Natural products with anti-tumorigenesis potential targeting macrophage.

Background: Inflammation is a risk factor for tumorigenesis. Macrophage, a subset of immune cells with high plasticity, plays a multifaceted role in this process. Natural products, which are bioactive compounds derived from traditional herbs or foods, have exhibited diverse effects on macrophages and tumorigenesis making them a valuable resource of drug discovery or optimization in tumor prevention.

Purpose: Provide a comprehensive overview of the various roles of macrophages in tumorigenesis, as well as the effects of natural products on tumorigenesis by modulating macrophage function.

Methods: A thorough literature search spanning the past two decades was carried out using PubMed, Web of Science, Elsevier, and CNKI following the PRISMA guidelines. The search terms employed included "macrophage and tumorigenesis", "natural products, macrophages and tumorigenesis", "traditional Chinese medicine and tumorigenesis", "natural products and macrophage polarization", "macrophage and tumor related microenvironment", "macrophage and tumor signal pathway", "toxicity of natural products" and combinations thereof. Furthermore, certain articles are identified through the tracking of citations from other publications or by accessing the websites of relevant journals. Studies that meet the following criteria are excluded: (1) Articles not written in English or Chinese; (2) Full texts were not available; (3) Duplicate articles and irrelevant studies. The data collected was organized and summarized based on molecular mechanisms or compound structure.

Results: This review elucidates the multifaceted effect of macrophages on tumorigenesis, encompassing process such as inflammation, angiogenesis, and tumor cell invasion by regulating metabolism, non-coding RNA, signal transduction and intercellular crosstalk. Natural products, including vitexin, ovatodiolide, ligustilide, and emodin, as well as herbal remedies, have demonstrated efficacy in modulating macrophage function, thereby attenuating tumorigenesis. These interventions mainly focus on mitigating the initial inflammatory response or modifying the inflammatory environment within the precancerous niche.

Conclusions: These mechanistic insights of macrophages in tumorigenesis offer valuable ideas for researchers. The identified natural products facilitate the selection of promising candidates for future cancer drug development.