INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2026
·
IF 8.5
Yu Cheng,Yao Wen,Zhaohan Wang,Lizhen Yang,Junming Liao,Jieyu Xing,Zheng Liu,Xiaoyan Sheng,Lingli Zhou,Sigui Zhou,Jian Zou,Haiyun Chen
Our previous investigations have revealed that Perilla frutescens -derived polysaccharide PFP50-1 exhibited significant neuroprotective activity by attenuating lipopolysaccharide (LPS)-induced neuroinflammatory responses in microglia. Nonetheless, the protection and mechanisms of its anti-neuroinflammatory activities are still poorly understood. The neuroprotection effects of PFP50-1's underlying mechanisms were evaluated in MPTP-stimulated Parkinson's disease (PD) mice and LPS-induced microglia, respectively. In vitro , PFP50-1 effectively suppressed the excessive release of pro-inflammatory cytokines. Meanwhile, PFP50-1 significantly downregulated the levels of Toll-like receptor 4 (TLR4), myeloid differentiation primary response protein gene 88 (MyD88), nuclear factor kappa-B (NF-κB), p-PI3K (phosphorylated phosphatidylinositol 3-Kinase), and p-Akt (phosphorylated Protein Kinase B). Subsequently, investigations revealed that TLR4 inhibitor (TAK242) and PI3K inhibitor (LY294002) significantly potentiated PFP50-1's inhibitory effects on LPS-induced pro-inflammatory mediators. Moreover, the excessive releases of Caspase-1, IL-18, and IL-1β were reversed by suppressing NLRP3 inflammasome activation. In conditioned medium-stimulated N2a cells, PFP50-1 exhibited a strong neuroprotective effect against neuroinflammation-mediated neurotoxicity by preventing MMP depolarization and ROS production. Notably, PFP50-1 effectively ameliorated MPTP-induced dopaminergic (DA) neuronal degeneration in vivo , which was associated with the downregulation of the TLR4-mediated and PI3K-mediated signaling pathways, as well as the NLRP3 inflammasome. Collectively, our data indicated that PFP50-1's anti-neuroinflammation effect is related to downregulating the TLR4/NF-κB and PI3K/Akt signaling pathways and suppressing NLRP3 inflammasome activation, making it a promising candidate for PD.
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高影响因子
RARE METALS
·
2026
·Vol. 45
·期 9
·e70620
·
IF 12.1
Minghe Jiang,Ruikai Zhu,Shurong Chen,Xuwen Pan,Leiyuan Peng,Yaohui Huang,Wenquan Lv,Mingjing Yin,Xiaoxuan Guan,Mingyang Jiang,Ming Gao,Wei Wang,Yan Liu
en This link goes to a English section zh This link goes to a Chinese section Cisplatin-related acute kidney injury (CP-AKI) is a serious complication of cisplatin (CP) treated patients with cancer with high morbidity and mortality rates. It is directly related to the abnormal accumulation of CP in renal tubular epithelial cells, causing metabolic toxicity, DNA damage, and oxidative stress. Herein, we developed a polyphenol nanozyme (SrEG) by the coordination of strontium ions (Sr 2+ ) and epigallocatechin gallate. It was demonstrated that SrEG, combined with NIR irradiation, exhibited excellent capabilities of scavenging various types of reactive oxygen species (ROS). It was also determined that SrEG + NIR efficiently eliminated intracellular ROS levels, inhibited inflammation related cytokines expression, and induced macrophage M2 directional polarization, thus preventing cellular damage. By intravenous (IV) administration, SrEG was efficiently accumulated in the kidney and gradually degraded. Accordingly, the administration of SrEG + NIR offered the perfect therapeutic effects in CP-AKI rats by inhibiting the PI3K/AKT pathway, thus accelerating kidney function repair. Overall, the strategy of SrEG + NIR showed substantial clinical promise as a potential therapeutic strategy in ROS-related diseases. 摘要 en This link goes to a English section zh This link goes to a Chinese section 顺铂相关的急性肾损伤(CP-AKI)是癌症患者进行顺铂(CP)治疗时的严重并发症,具有较高的致病率和死亡率。CP-AKI与CP在肾小管上皮细胞中的异常积聚直接相关,从而导致代谢毒性、DNA损伤和氧化应激。在此,我们通过锶离子(Sr 2+ )和表没食子儿茶素没食子酸酯的配位开发了一种多酚纳米酶(SrEG)。结果表明,SrEG结合近红外光照展现出优异的清除各种类型活性氧(ROS)的能力。而且SrEG + NIR有效地降低细胞内ROS水平,抑制炎症相关因子的表达,并诱导巨噬细胞M2定向极化,从而防止细胞损伤。通过静脉注射(IV)给药,SrEG在肾脏中有效积聚并逐渐降解。因此,SrEG + NIR的治疗策略通过抑制PI3K/AKT通路,从而加速肾功能修复,为CP-AKI大鼠提供了完美的治疗效果。总体而言,SrEG + NIR作为ROS相关疾病的潜在治疗策略显示出巨大的临床前景。
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高影响因子
INTERNATIONAL UROLOGY AND NEPHROLOGY
·
2023
·
IF 2
