Advances towards the analysis, metabolism and health benefits of punicalagin, one of the largest ellagitannin from plants, with future perspectives

Background: Punicalagin (PG), a component of Punica granatum L., present a significant nutraceutical value in view of its numerous health-promoting properties and abundance. Interest in PG is driven by its complex structure, as the largest molecular weight ellagitannin. Promising results from the consumption of pomegranate juice in clinical trials against several ailments i.e., cardiovascular diseases, diabetes, and prostate cancer have been mostly attributed to its PG content. In recent years, PG has been demonstrated to exhibit excellent pharmacological bioactivities and has been proposed as a safe candidate for chemoprevention. Purpose: To assess the underlying PG's action mechanisms towards chronic diseases with high mortality and morbidity. Methods: Electronic databases including PubMed, ScienceDirect and Scopus were used to compile the literature. Papers describing the biological effects of punicalagin in vitro conditions, experimental animal models, and humans were selected and discussed. In addition, the extraction and isolation procedure with the highest punicalagin yield was included. Results: Among the 1757 primarily selected papers, only a final number of 119 studies were included. The mechanisms of actions ranged from selective induction of apoptosis of cancer cells, autophagy of cancer cells, decrease in oxidative stress, reduction of inflammation via down-regulation of pro-inflammatory factors and up-regulation of anti-inflammatory mediators to maintaining neuronal integrity. This review presents the latest research progress made towards PG role in the prevention and treatment of various chronic diseases and its protective health effects highlighting the need for future research in nutraceuticals. Despite the promising effects of punicalagin, there seems to be a need for human trials to confirm the effects at physiological levels as there can be substantial human inter-individual variability in response to punicalagin metabolism. Further, comparison of the different extraction and isolation methods are presented to highlight the most optimum for PG recovery. Conclusion: This review aims at improving the value-added applications of this unique dietary bioactive phenolic at a commercial scale in view of its role in health and disease management.