Current Issues in Molecular Biology最新文献

{"title":"Geniposide Inhibits Oral Squamous Cell Carcinoma by Regulating PI3K-Akt Signaling-Mediated Apoptosis: A Multi-Method Validation Study.","authors":"Xue Wang, Jianbo Wang, Hua Hua, Ping Wei, Xue Chen, Yusheng Peng, Li Liu, Dongmei Yu, Xiaozhou You, Siye Yang","doi":"10.3390/cimb47090786","DOIUrl":"10.3390/cimb47090786","url":null,"abstract":"<p><p><i>Gardenia jasminoides</i> J.Ellis is an important medicinal and edible resource. The fruit of <i>Gardenia jasminoides</i> J.Ellis contains a natural iridoid called geniposide, which has the ability to dramatically suppress the growth of a number of cancer cell lines. This work examined the impact and potential mechanism of action of geniposide on oral squamous cell carcinoma using network pharmacology, molecular docking, molecular dynamics simulation, and cellular experiments. Based on network pharmacology, 145 potential targets of geniposide in the treatment of OSCC were found. The top five core targets were selected according to the degree values of the nodes, AKT1, EGFR, SRC, HSP90AA1, and PIK3R1, which involved signaling pathways and biological processes, such as the PI3K-Akt signaling pathway, pathways in cancer, phosphorylation, and the regulation of the apoptotic process. Molecular docking showed that geniposide exhibited good binding ability with the core targets AKT1 and EGFR. Molecular dynamics simulations further confirmed the stability of the binding between geniposide and the targets. The results of cell experiments showed that the activity of HSC-3 cells was dose-dependently inhibited by geniposide, and AO/EB staining showed that geniposide was able to induce programmed apoptosis. Meanwhile, it was found that the expressions of p-EGFR, p-AKT, and Bcl-2 were downregulated in HSC-3, and the expressions of PTEN, Bax, and Caspase-3 were upregulated. Geniposide may inhibit OSCC by affecting the PI3K-Akt signaling pathway and apoptotic process by regulating the expressions of p-EGFR, p-AKT, Bcl-2, Bax, Caspase-3, and PTEN.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"47 9","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468547/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"miR-145-5p and miR-148b-3p Expression Is Inversely Associated with Pten Expression in Prostate Pathologies.","authors":"Karla Lizbeth Morales Hernández, Noemí García Magallanes, Marco Alvarez Arrazola, Fred Luque Ortega, Martín Irigoyen Arredondo, Fernando Bergez Hernandez, Eliakym Arambula Meraz","doi":"10.3390/cimb47090782","DOIUrl":"10.3390/cimb47090782","url":null,"abstract":"<p><p>Prostate cancer (PCa) represents a significant cause of cancer-associated mortality in the male population worldwide and constitutes a multifactorial disease influenced by genetic and epigenetic factors. Deregulation of genes such as AR and PTEN, as well as alteration in the expression of microRNAs (miRNAs), including miR-145-5p and miR-148b-3p, has been observed in this pathology. This study aimed to explore the correlation between the expression of miR-145-5p, miR-148b-3p, and PTEN in prostate tissue, providing initial insight into their potential interaction in cancer biology. We analyzed 71 samples, comprising 41 from patients with confirmed prostate cancer (PCa group) and 30 from patients with benign prostatic disease (BPD group). Our findings demonstrated a statistically significant association between both miRNAs and the PTEN gene, specifically between miR-148b-3p and PTEN (<i>p</i> = 0.00001) and between miR-145-5p and PTEN (<i>p</i> = 0.0078). These findings support the hypothesis that reduced levels of these miRNAs may be linked to PTEN regulation in prostate pathologies and underscore their potential relevance in PCa biology.