The therapeutic potential of pomegranate in the prevention and management of noncommunicable diseases

Noncommunicable diseases (NCDs), including cardiovascular diseases, cancer, respiratory conditions, and metabolic and central nervous system disorders, are the leading causes of morbidity and mortality worldwide. These diseases are primarily driven by unhealthy diets and sedentary lifestyles. Pomegranate (Punica granatum L.), a fruit rich in diverse functional phytoconstituents, has emerged as a promising natural therapeutic agent for the prevention and management of NCDs. Every part of the fruit harbors distinct bioactive compounds that contribute to its health-promoting properties. The peels are particularly rich in punicalagins, the arils are abundant in anthocyanins and ellagic acid, and the seeds contain significant amounts of punicic acid, ellagic acid, and quercetin. Pomegranate peel extracts and juice demonstrate cardioprotective effects through inhibition of angiotensin-converting enzyme (ACE) activity, reduction of inflammatory cytokines, e.g., interleukins and TNF-alpha, and improvements in lipid profiles. Additionally, their anticancer properties are associated with the upregulation of pro-apoptotic markers (Bax, cytochrome c, caspases 3 and 9, and p53) and the downregulation of tumor-promoting and inflammatory markers (Bcl-2, MMP-2, MMP-9, GOLPH-3, and N-cadherin), as well as the attenuation of reactive oxygen species (ROS) generation. Moreover, pomegranate extracts have exhibited hypoglycemic, nephroprotective, hepatoprotective, antidepressant, anti-Alzheimer's, and anti-Parkinson's properties, as demonstrated in in vitro and in vivo studies, and clinical trials. Recent investigations have identified key bioactive constituents, including punicalagin, ellagic acid, gallic acid, and urolithin A, as major contributors to these therapeutic effects. This review provides an overview of the metabolomic profile of pomegranate, its therapeutic potential, safety, and quality control assessments, and strategies to enhance the stability and bioavailability of its active constituents, thus underscoring its potential as a natural intervention for the prevention and treatment of NCDs.