Journal of Nutritional Biochemistry最新文献

{"title":"Sculpting liver-related injury in type 2 diabetes mellitus: Decoding serum ferritin's correlation and ferroptosis pathways","authors":"Bin Huang ,&nbsp;Wenjie Wen ,&nbsp;Xiangyu Ding ,&nbsp;Shandong Ye","doi":"10.1016/j.jnutbio.2025.110044","DOIUrl":"10.1016/j.jnutbio.2025.110044","url":null,"abstract":"<div><div>We aimed to assess whether serum ferritin levels are a risk factor for hepatic-related injury in patients with type 2 diabetes mellitus (T2DM) and investigate the role of ferroptosis in this pathological process. A retrospective cohort study and Mendelian randomization analysis were conducted to investigate the association between serum ferritin levels and liver-related outcomes. Furthermore, dB/dB mice and the GSE230674 dataset were used to analyze liver iron metabolism-related indicators and the ferroptosis pathway. Findings from this retrospective cohort study revealed that an elevated serum ferritin level is a relatively independent risk factor for liver-related injuries in patients with T2DM, including nonalcoholic fatty liver disease, hepatocellular injury, and cholestasis. Subgroup analysis suggested that this relationship was absent in patients with anemia. Mendelian randomization analysis indicated a causal relationship between increased hepatic iron storage and disruptions in iron metabolism, leading to elevated alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and direct bilirubin levels. Furthermore, diabetic mice with concomitant nonalcoholic fatty liver disease exhibited hepatic iron overload and activation of ferroptosis pathways. After intervention with ferrostatin-1, there was a reduction in liver injury-related biomarkers and suppression of ferroptosis. Serum ferritin is a risk factor for liver-related injuries in patients with T2DM with normal hemoglobin levels. In this context, activation of the ferroptosis pathway due to hepatic iron overload may play a crucial role. In addition, treatment strategies focused on inhibiting the hepatic ferroptosis pathway are promising.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"146 ","pages":"Article 110044"},"PeriodicalIF":4.9,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144731861","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":"Hydroxytyrosol improved insulin resistance in male offspring born to high-fat diet dams by remodeling gut microbiota","authors":"Dongxin Yi ,&nbsp;Tao Li ,&nbsp;Yuji Xiao ,&nbsp;Xiao Li ,&nbsp;Bing Shao ,&nbsp;Ziyi Wu ,&nbsp;Qiangqiang Hao ,&nbsp;Feng Zhang ,&nbsp;Xue Zhang ,&nbsp;Guang Yang ,&nbsp;Cong Zhang ,&nbsp;Haoyuan Deng ,&nbsp;Xiance Sun ,&nbsp;Ningning Wang","doi":"10.1016/j.jnutbio.2025.110041","DOIUrl":"10.1016/j.jnutbio.2025.110041","url":null,"abstract":"<div><div>Maternal obesity during pregnancy and lactation critically influences offspring metabolic programming, increasing insulin resistance (IR) risk through gut microbiome alterations. This study investigated whether hydroxytyrosol (HT), a polyphenol, could exert metabolic benefits through intergenerational regulation of gut microbiota. Through dietary intervention and fecal microbiota transplantation experiments in pregnant and lactating C57BL/6 J dams, combined with 16S rRNA sequencing and interaction analysis, we found that maternal high-fat diet (60% fat for energy) during gestation and lactation caused obesity and IR-associated phenotypes in male offspring at 4 weeks of age, but not in female young pups. Oral gavage of HT (50 mg/kg) during pregnancy and lactation alleviated abnormal adipocyte hypertrophy, hyperplasia, and excessive leptin secretion in male offspring born to obese dams. Additionally, HT reduced systemic insulin intolerance, hyperglycemia, and hyperinsulinemia, decreased liver index and liver injury, attenuated hepatocyte ballooning, hepatic oxidative stress, and systemic inflammation, and restored hepatic PI3K/AKT signaling in male offspring. Furthermore, HT recovered intestinal barrier function and gut microbiota homeostasis in male offspring, especially the community structure represented by β-diversity, microbial dysbiosis index, and short-chain fatty acids content. Importantly, the beneficial effects of maternal HT ingestion on offspring IR were closely associated with gut microbiota remodeling and could be transmitted through intergenerational microbial inheritance between mothers and offspring. Together, our study indicated that the intergenerational transmission of microbiota may underlie maternal obesity-induced IR and that HT intake could be a promising intervention.