Pumpkin (Cucurbita pepo) Seeds as a Source of Natural Histamine Inhibitors: Phytochemistry and Anti-Inflammatory Potential

Histamine is a key mediator involved in allergic and inflammatory disorders, contributing to vasodilation, increased vascular permeability, immune cell recruitment, and cytokine release. Although conventional antihistaminic drugs are widely used in clinical practice, their long-term use is often associated with adverse effects, limited efficacy in chronic inflammation, and single-target mechanisms of action. Consequently, there is growing interest in identifying natural, food-derived alternatives capable of modulating histamine release and inflammatory pathways with improved safety profiles. Pumpkin (Cucurbita pepo) seeds are nutritionally rich and contain a wide spectrum of bioactive phytochemicals, including phenolic compounds, flavonoids, unsaturated fatty acids, phytosterols, tocopherols, carotenoids, and bioactive peptides. Emerging experimental evidence suggests that these constituents exert antihistaminic and anti-inflammatory effects through multiple mechanisms, such as mast cell stabilization, inhibition of histidine decarboxylase, modulation of histamine receptor signaling, suppression of pro-inflammatory mediators, cytokine regulation, and attenuation of oxidative stress. This review provides a comprehensive overview of the botanical characteristics, nutritional composition, and phytochemical profile of Cucurbita pepo seeds, with particular emphasis on their role as natural histamine inhibitors. The mechanistic links between histamine regulation and anti-inflammatory activity are critically discussed, along with available in vitro, in vivo, and nutraceutical evidence. Safety, bioavailability, and potential therapeutic applications in allergic and inflammatory disorders are also addressed. Overall, pumpkin seeds represent a promising functional food and nutraceutical candidate for the management of histamine-mediated inflammatory conditions, warranting further molecular and clinical investigations.