Treatment of non-alcoholic steatosis: Preclinical study of a new nutraceutical multitarget formulation

Laura Micheli, Alessandra Pacini, Lorenzo Di Cesare Mannelli, Elena Trallori, Roberta D’ambrosio, Carlo Bianchini, Pietro Lampertico, Carla Ghelardini

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Article number1819
Number of pages24
JournalNutrients
Volume12
Issue number6
DOIs
Publication statusPublished - Jun 2020

Keywords

  • AP-NHm
  • Choline
  • Dl-α-tocopheryl acetate
  • Fatty liver
  • Green coffee Arabic extract
  • Non-alcoholic fatty liver disease (NAFLD)
  • Non-alcoholic steatohepatitis (NASH)
  • Polyunsaturated fatty acid (PUFA)
  • Silybum marianum extract
  • Tanacetum parthenium extract

ASJC Scopus subject areas

  • Food Science
  • Nutrition and Dietetics

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