{"title":"Remodeling of macrophage lipid metabolism by phytosterol suppresses inflammation: Insights from targeted lipidomics","authors":"X. Wang, Lili Xu, Yanhong Zhang, Aizhen Zong, Fangling Du, Hao Yue, Tongcheng Xu","doi":"10.26599/fshw.2026.9251026","DOIUrl":"https://doi.org/10.26599/fshw.2026.9251026","url":null,"abstract":"Phytosterols are widely recognized bioactive compounds exhibiting anti-inflammatory effects. Macrophages adopt a distinct lipid metabolic state during inflammatory responses. However, the specific mechanisms by which phytosterols influence macrophage lipid metabolism and subsequently regulate inflammation through metabolic remodeling remain unclear. In this study, we elucidate how phytosterols reprogram macrophage lipid metabolism to attenuate inflammatory responses. Quantitative lipidomic analysis revealed that phytosterol-induced lipid remodeling predominantly affects long-chain triglycerides. Further mechanistic studies demonstrated that phytosterols increase lipid droplet accumulation and regulate their metabolism by suppressing adipose triglyceride lipase (ATGL), upregulating hypoxia inducible lipid droplet associated proteins (HILPDA), and reducing the production of pro-inflammatory intermediates, including arachidonic acid. Consequently, phytosterol treatment decreased prostaglandin E<sub>2</sub> (PGE<sub>2</sub>) levels and reduced the secretion of pro-inflammatory cytokines such as IL-1β. Collectively, these findings provide novel mechanistic insights into how phytosterols reduce macrophage-driven inflammation through lipid metabolic reprogramming.","PeriodicalId":12406,"journal":{"name":"Food Science and Human Wellness","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciopen.com/local/article_pdf/10.26599/FSHW.2026.9251026.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147879561","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}
Tunyu Jian, Zhen Tang, Yuwen Tian, Weichen Zhang, Xiaoqin Ding, Xiuhua Meng, Han Lv, Bei Tong, Yanan Gai, Weilin Li, Lan Wu, Guanting Niu, Jian Chen
{"title":"Chicory Sesquiterpene Lactones Trained Faeces-derived Extracellular Vesicles Alleviated Ulcerative Colitis by Modulating Gut Microbiota and Bile Acids Metabolism","authors":"Tunyu Jian, Zhen Tang, Yuwen Tian, Weichen Zhang, Xiaoqin Ding, Xiuhua Meng, Han Lv, Bei Tong, Yanan Gai, Weilin Li, Lan Wu, Guanting Niu, Jian Chen","doi":"10.26599/fshw.2026.9251045","DOIUrl":"https://doi.org/10.26599/fshw.2026.9251045","url":null,"abstract":"<p class=\"0000\" style=\"margin-top: 6.0pt;\"><span lang=\"EN-US\">The gut microbiota communicates with the host via extracellular vesicles (EVs), offering a promising therapeutic target for ulcerative colitis (UC). This study investigates the therapeutic potential of sesquiterpene lactones (SL) from chicory and the EVs derived from the faeces of SL-treated mice (SL-trained FEVs) in a dextran sulfate sodium (DSS)-induced UC model. Oral administration of SL significantly ameliorated colitis symptoms, reduced intestinal inflammation, preserved intestinal barrier integrity by maintaining tight junction proteins, and attenuated colonic tissue damage. These protective effects were mechanistically linked to the attenuation of gut microbiota dysbiosis and the restoration of bile acid metabolism homeostasis. Notably, gavage of SL-trained FEVs recapitulated the therapeutic benefits of direct SL treatment, demonstrating the critical role of microbiota-derived EVs in mediating SL's effects. Profiling revealed that SL treatment enriched specific microRNAs (e.g., miR-26a-5p, miR-200b-3p, and miR-194-5p) within these FEVs. Both SL and SL-trained FEVs induced comparable and significant shifts in the gut microbiota composition, notably modulating the relative abundance of genera including <em>Odoribacter</em>, <em>Oscillibacter</em>, <em>Escherichia-Shigella</em>, <em>g-Clostridia_UCG-014_unclassified</em>, and phyla such as p-Actinobacteriota and p-Patescibacteria. Concomitantly, both interventions significantly altered key bile acid profiles, affecting levels of taurocholic acid (TCA), lithocholic acid (LCA), nor-deoxycholic acid (NorDCA), and taurochenodeoxycholic acid (TCDCA). In conclusion, our findings highlight SL and SL-trained FEVs as promising agents for UC treatment, acting through the coordinated modulation of the gut microbiota-bile acid axis, and propose FEVs as a novel, targeted delivery system for microbiota-based therapeutics.</span>","PeriodicalId":12406,"journal":{"name":"Food Science and Human Wellness","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciopen.com/local/article_pdf/10.26599/FSHW.2026.9251045.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147877347","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}