Wang Hongjie,Zhang Yunxia,Liu Huan,Li Shuang
Purpose To investigate the role and underlying mechanism of GDF11 on diabetic nephropathy (DN)-related mitochondrial dysfunction and apoptosis. Methods A DN model of rats was established in this study. Human Kidney-2 (HK-2) cells were cultured under high-glucose (HG) condition with or without recombinant GDF11 (rGDF11). Mitochondrial morphology of HK-2 cells was analyzed by transmission electron microscope and MitoTracker Red CMXRos staining. Mitochondrial membrane potential (MMP) and ROS production were monitored using JC-1 assay kit and MitoSOX staining, respectively. Cell apoptosis was detected by TUNEL or flow cytometry assays. Results Herein, we observed that GDF11 was down-regulated in renal cortex and serum of DN rats, which was accompanied by renal mitochondrial morphological abnormalities. In line with the findings in vivo, HK-2 cells exposed to HG presented with mitochondrial morphological alterations and further apoptosis accompanied by GDF11 reduction. In addition, HG promoted a decrease in MMP while an increase in mitochondrial ROS production. Conversely, rGDF11 treatment significantly alleviated these HG-induced mitochondrial defects in HK-2 cells. Meanwhile, HK-2 cell apoptosis induced by HG was simultaneously suppressed by rGDF11. Mechanistically, the decreased levels of p-AKT induced by HG were attenuated after rGDF11 administration. Inhibition of the PI3K/AKT pathway resisted the effects of rGDF11 on the MMP and apoptosis of HK-2 cells. In addition, we identified that GDF11 is a target of miR-32-5p. Up-regulation of miR-32-5p could inhibit the expression of GDF11. Conclusion rGDF11 treatment rescued HG-induced HK-2 cell mitochondrial dysfunction and apoptosis, which may be dependent on the activation of the PI3K/AKT pathway.
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JOURNAL OF ETHNOPHARMACOLOGY
·
2022
·
IF 5.195
Xu-guang Zhang,Ai-xia Liu,Yu-xin Zhang,Ming-yan Zhou,Xiang-yi Li,Ming-hai Fu,Yi-peng Pan,Jian Xu,Jun-qing Zhang
Ethnopharmacological relevance Alpinia officinarum Hance, a perennial natural medicine-food herb, has been traditionally used to treat colds, stomachache, and diabetes for thousands of years. 1,7-Diphenyl-4E-en-3-heptanone (DPH5), a diarylheptanoid isolated from the rhizome of A. officinarum has been reported to be safe and to have antioxidant and hypoglycemic effects, suggesting its potential in the treatment of insulin resistance (IR). Aim of the study : Aim of to investigate the protective effect of DPH5 on IR and elucidate its underlying mechanism of action. Materials and methods HepG2 cells were used as the research objects. Glucose uptake and reactive oxygen species (ROS) levels in high glucose–induced insulin-resistant HepG2 cells were assessed using flow cytometry. Glucose consumption and the levels of malondialdehyde (MDA) and superoxide dismutase (SOD) were analyzed using the corresponding assay kits. The expression of mRNA and proteins related to insulin signaling, glucose metabolism, and antioxidant factor, including insulin receptor substrate-1 (IRS1), phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), translocation of glucose transporter-4, glycogen synthase kinase-3β (GSK3β), glucokinase (GCK), pyruvate kinase (PK), phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase (G6Pase), nuclear factor-erythroid 2 related factor 2 (Nrf2), heme oxygenase-1 (HO-1), NADPH quinoneoxidoreductase (NQO1), and glutathione peroxidase (GSH-Px) was determined using real-time quantitative polymerase chain reaction and western blotting . Furthermore, molecular docking was performed to determine the spatial mechanism of DPH5 on the key targets PI3K, AKT, Nrf2 , and GSK3β. Results DPH5 could improve IR that manifested as increased glucose uptake and glucose consumption in insulin-resistant HepG2 cells. Moreover, DPH5 could enhance antioxidant capacity by activating Nrf2/HO-1 elements, including increasing Nrf2, HO-1, SOD, NQO1, and GSH-Px expression and reducing MDA, ROS, and JNK levels, thereby improving oxidative stress and ultimately alleviating IR. Additionally, DPH5 could promote the expression of IRS1, PI3K, AKT, GSK3β, GCK, and PK, and downregulate the expression of PEPCK and G6pase, thereby