Mehmet Başeğmez, Abdullah Eryavuz, Hasan Hüseyin Demirel
{"title":"Effects of Vitamin C Supplementation on Total Antioxidant Status, Inflammation, and Histopathological Changes in Aged Rats","authors":"Mehmet Başeğmez, Abdullah Eryavuz, Hasan Hüseyin Demirel","doi":"10.1002/jbt.70324","DOIUrl":"https://doi.org/10.1002/jbt.70324","url":null,"abstract":"<p>This study aims to determine the effect of orally administered vitamin C (Vit C) supplementation on physiological and histopathological changes in aged rats of different genders. A total of 28 Sprague-Dawley aged male and female rats were randomly divided into four groups of seven animals per group. The study groups included the aged male control (MC), aged male with Vit C (MVC) (500 mg/kg vitamin C, orally) supplementation, female aged control (FC), and female aged with vitamin C (FVC) (500 mg/kg vitamin C, orally) supplementation groups. At the end of the study, which lasted 31 days, blood, brain, heart, liver, and kidney tissues were collected from rats under ketamine (87 mg/kg) and xylazine (13 mg/kg) anesthesia. The results indicated that although Vit C supplementation had no effect on serum Vit C levels, gender had an effect on serum Vit C levels (<i>p</i> < 0.05). However, Vit C supplementation and gender did not affect serum IL-6, IL-1β, TOS, and OSI levels (<i>p</i> > 0.05). Vit C supplementation, without the effect of gender, significantly increased TNF-α levels in MVC groups compared to MC groups (<i>p</i> < 0.05), while it significantly decreased them in FVC groups compared to FC groups (<i>p</i> < 0.05). In addition, Vit C significantly reduced histopathological alterations in brain, heart, and liver tissues associated with aging, including oxidative stress and inflammation. In conclusion, it was observed that orally administered 500 mg/kg Vit C supplementation to old rats is not an effective way to increase the Vit C pool in the body, but gender has an impact on the blood Vit C concentrations.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 6","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbt.70324","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144171559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Furkan Yuksel, Asli Taslidere, Mete Ozcan, Cigdem Tekin, Suat Tekin
{"title":"The Effects of Meteorin-Like Protein on Diabetic Neuropathy: In Vivo and In Vitro Model Studies","authors":"Furkan Yuksel, Asli Taslidere, Mete Ozcan, Cigdem Tekin, Suat Tekin","doi":"10.1002/jbt.70323","DOIUrl":"https://doi.org/10.1002/jbt.70323","url":null,"abstract":"<div>\u0000 \u0000 <p>Diabetes is a disease characterized by insulin metabolism, and diabetic neuropathy (DN) develops as a result of prolonged hyperglycemia. Meteorin-like protein (Metrnl), which has been found to regulate insulin resistance in conducted studies, is thought to be therapeutic for type-2 diabetes. This study was conducted to investigate the efficacy of Metrnl on In Vivo and In Vitro diabetic neuropathy model. In study, 40 normoglycemic male <i>Balb-C</i> mice were divided into 4 groups (<i>n</i> = 10). Except for control, all groups received a single intraperitoneal (ip) injection of streptozotocin (STZ). After 72 h, blood glucose level was measured and animals above 250 mg/dL were considered diabetic. 14-day experiments were initiated 21 days after the onset of diabetes. Every day for 14 days, 0.9% isotonic sodium chloride was administered to DN group, and 2–4 µg/kg/day ip Metrnl was administered to treatment groups, and nociceptive behavior tests were performed simultaneously. End of experiment, animals were decapitated, and pancreatic tissues were collected. Dorsal root ganglion (DRG) isolated from <i>Wistar Albino</i> rats aged 1-2 days were exposed to high glucose for 24 , and the effect of Metrnl on cell viability and cellular pathway it utilizes were determined. It was observed that Metrnl injection increased the pain threshold (<i>p</i> < 0.05), improved oxidative stress parameters (<i>p</i> < 0.05), and restored histopathological damage of the pancreas (<i>p</i> < 0.05) compared to the DN group. Furthermore, Metrnl was detected to increase cell viability by utilizing mitogen-activated protein kinase pathway in DRG (<i>p</i> < 0.05). These findings suggest that Metrnl has neuroprotective and analgesic efficacy and ameliorates oxidative damage and histopathologic status of pancreas.</p>\u0000 </div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 6","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144171560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rehab E. Abdelrahman, Mohamed S. Hassan, Ashraf M. Morgan, Marwa A. Ibrahim, Eman I. Hassanen
