Cyclo (His-Pro): a further step in the management of steatohepatitis

Background & AimsNon-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) have become the world's most common diseases, placing a growing strain on healthcare systems worldwide, yet no pharmacological treatment has been approved. The naturally occurring compound Cyclo (His-Pro) (CHP) appears an interesting candidate for NAFLD management, given its safety records anti-inflammatory effect.MethodsWe show here that CHP administration protects two different mouse models of from progressing towards fibrosis: model dietary NAFLD/NASH, achieved by thermoneutral housing (TN) in combination with western diet (WD) feeding, fibrosis caused repeated injections carbon tetrachloride (CCl4).ResultsTreatment limited overall lipid accumulation, lowered systemic inflammation prevented hyperglycemia. Histo-pathology transcriptomics highlight reduced steatosis demonstrate remarkable protection development fibrosis, features which herald progression NAFLD. We identified extracellular signal-regulated kinases (ERK) pathway as early mediator response.ConclusionsCHP was active both preventive therapeutic setting, reducing steatosis, ameliorating several markers disease.Impact implicationsConsidering incidence lack approved treatments, it is urgent to find new strategies prevent manage proved efficacy against animal disease. Overall, our work points novel efficacious strategy NAFLD, fuelling optimism potential clinical studies.