The New Phytocomplex AL0042 Extracted from Red Orange By-Products Inhibits the Minimal Hepatic Encephalopathy in Mice Induced by Thioacetamide.

IF 3.9 3区 工程技术 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Loredana Vesci, Giulia Martinelli, Yongqiang Liu, Luca Tagliavento, Mario Dell'Agli, Yunfei Wu, Sara Soldi, Valeria Sagheddu, Stefano Piazza, Enrico Sangiovanni, Francesco Meneguzzo
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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.

背景/目的:轻度肝性脑病(MHE)是一种临床病症,其特点是神经系统受损,包括脑部炎症,这是因为与肝功能障碍和肠道渗漏有关的有毒代谢产物积累所致。本研究调查了一种利用流体动力空化技术从红橘副产品(AL0042)中提取的新型植物复合物的药理活性,该复合物由果胶、多酚和精油混合物组成。方法:初步体外研究评估了促炎鸡尾酒对肠细胞上皮完整性(TEER)的影响。然后在硫代乙酰胺(TAA)处理的小鼠模型中评估了 AL0042 的效果,该模型模拟了 MHE。一组 8-10 周大的雄性 C57BL/6 小鼠腹腔注射 TAA 以建立 MHE 模型。干预组接受 TAA 和 AL0042(20 毫克/千克,每天口服一次,连续 7 天)。治疗结束后,对小鼠进行转体测试以评估其运动能力,同时评估血液生化指标、肝脏指标和脑指标。研究结果在体外,AL0042(250 微克/毫升)部分恢复了 TEER 值,但抗炎机制的作用微乎其微。在体内,与对照组相比,试验组表现出显著的行为差异,同时血浆氨、血清 TNF-α、ALT、AST、皮质酮水平和 SOD 活性也发生了变化。此外,组织学数据证实了在肝脏和大脑水平上的抗炎作用。结论AL0042对TAA诱导的MHE小鼠模型有明显的治疗作用,能抑制氧化应激和外周及中枢炎症,因此其药理活性值得在临床研究中进一步探讨。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Biomedicines
Biomedicines Biochemistry, Genetics and Molecular Biology-General Biochemistry,Genetics and Molecular Biology
CiteScore
5.20
自引率
8.50%
发文量
2823
审稿时长
8 weeks
期刊介绍: Biomedicines (ISSN 2227-9059; CODEN: BIOMID) is an international, scientific, open access journal on biomedicines published quarterly online by MDPI.
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