{"title":"Resveratrol Mitigates Acetamiprid-Induced Cardiotoxicity in Rats via Modulation of Jak/Stat, p38 Mapk and mTOR Signaling Pathways","authors":"Rehab E. Abdelrahman, Mohamed S. Hassan, Ashraf M. Morgan, Marwa A. Ibrahim, Eman I. Hassanen","doi":"10.1002/jbt.70321","DOIUrl":"https://doi.org/10.1002/jbt.70321","url":null,"abstract":"<div>\u0000 \u0000 <p>Acetamiprid (ACP) is a novel neonicotinoid insecticide used frequently to eradicate insect pests. Resveratrol (RSV) is a polyphenol used as a potential antioxidant, anti-inflammatory and antiapoptotic compound. The current research aimed to investigate the modulation of Jak/Stat, p38 Mapk, and mTOR signaling pathways by RSV in ACP-induced cardiotoxicity. Four equal groups of male rats (10 rats each) were treated daily for 90 days via oral intubation. Group 1 was the control; Group 2 received ACP (25 mg/kg b. wt); Group 3 received RSV (20 mg/kg b. wt); and Group 4 received both ACP and RSV. Gene expression and tissue proteins were analyzed in the heart while biochemical changes were estimated in serum. Histopathological and histochemical alterations of the cardiac tissues were also investigated. ACP administration showed elevations of mRNA expression of the inflammation-related genes (Jak, Stat, NF-κB, p38 Mapk) and tissue proteins (mTOR and TNF-α) in the myocardium. Significant serum high sensitivity C-reactive protein (hs-CRP) level and lactate dehydrogenase (LDH) activity were also recorded. Histopathology and immunohistochemistry showed myocardial infarction and inflammatory cell infiltration besides increased IL-6 protein expression. On the other hand, RSV treatment alleviated ACP-induced cardiotoxic actions and modulated the expression levels of the inflammation-related genes signaling pathways.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 6","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144140800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sirui Hang, Liu Xu, Jin Wang, Caiqun Zhang, Chenxi Cao
{"title":"Toxicological Mechanism of Triptolide-Induced Liver Injury","authors":"Sirui Hang, Liu Xu, Jin Wang, Caiqun Zhang, Chenxi Cao","doi":"10.1002/jbt.70319","DOIUrl":"https://doi.org/10.1002/jbt.70319","url":null,"abstract":"<div>\u0000 \u0000 <p>This study aimed to investigate the hepatotoxicity of triptolide (TRI) and its mechanism of action. The TRI-liver injury-pyroptosis association and the possible action targets were analyzed through network pharmacology, the molecular-protein docking analysis was conducted by the molecular docking method, and the binding mode between TRI and candidate targets was analyzed with dynamics simulation. In addition, the mouse model of TRI-induced liver injury was constructed in vitro to examine the influence of TRI on liver function. The expression levels of inflammatory factors were detected by ELISA, while pathological analysis was conducted by H&E staining and histochemical staining. As figured out from the network pharmacology analysis results, Caspase-3 might be the major action target of TRI, which was verified by molecular docking and dynamics simulation. Besides, the in vitro experimental results demonstrated that TRI induced liver injury in mice, enhanced the tissue inflammatory response. Caspase-3 may be the major target of TRI in liver injury, and TRI can mediate pyroptosis and tissue inflammatory response through Caspase-3 to induce acute liver injury.