Phytochemical Extract from Carica papaya Leaves and Punica granatum Seeds as Therapy Against Cognitive Impairment in a Murine Model.

Mild cognitive impairment (MCI) is defined as inter-stage between normal cognitive aging and major neurocognitive disorder (MND). This state of decay is a crucial factor in treatment to prevent the progression to MND. In this study, our group developed a virtual screening process to evaluate 2568 phytochemical compounds against 5 key proteins associated with MCI and MND. As a result, two potential candidates were identified: carpaine, found in Carica papaya leaves, and punicalagin, present in Punica granatum. A model of cognitive impairment (CI) was developed in 10-month-old male Sprague Dawley rats by administering aluminum chloride (AlCl3) at a dose of 100 mg/kg/day for 30 days. After AlCl3 administration period, one of the groups received carpaine and punicalagin in a phytochemical extract (PE) by oral gavage for 30 days. Novel object recognition test (NOR) was assessed at three different time points (T1 - before CI, T2 - after CI, and T3 - after PE treatment). Glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) were identified in the hippocampus of rats at the end of the study period. After administration of AlCl3, a reduction in discrimination index vs control rats (CI = 0.012 ± 0.08 vs Control = 0.076 ± 0.03), was observed. After phytochemical extract treatment, a significant increase in discrimination index values was observed in the PE group 0.4643 ± 0.13 vs CI group 0.012 ± 0.08. Additionally, the evaluation of immunohistochemistry showed an increase in GFAP positivity in the hippocampus of the CI groups, while a slight decrease was observed in the PE group. This work addressed a comprehensive methodology that utilized in silico tools to identify phytochemical compounds (carpaine and punicalagin) as potential candidates for affecting key proteins in CI. The phytochemical extract containing carpaine and punicalagin resulted in a trend in the decrease of GFAP expression in the hippocampus and improved recognition memory in rats with CI induced by age and AlCl3 administration.

Is it possible to treat nonalcoholic liver disease using a flavanol-based nutraceutical approach? Basic and clinical data.

Nonalcoholic fatty liver disease (NAFLD) is characterized by a spectrum of diseases, ranging from simple steatosis to hepatocellular carcinoma. The main factors for NAFLD are closely related to obesity, insulin resistance, intestinal microbiota alterations, hyperinsulinism, low-grade systemic inflammation, nitroxidative stress, lipid peroxidation, and mitochondrial dysfunction. Currently, the treatment of NAFLD is based on diet and exercise because, to date, there is no specific pharmacological agent, already approved, that raises the need for new therapeutic strategies. Nutraceuticals, such as polyphenols, have potential beneficial effects for health. In this article, the beneficial effects of epigallocatechin-3-gallate (EGCG) and (-)-epicatechin (EC) are discussed. EGCG is the main catechin in green tea, which has shown in various studies its potential effect preventing and treating NAFLD since it has shown antihyperlipidemic, anti-inflammatory, antifibrotic, antioxidant, and improvement of liver lipid metabolism. However, it has been found that excessive consumption may cause hepatotoxicity. EC is widely distributed in nature (fruits and vegetables). This flavanol has shown many beneficial effects, including antihypertensive, anti-inflammatory, anti-hyperglycemic, antithrombotic, and antifibrotic properties. It increases mitochondrial biogenesis, and it also has effects on the regulation of synthesis and metabolism of lipids. This flavanol is a nontoxic substance; it has been classified by the United States Food and Drug Administration as harmless. The EC-induced effects can be useful for the prevention and/or treatment of NAFLD.