Natural Flavonoids as an Intervention for Hepatic Encephalopathy: Preclinical Evidence-based Review

Hepatic encephalopathy (HE) is a serious neuropsychiatric disorder caused in patients with both; acute and chronic liver diseases, which consists of various complications ranging from cognitive impairment, disorientation, confusion, and coma. The available therapies mainly focus on decreasing ammonia levels either through increasing its elimination or decreasing its production, some medications may subside the duration and limit the consequences of HE, but there is no complete available treatment for HE-like manifestation. Thus, there is a need to explore new pharmacotherapy for the treatment and management of HE. Flavonoids are polyphenolic compounds easily found in vegetables, fruits, flowers, beverages, and plants based foods. In modern research, flavonoids have gained attention due to their broad pharmacological properties, like anti-oxidant, antiviral, anti-inflammatory, cardioprotective, cytoprotective, and neuroprotective activity. Several preclinical studies suggest that various flavonoids have a potential therapeutic role in a variety of metabolic- related neurological disorders, including HE. This review focuses on all pre-clinical reports that highlight the neuroprotective potential of natural flavonoids for the management of HE. Based on numerous pre-clinical studies and taking into account the therapeutic effects of natural flavonoids, the present study illustrates the cellular and molecular mechanisms responsible for the potential role of natural flavonoids as pharmacotherapy for the management and treatment of HE.