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"47 9","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468045/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synergistic Induction of Apoptosis by Boswellic Acid and Cisplatin in A549 Lung Cancer Cells Through NF-κB Modulation and p53 Pathway Activation.","authors":"Mehmet Uğur Karabat, Mehmet Cudi Tuncer","doi":"10.3390/cimb47090785","DOIUrl":"10.3390/cimb47090785","url":null,"abstract":"<p><p>The increasing resistance to chemotherapeutic agents in lung cancer significantly contributes to its high mortality. Natural compounds such as acetyl-11-keto-β-boswellic acid (AKBA) have emerged as promising adjuncts to standard therapies. This study investigated the synergistic apoptotic and cytotoxic effects of AKBA in combination with cisplatin (Cis) on A549 non-small-cell lung cancer (NSCLC) cells. Cell viability, apoptosis, and gene expression were evaluated using MTS assay, Annexin V-FITC/PI staining, caspase activity, RT-qPCR, and ELISA, complemented by molecular docking (AKBA-p53) and molecular dynamics (AKBA-p53 and Cis-p53) analyses. Combined AKBA + Cis treatment significantly enhanced apoptosis and reduced cell viability compared to monotherapies (<i>p</i> < 0.001), accompanied by upregulation of p53 and caspase-3 and suppression of NF-κB. In silico results further supported direct and stable binding of p53, particularly with AKBA. These findings indicate that AKBA synergizes with Cis to potentiate apoptotic and anti-inflammatory responses in NSCLC and may provide a novel dose-sparing strategy with improved therapeutic efficacy, warranting further in vivo validation.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"47 9","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468240/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomic Analysis of Low-Temperature Stress Response in Maize (<i>Zea mays</i> L.) at the Seedling Stage.","authors":"Tao Yu, Jianguo Zhang, Xuena Ma, Shiliang Cao, Wenyue Li, Gengbin Yang","doi":"10.3390/cimb47090784","DOIUrl":"10.3390/cimb47090784","url":null,"abstract":"<p><p>Low temperature severely restricts maize seedling establishment and yield in northern China, but the proteomic basis of low-temperature tolerance in maize remains unclear. This study used TMT-labeled quantitative proteomics combined with data-independent acquisition (DIA) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) to analyze dynamic proteome changes in two maize inbred lines (low-temperature-tolerant B144 and low-temperature-sensitive Q319) at the three-leaf stage under 5 °C treatment. A total of 4367 non-redundant proteins were identified. For differentially expressed proteins (DEPs, fold change >2.0 or <0.5, ANOVA-adjusted <i>p</i> < 0.05, false discovery rate [FDR] < 0.05), B144 showed exclusive upregulation under stress (6 DEPs at 24 h; 16 DEPs at 48 h), while Q319 exhibited mixed regulation (9 DEPs at 24 h: 6 upregulated, 3 downregulated; 21 DEPs at 48 h: 19 upregulated, 2 downregulated). Functional annotation indicated that ribosomal proteins, oxidoreductases, glycerol-3-phosphate permease, and actin were significantly upregulated in both lines. Pathway enrichment analysis revealed associations with carbohydrate metabolism, amino acid biosynthesis, and secondary metabolite synthesis. Weighted gene co-expression network analysis (WGCNA) identified genotype-specific expression patterns: B144 showed differential expression of proteins related to acetyl-CoA synthetase and fatty acid β-oxidation at 24 h and of proteins related to D-3-phosphoglycerate dehydrogenase at 48 h; Q319 showed differential expression of proteasome-related proteins at 24 h and of proteins related to elongation factor 1α (EF-1α) at 48 h. Venn analysis found no shared DEPs between the two lines at 24 h but four overlapping DEPs at 48 h. These results clarify proteomic differences underlying low-temperature tolerance divergence between maize genotypes and provide candidate targets for molecular breeding of low-temperature-tolerant maize.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"47 9","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468504/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of Potential Q-Markers for Salt-Processed Alismatis Rhizoma in Diuresis Based on Fingerprinting Technology and Network Analysis.","authors":"Lin Yan, Zemin Ou, Yun Wang, Yan Tong, Jinyu Wang, Dewen Liu","doi":"10.3390/cimb47090783","DOIUrl":"10.3390/cimb47090783","url":null,"abstract":"<p><strong>Introduction: </strong>The ability of salt-processed Alismatis Rhizoma (SAR) (<i>Alisma plantago-aquqtica</i> L.) to nourish Yin and promote urination is stronger than that of Alismatis Rhizoma (AR). However, there are few studies focused on evaluating the quality of its medicinal materials.