Journal of Nutritional Biochemistry最新文献

{"title":"Effects of pubertal dietary energy-protein levels and breeding strategies on mammary gland development and lactational performance in mice","authors":"Xusheng Dong ,&nbsp;Siyu Tian ,&nbsp;Wenjing Yu,&nbsp;Xueyan Lin,&nbsp;Zhonghua Wang,&nbsp;Qiuling Hou","doi":"10.1016/j.jnutbio.2025.110236","DOIUrl":"10.1016/j.jnutbio.2025.110236","url":null,"abstract":"<div><div>Determining dietary energy and protein level to accelerate heifer growth while ensuring mammary development remains challenging. Technical and economic constraints in cattle hinder defining optimal energy protein levels and breeding timing. Thus, we used mice as a model to examine how post-weaning diets differing in energy and protein concentrations, combined with two breeding strategies, affect mammary development and lactation. Two hundred forty female mice (21 d) were divided into five dietary groups: high-energy moderate-protein, high-energy low-protein, moderate-energy moderate-protein, low-energy moderate-protein and low-energy low-protein. Mammary tissue and serum were collected at target mating weight (27±1 g) and body maturity (56 d). Breeding was initiated either upon attainment of target weight or at 63 d of age, with collection of mammary and serum samples at gestation 15 d as well as serum samples at lactation 13 d. The results showed that moderate increases in dietary energy accelerate growth, enhance mammary development, and improve lactational performance in mice. Under low-energy intake, maintaining adequate protein is critical for mammary and overall growth. High-energy feeding combined with a weight-based mating strategy markedly increased milk yield, whereas age-based mating provided nutrient-restricted mice with the necessary developmental window. These findings provide a theoretical foundation for advancing age at first calving through high energy feeding strategies in heifer management.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"150 ","pages":"Article 110236"},"PeriodicalIF":4.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145774712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"3,3′-Diindolylmethane ameliorate obesity-related skeletal muscle atrophy via regulating mitochondrial function","authors":"Yuquan Zhong ,&nbsp;Siyuan Chen ,&nbsp;Jingyun Pan ,&nbsp;Ruomei Niu ,&nbsp;Junqiang Du ,&nbsp;Qiuxia Dong ,&nbsp;Yanxi Liu ,&nbsp;Yilu Yao ,&nbsp;Yunfeng Lin ,&nbsp;Heng Fang ,&nbsp;Jiewen Su ,&nbsp;Xudong Li ,&nbsp;Yan Zhang ,&nbsp;Guangyu Yang ,&nbsp;Jinyin Wu ,&nbsp;Juntao Li ,&nbsp;Weiwen Liu ,&nbsp;Bing Huang ,&nbsp;Jie Tang ,&nbsp;Wei Zhu","doi":"10.1016/j.jnutbio.2025.110223","DOIUrl":"10.1016/j.jnutbio.2025.110223","url":null,"abstract":"<div><div>Skeletal muscle is the primary storage and metabolic site for amino acids and proteins in the body, and its mass and function are affected by various pathological factors. Studies have shown that mitochondrial dysfunction is associated with skeletal muscle atrophy. Indole-3-carbinol (I3C) and its active metabolite 3,3′-Diindolylmethane (DIM) have bioactivities such as inhibiting fat formation, but it is unclear whether they can affect skeletal muscle atrophy in obesity by improving mitochondrial function. Our research found that high-fat factors can induce obesity-related skeletal muscle atrophy, characterized by decreased muscle mass and function, reduced mitochondrial number, and impaired function in muscle cells. DIM can improve obesity-related skeletal muscle atrophy caused by a high-fat diet, and the mechanism may be related to the regulation of AMPK/SIRT1/PGC-1α pathway protein expression and improved mitochondrial function in muscle cells.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"150 ","pages":"Article 110223"},"PeriodicalIF":4.