology; Plant extracts; Plant Extracts - chemistry; Plant Extracts - pharmacology; Plant Extracts - therapeutic use; Reactive Oxygen Species - metabolism; Review; Sesquiterpenes - chemistry; Sesquiterpenes - pharmacology; Sesquiterpenes - therapeutic use; Side effects; Temperate zones; Tumor cell lines; Xenoestrogens
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules25235768

The employment studies of natural extracts in the prevention and treatment of several diseases highlighted the role of different species of genus L., belonging to the Apiaceae family, dicotyledonous plants present in many temperate zones of our planet. L. is the main source of sesquiterpene ferutinin, a bioactive compound studied both in vitro and in vivo, because of different effects, such as phytoestrogenic, antioxidant, anti-inflammatory, but also antiproliferative and cytotoxic activity, performed in a dose-dependent and cell-dependent way. The present review will focus on the molecular mechanisms involved in the different activities of Ferutinin, starting from its antioxidant potential at low doses until its ionophoric property and the subsequent mitochondrial dysfunction induced through administration of high doses, which represent the key point of its anticancer action. Furthermore, we will summarize the data acquired from some experimental studies on different cell types and on several diseases. The results obtained showed an important antioxidant and phytoestrogenic regulation with lack of typical side effects related to estrogenic therapy. The preferential cell death induction for tumor cell lines suggests that ferutinin may have anti-neoplastic properties, and may be used as an antiproliferative and cytotoxic agent in an estrogen dependent and independent manner. Nevertheless, more data are needed to clearly understand the effect of ferutinin in animals before using it as a phytoestrogen or anticancer drug.