Food Science and Human Wellness最新文献

{"title":"Cascade Response of Encapsulated Polysaccharide Structure and Anti-inflammatory Properties to <em>Ganoderma lucidum</em> Spore Wall Disruption","authors":"Hanqi Chen, Ruiyu Wu, Jiali Zhou, Kai Li, Zhixu Zhang, Y.‐Z. Zhu, Ke Cao, Xixi Cai, Shaoyun Wang, Xuan Chen, Dongbo Liu","doi":"10.26599/fshw.2026.9250935","DOIUrl":"https://doi.org/10.26599/fshw.2026.9250935","url":null,"abstract":"There has been controversy regarding the optimal processing technology that destroys the special spore wall of <em>Ganoderma lucidum</em> so that the functional activity of the internal polysaccharides can be maintained in the most primitive state. Here, high-purity spore polysaccharides derived from the same variety were obtained respectively by three maturation methods, including enzymatic (EW-IB), laser (LW-IB) and mechanical (MW-IB).Structural characterization showed that EW-IB mildly increased the branching degree (0.523) while preserving →3)-β-D-Glcp-(1→; LW-IB slightly reduced it (0.464) without disrupting the main chain glycosidic bonds; MW-IB partially cleaved →6)-β-D-Glcp-(1→ and moderately decreased the branching degree (0.21). Functionally, the experimental results of the LPS-induced inflammation model revealed that the obtained three polysaccharides exerted their regulatory effects by applying differential forces to specific binding sites in the cell. Remarkably, preservation of →3)-β-D-Glcp-(1→ and moderate branching degree correlated with immunomodulatory activity, while excessive glycosidic bond cleavage (MW-IB) or increased branching degree (EW-IB) slightly reduced regulation of inflammatory factors NO and IL-1β. Overall, our findings point towards a valuable approach for the high-value processing and utilization of medicinal fungal polysaccharides.","PeriodicalId":12406,"journal":{"name":"Food Science and Human Wellness","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147908212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<em>Flammulina velutipes</em> polysaccharide boosts the anti-tumor immunity by reversing M1/M2 polarization through TLR4/NF-κB activation","authors":"Chenghao Fu, Ning Chen, Zemiao Niu, Zhenhua Liang, Yanwei Huo, Rong Chen, Yingying Wu, Jing Yang, Yan Zhang, Pin Lv","doi":"10.26599/fshw.2026.9250912","DOIUrl":"https://doi.org/10.26599/fshw.2026.9250912","url":null,"abstract":"Macrophage polarization is a pivotal determinant in the modulation of immune responses and the formation of the tumor-microenvironment (TME), therefore represents a promising avenue for the development of cancer immunotherapy. Recent research highlights the potential of edible mushroom polysaccharides in inducing M1/M2 polarization of macrophages. Here, we report that oral administration of <em>Flammulina (F.) velutipes </em>polysaccharide (FVP) reduced the tumor volume of grafted 4T1 mammary and lewis lung carcinoma (LLC), and increased the overall survival rate of mice. Moreover, this polysaccharide induced the generation of CD11b⁺Ly6C^hig^hF4/80⁺ macrophage cells in LLC and 4T1 tumor-bearing mice. Further investigation found that FVP decreased the ratio of M2-macrophages and regulatory T cells in TME, which is known to support tumor growth and metastasis. Mechanistically, FVP reversed the IL-4 induced M2-polarization by activating the TLR4/ NF-κB axis, and in vitro assays confirmed the expression of pro-inflammatory genes and the antitumor effects of the polysaccharide. Additionally, the expression of Th1 response relative genes also enhanced by FVP polarized macrophage secretions. In summary, these results suggest that FVP may represent a promising immunomodulatory agent for the reversal of macrophage polarization.","PeriodicalId":12406,"journal":{"name":"Food Science and Human Wellness","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciopen.com/local/article_pdf/10.26599/FSHW.2026.9250912.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147913472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Angelica sinensis polysaccharides enhance the production and bactericidal ability of macrophages for resisting leptospiral infection through the gut microbiota","authors":"Tianbao Lv, Lingling Gong, Luteng Diao, Yilin Liu, Yue Ding, Hongkai He, Xufeng Xie, Wenlong Zhang, Jiuxi Liu, Yongguo Cao","doi":"10.26599/fshw.2025.9250910","DOIUrl":"https://doi.org/10.26599/fshw.2025.9250910","url":null,"abstract":"Leptospirosis, a globally re-emerging zoonotic disease, poses a significant threat to public and veterinary health, with current prevention strategies being limited. <em>Angelica