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145774736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dietary fiber-derived butyrate ameliorates pulmonary fibrosis by inhibiting YBX1 ubiquitination","authors":"Mengyu Li ,&nbsp;Tianyu Pan ,&nbsp;Xiaoli Ma ,&nbsp;Xiaofang Hu ,&nbsp;Ji Jiang ,&nbsp;Yafei Zhang ,&nbsp;Lei Zhang ,&nbsp;Xin Pan ,&nbsp;Yuanyuan Wang","doi":"10.1016/j.jnutbio.2025.110210","DOIUrl":"10.1016/j.jnutbio.2025.110210","url":null,"abstract":"<div><div>Pulmonary fibrosis (PF) is a progressive and fatal interstitial lung disease characterized by aberrant epithelial-mesenchymal transition (EMT) and extracellular matrix deposition. Dietary fiber, fermented by gut microbiota into butyrate, exerts anti-fibrotic effects, yet the underlying mechanisms are not fully elucidated. YBX1 plays a crucial role in the regulation of fibrosis and EMT. However, its function in PF remains unclear. This study aims to investigate the role of dietary fiber in PF and whether YBX1 mediates the anti-fibrotic effect of butyrate in PF. The roles of the high fiber (HF) diet and butyrate in PF and the changes in butyrate content were evaluated using RT-qPCR, Western blotting, immunofluorescence (IF) and GC-MS. RNA sequencing was used to analyze the downstream action sites of butyrate. The function of YBX1 in PF was elucidated through overexpression of YBX1, RNA sequencing, and KEGG pathway analysis. The interaction between YBX1 and butyrate was examined using ubiquitination and CHX assays. The results showed that the HF diet increased butyrate levels, thereby ameliorating PF by inhibiting EMT. The expression of YBX1 was downregulated in PF and overexpression of YBX1 inhibited EMT by regulating CYP1A1/NF-κB signaling pathway, thereby improving the progression of PF. Butyrate upregulated YBX1 protein expression by reducing its ubiquitination. This work provides new insights and promising strategies for the prevention and treatment of PF through dietary interventions.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"150 ","pages":"Article 110210"},"PeriodicalIF":4.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145677725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Geniposidic acid from ginger-processed Eucommiae Cortex alleviates rheumatoid arthritis by modulating macrophage lactylation induced by exosomes from inflammatory fibroblast-like synoviocytes","authors":"Yijing Pan ,&nbsp;Chenxi Deng ,&nbsp;Xinyue Liu ,&nbsp;Shunshun Wang ,&nbsp;Lin Chen ,&nbsp;Anzheng Li ,&nbsp;Jinsong Shu ,&nbsp;Kang Xu ,&nbsp;Xiong Ku ,&nbsp;Chunli Wang","doi":"10.1016/j.jnutbio.2025.110213","DOIUrl":"10.1016/j.jnutbio.2025.110213","url":null,"abstract":"<div><div><em>Eucommiae Cortex</em> (EC), a Traditional Chinese health food product, is known for its anti-inflammatory, antioxidant, and hepatoprotective effects, with promising potential in treating rheumatoid arthritis (RA). This study used liquid chromatography-tandem mass spectrometry (LC-MS) to profile the bioactive compounds of ginger-processed EC (G-EC), focusing on its absorbed constituents and metabolic fate <em>in vivo</em>. Network pharmacology identified geniposidic acid (GPA) as a key bioavailable compound in G-EC, potentially alleviating RA. <em>In vivo</em>, GPA significantly improved RA symptoms. Additionally, exosomes from inflammatory fibroblast-like synoviocytes (FLSs) (LPS-exo) promoted M1 macrophage polarization, glycolytic activation, and synovial inflammation. GPA inhibited glycolysis, reduced M1 polarization induced by LPS-exo, and downregulated H3K56la histone lactylation. Mechanistic analysis suggested these effects involve the regulation of ATP-citrate lyase (ACLY) and Histone deacetylase 6 (HDAC6) expression. This study supports the therapeutic potential of GPA in RA and provides a foundation for further clinical research.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"150 ","pages":"Article 110213"},"PeriodicalIF":4.