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"146 ","pages":"Article 110041"},"PeriodicalIF":4.9,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144731860","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":"Effects of zingerone supplementation on ovarian steroidogenesis and folliculogenesis in mouse","authors":"Ayushmita Dutta,&nbsp;Guruswami Gurusubramanian,&nbsp;Vikas Kumar Roy","doi":"10.1016/j.jnutbio.2025.110043","DOIUrl":"10.1016/j.jnutbio.2025.110043","url":null,"abstract":"<div><div>Zingerone (4-(4‑hydroxy-3-methoxyphenyl)-2-butanone) has various pharmacological and biological activities, such as anti-inflammatory, anticancer, antimicrobial, and hepatoprotective. However, there is no evidential circumstance that shows a specific effect on the ovary. Therefore, this study has investigated the effects of zingerone on ovarian steroidogenesis and folliculogenesis. Mice were divided into four groups: control and zingerone doses of 10 mg/kg, 25mg/kg, and 50 mg/kg. Doses were administered orally for 28 days. Our results showed the changes in food consumption in zingerone-treated mice (10 mg/kg group). Body weight, ovary weight, and relative ovary weight were decreased in zingerone-treated mice(10 mg/kg). Folliculogenesis was stimulated in the zingerone 25 mg/kg group. The levels of testosterone increased in all the zingerone-treated groups, whereas estrogen and progesterone levels were elevated in 25 mg/kg and 50 mg/kg groups. Ovarian proliferation also increased in the zingerone 10 mg/kg and 25 mg/kg groups. Expression of steroidogenic markers was up-regulated in the zingerone-treated groups. The expression of anti-apoptotic marker was suppressed in high-dose groups, and pro-apoptotic markers were significantly increased in the 25 mg/kg group. Androgen receptor expression showed no significant variation, whereas the expression of ERs increased in the zingerone-treated groups. Thus, it can be suggested that zingerone might have a stimulatory role in ovarian steroidogenesis and folliculogenesis in the mouse.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"145 ","pages":"Article 110043"},"PeriodicalIF":4.9,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144718047","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":"Gut microbiota-related glutathione metabolism is key mechanism for sulforaphane ameliorating ulcerative colitis","authors":"Yanan Lv ,&nbsp;Jian He ,&nbsp;Jing Peng ,&nbsp;Hao Li ,&nbsp;Yayuan Yang ,&nbsp;Zeyi Liang ,&nbsp;Wenxiang Shen ,&nbsp;Ghasem Hosseini Salekdeh ,&nbsp;Xuezhi Ding","doi":"10.1016/j.jnutbio.2025.110042","DOIUrl":"10.1016/j.jnutbio.2025.110042","url":null,"abstract":"<div><div>Gut barrier dysfunction is associated with dysbiosis of the gut microbiota and its metabolites, which is closely linked to the pathogenesis of ulcerative colitis (UC). Recent studies have demonstrated that Sulforaphane (SFN) exerts beneficial effects on UC. However, the role of the gut microbiota and microbial metabolism in the anti-UC mechanisms of SFN remains inadequately understood. In this study, we observed that SFN administration significantly improved the pathological phenotype, restored gut barrier integrity, and reduced colon inflammation in dextran sulfate sodium (DSS)-induced colitis mice. Gut microbiota analysis illustrated that SFN administration rebalances the alterations in gut microbiota composition, including genera such as <em>Turicibacter, Lactobacillus</em> and <em>Bacteroides</em>, in DSS-induced mice. Furthermore, untargeted metabolomics analysis indicated that the levels of microbial arachidonic acid metabolism, as well as the metabolism of alanine, aspartate, and glutamate, and glutathione metabolism in the gastrointestinal tract, were significantly altered in DSS-induced mice. Interestingly, SFN treatment significantly restore the alterations in glutathione metabolism and the levels of associated metabolites. Additionally, we observed that the MAPK/NF-κB signaling pathway, regulated by glutathione metabolism, was inhibited in the colon of DSS-induced mice following SFN treatment. Collectively, these results suggest that SFN can alleviate DSS-induced colitis in mice by restoring dysregulated gut microbiota and glutathione metabolism, thereby modulating the MAPK/NF-κB signaling pathway, enhancing intestinal barrier function and reducing colonic inflammation. Importantly, our findings elucidate a novel mechanism by which SFN improves gut barrier function, highlighting its potential to advance the development of SFN-derived therapeutics for the clinical management of colitis.