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New Neuroprotective Effect of Lemon IntegroPectin on Neuronal Cellular Model - PubMed

️Fri Jan 01 2021

doi: 10.3390/antiox10050669.

Pasquale Picone^{1

2}, Costanza Giardina³, Miriana Scordino³, Giuseppa Mudò³, Mario Pagliaro⁴, Antonino Scurria⁴, Francesco Meneguzzo⁵, Laura M Ilharco⁶, Alexandra Fidalgo⁶, Rosa Alduina², Alessandro Presentato², Rosaria Ciriminna⁴, Valentina Di Liberto³

Affiliations

PMID: 33923111
PMCID: PMC8145755
DOI: 10.3390/antiox10050669

New Neuroprotective Effect of Lemon IntegroPectin on Neuronal Cellular Model

Domenico Nuzzo et al. Antioxidants (Basel). 2021.

Abstract

Lemon IntegroPectin obtained via hydrodynamic cavitation of organic lemon processing waste in water shows significant neuroprotective activity in vitro, as first reported in this study investigating the effects of both lemon IntegroPectin and commercial citrus pectin on cell viability, cell morphology, reactive oxygen species (ROS) production, and mitochondria perturbation induced by treatment of neuronal SH-SY5Y human cells with H₂O₂. Mediated by ROS, including H₂O₂ and its derivatives, oxidative stress alters numerous cellular processes, such as mitochondrial regulation and cell signaling, propagating cellular injury that leads to incurable neurodegenerative diseases. These results, and the absence of toxicity of this new pectic substance rich in adsorbed flavonoids and terpenes, suggest further studies to investigate its activity in preventing, retarding, or even curing neurological diseases.

Keywords: antioxidant; flavonoids; hesperidin; mitochondria; neurological disease; neuroprotective; oxidative stress; pectin.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

**Figure A1**
Effects of commercial (citrus) and lemon IntegroPectin (lemon) pectins on DNA damage: microscopy inspection for (a) pretreatment, and (b) co-treatment images of untreated cells (Ctrl) or treated with pectins or with H₂O₂ alone, or in combination with pectins. Bar: 100 μm. The square of the enlargements highlights the normal end of the damaged DNA.

**Figure 1**
Dose and time dependent effects of commercial (citrus) and lemon IntegroPectin (lemon) pectins on neuronal cell viability: (a) Cell viability of citrus in dose dependent experiment; (b) Cell viability of citrus in time dependent experiment; (c) Cell viability of Lemon IntegroPectin in dose dependent experiment; (d) Cell viability of Lemon IntegroPectin in time dependent experiment.

**Figure 2**
Oxidative insult during pretreatment and co-treatment with commercial (citrus) and lemon IntegroPectin (lemon) pectins: (a) Scheme of cell pretreatment with pectins; (b) Scheme of cell co-treatment with pectins; (c) Cell viability of pretreatment in dose dependent experiment; (d) Cell viability of co-treatment in dose dependent experiment. Tukey test: ### p < 0.001 as compared to control (Ctrl) group; * p < 0.05, ** p < 0.01, *** p < 0.001.

**Figure 3**
Effects of commercial (citrus) and lemon IntegroPectin (lemon) pectins on neuronal cell morphology in pretreatment and co-treatment: (a) Representative morphological images of the pretreatment of untreated cells (Ctrl) or treated with pectins or with H₂O₂ alone or in combination with pectins; examples of cell debris are indicated by arrows; (b) Histogram of the pretreatment of untreated cells (Ctrl) or treated or with H₂O₂ alone or in combination with pectins, cell body area; (c) Histogram of the pretreatment of untreated cells (Ctrl) or treated or with H₂O₂ alone or in combination with pectins, number of cells debris; (d) Representative morphological images of co-treatment of untreated cells (Ctrl) or treated with pectins or with H₂O₂ alone or in combination with pectins; examples of cell debris are indicated by arrows; (e) Histogram of the co-treatment of untreated cells (Ctrl) or treated or with H₂O₂ alone or in combination with pectins, cell body area; (f) Histogram of the co-treatment of untreated cells (Ctrl) or treated or with H₂O₂ alone or in combination with pectins, number of cells debris. Bar: 50 μm. Tukey test: ## p < 0.01, ### p < 0.001 as compared to control (Ctrl) group; * p < 0.05, *** p < 0.001.