sinensis</em> polysaccharide (ASP), a natural bioactive compound, is known for its immunomodulatory and microbiota-regulating properties, yet its efficacy against leptospirosis remains unexplored. This study aimed to investigate the preventive effect of ASP and its underlying mechanism in a murine model. We demonstrated that oral pre-treatment with ASP significantly attenuated the leptospiral burden in the kidneys, liver, and lungs, alleviated tissue damage, and reduced systemic inflammation following <em>Leptospira</em> infection. Mechanistically, ASP promoted hematopoiesis in the bone marrow, leading to an increased production of mononuclear-macrophages. These macrophages exhibited enhanced phagocytic and bactericidal capacities against <em>Leptospira</em>, and their depletion abrogated ASP's protective effect. Furthermore, ASP administration markedly altered the gut microbiota composition. Crucially, the protective efficacy of ASP was eliminated upon antibiotic depletion of the gut microbiota, while fecal microbiota transplantation (FMT) from ASP-treated mice conferred significant resistance to leptospiral infection in recipient mice. Our findings reveal that ASP enhances host defense against leptospirosis by modulating the gut microbiota and subsequently boosting the production and antimicrobial functions of macrophages. This study identifies ASP as a promising preventive agent against leptospirosis and provides novel insights into the gut microbiota-macrophage axis as a potential target for intervention.","PeriodicalId":12406,"journal":{"name":"Food Science and Human Wellness","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147877767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolomics-based analysis of the effect of <em>Cucumaria frondosa</em> intestinal and ovum hydrolysates on cytoxan-induced premature ovarian failure in mice","authors":"Leilei Sun, Shunmin Gong, Mingbo Li, Shijia Huang","doi":"10.26599/fshw.2025.9250880","DOIUrl":"https://doi.org/10.26599/fshw.2025.9250880","url":null,"abstract":"Premature ovarian failure (POF) poses a significant health threat to women of reproductive age. This study investigated the protective effects of <em>Cucumaria frondosa</em> intestinal and ovum hydrolysates (CFH) in a mouse model of POF, utilizing metabolomic analysis to reveal potential underlying mechanisms. In the present study, female ICR mice treated with 100 mg/kg of cytoxan (CTX) were employed to assess the therapeutic effects of CFH on ovarian dysfunction. The ameliorative effects of CFH on POF were evaluated based on the estrous cycle, ovarian reserve, serum sex hormone levels, as well as the antioxidant and anti-apoptotic effects. The results indicated that oral administration of CFH effectively regulated the disordered estrous cycle, increased the number of follicles, significantly elevated serum estradiol (E2) and anti-Müllerian hormone (AMH) levels, while decreasing testosterone (T), follicle stimulating hormone (FSH) and luteinizing hormone (LH) levels in POF mice. Additionally, CFH supplementation resulted in increased superoxide dismutase (SOD) activity and decreased malondialdehyde (MDA) levels. Furthermore, CFH supplementation reduced ovarian granulosa cell apoptosis compared to the POF group. Metabolomic studies ultimately identified metabolites such as tryptophan, citric acid, and arachidonic acid as potential targets of CFH′s action on POF. Collectively, these findings suggest that CFH can improve POF and provide mechanistic insights from metabolomics, supporting the application of <em>Cucumaria frondosa</em> intestinal and ovum in the field of functional foods.","PeriodicalId":12406,"journal":{"name":"Food Science and Human Wellness","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciopen.com/local/article_pdf/10.26599/FSHW.2025.9250880.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147893551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polysaccharides from Millettia speciosa Champ. alleviate obesity-associated metabolic dysfunction through the 'gut microbiota-leptin' axis","authors":"Caihong Chen, Zhengrong Wu, Yanfei Lu, Jiaquan Liu, Hengxing Ran, Lishe Gan, Rihui Wu, Jiming Ye, Jingwei Jin, Dongli Li","doi":"10.26599/fshw.2025.9250874","DOIUrl":"https://doi.org/10.26599/fshw.2025.9250874","url":null,"abstract":"The roots of <em>Millettia speciosa </em>Champ., a medicinal-edible plant, contain bioactive polysaccharides (MSCPs) that demonstrate potential prebiotic effects. Studies in diet-induced obese (DIO) mice have shown that MSCPs can modulate gut microbiota dysbiosis, suppress appetite, and ultimately alleviate obesity.