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"146 ","pages":"Article 110042"},"PeriodicalIF":4.9,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144718048","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":"Lactoferrin attenuates renal fibrosis and uremic sarcopenia in a mouse model of adenine-induced chronic kidney disease","authors":"Yukina Iwamoto ,&nbsp;Seiko Yamakoshi ,&nbsp;Akiyo Sekimoto ,&nbsp;Koji Hosomi ,&nbsp;Takashi Toyama ,&nbsp;Yoshiro Saito ,&nbsp;Jun Kunisawa ,&nbsp;Nobuyuki Takahashi ,&nbsp;Eikan Mishima ,&nbsp;Emiko Sato","doi":"10.1016/j.jnutbio.2025.110039","DOIUrl":"10.1016/j.jnutbio.2025.110039","url":null,"abstract":"<div><div>The prevalence of chronic kidney disease (CKD) continues to rise, highlighting the urgent need for effective therapeutic interventions to address its various complications including sarcopenia. Lactoferrin, a multifunctional iron-binding glycoprotein found in mammalian breast milk, exhibits various biological activities and holds potential for treating CKD and its complications. This study investigated the effects of lactoferrin on CKD progression, its complications, and underlying mechanisms. A mouse model of adenine-induced renal failure was used as a CKD model. Lactoferrin was administered during the same period as adenine administration to assess its preventative effect on the progression of CKD. In another experiment, lactoferrin was administered after the adenine administration period to examine its effect on already advanced CKD. Effects of lactoferrin on renal function, renal pathology, and muscle atrophy were evaluated. Additionally, mechanistic insights were explored through mRNA and protein expression profiling, gut microbiota characterization, and metabolomic analysis. Lactoferrin administration improved reduction of renal function, and mitigated renal atrophy, and tubulointerstitial damage, and ameliorated skeletal muscle atrophy in CKD mice. In the skeletal muscle, CKD induced aberrant activation of mTOR1, impaired autophagy, and disrupted branched-chain amino acid metabolism. This abnormal activation of the proteolysis pathways was ameliorated by lactoferrin. Furthermore, lactoferrin attenuated dysbiosis-induced production of microbiota-derived uremic toxins, thereby reducing the indoxyl sulfate accumulation in blood and muscle. These effects contributed to decreased renal damage and delayed sarcopenia progression. Collectively, these findings suggest that lactoferrin may serve as a promising preventive and therapeutic agent for CKD-associated sarcopenia via the gut-kidney-skeletal muscle axis.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"146 ","pages":"Article 110039"},"PeriodicalIF":4.9,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144718049","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 cannabidiol oil mitigates metabolic dysfunction in mice with high-fat diet-induced obesity","authors":"Alejandro Bravo Iniguez ,&nbsp;Qi Sun ,&nbsp;Qiyu Tian ,&nbsp;Min Du ,&nbsp;Mei-Jun Zhu","doi":"10.1016/j.jnutbio.2025.110040","DOIUrl":"10.1016/j.jnutbio.2025.110040","url":null,"abstract":"<div><div>Metabolic syndrome (MetS) is a widespread health concern driven largely by lifestyle behaviors such as dietary choices and physical inactivity. Excessive caloric intake promotes adiposity and dysregulation of metabolic signaling in adipose tissue. This study employed a mouse model of diet-induced obesity to evaluate the ability of cannabidiol (CBD), a cannabis-derived phytochemical, to mitigate metabolic dysfunction. Five-week-old mice received a standard diet or a high-fat diet (HF) with or without CBD (25 mg/kg bw) for 9 weeks. CBD supplementation reduced weight gain and lowered serum glucose concentration in HF mice. These improvements were accompanied by reduced white adipose tissue mass and smaller adipocyte size. Additionally, CBD treatment recovered protein levels of key metabolic regulators, including peroxisome proliferator-activated receptor-γ coactivator 1 alpha and Sirtuin 1, in both inguinal and epididymal adipose tissues. Consistently, CBD supplementation upregulated the mRNA expression of <em>Prdm16</em> and promoted uncoupling protein 1 at both mRNA and protein levels, showing the browning of adipose tissues. Upstream, CBD supplementation increased transient receptor potential vanilloid 1 (TRPV1) in HF mice at both the mRNA and protein levels, which possibly helped orchestrate the observed improvements. In summary, dietary CBD mitigates weight gain and improves the metabolic health of HF-challenged mice, potentially through the promotion of white adipose tissue browning.