accelerating glucose utilization and enhancing insulin sensitivity. The mechanism underlying the effect of DPH5 in alleviating IR was related to the PI3K/AKT- and Nrf2/HO-1-mediated regulation of the GSK3β signaling pathway, and the results were further confirmed using the specific inhibitors LY294002 and ML385. Results from molecular docking indicated that there were different regulatory sites and interacting forces between DPH5 and PI3K, AKT, Nrf2, and GSK3β; however, the binding force was relatively strong. Conclusions DPH5 improved oxidative stress and glucose metabolism via modulating the PI3K/AKT-Nrf2-GSK3β pathway, thereby ameliorating IR. Overall, our findings suggest the potential of DPH5 as a natural medicine to treat type-2 diabetes mellitus.
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高影响因子
ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH
·
2023
·Vol. 30
·期 32
·79423-79436
·
IF 5.8
Zhang Jingni,Wang Hongjuan,Chen Huan,Liu Yong,Wang An,Hou Hongwei,Hu Qingyuan
Long-term use of alcohol and cigarettes is associated with millions of deaths each year, directly or indirectly. The carcinogen acetaldehyde is both a metabolite of alcohol and the most abundant carbonyl compound in cigarette smoke, and co-exposure of them is usual and primarily leads to liver and lung injury, respectively. However, few studies have explored the synchronic risk of acetaldehyde on the liver and lung. Here, we investigated the toxic effects and related mechanisms of acetaldehyde based on normal hepatocytes and lung cells. The results showed that acetaldehyde caused significant dose-dependent increases of cytotoxicity, ROS level, DNA adduct level, DNA single/double-strand breakage, and chromosomal damage in BEAS-2B cells and HHSteCs, with similar effects at the same doses. The gene and protein expression and phosphorylation of p38MAPK, ERK, PI3K, and AKT, key proteins of MAPK/ERK and PI3K/AKT pathways regulating cell survival and tumorigenesis, were significantly upregulated on BEAS-2B cells, while only protein expression and phosphorylation of ERK were upregulated significantly, the other three decreased in HHSteCs. When either the inhibitor of the four key proteins was co-treated with acetaldehyde, cell viabilities were almost unchanged in BEAS-2B cells and HHSteCs. Thus, acetaldehyde could synchronically induce similar toxic effects in BEAS-2B cells and HHSteCs, and MAPK/ERK and PI3K/AKT pathways seem to be involved in different regulatory mechanisms.
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Frontiers in Pharmacology
·
2020
·
IF 4.225
Li Shaoguang,Wang Xuewen,Wang Gang,Shi Peiying,Lin Shilan,Xu Dafen,Chen Bing,Liu Ailin,Huang Liying,Lin Xinhua,Yao Hong
Colorectal cancer is one type of cancer with high incidence rate and high mortality worldwide. Thus, developing new chemotherapeutic drugs is important. The Selaginella doederleinii Hieron ethyl acetate (SDEA) extract showed good anti-colon cancer effect in vitro and in vivo, but its mechanism is unclear. This study aimed to further reveal the anti-colon cancer effect of SDEA and its possible mechanism. The effects on cell viability, apoptosis, autophagy, and cell cycle in colorectal cells (HT29 and HCT116) were studied using MTT assay, fluorescence microscopy, transmission electron microscopy, and flow cytometry. The mechanisms were further studied using cell transfection, Western blot, and real-time quantitative polymerase chain reaction assay. The effect of xenotransplantation in vivo was observed using immunohistochemistry. Results showed that SDEA inhibited cell proliferation and induced cell morphological changes, cell cycle arrest, autophagy, and apoptosis. It also induced loss of mitochondrial membrane potential, increased the autophagic flux, raised the ratio of Bax/Bcl-2, activated caspases, and inhibited PI3K-Akt-mTOR signaling pathways. Furthermore, SDEA inhibited the growth of xenograft tumors in a dose-dependent manner. Immunohistochemistry analysis confirmed the alteration of autophagy- and apoptosis-related proteins and immunohistochemical microvascular density in xenografts, which were consistent with the results in vitro. Therefore, SDEA is important for developing candidate drugs against colorectal cancers.
