The New Phytocomplex AL0042 Extracted from Red Orange By-Products Inhibits the Minimal Hepatic Encephalopathy in Mice Induced by Thioacetamide
<b>Background/Objectives</b>: Minimal hepatic encephalopathy (MHE) is a clinical condition characterized by neurological impairments, including brain inflammation, arising from the accumulation of toxic metabolites associated with liver dysfunction and leaky gut. This study investigated...
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2025-03-01
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| author | Loredana Vesci Giulia Martinelli Yongqiang Liu Luca Tagliavento Mario Dell’Agli Yunfei Wu Sara Soldi Valeria Sagheddu Stefano Piazza Enrico Sangiovanni Francesco Meneguzzo |
| author_facet | Loredana Vesci Giulia Martinelli Yongqiang Liu Luca Tagliavento Mario Dell’Agli Yunfei Wu Sara Soldi Valeria Sagheddu Stefano Piazza Enrico Sangiovanni Francesco Meneguzzo |
| author_sort | Loredana Vesci |
| collection | DOAJ |
| description | <b>Background/Objectives</b>: Minimal hepatic encephalopathy (MHE) is a clinical condition characterized by neurological impairments, including brain inflammation, arising from the accumulation of toxic metabolites associated with liver dysfunction and leaky gut. This study investigated the pharmacological activity of a new phytocomplex extracted from red orange by-products (AL0042) using hydrodynamic cavitation and consisting of a mixture of pectin, polyphenols, and essential oils. <b>Methods</b>: Preliminary in vitro studies evaluated the impact on the epithelial integrity (TEER) of enterocytes challenged by a pro-inflammatory cocktail. The effect of AL0042 was then evaluated in a model of thioacetamide (TAA)-treated mice that mimics MHE. A group of 8–10-week-old male C57BL/6 mice was intraperitoneally injected with TAA to establish the MHE model. The intervention group received TAA along with AL0042 (20 mg/kg, administered orally once daily for 7 days). At the end of the treatment, the rotarod test was conducted to evaluate motor ability, along with the evaluation of blood biochemical, liver, and brain parameters. <b>Results</b>: In vitro, AL0042 (250 μg/mL) partially recovered the TEER values, although anti-inflammatory mechanisms played a negligible role. In vivo, compared with the control group, the test group showed significant behavioral differences, together with alterations in plasma ammonia, serum TNF-α, ALT, AST, corticosterone levels, and SOD activity. Moreover, histological data confirmed the anti-inflammatory effect at liver and brain level. <b>Conclusions</b>: AL0042 treatment revealed a significant therapeutic effect on the TAA-induced MHE mouse model, curbing oxidative stress and peripheral and central inflammation, thus suggesting that its pharmacological activity deserves to be further investigated in clinical studies. |
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| institution | OA Journals |
| issn | 2227-9059 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | MDPI AG |
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| series | Biomedicines |
| spelling | doaj-art-24e10b306c6347fda9fb997a776846b62025-08-20T02:11:15ZengMDPI AGBiomedicines2227-90592025-03-0113368610.3390/biomedicines13030686The New Phytocomplex AL0042 Extracted from Red Orange By-Products Inhibits the Minimal Hepatic Encephalopathy in Mice Induced by ThioacetamideLoredana Vesci0Giulia Martinelli1Yongqiang Liu2Luca Tagliavento3Mario Dell’Agli4Yunfei Wu5Sara Soldi6Valeria Sagheddu7Stefano Piazza8Enrico Sangiovanni9Francesco Meneguzzo10Research and Development, Alfasigma S.p.A., 00071 Pomezia, ItalyDepartment of Pharmacological and Biomolecular Sciences “Rodolfo Paoletti”, Università degli Studi di Milano, 20133 Milano, ItalyDepartment of Pharmacology, Discovery Services, BioDuro-Sundia, Shanghai 200131, ChinaHyRes S.r.l, 82100 Benevento, ItalyDepartment of Pharmacological and Biomolecular Sciences “Rodolfo Paoletti”, Università degli Studi di Milano, 20133 Milano, ItalyDepartment of Pharmacology, Discovery Services, BioDuro-Sundia, Shanghai 200131, ChinaAAT