</p><p><strong>Objectives: </strong>This study aimed to identify potential quality markers (Q-markers) for SAR, thereby providing a more reliable basis for its quality control and clinical application.</p><p><strong>Methods: </strong>Q-markers were identified through fingerprinting and chemical pattern recognition analysis of 15 batches of SAR. The diuretic effects of these markers were then verified by network analysis and molecular docking.</p><p><strong>Results: </strong>HPLC fingerprints of 15 SAR batches were established, with similarity analysis showing values > 0.85 (0.852-0.990). Chemical pattern recognition identified six critical compounds contributing to SAR quality: alisol F, alisol C 23-acetate, alisol A, alisol A 24-acetate, alisol B 23-acetate, and an alisol O isomer (VIP > 1.0). Network analysis revealed 76 overlapping targets between these compounds and diuretic-related diseases, with core targets including non-receptor tyrosine kinase (SRC), epidermal growth factor receptor (EGFR), mitogen-activated protein kinase 1 (MAPK1), which were identified through protein-protein interaction (PPI) network analysis, with degrees of 27, 24, and 22, respectively. Key pathways involved were the EGFR tyrosine kinase inhibitor resistance pathway, calcium signaling pathway, tumor necrosis factor signaling pathway, etc. Molecular docking confirmed strong binding interactions between the Q-markers and the hub targets, particularly alisol B 23-acetate with MAPK1 (-60.10 kcal·mol^-1) and alisol A 24-acetate with EGFR (-46.14 kcal·mol^-1) and SRC (-48.86 kcal·mol^-1). The diuretic effects of SAR are likely mediated through anti-inflammatory actions and regulation of water-sodium balance via multi-target and multi-pathway mechanisms.</p><p><strong>Conclusion: </strong>This study provides a robust foundation for quality control and clinical application of SAR, though further in vivo validation is warranted.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"47 9","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468721/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacological Potential of <i>Arthrospira platensis</i> in Mitigating Sub-Chronic Colitis: Redox Homeostasis and Gut Microbiota Modulation.","authors":"Meriem Aziez, Betitera Yanat, Cristina Rodriguez-Diaz, Ramona Suharoschi, Romana Vulturar, Simona-Codruta Heghes, Nawel Guenaoui, Awadh M Ali, Eduardo Garcia-Fuentes, Noureddine Bribi","doi":"10.3390/cimb47090778","DOIUrl":"10.3390/cimb47090778","url":null,"abstract":"<p><p>Inflammatory bowel diseases (IBDs) are complex disorders involving interconnected immune, oxidative, and microbial dysregulations. <i>Arthrospira platensis</i> (Spirulina) is a rich source of bioactive compounds with antioxidant, anti-inflammatory, and immunomodulatory properties. This study investigates the pharmacological efficacy of its aqueous extract (APA) in mitigating 2,4-Dinitrobenzene Sulfonic Acid (DNBS)-induced sub-chronic colitis with a focus on restoring redox balance and modulating gut microbiota composition. APA's antioxidant capacity was assessed in vitro by 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis (3-ethylbenzthiazoline-6-sulphonic) acid (ABTS) radical scavenging, and metal chelation assays. In vivo, BALB/c mice received two DNBS inductions to establish sub-chronic colitis and were treated with APA (50, 100, and 200 mg/kg). Therapeutic efficacy was assessed through clinical scoring, histopathological assessment, biochemical analysis, and gut microbiota profiling based on 16S rRNA gene sequencing. APA exhibited strong antioxidant activity and significantly attenuated colitis severity, as evidenced by reduced Disease Activity Index (DAI) scores, decreased colon inflammation, suppression of Myeloperoxidase (MPO)-mediated neutrophil infiltration, and modulation of redox biomarkers. Moreover, metagenomic profiling revealed APA-induced modulation of the gut microbiota, mainly through a decreased abundance of pathogenic genera such as <i>Staphylococcus</i> and <i>Enterobacteriaceae</i>. APA demonstrates potent antioxidant, anti-inflammatory, and microbiota-modulating activities, supporting its potential as a complementary therapy for IBDs and encouraging further clinical studies.