<em> </em>However, the mechanism by which MSCPs regulate appetite and ameliorate obesity-associated metabolic dysfunction through modulating the gut microbiota still requires further investigation. In this study, we observed that MSCPs improved diet-induced obesity to the same extent as the pair-fed group, suggesting that MSCPs can ameliorate obesity in DIO mice by reducing appetite and energy intake. Through RT-qPCR, Western blot, and immunohistochemical experiments, it was found that MSCPs regulate the expression of appetite-related peptides and activate the JAK2/STAT3 signaling pathway to improve obesity in DIO mice; however, MSCPs did not ameliorate obesity in leptin receptor-deficient (db/db) mice, indicating that the leptin pathway is a critical target for treating DIO mice. Furthermore, MSCPs beneficially modulate gut microbiota; fecal microbiota transplantation experiment (FMT) restored the gut microbiota structure in mice, and the FMT group still alleviated obesity through the same signaling pathway. Additionally, 16S rRNA gene sequencing revealed that both MSCPs and FMT upregulated beneficial microbiota such as Lachnospiraceae_UCG_006 and<em> Faecalibaculum</em>, and promoted the production of short-chain fatty acids (SCFAs).<strong> </strong>Notably, in db/db mice, although MSCPs significantly elevated SCFAs levels, they failed to ameliorate obesity or metabolic disorders, further confirming that the leptin pathway serves as a critical requirement for MSCPs-mediated obesity improvement. In summary, MSCPs may alleviate obesity in DIO mice by enriching Lachnospiraceae_UCG_006 and <em>Faecalibaculum</em> to promote SCFAs production, thereby modulating the leptin pathway.","PeriodicalId":12406,"journal":{"name":"Food Science and Human Wellness","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciopen.com/local/article_pdf/10.26599/FSHW.2025.9250874.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147905478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tea polyphenol-fortified parboiled rice as a functional food for obesity prevention via gut microbiota regulation","authors":"Kai Du, Qiqi Xie, Zhaoxie He, Xuefei Yang, Zhi Zheng, Xianfeng Du","doi":"10.26599/fshw.2025.9250904","DOIUrl":"https://doi.org/10.26599/fshw.2025.9250904","url":null,"abstract":"<p class=\"0000\" style=\"margin-top: 6.0pt;\"><span lang=\"EN-US\">Digestive properties of starch can be significantly modified by its interaction with polyphenols. This study focused on the modulatory effect of tea polyphenol-fortified parboiled rice (TP) on high-fat diet (HFD)-induced obesity in mice through the regulation of gut microbiota. TP was prepared with parboiled rice (PR) by soaking with tea polyphenols (TPs). The results showed that average body weight of mice fed with an HFD containing parboiled rice (PR-H) or tea polyphenol-fortified parboiled rice (TP-H) decreased by 24.5% and 48.7% compared with the group of an HFD containing white rice (WR-H), respectively. The levels of total triglyceride and total cholesterol were ranked as WR-H &gt; PR-H &gt; TP-H. Histological sections of the liver and epididymal adipose tissue showed that TP reduced lipid accumulation in mice fed with an HFD. Additionally, TP enhanced the liver antioxidant capacity and reduced oxidative damage in mice, thereby ameliorating liver oxidative stress caused by the HFD. Besides, TP modified the microbial community of mice by improving the gut microbiota diversity with the abundance of <em>Akkermansiaceae</em>,<em> Muribaculaceae</em>,<em> and Bacteroidaceae</em> increased. These findings suggested that TP can improve the intestinal microecological environment of mice, regulate lipid metabolism levels, and thereby exert a certain anti-obesity effect.</span>","PeriodicalId":12406,"journal":{"name":"Food Science and Human Wellness","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147381854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioactive potential of black garlic melanoidins: impact of storage conditions on digestibility and prebiotic activity","authors":"Jiangxiong Zhu, Hao Yin, Bobo Wang, Yu Zhong, Danfeng Wang, Yuncheng Li, Yun Deng","doi":"10.26599/fshw.2025.9250497","DOIUrl":"https://doi.org/10.26599/fshw.2025.9250497","url":null,"abstract":"Melanoidins (MLDs), the final products of the Maillard reaction, are high molecular-weight polymers formed during the processing of black garlic. These compounds contribute to the distinctive color, flavor, and bioactive properties of black garlic. However, the impact