**Figure 4**
Effects of commercial (citrus) and lemon IntegroPectin (lemon) pectins on ROS production driven by exposure to aqueous H₂O₂: (a) fluorescence microscopy images of the pretreatment of untreated cells (Ctrl) or treated with pectins or with H₂O₂ alone or in combination with pectins; (b) fluorescence intensity of the pretreatment of untreated cells (Ctrl) or treated with pectins or with H₂O₂ alone or in combination with pectins measured by the DCFH-DA fluorescence assay; (c) oxidation kinetics of the pretreatment of untreated cells (Ctrl) or treated with pectins or with H₂O₂ alone or in combination with pectins; (d) fluorescence microscopy images of the co-treatment of untreated cells (Ctrl) or treated with pectins or with H₂O₂ alone or in combination with pectins; (e) fluorescence intensity of the co-treatment of untreated cells (Ctrl) or treated with pectins or with H₂O₂ alone or in combination with pectins measured by the DCFH-DA fluorescence assay; (f) oxidation kinetics of the co-treatment of untreated cells (Ctrl) or treated with pectins or with H₂O₂ alone or in combination with pectins. Bar: 50 μm. Tukey test: # p < 0.05, ### p < 0.001 as compared to control (Ctrl) group; ** p < 0.01, *** p < 0.001.

**Figure 5**
Effects of commercial (citrus) and lemon IntegroPectin (lemon) pectins on JC-1 red and green fluorescence affected by exposure to aqueous H₂O₂: (a) Fluorescence microscope inspection of cells treated with pectins alone submitted to JC-1 assay, the magnifications highlight the shape of the mitochondria, (b) histogram representing the ratio between red and green fluorescence intensity; (c) Fluorescence microscope inspection of cells untreated (Ctrl), treated with H₂O₂ alone, or pretreated with pectins and then with H₂O₂ submitted to JC-1 assay; (d) histogram representing the ratio between red and green fluorescence intensity in pretreatment experiment; (e) fluorescence microscope examination of cells untreated (Ctrl), treated with H₂O₂ alone or co-treated with pectins and H₂O₂ submitted to JC-1 assay; (f) histogram representing the ratio between red and green fluorescence intensity in cotreatment experiment. Bar: 100 μm. Tukey test: ## p < 0.01, ### p < 0.001 as compared to control (Ctrl) group; ** p < 0.01, *** p < 0.001.

**Figure 6**
Effects of commercial (citrus) and lemon IntegroPectin (lemon) pectins on mitochondrial morphology and remodeling affected by exposure to aqueous H₂O₂: (a) Mitochondria remodeling of the pretreatment of untreated cells (Ctrl) or treated with pectins or with H₂O₂ alone or in combination with pectins; (b) Mitochondria remodeling of the co-treatment of untreated cells (Ctrl) or treated with pectins or with H₂O₂ alone or in combination with pectins; (c) Representative fluorescence microscopy images of mitochondria stained with the MitoTracker Deep Red in untreated cells (Ctrl) or treated with H₂O₂ alone or in combination with lemon IntegroPectin (pretreatment and co-treatment); (d,e) Histograms representing quantification of mitochondria perimeter and length, respectively, in untreated cells (Ctrl) or treated with H₂O₂ alone or in combination with lemon IntegroPectin (pretreatment and co-treatment). Bar: 50μm. Tukey test: # p < 0.05, ## p < 0.01, ### p < 0.001 as compared to control (Ctrl) group; * p < 0.5, ** p < 0.01, *** p < 0.001.

**Figure 7**
Comparison of the DRIFT spectra of lemon IntegroPectin (Lemon-A and Lemon-B) and commercial (Citrus) pectin: (a) 4000–2100 cm⁻¹ and (b) 200–950 cm⁻¹ spectral regions.

**Scheme 1**
Simplified structure of pectin.

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