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高影响因子
BIOLOGICAL & PHARMACEUTICAL BULLETIN
·
2020
·
IF 1.863
Yuanguo Xiong,Hao Lu,Hanlin Xu
Hepatic fibrosis (HF) is a common disease, with currently no available treatment. Galangin, a natural flavonoid extracted from Alpinia officinaruim Hance, has multiple effects demonstrated in previous studies. The aim of the present study was to explore the anti-fibrogenic effect of galangin in vitro, and research its potential molecular mechanisms. LX-2 cells were chosen as an in vitro HF model, and were treated with galangin in different concentrations. Cell viability was analyzed using Cell Counting Kit-8 (CCK-8) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, cell apoptosis was measured using flow cytometry, and the anti-fibrogenic effect of galangin was determined using quantitative reverse transcription polymerase chain reaction (RT-qPCR), immunofluorescence, and western blotting. The results show that the proliferation of LX-2 cells was efficiently inhibited by galangin, and apoptosis was induced in a dose-dependent manner. Both the mRNA and protein expression of α-SMA and collagen I were markedly downregulated. Galangin also inhibited the PI3K/Akt and Wnt/β-catenin signaling pathways and increased the Bax/Bcl-2 ratio. The results of this study suggest that galangin has an anti-fibrogenic effect and may represent a promising agent in the treatment of hepatic fibrosis.
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JOURNAL OF ETHNOPHARMACOLOGY
·
2021
·
IF 4.36
Yang Wang,Shi-Yang Shen,Lei Liu,Xiao-Dong Zhang,Dan-Yang Liu,Na Liu,Bing-Hua Liu,Lei Shen
Ethnopharmacological relevance The diterpenoids extracted from Euphorbia kansui S.L. Liou ex S.B.Ho, Euphorbia fischeriana Steud. have good antitumor effects. Jolkinolide B has anti-breast cancer effect, but it is unclear whether it has different therapeutic effects between luminal A subtype and luminal B subtype breast cancer. Aim of the study This study investigated the Jolkinolide B has different therapeutic, important targets and pathways effects between luminal A subtype and luminal B subtype breast cancer. Materials and methods We used bioinformatics to predict the biological process and molecular mechanism of Jolkinolide B in treating two types of breast cancer. Then, in vitro, cultured MCF-7 cells and BT-474 cells were divided into control group, PI3K inhibitor + control group, Jolkinolide B group and PI3K inhibitor + Jolkinolide B group. The CCK-8 assay, Flow cytometric analysis and Transwell cell migration assay was used to detect the cell proliferation, apoptosis, and migration in each group, respectively. ELISA was used to measure the content of Akt and phosphorylated Akt (p-Akt) in cell lysis buffer. Results Compared to luminal A breast cancer, Jolkinolide B had more targets, proliferation, migration processes and KEGG pathways when treating luminal B subtype breast cancer. Jolkinolide B significantly prolonged the survival time of luminal B subtype breast cancer patients. Compared to the control group, the cell proliferation absorbance value (A value) and migration number of the two kinds of breast cancer cells in the Jolkinolide B group were decreased ( P < 0.01, n = 6), and the number of apoptotic cells was increased ( P < 0.01, n = 6). Compared to the Jolkinolide B group, the A value and migration number of the two types of breast cancer cells were significantly decreased in the PI3K inhibitor + Jolkinolide B group ( P < 0.01, n = 6), and the number of apoptotic cells was significantly increased ( P < 0.01, n = 6). In addition, compared to MCF-7 cells, the A value and migration number of BT-474 cells stimulated with Jolkinolide B were significantly decreased ( P < 0.01, n = 6), and the number of apoptotic cells was significantly increased ( P < 0.01, n = 6). Akt and p-Akt protein levels in the two breast cancer cell lines in the Jolkinolide B group were all decreased ( P < 0.01, n = 6), especially in BT-474 cells stimulated by Jolkinolide B. Conclusion Jolkinolide B regulates the luminal A and luminal B subtypes of breast cancer through PI3K-Akt, EGFR and other pathways. Jolkinolide B has more significant therapeutic effect on luminal B subtype breast cancer. In vitro, experiments verified that Jolkinolide B significantly inhibited the proliferation and migration activity of BT-474 breast cancer cells by downregulating the PI3K-Akt pathway.
