Cardioprotective Effects of Grapefruit Integropectin Extracted via Hydrodynamic Cavitation from By-Products of Citrus Fruits Industry: Role of Mitochondrial Potassium Channels

Abstract

Citrus flavonoids are well-known for beneficial effects at the cardiovascular and cardio-metabolic level, but often the encouraging in vitro results are not confirmed by in vivo approaches; also clinical trials are inconsistent. The limited bioavailability of them can be, at least in part, the reason of these discrepancies. Therefore many efforts were performed towards the improvement of their bioavailability. Hydrodynamic cavitation methods were successfully applied to the extraction of byproducts of the Citrus fruits industry, showing high process yields and affording stable phytocomplexes, known as IntegroPectin, endowed with great amounts of bioactive compounds and high water solubility. Cardioprotective effects of grapefruit IntegroPectin were evaluated by an ex vivo ischemia/reperfusion protocol. A further pharmacological characterization was carried out to assess the involvement of mitochondrial potassium channels. Grapefruit IntegroPectin, where naringin represented 98% of flavonoids, showed anti-ischemic cardioprotective activity, better than pure naringenin (the bioactive aglycone of naringin). On cardiac isolated mitochondria, this extract confirmed that naringenin/naringin were involved in the activation of mitochondrial potassium channels. The hydrodynamic cavitation-based extraction confirmed a valuable opportunity for the exploitation of Citrus fruits waste, with the end product presenting high levels of Citrus flavonoids and an improved bioaccessibility that enhances its nutraceutical and economic value.

Anti-apoptotic and anti-inflammatory properties of grapefruit IntegroPectin on human microglial HMC3 cell line

“…Grapefruit IntegroPectin is a highly water-soluble Citrus pectin characterized by the preservation of the Rhamnogalacturonan-I (RG-I) backbone and endowed with large amounts of bioactive molecules, including flavonoids (Scurria et al, 2021) and terpenes (Scurria et al, 2020) well known for their robust anti-oxidant and anti-inflammatory properties. In line with the results of the present study, previous data have described the neuroprotective (Nuzzo et al, 2021b) effects of grapefruit IntegroPectin in neuronal-like cells and its anti-ischemic cardioprotective (Flori et al, 2022) activity, suggesting the activation of multi-target beneficial effects by this biopolymer.…”

“…Coupled to successful in vivo tests proving the powerful cardioprotective activity of this pectin (Flori et al, 2022), these results strongly support further investigations aimed at exploring the therapeutic role of this new pectin in in vivo models of oxidative stress-neuroinflammatory based-diseases, including neurodegenerative disorders. Indeed, a recent study concerning the in vivo administration of a similar Citrus pectin derived via hydrodynamic cavitation from the peels of Citrus reticulata (mandarin) has shown immunomodulatory activity and reduction in LPS-induced lymphocytes in rats, though not linearly associated with dosage (Putri et al, 2022).…”

“…All this favours the interaction of the IntegroPectin chains rich in hydrophilic carboxylate and hydroxyl groups with the HMC3 cell membrane, enhancing the delivery of bioactive molecules, including the otherwise poorly soluble naringin, well-known for its anti-inflammatory and antioxidant activity (Tutunchi et al, 2020). Taking into account the recently discovered antibacterial (Piacenza et al, 2022) (Presentato et al, 2020), cardioprotective (Flori et al, 2022), mitoprotective, antioxidant and antiproliferative properties of grapefruit IntegroPectin (Nuzzo et al, 2021b), these new findings suggest that this novel pectin derived from Citrus paradisi peel residues of the industrial juice extraction using water and electricity constitutes one of the single most eminent examples of pectin as universal medicine (Zaitseva et al, 2020).…”

“…"IntegroPectin" is the name of a new family of Citrus pectins obtained via hydrodynamic cavitation of Citrus fruit processing industrial biowaste rich in adsorbed flavonoids (Scurria et al, 2021) and terpenes (Scurria et al, 2020) characterized by a broad biological activity. In the first in vivo experiments, grapefruit IntegroPectin recently showed anti-ischemic cardioprotective activity, significantly higher than pure naringenin, namely the bioactive aglycone of naringin (Flori et al, 2022).…”