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145661458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Olive-derived elenolic acid surpasses metformin and rivals liraglutide in managing blood glucose and obesity in a mouse model of type 2 diabetes","authors":"Yao Wang ,&nbsp;Hana Alkhalidy ,&nbsp;Xinyi Cao ,&nbsp;Reagan Vaughan ,&nbsp;MD Abu T. Rachi ,&nbsp;Bin Xu ,&nbsp;Balaji Kale ,&nbsp;Abeje Silte ,&nbsp;Jennifer Rainville ,&nbsp;Georgia E. Hodes ,&nbsp;Yan Zhang ,&nbsp;Dongmin Liu","doi":"10.1016/j.jnutbio.2025.110206","DOIUrl":"10.1016/j.jnutbio.2025.110206","url":null,"abstract":"<div><div>Obesity and type 2 diabetes (T2D) are among the most common metabolic diseases that are associated with increased risk of noncommunicable diseases globally. Elenolic acid (EA), derived from olives, was shown to possess potent acute effects on obesity and diabetes that were associated with increased gut hormone secretion. Here, we investigate the long-term effects of EA in two mouse models of obesity and diabetes. In diet-induced obese mice, oral administration of EA (50 mg/kg/day) for 7 weeks, normalized fasting blood glucose (from 176.6±4.5 mg/dL to 120.8±4.0 mg/dL), and restored glucose tolerance and insulin sensitivity to levels comparable to lean mice. These improvements were associated with increased circulating peptide YY and gastric inhibitory polypeptide concentrations, downregulation of hypothalamic agouti-related peptide (AgRP), reduced food intake (∼20%), and weight loss. Acutely, EA slowed gastric emptying rate by about 50% and increased glucagon like peptide-1 levels. In <em>db/db</em> mice, EA reduced non-fasting blood glucose from 459.0±51.1 mg/dL to 208.9±10.3 mg/dL, an effect comparable to liraglutide and greater than metformin. EA also lowered fasting blood glucose levels similar to liraglutide and significantly below those observed with metformin. Moreover, EA-treated mice exhibited less weight gain than those receiving either drug. These effects were accompanied by decreased AgRP expression and increased c-fos activation. These results suggest that EA is a novel, multi-target agent with therapeutic potential for treating T2D and obesity.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"150 ","pages":"Article 110206"},"PeriodicalIF":4.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145634715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diosmetin alleviates hyperuricemic nephropathy by activating the BNIP3/Nrf2/GPX4 pathway to inhibit ferroptosis of renal tubular epithelial cells induced by monosodium urate crystals","authors":"Chengming Hu ,&nbsp;Changle Dong ,&nbsp;Huimin Yang ,&nbsp;Zejun Yu ,&nbsp;Yang Li ,&nbsp;Yinsheng Qiu ,&nbsp;Zhinan Mei ,&nbsp;Lingyun Xu","doi":"10.1016/j.jnutbio.2025.110241","DOIUrl":"10.1016/j.jnutbio.2025.110241","url":null,"abstract":"<div><div>Hyperuricemic nephropathy (HN) is a serious kidney complication of hyperuricemia, yet effective treatments are lacking. Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, has been implicated in renal tubular injury, but its regulatory mechanisms in HN remain unclear. This study investigated the protective effects of diosmetin (DIOS), a natural flavonoid with antioxidant properties, against monosodium urate (MSU)-induced damage in HK-2 human renal tubular cells. We confirmed that MSU-induced cell death was characteristic of ferroptosis. Through a combination of transcriptomic analysis and network pharmacology, we identified the BNIP3/Nrf2/GPX4 pathway as the primary potential target of DIOS. Molecular docking and subsequent experimental validation demonstrated that DIOS directly interacts with and modulates BNIP3, leading to the activation of Nrf2 and the upregulation of its downstream target, GPX4. This cascade enhanced the cellular antioxidant defense system, effectively suppressing lipid peroxidation and ferroptosis. Our findings reveal a novel mechanism by which DIOS protects against MSU-induced renal tubular injury and highlight the BNIP3/Nrf2/GPX4 axis as a promising therapeutic target for mitigating ferroptosis in HN.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"150 ","pages":"Article 110241"},"PeriodicalIF":4.