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JOURNAL OF ETHNOPHARMACOLOGY
·
2017
·
IF 2.981
Zhongcheng Ke,Gang Wang,Lei Yang,Huihui Qiu,Hao Wu,Mei Du,Juan Chen,Jie Song,Xiaobin Jia,Liang Feng
Ethnopharmacological relevance Radix paeoniae rubra , also known as chishao (CS), is a frequently used traditional Chinese medicine that can promote blood circulation to remove blood stasis . It has been widely used for the prevention and treatment of cardiovascular diseases in China. Although terpene glycoside (TG), the major component in CS, has been shown to possess cardioprotective properties, the mechanism underlying CS-TG's preventive effect against myocardial ischemia injury is unknown. This study was conducted to explore the protective and curative effects of CS-TG against isoproterenol (ISO)-induced myocardial ischemic injury in rats and investigate the underlying myocardial protective mechanisms. Materials and methods A rat model of ISO-induced myocardial ischemia was established to evaluate the protective effect of CS-TG in ameliorating heart injury. Myocardial ischemia was induced by administering ISO (40 mg/kg/d) subcutaneously for 2 days. Serum was collected and analyzed for the levels of different cardiac biomarkers, and heart tissues were isolated and prepared for ATP analysis, glycogen content determination, histopathology assay, and ultrastructure observation. The regulatory effects of CS-TG on myocardial apoptosis in rats were studied by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, and the levels of cleaved caspase-3, Bax, and Bcl-2 were detected by western blotting . Furthermore, in vitro experiments were conducted to examine whether the CS-TG's cardioprotective effects were linked to the inhibition of apoptosis via activation of the phosphoinositide-3-kinase/serine-threonine kinase AKT/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway. Results CS-TG (300 mg/kg/d) significantly decreased serum levels of creatine kinase and lactate dehydrogenase in ISO-induced myocardial ischemic rats. Analysis of ATP and glycogen contents, myocardial ultrastructure, and pathological examination showed that CS-TG (300 mg/kg/d) significantly improved energy metabolism and alleviated myocardial injury in vivo. In addition, the expression of p-AKT and p-mTOR in rats subjected to CS-TG significantly elevated, while the levels of caspase-3 and Bax/Bcl-2 dramatically reduced. Moreover, treatment with LY294002 , a PI3K inhibitor, abrogated CS-TG (200 μg/mL) induced down-regulation of cleaved caspase-3, Bax/Bcl-2 in the serum. Conclusions CS-TG protects the heart from ISO-induced myocardial ischemia, potentially by improving cardiac energy metabolism and inhibiting cardiomyocyte apoptosis via activation of the PI3K/AKT/mTOR signaling pathway. Thus, CS -TG might be a potential therapeutic candidate for the prevention and treatment of myocardial ischemia.
