Mechanisms of wolfberry in the treatment of liver diseases

The fruit of Lycium barbarum (the wolfberry or goji berry) has been widely used as a drug and functional food in many traditional Chinese medicine literature. However, only in recent years has its specific health-promoting mechanism been investigated. Modern technology of pharmacology has identified a variety of bioactive ingredients from the Goji berry, such as polysaccharide, pigments, and lycibarbarspermidines, with properties of anti-inflammation, antioxidant, anti-apoptosis, anti-fibrosis, and anti-tumor. Acute and chronic liver diseases represent a major world public health problem. The clinical curative rate for some liver diseases, such as chronic hepatitis B, cirrhosis, and liver cancer remains unsatisfactorily low. In the current review, we summarized the updated mechanisms of bioactive ingredients derived from the Goji berry in liver diseases, which may pave the way for their future clinical application. The hepatoprotective properties of Lycium barbarum polysaccharide (LBP) have been characterized in several liver disease models, including acute liver injury, liver failure, non-alcoholic liver disease, alcoholic liver disease, liver fibrosis, and liver cancer. However, delineating the active ingredient(s) from LBP in different types of liver diseases is a challenge. Wolfberry also contains the highest concentration of the antioxidant xanthophyll carotenoid zeaxanthin dipalmitate (ZD). ZD is a zeaxanthin diester formed from zeaxanthin (ZE) and palmitic acid. Inducing non-alcoholic in the transgenic HBV mice model reactivated HBV replication, while ZD administration reduced HBV DNA replication and serum HBsAg levels. The immediate hepatocyte membrane receptors of ZD during alcoholic liver injury have also be identified. Treating human adipose-derived mesenchymal stem cells (hADMSC) with ZD before transplantation increased stem cell survival and improved the therapeutic outcome in acute liver disease/failure models. Betaine is a natural amino acid and one of the major constituents of Lycium barbarum. It is shown to play antioxidant and anti-inflammatory roles in toxin-induced liver injury and fatty liver disease model. Recently, we identified fifteen new dicaffeoylspermidine derivatives, lycibarbarspermidines A-O, from wolfberry. The oxygen radical absorbance capacity assay revealed that A-O all displayed antioxidant capacity and are related to the effects of wolfberry. Our pilot study results also revealed their potential hepatoprotective properties in alcoholic and non-alcoholic liver diseases. Of note, all published papers reported no side effects from LBP, ZD, betaine, or lycibarbarspermidines. Nonetheless, since the investigation of the properties of herbal active compounds is on the rise and with wolfberry's increasing popularity and commercialization as a food supplement, those major ingredients will likely get more attention from the scientific community, and its effect on liver disease might be studied further.