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 6","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144140482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Expression of NUF2 and CD52 and Their Correlation With Chemotherapy Resistance and Prognosis in Patients With Non-Small Cell Lung Cancer","authors":"Jun Han, Rui Ding, Xue Xiong","doi":"10.1002/jbt.70308","DOIUrl":"https://doi.org/10.1002/jbt.70308","url":null,"abstract":"<div>\u0000 \u0000 <p>Lung cancer is one of the most common malignant tumors. This study aim to investigate the expression of cell division related gene cell division cycle related protein 2 (NUF2) and immune-related gene CD52 in patients with non-small cell lung cancer (NSCLC) and their correlation with chemotherapy resistance and clinical prognosis. The cancer tissues and adjacent tissues of 72 patients with NSCLC were collected. According to the staining results, the patients were divided into NUF2 positive and negative expression groups, and CD52 positive and negative expression groups. The relationship of NUF2 and CD52 with clinicopathological features and chemoresistance was analyzed. The patients were followed up for 5 years, and Kaplan-Meier survival curve was used to analyze the relationship. COX regression analysis was used to analyze the risk factors. The positive expression rate of NUF2 in NSCLC tissues was 66.67% (48/72), which was significantly higher than 38.89% (28/72) in adjacent tissues (<i>p</i> < 0.05). The positive expression rate of CD52 in NSCLC tissues was also higher than the adjacent tissues (<i>p</i> < 0.05). NUF2 expression was related to the degree of differentiation, TNM stage, lymph node metastasis and pleural invasion in NSCLC patients (<i>p</i> < 0.05). The expression of CD52 was related to TNM stage, lymph node metastasis, vascular tumor thrombus and pleural invasion (<i>p</i> < 0.05). The median survival time of patients with positive CD52 and NUF2 expression was lower than patients with negative expression (<i>p</i> < 0.05). Platinum-resistance, lymph node metastasis, pleural invasion, NUF2 and CD52 positive expression were independent risk factors for poor prognosis of NSCLC (<i>p</i> < 0.05). In conclusion, NUF2 and CD52 are independent risk factors for poor prognosis of patients with NSCLC. They may be used as one of the indicators to evaluate drug resistance and prognosis of patients.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 6","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144140794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Heba M. Hafez, Mohamed F. Abed El Baky, Sahar A. Mokhemer, Salma M. Hassan, Mervat Z. Mohamed
{"title":"Vinpocetine Alleviates Valproic Acid-Induced Hepatotoxicity and Neurotoxicity Through Activation of cAMP and PI3K/AKT/CREB Pathway in Rats","authors":"Heba M. Hafez, Mohamed F. Abed El Baky, Sahar A. Mokhemer, Salma M. Hassan, Mervat Z. Mohamed","doi":"10.1002/jbt.70316","DOIUrl":"https://doi.org/10.1002/jbt.70316","url":null,"abstract":"<div>\u0000 \u0000 <p>Valproic acid (VPA) is a frequently prescribed treatment for many psychiatric disorders, particularly for epilepsy. However, it has been associated with possible side effects including hepatotoxicity and neurotoxicity. The present study investigated the protective effect of vinpocetine (Vinpo) against VPA-induced hepatotoxicity and hippocampal neurotoxicity in rats. Vinpo (5 and 10 mg/kg/day; p.o) was given for 14 days, with/without VPA (500 mg/kg/day; p.o) in adult male Wistar rats. VPA showed marked increase in hepatic and hippocampal MDA levels with increased liver function enzymes as well as a marked decline in serum total antioxidant capacity (TAC). Simultaneously, VPA administration resulted in a significant reduction in cAMP, cAMP response element binding protein (CREB), and PI3K/AKT protein levels in liver tissue and hippocampus. These results were confirmed by histological degenerative changes in both tissues. VPA also associated with increased hepatic and dentate gyrus nuclear factor kappa (NF-κB) immunoexpression with increased Glial fibrillary acidic protein (GFAP) expression in the dentate gyrus. Administration of Vinpo markedly attenuated VPA-induced toxicity in rats by its anti-oxidant effect on MDA and TAC levels. Vinpo resulted in a significant increase in the levels of cAMP/CREB and PI3K/AKT in liver and hippocampus tissues, together with significant decrease in NF-κB nuclear expression. Vinpo ameliorated astrogliosis as indicated by reduction in the expression of GFAP. Vinpo exerted a hepatoprotective and neuroprotective role against VPA-induced toxicity by cAMP and PI3K/AKT dependent activation of CREB and this hold a promise as a safe and effective adjuvant while treating psychiatric patients with VPA.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 6","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144140484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Basak Gulakar, Saime Ozbek Sebin, Esra Laloglu, Ayhan Tanyeli, Mustafa Can Güler, Elif Erbas, Serpil Can