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145805018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ferroptosis inhibition by spermidine via the NCOA4/Ferritin axis and polyamine–microbiota dysbiosis in ulcerative colitis","authors":"Mengjie Zhang ,&nbsp;Ziyue Dou ,&nbsp;Langlang Yang ,&nbsp;Hongqian Wang ,&nbsp;Beibei Tian ,&nbsp;Shaocheng Hong ,&nbsp;Qi Yang ,&nbsp;Jian Lu ,&nbsp;Xi Chen","doi":"10.1016/j.jnutbio.2025.110222","DOIUrl":"10.1016/j.jnutbio.2025.110222","url":null,"abstract":"<div><div>Spermidine (SPD), a microbiota‑derived polyamine, exerts potent anti‑inflammatory effects in colitis. This study investigated how SPD mitigates dextran sulfate sodium (DSS)–induced ferroptosis and explored the association between gut microbiota composition and polyamine metabolites in patients with ulcerative colitis (UC). DSS‑induced UC models were established in mice and HT‑29 cells, followed by SPD treatment. RNA sequencing was used to profile transcriptomic changes in HT‑29 cells, and the effects of SPD on NCOA4 and Ferritin were evaluated both <em>in vivo</em> and <em>in vitro</em>. NCOA4 silencing was performed to clarify its role in SPD‑mediated protection against ferroptosis. Fecal polyamines and gut microbiota profiles from UC patients and healthy controls were analyzed using UHPLC‑MS/MS and 16S rRNA sequencing. SPD significantly alleviated DSS‑induced colitis. Gene set enrichment analysis (GSEA) of differentially expressed genes in HT‑29 cells highlighted iron‑metabolism pathways as prominently affected. SPD mitigated DSS‑induced ferroptosis <em>in vitro</em> and <em>in vivo</em>, likely by limiting NCOA4‑dependent ferritin turnover and maintaining iron balance. In UC patients, disturbances in fecal polyamine levels corresponded closely with shifts in gut microbial composition, with 27 genera showing significant correlations with polyamine metabolites. Together, these findings position SPD as a modulator of ferroptosis via the NCOA4–ferritin axis and point to a potential therapeutic avenue. In UC, disrupted polyamine metabolites are closely linked to microbial alterations, implicating microbe–polyamine interactions in disease pathogenesis.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"150 ","pages":"Article 110222"},"PeriodicalIF":4.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145695817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of lactation time and dietary patterns on human milk nucleotides: A longitudinal and cross-sectional study","authors":"Hai-Tao Yu ,&nbsp;Lu-Tong Yang ,&nbsp;Miao Yu ,&nbsp;Yi-Ru Chen ,&nbsp;Song Ni ,&nbsp;Mo-Tong Liu ,&nbsp;Wen-Hui Xu ,&nbsp;Lin Xie","doi":"10.1016/j.jnutbio.2025.110224","DOIUrl":"10.1016/j.jnutbio.2025.110224","url":null,"abstract":"<div><div>Nucleotides play a crucial role in the growth and development of infants. Studying the dynamics of nucleotides variation in human milk and the influencing factors can provide insights to guide the diets of lactating mothers. The colostrum milk (CM, 0–5 d), transitional milk (TM, 10–15 d), and mature milk (MM1, 40–45 d) were collected as longitudinal study. Additionally, late term mature milk (MM2, 200–240 d; MM3, 300–400 d) were collected as the cross-sectional study. The human milk free nucleotides, including cytidine monophosphate (CMP), uridine monophosphate (UMP), guanosine monophosphate (GMP), and adenosine monophosphate (AMP), were assessed using High Performance Liquid Chromatography (HPLC), and the total potentially available nucleosides (TPAN) were calculated. The food frequency questionnaire (FFQ) was used to investigate the types and quantities of food consumed by lactating mothers. Principal component analysis (PCA) was then employed to identify their dietary patterns. The interaction of dietary patterns and lactation time on the levels of nucleotides was analyzed by factorial analysis. The levels of nucleotides in breast milk varied throughout the period of lactation. GMP and AMP decreased over time, while UMP, CMP, and TPAN decreased in the TM stage and then increased in the MM1 stage. Factorial analysis showed that lactation time affected all human milk nucleotides and an interaction of lactation time and dietary pattern could be observed on GMP and AMP. Further analysis indicated that dietary patterns influenced nucleotides during the late term mature milk stages (MM2 and MM3), while nucleotides in CM were not influenced by diet. Mothers who consumed the Beans-Nuts dietary pattern exhibited the highest nucleotides in their mature milk, followed by those who consumed the Potato-Vegetable dietary pattern. The levels of nucleotides in human milk are influenced by both the stage of lactation and maternal dietary patterns.