Pomegranate (Punica granatum L.) has long been recognised for its rich antioxidant profile and potential health benefits. Recent research has expanded its therapeutic potential to include antiangiogenic properties, which are crucial for inhibiting the growth of tumours and other pathological conditions involving aberrant blood vessel formation. This review consolidates current findings on the antiangiogenic effects of pomegranate extracts. We explore the impact of pomegranate polyphenols, including ellagic acid, punicalagin, anthocyanins, punicic acid and bioactive polysaccharides on key angiogenesis-related pathways and endothelial cell function. Emphasis is placed on the effects of these extracts as phytocomplexes rather than isolated compounds. Additionally, we discuss the use of pomegranate by-products, such as peels and seeds, in the preparation of extracts within a green chemistry and circular economy framework, highlighting their value in enhancing extract efficacy and sustainability. By primarily reviewing in vitro and in vivo preclinical studies, we assess how these extracts modulate angiogenesis across various disease models and explore their potential as adjunctive therapies for cancer and other angiogenesis-driven disorders. This review also identifies existing knowledge gaps and proposes future research directions to fully elucidate the clinical utility of pomegranate extracts in therapeutic applications.

Angiogenesis plays a critical role in both tumor progression and wound healing. This systematic review investigates the effect of pomegranate (Punica granatum, PG) extracts as both anti‐ and pro‐angiogenic agents in preclinical models of cancer and chronic wound healing (CWH), respectively. Following PRISMA guidelines, 14 studies (10 cancer, 4 CWH) were identified from PubMed, Scopus, and Google Scholar databases. In cancer models, PG extracts (juice, peel extract, seed oil) reduced vascular endothelial growth factor (VEGF) expression, and endothelial tube formation across multiple cancer types, with concomitant decrease in matrix metalloproteinases and inflammatory mediators. Conversely, in CWH models, topical PG peel extract applications enhanced VEGF expression and wound closure in diabetic and burn injuries. This dual angiogenic effect appears mechanistically linked to peroxisome proliferator‐activated receptor signaling pathways and synergistic interactions among PG polyphenols, particularly ellagitannins. Assessment of study quality revealed generally low risk of bias across in vitro studies, while animal studies demonstrated variable methodological rigor. Despite promising preclinical evidence, standardization of extraction methods, exploration of molecular mechanisms, and translation to clinical investigations remain critical research priorities. This comprehensive analysis validates PG extracts as a promising therapeutic strategy for both inhibiting pathological angiogenesis in cancer and promoting beneficial angiogenesis in CWH.

Pomegranate marc is a major, underutilized juice industry by-product rich in lipophilic polyunsaturated fatty acids—notably conjugated α-linolenic acids (CLnAs)—and hydrophilic polyphenols with potent antioxidant and anti-inflammatory properties. Despite its potential for nutraceutical, cosmetic, and pharmaceutical applications, this matrix remains largely unexploited. This study presents a novel, sequential in-line extraction strategy combining supercritical CO₂ (ScCO₂) and subcritical water (scW) to recover complementary bioactive fractions. Both extraction steps were optimized via Response Surface Methodology (RSM). Box–Behnken optimization of ScCO₂ (43 MPa, 76 °C, 6.4 L min⁻¹, 124 min) yielded 30 g kg⁻¹ dry weight (dw) of oleoresin, achieving a 68% recovery of total oil. Subsequent scW extraction was optimized at 149 °C, with a 40 L kg⁻¹ water-to-solute ratio and 73 min extraction time, yielding 47 g kg⁻¹ dw of total phenolics (58% recovery). Strong agreement between experimental and predicted values confirmed the robustness of the models. Comprehensive profiling revealed a diverse phytocomplex including fatty acids, tocopherols, flavonoids, soluble sugars, and polysaccharides. Antioxidant assays confirmed that both γ-tocopherol and polyphenols significantly contribute to the extracts’ bioactivity. To improve physical handling, the aqueous fractions were converted into solid dispersions via spray drying with maltodextrin. Preliminary in vitro biological assessments on HEK-293 (human embryonic kidney) and MCF-7 (Michigan Cancer Foundation-7) cell lines suggested that the maltodextrin-based formulations may modulate the cytotoxic profile compared to the free extract, with exploratory results showing dosage-dependent variations in cell viability across the two lines. This work suggests a potentially scalable and sustainable biorefinery approach for the integral valorisation of pomegranate marc, offering a basis for a pathway to produce solvent-free bioactives.

Epidermal lipid homeostasis is crucial for skin barrier integrity. This study investigated the effects of an aqueous extract from Beta vulgaris subsp. vulgaris Beetroot Group (BvE) on stress responses and lipid metabolism in HaCaT keratinocytes. BvE, obtained from leaves grown in SETIS^® bioreactors as a standardized biomass source, was chemically characterized by ¹H NMR and ¹³C NMR. HaCaT cells were treated with BvE (1 µg/mL), H₂O₂, or palmitic/oleic acids (PA/OA) to evaluate its protective effects against oxidative damage and lipotoxic stress. Under these conditions, BvE exhibited a distinctive dual action as a reactive oxygen species (ROS) scavenger and triacylglycerol (TAG)-lowering agent. On the one hand, BvE was associated with decreased intracellular ROS levels and changes in NRF2 protein expression, suggesting involvement of redox-regulatory pathways. On the other hand, it was associated with attenuation of lipotoxicity, as evidenced by reduced lipid droplet (LD) formation and decreased expression of DGAT1 and PLIN2. Furthermore, these effects were accompanied by a reduction in Unfolded Protein Response (UPR) markers, modulation of AMPK-associated signaling, attenuation of mitochondrial disfunction, and decreased p53 phosphorylation, findings collectively consistent with a coordinated cytoprotective response. In conclusion, BvE shows potential to protect keratinocytes against lipotoxicity and oxidative stress through mechanisms that may involve both chemical and biological antioxidant activity and metabolic reprogramming, supporting its further investigation for dermatological applications.