{"title":"New Potential Agent in Ovarian Ischemia Reperfusion Injury: Alpha Pinene","authors":"Basak Gulakar, Saime Ozbek Sebin, Esra Laloglu, Ayhan Tanyeli, Mustafa Can Güler, Elif Erbas, Serpil Can","doi":"10.1002/jbt.70318","DOIUrl":"https://doi.org/10.1002/jbt.70318","url":null,"abstract":"<p>Ovarian torsion causes problems such as infertility in women due to ischemia-reperfusion (I/R) injury. α-Pinene (AP) is a monoterpene with known anti-inflammatory, antioxidant, and antiapoptotic impacts. In the present investigation, the protective impact of AP was examined in the ovarian I/R model. 28 Wistar-Albino female rats were used in the study. TNF-α, IL-1β, IL-10, MDA, IMA, SOD, and SIRT-1 levels were determined in ovarian tissue by ELISA method. Histopathological and immunohistochemical analyses were conducted to determine Bcl-2, Caspase-3, LC3B, and NFκB levels in ovarian tissues. TNF-α, IL-1β, IMA, and MDA levels were reduced in the treatment groups than the I/R group dose-dependent, while IL-10, SOD, and SIRT-1 levels increased substantially. Caspase-3 immunoreactivity declined in the treatment groups while Bcl-2 levels increased. LC3B and NFκB levels, which rise with I/R injury, were reduced considerably in the treatment groups. In addition, hemorrhage, edema, vascular congestion, and follicular degeneration due to I/R injury decreased in the treatment groups. The present investigation shows that AP has anti-inflammatory, antiapoptotic, and autophagy inhibitory effects against I/R damage in ovarian tissues and reduces oxidative stress. The results indicate that AP may be a potential protective agent in clinical use. Further research is needed before AP can be used in the clinic.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 6","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbt.70318","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144140793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jinchao Qiu, Guosheng Chen, Guoxuan Peng, Guoxin Qu, Tingguo Ren, Jin Deng
{"title":"Kisspeptin-10 Protects Against TNF-α-Induced Chondrocyte Senescence via the SIRT1/p53/p21 Signaling","authors":"Jinchao Qiu, Guosheng Chen, Guoxuan Peng, Guoxin Qu, Tingguo Ren, Jin Deng","doi":"10.1002/jbt.70298","DOIUrl":"https://doi.org/10.1002/jbt.70298","url":null,"abstract":"<div>\u0000 \u0000 <p>In Osteoarthritis (OA), the senescence of chondrocytes plays a pivotal role, contributing to cartilage degradation and impairing tissue repair mechanisms. (Kp-10), a peptide hormone, exerts diverse biological functions across multiple cell types and tissues via its receptor Gpr54. However, its role in chondrocytes and OA has been understudied. This study investigates the role of Kp-10 in mitigating TNF-α- induced senescence in primary chondrocytes, a hallmark of OA pathogenesis. Gpr54 expression was confirmed in both primary chondrocytes and the ATDC5 chondrogenic cell line, with TNF-α treatment leading to a dose-dependent decrease in Gpr54 expression. Kp-10 treatment at concentrations of 50 and 100 nM effectively ameliorated TNF-α-induced senescence, as evidenced by diminished senescence-associated β-galactosidase staining and enhanced telomerase activity. Moreover, Kisspeptin-10 modulated the expression of key regulators involved in cellular aging, including hTERT and TERF2, and suppressed the activation of the p53/p21 pathway. Notably, Kp-10 restored SIRT1 expression, which was downregulated by TNF-α. Silencing SIRT1 abolished the protective effects of Kp-10, highlighting the essential role of SIRT1 in its anti-senescence action. These findings suggest that Kp-10 may be a promising therapeutic strategy for OA by mitigating chondrocyte senescence and improving cellular function by modulating the SIRT1 and p53/p21 pathways.