of storage conditions on the structural integrity and bioactivities of black garlic melanoidins (BG-MLDs) remains largely unexplored. By using various <i>in vitro</i> simulations, this study investigated the effects of different storage conditions (at 4 and 35 ℃ for 0, 3, and 6 months) on the digestion, absorption, metabolism, and intestinal microbial profile of BG-MLDs during in vitro gastrointestinal digestion. Our results demonstrated that BG-MLDs resisted digestion regardless of storage conditions. BG-MLDs stored at 4 ℃ for 3 months significantly enriched the abundance of beneficial bacteria like <i>Bifidobacterium longum</i> and decreased harmful bacteria like <i>Escherichia</i>. Additionally, MLD treatment significantly increased the production of short-chain fatty acids (SCFAs), particularly propionate, butyrate, and isovalerate, with the 35 ℃ for 3 months of storage showing the most significant effect (increased by 3.74-fold). However, a longer storage at 35 ℃ (6 months) showed a decline in SCFA production. These findings highlight the critical role of a certain storage time (3 months) in preserving and potentially enhancing the prebiotic activity of BG-MLDs. By optimizing storage parameters, the bioactive potential of BG-MLDs can be used for their potential application as functional food ingredients or nutraceuticals, contributing to the prevention and management of chronic diseases associated with gut dysbiosis.","PeriodicalId":12406,"journal":{"name":"Food Science and Human Wellness","volume":"15 1","pages":"9250497-9250497"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciopen.com/local/article_pdf/10.26599/FSHW.2025.9250497.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147877299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lard promotes intestinal stem/progenitor cell proliferation and differentiation with improved gut microbiota","authors":"Wusun Li, Xiaoyan Tang","doi":"10.26599/fshw.2025.9250886","DOIUrl":"https://doi.org/10.26599/fshw.2025.9250886","url":null,"abstract":"The effects of dietary fats on the intestinal barrier have been widely studied, yet their role in intestinal repair remains unclear. Previous studies have primarily focused on fat quantity (e.g., high-fat vs. low-fat diets) and quality (e.g., saturated vs. unsaturated fats), while neglecting the importance of structural properties. This study evaluated the impact of dietary fats with varying <em>sn</em>-2 palmitate levels on intestinal repair using a DSS-induced murine injury model under moderate intake levels. The results indicated that lard, rich in <em>sn</em>-2 palmitate, significantly lowered intestinal permeability, reduced crypt damage, and decreased apoptosis in mice compared to fats low in <em>sn</em>-2 palmitate (corn oil and beef tallow). Immunohistochemical analysis demonstrated that lard significantly increased the number of SOX9, Ki67, MUC2, and PAS-positive cells per crypt, indicating enhanced proliferation and differentiation of intestinal stem/progenitor cells, thereby facilitating intestinal repair. Untargeted metabolomics analysis revealed distinct metabolic profiles of intestinal digestive products derived from dietary fats, with lard leading to enrichment of metabolites such as diacylglycerols, palmitoylcarnitine, and adhumulinic acid. The microbial results showed that lard improved α-diversity and increased the abundance of beneficial bacteria such as <em>unclassified_Lachnospiraceae, unclassified_Muribaculaceae</em>, and <em>Ligilactobacillus</em>. KEGG pathway analysis further demonstrated that lard enriched microbial pathways associated with replication and repair, translation, and amino acid metabolism. Our findings reveal that moderate intake of lard promotes intestinal repair, which is associated with beneficial shifts in metabolite profiles and gut microbiota composition. These results highlight the significance of the <em>sn</em>-2 palmitate structure in dietary fat interventions for promoting intestinal repair.","PeriodicalId":12406,"journal":{"name":"Food Science and Human Wellness","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciopen.com/local/article_pdf/10.26599/FSHW.2025.9250886.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147894050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"3D-printed structure design enhances solid-state fermentation of soybean meal&amp;ndash;okara substrates","authors":"Yifei Liu, Yiqiang Dai, Xiudong Xia, Mingsheng Dong","doi":"10.26599/fshw.2025.9250906","DOIUrl":"https://doi.org/10.26599/fshw.2025.9250906","url":null,"abstract":"Conventional solid-state fermentation is often limited by heterogeneous mass transfer and poor process controllability. 