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"150 ","pages":"Article 110224"},"PeriodicalIF":4.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145695750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effects of different forms of vitamin E on gut microbiota, mechanisms, and implications in disease prevention","authors":"Qing Jiang","doi":"10.1016/j.jnutbio.2025.110235","DOIUrl":"10.1016/j.jnutbio.2025.110235","url":null,"abstract":"<div><div>The gut microbiota plays an important role in host health and dysbiosis contributes to disease development. Natural forms of vitamin E consist of eight lipophilic antioxidants, <em>i.e.</em>, alpha-, beta-. gamma- and delta-tocopherol (αT, βT, γT and δT) and alpha-, beta-. gamma- and delta-tocotrienol (αTE, βTE, γTE and δTE). Vitamin E forms and their metabolites including 13′-carboxychromanols (13′-COOHs) have been shown to possess anti-inflammatory activities. Interestingly, recent human and animal studies reveal that vitamin E forms and δTE-13′-COOH (metabolite of δTE) can modulate gut microbiota. Specifically, supplementation of αT, γT, tocotrienols or δTE-13′-COOH elevated some beneficial bacteria or attenuated disease-associated decrease of probiotics including butyrate producers. This review focuses on the current knowledge of the effects of different forms of vitamin E and δTE-13′-COOH on gut microbiome. Although the mechanisms underlying modulation of gut microbiota remain to be determined, this author proposes that promotion of beneficial gut microbes by vitamin E forms may in part be rooted in their antioxidant and anti-inflammatory activities as well as protection of intestinal barrier integrity, and that the modulatory effects on gut microbes likely contributes to vitamin E-facilitated disease prevention. Finally, this review discusses knowledge gaps and future research efforts needed to uncover how vitamin E forms interact with gut microbiota and utilize such knowledge for improving human health.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"150 ","pages":"Article 110235"},"PeriodicalIF":4.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145756935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Naringenin prevents osteoblast senescence in d-galactose-induced aging conditions via estrogen receptor-mediated pathway","authors":"Saurabh Kumar Kaushal ,&nbsp;Devendra Pratap Singh ,&nbsp;Ankita Paul ,&nbsp;Megha Dixit ,&nbsp;Divya Singh","doi":"10.1016/j.jnutbio.2025.110238","DOIUrl":"10.1016/j.jnutbio.2025.110238","url":null,"abstract":"<div><div>Naringenin is a plant-derived flavonoid having anti-proliferative, anti-inflammatory, and anti-angiogenic properties against various metabolic disorders. Though there are reports demonstrating the osteogenic potential of naringenin, its effect remains largely unexplored in senile osteoporosis. The current study was planned with the objective to demonstrate the osteoprotective effect of naringenin in conditions of senile osteoporosis induced by <span>d</span>-galactose (D-gal). The results in the <span>d</span>-gal aging bone loss animal model suggest that naringenin improves bone microarchitecture, promotes ex-vivo mineralization, and alters bone serum markers. To check the mode of action of naringenin behind its protective effect, further experiments were performed at the cellular level. Naringenin facilitates osteoblast differentiation and suppresses osteoblast senescence, apoptosis, and cellular reactive oxygen species production in primary osteoblast cells after <span>d</span>-gal stimulation. Mechanistically, naringenin mitigates senescence through the estrogen receptor-mediated pathway, as confirmed when calvarial osteoblast cells treated with ICI182.780, an estrogen pathway inhibitor, greatly decrease its effectiveness. Taken together, these results lead us to conclude that naringenin may function as a potential therapeutic agent for senile osteoporosis.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"150 ","pages":"Article 110238"},"PeriodicalIF":4.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145794207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}