Pomegranate Extracts as Dual Regulators of Angiogenesis: A Systematic Review of Preclinical Evidence in Cancer and Chronic Wound Healing

IF 4.5 2区农林科学 Q1 FOOD SCIENCE & TECHNOLOGY

Molecular Nutrition & Food Research Pub Date : 2025-04-09 DOI:10.1002/mnfr.70060

Anna Eleonora Caprifico, Gianpiero Calabrese, Riccardo Tornese, Anna Montefusco, Rocco Placì, Teodoro Semeraro, Miriana Durante, Monica De Caroli, Marcello Salvatore Lenucci

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引用次数: 0

Abstract

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.

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石榴提取物作为血管生成的双重调节剂：癌症和慢性伤口愈合的临床前证据的系统综述

血管生成在肿瘤进展和伤口愈合中起着至关重要的作用。本系统综述研究了石榴提取物在癌症和慢性伤口愈合（CWH）的临床前模型中分别作为抗和促血管生成剂的作用。根据PRISMA指南，从PubMed、Scopus和谷歌Scholar数据库中确定了14项研究（10项癌症研究，4项CWH研究）。在癌症模型中，PG提取物（果汁、果皮提取物、籽油）降低了多种癌症类型中血管内皮生长因子（VEGF）的表达和内皮管的形成，同时降低了基质金属蛋白酶和炎症介质的表达。相反，在CWH模型中，外用PG皮提取物可增强糖尿病和烧伤的VEGF表达和伤口愈合。这种双重血管生成效应似乎与过氧化物酶体增殖因子激活的受体信号通路和PG多酚（特别是鞣花单宁）之间的协同相互作用有机制联系。对研究质量的评估显示，体外研究的偏倚风险普遍较低，而动物研究则显示出不同的方法学严谨性。尽管有很好的临床前证据，但提取方法的标准化、分子机制的探索以及转化为临床研究仍然是关键的研究重点。这项综合分析验证了PG提取物作为一种有希望的治疗策略，既可以抑制癌症的病理性血管生成，又可以促进CWH的有益血管生成。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Nutrition & Food Research 工程技术-食品科技

CiteScore

8.70

自引率

1.90%

发文量

250

审稿时长

1.7 months

期刊介绍： Molecular Nutrition & Food Research is a primary research journal devoted to health, safety and all aspects of molecular nutrition such as nutritional biochemistry, nutrigenomics and metabolomics aiming to link the information arising from related disciplines: Bioactivity: Nutritional and medical effects of food constituents including bioavailability and kinetics. Immunology: Understanding the interactions of food and the immune system. Microbiology: Food spoilage, food pathogens, chemical and physical approaches of fermented foods and novel microbial processes. Chemistry: Isolation and analysis of bioactive food ingredients while considering environmental aspects.