Antioxidant and Anti-Inflammatory Activities of Flavanones from <i>Glycyrrhiza glabra</i> L. (licorice) Leaf Phytocomplexes: Identification of Licoflavanone as a Modulator of NF-kB/MAPK Pathway
Luca Frattaruolo,
Gabriele Carullo,
Matteo Brindisi,
Sarah Mazzotta,
Luca Bellissimo,
Vittoria Rago,
Rosita Curcio,
Vincenza Dolce,
Francesca Aiello,
Anna Rita Cappello
Affiliations
Luca Frattaruolo
Department of Pharmacy Health and Nutritional Sciences, Department of Excellence 2018–2022, University of Calabria, Edificio Polifunzionale, 87036 Arcavacata di Rende (CS), Italy
Gabriele Carullo
Department of Pharmacy Health and Nutritional Sciences, Department of Excellence 2018–2022, University of Calabria, Edificio Polifunzionale, 87036 Arcavacata di Rende (CS), Italy
Matteo Brindisi
Department of Pharmacy Health and Nutritional Sciences, Department of Excellence 2018–2022, University of Calabria, Edificio Polifunzionale, 87036 Arcavacata di Rende (CS), Italy
Sarah Mazzotta
Department of Pharmacy Health and Nutritional Sciences, Department of Excellence 2018–2022, University of Calabria, Edificio Polifunzionale, 87036 Arcavacata di Rende (CS), Italy
Luca Bellissimo
Department of Pharmacy Health and Nutritional Sciences, Department of Excellence 2018–2022, University of Calabria, Edificio Polifunzionale, 87036 Arcavacata di Rende (CS), Italy
Vittoria Rago
Department of Pharmacy Health and Nutritional Sciences, Department of Excellence 2018–2022, University of Calabria, Edificio Polifunzionale, 87036 Arcavacata di Rende (CS), Italy
Rosita Curcio
Department of Pharmacy Health and Nutritional Sciences, Department of Excellence 2018–2022, University of Calabria, Edificio Polifunzionale, 87036 Arcavacata di Rende (CS), Italy
Vincenza Dolce
Department of Pharmacy Health and Nutritional Sciences, Department of Excellence 2018–2022, University of Calabria, Edificio Polifunzionale, 87036 Arcavacata di Rende (CS), Italy
Francesca Aiello
Department of Pharmacy Health and Nutritional Sciences, Department of Excellence 2018–2022, University of Calabria, Edificio Polifunzionale, 87036 Arcavacata di Rende (CS), Italy
Anna Rita Cappello
Department of Pharmacy Health and Nutritional Sciences, Department of Excellence 2018–2022, University of Calabria, Edificio Polifunzionale, 87036 Arcavacata di Rende (CS), Italy
Inflammation represents an adaptive response generated by injuries or harmful stimuli. Natural remedies represent an interesting alternative to traditional therapies, involving several biochemical pathways. Besides, the valorization of agrochemical wastes nowadays seems to be a feasible way to reduce the health spending and improve the accessibility at bioactive natural compounds. In this context, the chemical composition of three Glycyrrhiza glabra L. (licorice) leaf extracts, obtained through maceration or ultrasound-assisted method (fresh and dried leaves) was investigated. A guided fractionation obtained three main components: pinocembrin, glabranin and licoflavanone. All the extracts showed similar antioxidant properties, evaluated by 2,2′-diphenyl-1-picrylhydrazyl (DPPH) or 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) Diammonium Salt (ABTS) assay, while, among the isolated compounds, licoflavanone exhibited the best antioxidant activity. The anti-inflammatory activity of the extracts and the purified compounds was investigated in lipopolysaccharide (LPS)-stimulated RAW 264.7 murine macrophages. Extract C and licoflavanone showed a good anti-inflammatory activity without affecting cell viability, as they decreased nitrite levels even when used at 12.5 μg/mL (p < 0.005) and 50 μM concentration (p < 0.001), respectively. Interestingly, licoflavanone markedly decreased pro-inflammatory cytokines and cyclooxygenase 2/inducible nitric oxide synthase (COX-2/iNOS) expression levels (p < 0.001). A modulation of nuclear factor kappa B/mitogen-activated protein kinases (NF-kB/MAPK) pathway underlay such behavior, highlighting the potential of this natural compound as a new scaffold in anti-inflammatory drug research.