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"146 ","pages":"Article 110040"},"PeriodicalIF":4.9,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144718046","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":"Antioxidant management to protect male offspring from the progression of MASLD programmed by maternal obesity in mice","authors":"Jialing Zhang ,&nbsp;Jiayu Wang ,&nbsp;Da Xu ,&nbsp;Fang Wu ,&nbsp;Yonghao Gui","doi":"10.1016/j.jnutbio.2025.110038","DOIUrl":"10.1016/j.jnutbio.2025.110038","url":null,"abstract":"<div><div>Background: Maternal obesity is a significant risk factor for liver dysfunction and metabolic dysfunction-associated steatotic liver disease (MASLD) in offspring, with oxidative stress playing a critical role in developmental programming. Understanding oxidative stress-mediated metabolic reprogramming during intrauterine overnutrition is crucial for developing MASLD preventive strategies. Methods: Female mice were fed a Western diet to induce obesity before mating. Biochemical detection and histopathological staining were employed to assess changes in lipid metabolism and liver fibrosis. Oxidative stress indices were measured using ELISA, while metabolic profiling was conducted through liquid chromatography-tandem mass spectrometry (LC-MS) analysis. Protein expression was evaluated by western blot. Results: Male offspring from obese dams (OffOb) exhibited increased activities of ALT, AST, GGT, and ALP, along with evident hepatic steatosis and fibrosis. These male offspring also showed impaired antioxidant defenses in liver. Administration of the antioxidant N-acetylcysteine during pregnancy (OffObnac) enhanced some antioxidant enzymes/substances and reversed these abnormal changes in the male offspring's liver. Notably, antioxidant treatment significantly mitigated the IL-6 increase induced by maternal obesity. According to KEGG analyses, the differential metabolites between OffOb and OffCon, as well as between OffObnac and OffOb, were primarily enriched in the forkhead box O (FoxO) signaling pathway. Protein expression results indicated that antioxidant treatment inhibited the phosphorylation activation of JAK2, STAT3, and FoxO6 in the liver of male offspring from obese mothers. Conclusions: Antioxidant management effectively alleviated oxidative stress conditions, blocked the IL-6-STAT3-FoxO6 axis, and had a robust impact on mitigating MASLD following intrauterine overnutrition-induced hepatic impairments in a mouse model.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"145 ","pages":"Article 110038"},"PeriodicalIF":4.9,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144682711","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":"Genistein maintains intestinal homeostasis in colitis mice via activating GPR30-Nrf2 signaling pathway","authors":"Ji Cao ,&nbsp;Donglin Shi ,&nbsp;Yong Cui ,&nbsp;Haiyan Zhu ,&nbsp;Haiping Liang ,&nbsp;Qing Wei ,&nbsp;Jianzhen Huang","doi":"10.1016/j.jnutbio.2025.110036","DOIUrl":"10.1016/j.jnutbio.2025.110036","url":null,"abstract":"<div><div>Genistein (GEN) is a natural polyphenolic compound widely present in leguminous plants, which has many biological functions such as anti-inflammatory and antioxidant activities, and has attracted attention in the treatment of inflammatory bowel disease (IBD). However, the molecular mechanism underlying the beneficial effects of GEN in IBD remains unclear. Here, we demonstrated that GEN enhanced the relative abundance of beneficial bacteria (e.g., <em>Akkermansia muciniphila</em>) and increased microbiota-derived short-chain fatty acids (SCFAs) levels in colitis mice. Further, the antibiotic cocktails (ABX) and fecal microbiota transplantation (FMT) experiments confirmed that gut microbiota at least partially mediated the anti-colitis effect of GEN. Interestingly, we found that GEN could also activate G protein-coupled receptor 30 (GPR30) and its downstream transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) in intestinal epithelial cells (IECs). The activation of the GPR30-Nrf2 signaling led to reduced reactive oxygen species (ROS) production, which consequently inhibited NLRP3 inflammasome activation and improved intestinal epithelial barrier dysfunction. In addition, studies using GPR30 knockout mice confirmed that GPR30 is crucial for inhibiting NLRP3 inflammasome activation and alleviating colitis. Collectively, our study unveils that GEN is an effective anti-inflammatory agent and suggests that both the gut microbiota and the GPR30-Nrf2 signaling pathway represent potential therapeutic targets for treating IBD.