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"47 9","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468418/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-TB Drugs for Drug-Sensitive and Drug-Resistant <i>Mycobacterium tuberculosis</i>: A Review.","authors":"Kara Lukas, Madeleine T Dang, Clare Necas, Vishwanath Venketaraman","doi":"10.3390/cimb47090776","DOIUrl":"10.3390/cimb47090776","url":null,"abstract":"<p><p>Tuberculosis (TB) is a global health challenge caused by <i>Mycobacterium tuberculosis,</i> with drug resistance, treatment toxicity, and treatment adherence challenges continuing to impede control efforts. The objective of this review is to explore current advancements in TB treatment, for both drug-sensitive and drug-resistant TB, focusing on pharmacologic regimens, diagnostics, and adjunctive therapies. For drug-sensitive TB, a 4-month rifapentine-moxifloxacin regimen has been proven to be non-inferior to the traditional 6-month standard, while optimized pyrazinamide dosing or faropenem substitution may improve culture conversion and reduce adverse events. In drug-resistant TB, regimens such as the bedaquiline, pretomanid, linezolid, and moxifloxacin have demonstrated efficacy with substantially shorter treatment duration; however, incidents of hepatotoxicity and linezolid-related neuropathy require careful monitoring. Adjunctive therapies, such as metformin, N-Acetylcysteine, aspirin, and statins, show promising effects in modulating host immunity and reducing long-term lung damage. Advances in diagnostics, including whole genome sequencing and CRISPR-based methods, are enabling rapid detection of resistance mutations and directed therapy. Vaccine development has advanced beyond the BCG vaccine to explore vaccines with enhanced immunogenicity or ones that are safe for immunocompromised patients. Implementation strategies such as video directly observed therapy are improving adherence; additionally, community-based, technology-supported interventions significantly improve TB knowledge and compliance. An integrated approach that combines optimized pharmacologic regimens, host-directed therapies, advanced diagnostics, and patient-centered public health strategies is essential to reduce TB incidence, long-term morbidity, and mortality.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"47 9","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468382/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In Silico Study of Natural Polyphenols as Potential Metabolic Modulators in Mitigating Lipotoxicity in Non-Alcoholic Fatty Liver Disease via Thyroid Hormone Receptor Alpha Activation.","authors":"Evangelia K Konstantinou, Athanasios A Panagiotopoulos, Maria Dimitriou","doi":"10.3390/cimb47090777","DOIUrl":"10.3390/cimb47090777","url":null,"abstract":"<p><p>Non-alcoholic fatty liver disease (NAFLD) is a metabolic disorder described by the deposition of triglycerides in the liver, which primarily occurs due to insulin resistance and obesity. Thyroid hormone receptor alpha (THRA) is involved in metabolic pathways that promote lipolysis, which can prevent the accumulation of liver fat. As a possible treatment for NAFLD, this in silico study examines the binding interactions between THRA and polyphenols and flavonoids present in fruits and vegetables. Including caffeic acid, curcumin, and chlorogenic acid, the binding affinities of the natural substances to THRA were found comparable to the hormone T3, boosting the THRA-TRAP220 complex, promoting fatty acid oxidation, while decreasing lipid accumulation in the liver.