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 their beneficial effects at the cardiovascular and cardio-metabolic level, but often the encouraging in vitro results are not confirmed by in vivo approaches; in addition, the clinical trials are also inconsistent. Their limited bioavailability can be, at least in part, the reason for these discrepancies. Therefore, many efforts have been made 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. The cardioprotective effects of grapefruit IntegroPectin were evaluated by an ex vivo ischemia/reperfusion protocol. Further pharmacological characterization was carried out to assess the involvement of mitochondrial potassium channels. Grapefruit IntegroPectin, where naringin represented 98% of the flavonoids, showed anti-ischemic cardioprotective activity, which was 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 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 [14] and terpenes [15] 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 [13] effects of grapefruit IntegroPectin in neuronal-like cells and its anti-ischemic cardioprotective [16] activity, suggesting the activation of multi-target beneficial effects by this biopolymer.…”

“…Coupled with successful in vivo tests proving the powerful cardioprotective activity of this pectin [16], these results strongly support further investigations aimed at exploring the therapeutic role of this new pectin in in vivo models of oxidative stress-neuroinflammatorybased diseases, including neurodegenerative disorders.…”

“…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 [45]. Taking into account the recently discovered antibacterial, cardioprotective [16], mitoprotective, antioxidant and antiproliferative properties of grapefruit IntegroPectin [13], these new findings suggest that this novel pectin derived from the Citrus paradisi peel residues of industrial juice extraction using water and electricity constitutes one of the single most eminent examples of pectin as a universal medicine [46].…”

“…"IntegroPectin" is the name of a new family of Citrus pectins obtained via the hydrodynamic cavitation of Citrus fruit processing's industrial biowaste that is rich in adsorbed flavonoids [14] and terpenes [15]. In the first in vivo experiments, grapefruit IntegroPectin has recently shown anti-ischemic cardioprotective activity, significantly higher than that of pure naringenin, namely the bioactive aglycone of naringin [16]. Indeed, the amount of naringin present in grapefruit IntegroPectin, is very high (73.66 mg/g) [14].…”

Improved Cardiovascular Effects of a Novel Pomegranate Byproduct Extract Obtained through Hydrodynamic Cavitation

“…Further research is warranted in regard to the structural features of the PPE, which could underlie some of its distinctive properties, such as the bioaccessibility and the improved cardiovascular profile. Based on the abundance of pectin in the pomegranate peel [ 51 ], such properties could have been boosted by an IntegroPectin-like structure of the extract [ 52 ], which is also deemed to have contributed to the cardioprotective effects of a HC-based extract of grapefruit by-products [ 53 ].…”