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The New Phytocomplex AL0042 Extracted from Red Orange By-Products Inhibits the Minimal Hepatic Encephalopathy in Mice
Loredana Vesci1, Giulia Martinelli2, Yongqiang Liu3
1Research and Development, Alfasigma S.p.A., 00071 Pomezia, Italy.
Abstract:
Background/Objectives: 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. Methods: 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. Results: 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. Conclusions: 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.
Insights
A novel red orange phytocomplex (AL0042) shows therapeutic potential for minimal hepatic encephalopathy (MHE). It reduced oxidative stress and inflammation in a mouse model, suggesting clinical utility.
Area of Science:
- Pharmacology and Gastroenterology
- Natural Product Chemistry
- Neuroscience
Background:
- Minimal hepatic encephalopathy (MHE) involves neurological deficits and inflammation due to toxic metabolite accumulation from liver dysfunction and increased intestinal permeability.
- A new phytocomplex (AL0042) from red orange by-products, containing pectin, polyphenols, and essential oils, was investigated for its therapeutic potential.
Purpose of the Study:
- To evaluate the pharmacological activity of AL0042 in vitro and in vivo.
- To assess AL0042's efficacy in a thioacetamide (TAA)-induced mouse model of MHE.
Main Methods:
- In vitro assessment of AL0042 on enterocyte epithelial integrity (TEER) using a pro-inflammatory cocktail.
- In vivo evaluation in TAA-treated mice receiving AL0042 (20 mg/kg/day orally for 7 days).
- Assessment of motor ability (rotarod test), blood biochemical markers, liver enzymes, and brain parameters.
Main Results:
- AL0042 partially restored TEER in vitro, with minimal direct anti-inflammatory effects observed.
- In vivo, AL0042 treatment significantly improved behavioral outcomes in TAA-induced MHE mice.
- AL0042 modulated plasma ammonia, serum TNF-α, ALT, AST, corticosterone, and SOD activity, with histological evidence of reduced liver and brain inflammation.
Conclusions:
- AL0042 demonstrated significant therapeutic effects in a preclinical MHE model.
- The phytocomplex effectively reduced oxidative stress and both peripheral and central inflammation.
- AL0042 warrants further investigation in clinical studies for MHE treatment.
