Depression is a common and heterogeneous mental health disorder that affects more than 322 million people across the world (4.4% of the world’s population). Antidepressant pharmacotherapies have a slow onset of clinical efficacy which is critical for therapeutic outcome and patient’s compliance. In recent years, an increasing number of studies suggests that phytochemical compounds activity on mood might be a clinically relevant co-adjuvant to current medications. Many authors suggested a positive association between fruits and vegetables-rich diet and prevention of depression, anxiety and cognitive decline; therefore, the consumption of a whole phytocomplex could increase bioavailability of plant- based secondary specialized metabolites both at central nervous system and systemic levels. To date, no data are available concerning the administration of whole fruits to assess antidepressant activity in vivo: only single compounds have been tested. The aim of this study was to evaluate the activity of kiwifruit (Actinidia deliciosa cv. Hayward) extracts on mood in murine models of depressive behavior. Moreover, kiwifruit is rich in polyphenols (e.g. ferulic acid, kaempferol, catechin, etc.) with a known inhibitory effect on both monoamine oxidases A and B. To reach this goal independent groups of naïve male C57BL/6J mice were used and fed with three increasing dilutions of kiwifruit extracts under chronic regime. Immobility time was then assessed in tail suspension test (TST) and forced swimming test (FST); additionally, the efficacy of kiwifruit with respect to vehicles and the selective serotonin reuptake inhibitor fluoxetine (20 mg/kg, i.p.) were investigated. The highest kiwifruit concentration produced a reduction of 45% and 40% in immobility time in TST and FST respectively, without causing hyperlocomotion in the open-field test (OFT). To find the molecules possibly responsible of these findings, pharmacokinetic profiles and metabolomic analyses were assessed and allow us to discover two kiwifruit molecules probably responsible to this effect, quinic acid and caffeic acid 3-β-D-glucoside. The two molecules were evaluated in immobility time in the above-mentioned behavioral test alone or in combination. Quinic acid and the combination of the two molecules produced a reduction of 42% and 54% in immobility time in TST and 29% and 27% in FST respectively, without causing hyperlocomotion in the OFT. Caffeic acid had proven to be ineffective when administered alone. Interestingly, when administered alone, the two molecules have lower serum and brain levels after UPLC-ESI-MS analysis indicating that, probably other molecules present in the fresh fruit are necessary for the correct adsorption and/or stability of the two metabolites. Moreover, evaluation of inhibitory activity on both MAOs isozymes were evaluated through an in vitro assay. Kiwifruit and its metabolites strongly inhibit both isoforms of the enzyme with quinic acid that is selective only against MAO- B. Taken together, these data suggest that kiwifruit may have a mood-improving effect through inhibition of the MAOs isozymes and could be used in clinical state such as depression.
|Titolo:||Antidepressant-like activity of green kiwifruit (Actinidia deliciosa) on mouse models of depression|
MARZO, CLAUDIO MARCELLO (Corresponding)
|Data di pubblicazione:||2021|
|Appare nelle tipologie:||07.13 Doctoral Thesis|