Watermelon ( Citrullus lanatus L.): a functional food with potential therapeutic by-products

Lifestyle modification in the global population is considered a significant health challenge and has a substantial impact on dietary patterns. To address the burden of ailments, researchers’ focus has shifted toward plant-based foods, including their byproducts. The current review comprehensively demonstrates the therapeutic properties of watermelon and its by-products (seed and rind). The literature was extracted from peer-reviewed research (2020-25) with specific medical subject headings at ScienceDirect, PubMed, Google Scholar, ResearchGate and Scopus. The studies have revealed that not only fruit pulp but also by-products like rind and seeds are also potential sources for medicinal attributes, such as cardioprotective, hepatoprotective, neuroprotective and antidiabetic due to the functional activity of peptides, fatty acids and phytochemicals. Unique chemical profile of rind and seeds affected numerous pathways, including activation of Nrf2/HO-1 and Nrf2/Keap1, regulation of nitric oxide (NO), based on endothelium-derived relaxing factor (EDRF), modulation of proton pump activity, and regulation of GLUT 2, 4. The biological effects against cancerous cell lines, i.e. A549, Caco-2, HCT116, H1299, HepG2 and MCF-7, significantly influenced cell apoptosis and proliferation. The presence of bioactive compounds improves T-SOD, GSH-Px and CAT, further emphasizing the need to promote their utilization at commercial levels to support functional products, nutraceuticals and cosmetics. The efficiency of the active ingredient in by-products supports current microbial challenges globally; however, there is still a need to explore the potent bioactive compound that exhibits antimicrobial activity against Shigella sonnei, Staphylococcus epidermidis, Pseudomonas fluorescens and Salmonella enterica, which further strengthens the remedial approach in a dose-dependent manner.