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"47 9","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468250/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Natural Products Targeting the Androgen Receptor Signaling Pathway: Therapeutic Potential and Mechanisms.","authors":"Sitong Wu, Esveidy Isabel Oceguera Nava, Dennis Ashong, Guanglin Chen, Qiao-Hong Chen","doi":"10.3390/cimb47090780","DOIUrl":"10.3390/cimb47090780","url":null,"abstract":"<p><p>The androgen receptor (AR) signaling pathway is the primary driver of prostate cancer initiation and progression, including the development of castration-resistant prostate cancer (CRPC). Because current AR-targeted therapies inevitably encounter drug resistance, novel strategies to suppress AR signaling are urgently needed. Natural products represent a rich and structurally diverse source of bioactive compounds capable of targeting AR at multiple regulatory levels. This review overviews the interactions between natural products and the AR signaling axis through distinct mechanisms, including inhibition of testosterone production and 5α-reductase activity, direct antagonism of AR, and induction of AR degradation. In addition, several compounds disrupt AR nuclear translocation, downregulate AR splice variants, or suppress AR signaling indirectly through epigenetic regulation, microRNA modulation, or interference with co-regulator networks. Preclinical studies provide compelling evidence that these agents can effectively interrupt AR signaling, thereby suppressing prostate cancer growth. However, challenges remain, particularly the limited pharmacokinetic characterization, lack of in vivo validation, and scarcity of clinical studies. Future research should focus on improving bioavailability, exploring synergistic combinations with existing therapies, and advancing well-designed in vivo and clinical investigations. Collectively, these efforts may establish natural products as lead compounds to modulate AR signaling for prostate cancer prevention and treatment.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"47 9","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468636/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioactive Component Screening and Mechanistic Study of the Anti-Diabetic Activity of <i>Lophatherum gracile</i> Brongn Extract.","authors":"Rong Wang, Xuefeng Liu, Kuan Yang, Shaojing Liu, Lili Yu, Yunmei Chen, Nana Wang, Yaqi Hu, Bei Qin","doi":"10.3390/cimb47090779","DOIUrl":"10.3390/cimb47090779","url":null,"abstract":"<p><p>Type 2 diabetes mellitus (T2DM), a metabolic disorder defined by glucose and lipid metabolism dysregulation, has become a major global health issue. Hence, effective measures to prevent T2DM are urgently required. <i>Lophatherum gracile</i> Brongn (LGB) has been used in managing diabetes-related systemic diseases. However, the hypoglycemic bioactive components in LGB and the mechanisms underlying their hypoglycemic activity remain elusive. The current study sought to characterize the bioactive components of LGB and elucidate its mechanism of action against T2DM. Six common characteristic peaks were identified from six batches of LGB, with 39 characteristic chemical components preliminarily identified. Through component-activity correlation analysis, three functional components-namely isoorientin, orientin, and isovitexin-were selected as key candidates. In T2DM mice, LGB effectively improved glucose and lipid metabolic dysfunction. Untargeted metabolomics analysis revealed that LGB modulated pathways related to lipid and carbon metabolism. 16S rRNA gene sequencing and targeted metabolomics analysis revealed that LGB decreased the ratio of Firmicutes to Bacteroidetes and increased the abundance of bacterial groups such as Lactobacillales and Bacteroides. Additionally, LGB elevated the levels of SCFAs, specifically acetic and butyric acid. Moreover, LGB alleviated intestinal inflammation and upregulated the expression of tight junction proteins by inhibiting the LPS/TLR4/NF-κB signaling pathway. This study demonstrated that LGB treated T2DM, with isoorientin, orientin, and isovitexin identified as the main contributing components. The hypoglycemic mechanism is linked to the \"gut microbiota-SCFAs-inflammatory response\" signaling axis.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"47 9","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468491/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}