文章基本信息

标题：Treatment of Non-Alcoholic Steatosis: Preclinical Study of a New Nutraceutical Multitarget Formulation
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作者：Laura Micheli ; Alessandra Pacini ; Lorenzo Di Cesare Mannelli 等
期刊名称：Nutrients
电子版ISSN：2072-6643
出版年度：2020
卷号：12
期号：6
页码：1819-1842
DOI：10.3390/nu12061819
出版社：MDPI Publishing
摘要：Multifactorial pathogenesis of non-alcoholic steatohepatitis (NASH) disease, a wide-spread liver pathology associated with metabolic alterations triggered by hepatic steatosis, should be hit by multitarget therapeutics. We tested a multicomponent food supplement mixture (AP-NHm), whose components have anti-dislipidemic, antioxidant and anti-inflammatory effects, on in vitro and in vivo models of NASH. In vitro, hepatic cells cultures were treated for 24 h with 0.5 mM oleic acid (OA): in the co-treatment set cells were co-treated with AP-NH mixtures (AP-NHm, 1:3:10 ratio) and in the post-injury set AP-NHm was added for 48 h after OA damage. In vivo, C57BL/6 mice were fed with high-fat diet (HFD) for 12 weeks, inducing NASH at 7th week, and treated with AP-NHm at two dosages (1:3 ratio) in co-treatment or post-injury protocols, while a control group was fed with a standard diet. In in vitro co-treatment protocol, alterations of redox balance, proinflammatory cytokines release and glucose uptake were restored in a dose-dependent manner, at highest dosages also in post-injury regimen. In both regimens, pathologic dyslipidemias were also ameliorated by AP-NHm. In vivo, high-dose-AP-NHm-co-treated-HFD mice dose-dependently gained less body weight, were protected from dyslipidemia, and showed a lower liver weight. Dose-dependently, AP-NHm treatment lowered hepatic LDL, HDL, triglycerides levels and oxidative damage; co-treatment regimen was anti-inflammatory, reducing TNF-α and IL-8 levels. Hepatic lipidic infiltration significantly decreased in co-treated and post-injury-AP-NHm-HFD animals. The multitarget approach with AP-NHm was effective in preventing and reducing NASH-related pathologic features, warranting for the clinical development of this compound.
关键词：fatty liver; non-alcoholic fatty liver disease (NAFLD); non-alcoholic steatohepatitis (NASH); polyunsaturated fatty acid (PUFA); Silybum marianum extract; choline; Tanacetum parthenium extract; green coffee Arabic extract; dl-α-tocopheryl acetate; AP-NHm fatty liver ; non-alcoholic fatty liver disease (NAFLD) ; non-alcoholic steatohepatitis (NASH) ; polyunsaturated fatty acid (PUFA) ; Silybum marianum extract ; choline ; Tanacetum parthenium extract ; green coffee Arabic extract ; dl-α-tocopheryl acetate ; AP-NHm