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"145 ","pages":"Article 110036"},"PeriodicalIF":4.9,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144675056","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":"Tetrahydrocurcumin ameliorates metabolic disorders associated with obesity by regulating gut microbiota homeostasis","authors":"Shuyang Zhang ,&nbsp;Liping Chen ,&nbsp;Yongzhong Wang","doi":"10.1016/j.jnutbio.2025.110034","DOIUrl":"10.1016/j.jnutbio.2025.110034","url":null,"abstract":"<div><div>Obesity, a global health crisis, demands novel therapeutic strategies. Tetrahydrocurcumin (THC), a natural compound, shows promise in mitigating obesity by regulating gut microbiota and lipid metabolism. Using in vitro (Hepa1-6 cells) and in vivo (<em>C. elegans</em> and HFD C57BL/6 J mice) models, we evaluated THC’s effects on lipid accumulation, oxidative stress, and key metabolic markers. In glucose-induced obese <em>C. elegans</em>, THC reduced lipid deposition and enhanced antioxidant capacity. In HFD mice, THC improved hepatic function (reduced AST/ALT), decreased liver fat content, and lowered oxidative stress. Mechanistically, THC downregulated Stearoyl-CoA desaturase-1 (SCD1) and Diacylglycerol O acyltransferase 1 (DGAT1) expression (Western blot/RT-qPCR), pivotal regulators of lipid metabolism. Fecal 16S rRNA sequencing revealed THC-modulated gut microbiota, including reduced <em>Firmicutes/Bacteroidetes</em> ratio and <em>Desulfobacterota</em> abundance, alongside elevated short-chain fatty acids (SCFAs). In vitro, THC suppressed lipid accumulation in Hepa1-6 cells. Collectively, THC alleviates obesity by targeting lipid metabolism, oxidative stress, and gut microbial homeostasis, highlighting its therapeutic potential.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"146 ","pages":"Article 110034"},"PeriodicalIF":4.9,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144667821","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":"Baicalein reduces cardiac inflammatory infiltration in EAM mice by blocking the CCL2-CCR2 signaling axis through its binding with TNF-α and CCR2","authors":"Huimin Tong ,&nbsp;Shuang Wang ,&nbsp;Meng Liu ,&nbsp;Tiantian Wang ,&nbsp;Xihui Jia ,&nbsp;Yuanyuan Li ,&nbsp;Dongyu Yu ,&nbsp;Ling Li","doi":"10.1016/j.jnutbio.2025.110029","DOIUrl":"10.1016/j.jnutbio.2025.110029","url":null,"abstract":"<div><div>Myocarditis refers to localized or diffuse inflammatory lesions of the myocardium. Experimental autoimmune myocarditis (EAM) in mice is commonly utilized as an animal model for studying the pathogenesis of myocarditis. Baicalein (BAI), the main active component extracted from <em>Scutellaria baicalensis</em> root, has been proven to possess diverse effects such as anti-inflammatory, anti-tumor, and antioxidant activities. However, further investigation is warranted to elucidate the mechanism of action underlying BAI's efficacy in EAM. The aim of this study is to the potential of BAI in combination with TNF-α to downregulate the TNF-α/TNFR1-AP-1 signaling pathway. Furthermore, we will explore whether BAI exhibits an inhibitory effect on the CCL2/CCR2-ROCK1 signaling pathway. In this study, we employed the EAM animal model to investigate the inhibitory effect of BAI on macrophage and Th1 cell chemotaxis towards cardiac tissue in EAM mice. Techniques such as HE staining, immunofluorescence, and other methods were utilized for assessment. Additionally, computer-simulated molecular docking, Streptavidin pull-down, and co-immunoprecipitation experiments were conducted to explore the potential binding of BAI with TNF-α and CCR2. Furthermore, real-time quantitative polymerase chain reaction (qPCR), western blotting, and flow cytometry were employed to elucidate the impact of BAI on the TNF-α/TNFR1-CCL2/CCR2 signaling pathway. BAI suppressed the expression of chemokine CCL2 in EAM mouse myocardial tissue and attenuated the infiltration of macrophages and Th1 cells. In vitro, BAI exhibited binding affinity to TNF-α, leading to downregulation of the TNF-α/TNFR1-AP-1 signaling pathway and subsequent inhibition of CCL2 secretion by macrophages and vascular endothelial cells. Additionally, BAI demonstrated binding capability to CCR2, resulting in downregulation of the CCL2/CCR2-ROCK1 pathway and consequent inhibition of chemotactic migration of macrophages and Th1 cells. This study demonstrates that BAI can downregulate the secretion of CCL2 and the CCL2/CCR2-ROCK1 signaling pathway by binding with TNF-α and CCR2, thereby inhibiting the migration of macrophages and Th1 cells to the lesion site, thus alleviating the inflammation severity in EAM.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"145 ","pages":"Article 110029"},"PeriodicalIF":4.9,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144626549","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}