3D printing offers a novel strategy to optimize fermentation by enabling precise structural design of the substrate. In this study, <em>Neurospora intermedia</em> was used to ferment soybean meal (SM) and okara (OK) substrates fabricated via 3D printing, systematically evaluating the effects of printed structures on hyphal growth and metabolite accumulation. By adjusting model height and infill density, the 3D-printed matrices exhibited distinct microstructural characteristics that significantly influenced hyphal spatial distribution and fermentation activity. Compared with conventional SSF, the 3D-printed structures not only promoted uniform mycelial colonization and enhanced metabolic activity—raising soluble protein content to (57.39 ± 1.6) mg/g and ergothioneine accumulation to (391.82 ± 4.3) mg/kg—but also delayed spore formation, resulting in lower early accumulation of carotenoids. Morphological and microstructural analyses indicated that <em>N. intermedia</em> preferentially grew along the printed scaffold within the matrix, enhancing gas exchange, improving nutrient availability, and forming interconnected mycelial networks that reinforced structural stability and improved the texture of the fermented products. These findings demonstrate that rationally designed 3D-printed structures can effectively regulate oxygen diffusion pathways and the spatial organization of nutrients and microbes, providing a tunable platform for the valorization of agro-industrial by-products such as SM and OK. This study highlights the potential of 3D printing to optimize SSF performance and develop structurally guided, sustainable food bioprocessing systems.","PeriodicalId":12406,"journal":{"name":"Food Science and Human Wellness","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147909292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<em>In silico</em> identification and biological evaluation of CXCR2 inhibitor naringin to suppress breast cancer premetastatic niche formation and metastasis","authors":"Bo Pan, Shengqi Wang, Yifeng Zheng, Neng Wang, Yingqi She, Shang Xu, Shicui Hong, Cheng Peng, Zhiyu Wang","doi":"10.26599/fshw.2025.9250911","DOIUrl":"https://doi.org/10.26599/fshw.2025.9250911","url":null,"abstract":"Distant metastasis greatly threatens the overall survival of breast cancer patients. C-X-C chemokine receptor 2 (CXCR2) expressed on myeloid-derived suppressor cells (MDSCs) has been proven to be an essential modulator for the formation of premetastatic niche (PMN), which facilitates cancer cell seeding and later metastasis. However, current CXCR2 inhibitors are challenged by serious side effects and toxicities, thus, increasing attention has been paid to discovering CXCR2 antagonists from dietary compounds. Herein, <em>in silico </em>CXCR2<em> </em>pharmacophore models were established and subsequently identified 9'''-methyl lithospermate B<strong>,&nbsp;</strong>thiostrepton, rhoifolin and naringin (NAR) as potential CXCR2 antagonists from the L6020 database of traditional Chinese medicine (TCM) compounds. NAR was further validated to possess the admirable target affinity with CXCR2 by BLI analysis, and DARTS detection also validated CXCR2 as the direct binding target of NAR. Further investigation revealed that NAR could suppress the metastasis of MDSC and reverse its immunosuppressive effects on CD8⁺T cells <em>via</em> CXCR2 inhibition. Subsequent investigations utilizing the zebrafish xenotransplantation model revealed that NAR inhibited the mobilization of MDSCs and the generation of PMNs by targeting CXCR2, ultimately resulting in diminished growth and metastasis of breast cancer. Meanwhile, the mouse breast cancer orthotopic model also validated that NAR could suppress breast cancer PMN formation, growth and metastasis by inhibiting CXCR2. This suppression is evidenced by a reduction in the population of MDSCs in the lung, tumor, and blood, as well as a decrease in CXCR2 phosphorylation within splenic MDSCs.&nbsp; Taken together, our study identifies NAR as a natural CXCR2 antagonist, and sheds novel light on utilizing NAR to prevent PMN formation and breast cancer metastasis <em>via</em> inhibiting MDSC recruitment.","PeriodicalId":12406,"journal":{"name":"Food Science and Human Wellness","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciopen.com/local/article_pdf/10.26599/FSHW.2025.9250911.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147381698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}