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Heliyon
·
2024
·
IF 3.4
Chunhua Liu,Yu He,Kun Zhou,Hong Wang,Meng Zhou,Jia Sun,Yuan Lu,Yong Huang,Yonglin Wang,Ting Liu,Yongjun Li
Background Gerberae Piloselloidis Herba (GPH) exhibits notable efficacy in alleviating allergic asthma. Previous studies in our research have identified a mixture of luteolin, arbutin, and marmesin as effective components of GPH in treating allergic asthma. However, the underlying mechanism remains unclear. This study aims to elucidate the molecular mechanism of these active components. Method Using an ovalbumin (OVA)-induced allergic asthma mouse model, various treatment groups were administered, including GPH, the active component mixture (termed "Mixture") containing luteolin, arbutin, and marmesin, and a positive drug (dexamethasone, DEX). Relevant indices were assessed, including behavioral characteristics, inflammatory cell counts, cytokine levels, histopathological examination of lung tissue, apoptosis, and expression of key proteins such as Caspase-3, Bax, Bcl-2, PI3K, p-PI3K, Akt, and p-Akt. The effect of the Mixture on the PI3K/Akt signaling pathway was further verified using the PI3K inhibitor LY294002. Results The Mixture significantly alleviated asthma symptoms, decreased IgE levels, cytokine levels (IL-4, IL-5, IL-13 and TNF-α), and the number of inflammatory cells in serum or bronchoalveolar lavage fluid (BALF), leading to the alleviation of lung pathological lesions. Additionally, the Mixture reduced the expression of Bax and Caspase-3 while increasing Bcl-2 expression, resulting in mitigated apoptosis in lung tissue. Furthermore, there appeared a decrease in the levels of PI3K and p-PI3K, as well as the ratio of p-Akt to Akt in the Mixture group, indicating the suppression of PI3K and Akt phosphorylation. Interestingly, the effects of the Mixture were comparable to those of GPH, LY294002, or the combination of LY294002 with the Mixture. Conclusion The study confirms that the Mixture containing luteolin, arbutin, and marmesin indeed alleviates allergic asthma induced by OVA in mice by suppressing the PI3K/Akt signaling pathway. These findings highlight the potential of the GPH-derived Mixture as a novel therapeutic for the treatment of allergic asthma.
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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2025
·Vol. 26
·期 5
·2118
·
IF 4.9
Xiyue Wang,Miaoyunhuan Wang,Yuqing Dong,Shuqing Yu,Shanshan Zhang,Pinghua Sun,Lu Wang,Jibin Liu,Houwen Lin,Xinhui Pan,Xiaobin Li
Chenopodium albumL., as a folkloric herb, is traditionally used to treat poisonous insect bites, vitiligo, and other ailments. However, its impact on thrombosis remains unknown. In this study, we discovered that the ethanol extract ofC. albumexhibited a remarkable antithrombotic effect using a zebrafish thrombosis model for the first time. Activity evaluation showed that fraction CA-C could improve thrombus aggregation in the caudal vein, increase blood return in the heart, and alleviate the slowing of blood flow compared with those in the model group. Then, analysis by ultra-high performance liquid chromatography-quadrupole time-of-flight tandem mass (UPLC-Q-TOF-MS) identified 58 constituents of CA-C, with most of them belonging to flavonoids, alkaloids, and steroidal saponin components. Moreover, using a comprehensive strategy of network pharmacological analysis, transcriptomic assay, and RT-qPCR validation, we found that CA-C could mediate the TLR’s signaling pathway and its downstream MAPKs and PI3K/AKT signaling pathways to exert an antithrombotic effect. This study broadens the clinical application of plantC. albumand provides new insight into the chemical profile, pharmacodynamics, and potential mechanisms of CA-C as candidate agents for treating thrombosis.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Donglei Zheng,Lulu Ma,Xiaojuan Xin,Ying Gao,Shijian Dong,Ying Huang,Jijun Wu,Jiaying Huo,Shugang Li
Ovotransferrin (OVT), a bioactive protein from egg white, has been demonstrated to exhibit anti-inflammatory efficacy and suppress the progression of ulcerative colitis. Nevertheless, its role in preserving intestinal barrier integrity has not been reported. This study investigated the role of OVT on intestinal barrier dysfunction in DSS-induced ulcerative colitis mice and its underlying mechanisms. OVT significantly attenuated the severity of intestinal barrier injury, reduced inflammatory infiltration, and restored goblet cell density (Model: 5.00 goblet cells/crypt, High: 12.75 goblet cells/crypt) alongside the expression of MUC2 (87.64 %), ZO-1 (83.98 %), and Occludin (74.93 %). Concurrently, OVT decreased intestinal permeability by 84.42 %. Furthermore, OVT downregulated pro-inflammatory cytokines (TNF-α, IL-1β, IL-6), while elevating anti-inflammatory IL-10 levels and restoring redox homeostasis. RNA-seq and Western blot analysis revealed that OVT inhibited the PI3K-Akt/MAPK pathway by decreasing the phosphorylation of p85α (31.73 %), Akt (69.59 %), p38 (25.00 %), and ERK (41.18 %). Metabolomics showed that OVT modulated key metabolites, including L-glutamate, serotonin, and d -fructose-6-phosphate, while decreasing glucose and L-asparagine. These results suggested that OVT regulated immune responses and metabolic pathways, highlighting its therapeutic potential in preserving intestinal barrier integrity.
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