Konglong Feng, Yilu Chen, Mingyue Song, Yu Song, Guo Liu, Meng Kang, Chi-Tang Ho, Hang Xiao, Yong Cao
{"title":"Comprehensive identification and semi-quantitative profiling of 3,5,6,7,8,3&prime;,4&prime;-heptamethoxyflavone metabolites in rats by UHPLC-LTQ-Orbitrap mass spectrometry","authors":"Konglong Feng, Yilu Chen, Mingyue Song, Yu Song, Guo Liu, Meng Kang, Chi-Tang Ho, Hang Xiao, Yong Cao","doi":"10.26599/fshw.2026.9250992","DOIUrl":"https://doi.org/10.26599/fshw.2026.9250992","url":null,"abstract":"3,5,6,7,8,3′,4′-Heptamethoxyflavone (HMF), one of the highest <em>O</em>-methyl numbers in the polymethoxyflavones, possesses various significant health benefits. However, the <em>in vivo</em> metabolic profile of HMF remains largely unexplored. In this study, a systematic identification and relative quantitation of HMF and its metabolites in rats were performed using UHPLC-LTQ-Orbitrap mass spectrometry combined with enzymatic hydrolysis. A total of 56 metabolites were tentatively identified, including 37 demethylated metabolites and 19 glucuronide conjugates of these demethylated products. Notably, all seven mono-demethylated metabolites of HMF were simultaneously detected and structurally discriminated for the first time in rats, along with other di-, tri-, tetra-, and penta-demethylated metabolites. Semi-quantitative analysis revealed that HMF underwent predominant biotransformation into mono-demethylated metabolites in rats, followed by progressive sequential demethylation of these metabolites to generate more di-, tri-, tetra-, and penta-demethylated metabolites. Demethylation and glucuronidation are the primary metabolic pathways of HMF <em>in vivo</em>. This study presents the first comprehensive elucidation of the <em>in vivo</em> metabolic profile of HMF, which is helpful for further understanding of its <em>in vivo</em> potential effective components and pharmacological mechanism.","PeriodicalId":12406,"journal":{"name":"Food Science and Human Wellness","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciopen.com/local/article_pdf/10.26599/FSHW.2026.9250992.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147879220","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}
Wenli Yang, Shiyun Chen, Rong Tong, Yuhang Yi, Dongsheng Wang, Fangfang Yan, Tao Li, Chenghao Lv, Si Qin
{"title":"Procyanidin B2 improves insulin resistance by regulating the IRS1/PI3K/AKT-Nrf2-GSK3&beta; based on computational biology, molecular evidence and direct binding proof","authors":"Wenli Yang, Shiyun Chen, Rong Tong, Yuhang Yi, Dongsheng Wang, Fangfang Yan, Tao Li, Chenghao Lv, Si Qin","doi":"10.26599/fshw.2026.9250965","DOIUrl":"https://doi.org/10.26599/fshw.2026.9250965","url":null,"abstract":"Procyanidin B2 (PB2), a dimer of oligomeric procyanidins, has been reported to ameliorate abnormal glucose metabolism; however, its efficacy in regulating redox-related insulin resistance (IR) and underlying mechanism has not yet been studied. Currently, antioxidant activity and digestive enzyme inhibitory tests were applied to screen the preliminary chemopreventive effect of PB2 on glucose metabolism dysfunction, further computational biology and molecular verification to elucidate its mechanism on improving IR. The results indicated that PB2 had limited antioxidant property against ROS and inhibitory property on digestive enzyme. Network pharmacology analysis implied that PI3K/AKT and FoxO pathways were the main targeted by PB2 to combating IR. Further molecular data demonstrated that PB2 promoted glycogen synthesis by activation of PI3K/AKT-Nrf2 signaling pathway via promoting posttranscriptional protein stability, nuclear translocation of Nrf2 and ARE binding ability, and inhibited gluconeogenesis by stimulating FoxO1 phosphorylation to reduce the expression of downstream G6Pase. Innovatively, molecular docking coupled with different Pull-Down assays revealed that PB2 could directly bind with AKT, Nrf2 and GSK3β, suggesting PB2 may improve IR via regulation of PI3K/AKT-Nrf2-GSK3β signaling, more than FoxO1 signaling pathway; subsequently, Nrf2 could directly bind with GSK3β, reinforcing evidence for PB2-Nrf2-GSK3β complex formation. Besides, co-treatment with PI3K/AKT and Nrf2 inhibitors or siRNAs highlighted the essential role of Nrf2 activation in PB2-contributed IR improvement. Moreover, PB2 has also been validated to exert its effect via regulation of PI3K/AKT-Nrf2-GSK3β signaling pathway <em>in vivo</em>. Therefore, these findings suggest that PB2 is a potent and promising compound to ameliorate glucose metabolism by targeting IR.","PeriodicalId":12406,"journal":{"name":"Food Science and Human Wellness","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147381471","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}