Srl–Advanced Analytical Technologies, 29017 Fiorenzuola d’Arda, ItalyAAT Srl–Advanced Analytical Technologies, 29017 Fiorenzuola d’Arda, ItalyDepartment of Pharmacological and Biomolecular Sciences “Rodolfo Paoletti”, Università degli Studi di Milano, 20133 Milano, ItalyDepartment of Pharmacological and Biomolecular Sciences “Rodolfo Paoletti”, Università degli Studi di Milano, 20133 Milano, ItalyInstitute of Bioeconomy, National Research Council of Italy, 50019 Florence, Italy<b>Background/Objectives</b>: Minimal hepatic encephalopathy (MHE) is a clinical condition characterized by neurological impairments, including brain inflammation, arising from the accumulation of toxic metabolites associated with liver dysfunction and leaky gut. This study investigated the pharmacological activity of a new phytocomplex extracted from red orange by-products (AL0042) using hydrodynamic cavitation and consisting of a mixture of pectin, polyphenols, and essential oils. <b>Methods</b>: Preliminary in vitro studies evaluated the impact on the epithelial integrity (TEER) of enterocytes challenged by a pro-inflammatory cocktail. The effect of AL0042 was then evaluated in a model of thioacetamide (TAA)-treated mice that mimics MHE. A group of 8–10-week-old male C57BL/6 mice was intraperitoneally injected with TAA to establish the MHE model. The intervention group received TAA along with AL0042 (20 mg/kg, administered orally once daily for 7 days). At the end of the treatment, the rotarod test was conducted to evaluate motor ability, along with the evaluation of blood biochemical, liver, and brain parameters. <b>Results</b>: In vitro, AL0042 (250 μg/mL) partially recovered the TEER values, although anti-inflammatory mechanisms played a negligible role. In vivo, compared with the control group, the test group showed significant behavioral differences, together with alterations in plasma ammonia, serum TNF-α, ALT, AST, corticosterone levels, and SOD activity. Moreover, histological data confirmed the anti-inflammatory effect at liver and brain level. <b>Conclusions</b>: AL0042 treatment revealed a significant therapeutic effect on the TAA-induced MHE mouse model, curbing oxidative stress and peripheral and central inflammation, thus suggesting that its pharmacological activity deserves to be further investigated in clinical studies.https://www.mdpi.com/2227-9059/13/3/686minimal hepatic encephalopathyinflammationpolyphenolshydrodynamic cavitationgreen extraction |
| spellingShingle | Loredana Vesci Giulia Martinelli Yongqiang Liu Luca Tagliavento Mario Dell’Agli Yunfei Wu Sara Soldi Valeria Sagheddu Stefano Piazza Enrico Sangiovanni Francesco Meneguzzo The New Phytocomplex AL0042 Extracted from Red Orange By-Products Inhibits the Minimal Hepatic Encephalopathy in Mice Induced by Thioacetamide Biomedicines minimal hepatic encephalopathy inflammation polyphenols hydrodynamic cavitation green extraction |
| title | The New Phytocomplex AL0042 Extracted from Red Orange By-Products Inhibits the Minimal Hepatic Encephalopathy in Mice Induced by Thioacetamide |
| title_full | The New Phytocomplex AL0042 Extracted from Red Orange By-Products Inhibits the Minimal Hepatic Encephalopathy in Mice Induced by Thioacetamide |
| title_fullStr | The New Phytocomplex AL0042 Extracted from Red Orange By-Products Inhibits the Minimal Hepatic Encephalopathy in Mice Induced by Thioacetamide |
| title_full_unstemmed | The New Phytocomplex AL0042 Extracted from Red Orange By-Products Inhibits the Minimal Hepatic Encephalopathy in Mice Induced by Thioacetamide |
| title_short | The New Phytocomplex AL0042 Extracted from Red Orange By-Products Inhibits the Minimal Hepatic Encephalopathy in Mice Induced by Thioacetamide |
| title_sort | new phytocomplex al0042 extracted from red orange by products inhibits the minimal hepatic encephalopathy in mice induced by thioacetamide |
| topic | minimal hepatic encephalopathy inflammation polyphenols hydrodynamic cavitation green extraction |
| url | https://www.mdpi.com/2227-9059/13/3/686 |
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