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 6","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144108817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Advances in Exosome Research: Multifaceted Roles in Myeloid Leukemia Progression and Therapy","authors":"Jianlan Zheng, Huafang Wang, Lili Ge","doi":"10.1002/jbt.70315","DOIUrl":"https://doi.org/10.1002/jbt.70315","url":null,"abstract":"<div>\u0000 \u0000 <p>Recent advancements in exosome research have revealed their crucial role in myeloid leukemia, encompassing chronic myeloid leukemia (CML) and acute myeloid leukemia (AML). Exosomes, small extracellular vesicles released by various cells, play a significant role in intercellular communication and impact key cellular processes such as growth, proliferation, angiogenesis, survival, and apoptosis. In leukemia, exosomes contribute to disease progression and therapeutic resistance by facilitating immune evasion, enhancing tumor cell proliferation, and promoting angiogenesis. For instance, exosomes derived from CML cells can transfer drug resistance to sensitive cells, and some exosomes derived from AML patients contain cytokines like TGF-β1 that inhibit immune cell activity. Exosomes also influence tumor organotropism by interacting with extracellular matrix molecules and modifying the tumor microenvironment. Despite their high potential, clinical applications of exosomes are limited. Their natural nanoparticle properties—such as adaptability, biodegradability, low toxicity, and the ability to cross biological barriers—make them promising candidates for targeted drug delivery and personalized medicine. Further research is necessary to scale up exosome production and harness their full therapeutic potential. By integrating advancements in exosome biology with innovative therapeutic strategies, there is significant potential for improved management and treatment of leukemia.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 6","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144108818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"β-Sitosterol Ameliorates Ulcerative Colitis Through Modulation of the AMPK/MLCK Anti-Inflammatory Pathway","authors":"Yuansen Zhang, Xiaosheng Jin, Huanhuan Xia, Xiaoqiu Wu, Wenjun Chen, Mengxiao Zhuang, Sensen Tang","doi":"10.1002/jbt.70287","DOIUrl":"https://doi.org/10.1002/jbt.70287","url":null,"abstract":"<div>\u0000 \u0000 <p>Ulcerative colitis (UC), a common inflammatory bowel disease, has become increasingly prevalent worldwide, posing significant health challenges. This study explored the anti-inflammatory effects of β-sitosterol on UC and its underlying molecular mechanisms. Using a dextran sulfate sodium (DSS)-induced colitis model in male C57BL/6 mice, the therapeutic potential of β-sitosterol at low (2 mg/kg) and high (6 mg/kg) doses was compared with sulfasalazine (300 mg/kg) as a positive control. Disease progression was assessed through Disease Activity Index (DAI) scores, histological analysis, and inflammatory marker expression. β-sitosterol significantly ameliorated colonic inflammation, demonstrated by lower DAI scores, improved histological architecture, and reduced levels of inflammatory mediators, including NO, MPO, IL-6, and iNOS, while upregulating the anti-inflammatory cytokine IL-10. Mechanistically, β-sitosterol promoted AMP-activated protein kinase (AMPK) expression and suppressed myosin light chain kinase (MLCK) expression. These findings were validated in vitro using LPS-stimulated Caco-2 cells, where β-sitosterol decreased inflammatory marker levels and modulated AMPK/MLCK signaling. Notably, the use of Compound C, an AMPK inhibitor, reversed these effects by suppressing AMPK activity and restoring MLCK expression, confirming that the anti-inflammatory actions of β-sitosterol are AMPK-dependent. In conclusion, this study highlights the therapeutic potential of β-sitosterol in UC through modulation of the AMPK/MLCK signaling pathway. These findings not only deepen our understanding of β-sitosterol's anti-inflammatory properties but also suggest its potential in developing novel AMPK-targeted therapies for inflammatory bowel disease management.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 6","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144108816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}