FOOD CHEMISTRY
·
2025
·
IF 9.8
Jinying Huang,Jiaying Ran,Jingtong Xia,Hongying Du,Lei Zhou
As one of the four major addictive substance globally, areca nut contains areca alkaloids as its principal active ingredients, which exhibit both medicinal potential and toxic effects. In this study, a concise and effective approach was developed for the simultaneous analysis of areca alkaloids using laboratory-built capillary electrophoresis (CE) with capacitively coupled contactless conductivity detection (C 4 D). The proposed method demonstrated satisfactory linearity (R 2 ≥ 0.995), precision (RSDs ≤ 6.56%) and quantification limits of 0.77–1.37 μM. This method has been successfully used to quantify areca products with recoveries of 92.2–110.1%. In addition, the effect of processing on the areca alkaloid content in areca nut-containing products was analyzed. On this basis, the conversions of areca alkaloids under various alkaline conditions were investigated through experimental studies and theoretical calculations. The separation parameters for CE-C 4 D were effectively transferred to CE-mass spectrometry (MS), and the above analytical results for areca alkaloids were validated by incorporating CE-MS related experiments.
研究领域:
药理学
·
分析化学
·
毒理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Oncology
·
2022
·
IF 5.738
Li Jinfei,Chen Shuangyi,Liao Yuxuan,Wang Hongyi,Zhou Dawei,Zhang Bo
Background: Metastatic disease remains the primary cause of death in patients with oral squamous cell carcinoma (OSCC), especially those who use betel nut. The different steps of the metastatic cascade rely on reciprocal interactions between cancer cells and the tumor microenvironment (TME). Cancer-associated fibroblasts (CAFs) are regarded as a significant component in the TME of OSCC. However, the precise mechanisms regulating CAFs in OSCC are poorly understood.Methods: Thirteen genes related to the arecoline were analyzed to explore the significant ones involved in arecoline-related OSCC metastasis. The GSE139869 (n = 10) and The Cancer Genome Atlas (TCGA)-OSCC data (n = 361) were mined for the identification of the differentially expressed genes. The least absolute shrinkage and selection operator (LASSO) regression was performed to identify the independent prognostic signatures. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted to explore the functional enrichment of selected genes, and gene set enrichment analysis of cuproptosis-related genes was completed. Spearman’s analysis and Tumor Immune Estimation Resource (TIMER) were used to visualize the correlation between the infiltration of CAFs and the gene expression. The correlation analysis of the cells and different genes, including CAF infiltration and transcripts per million expression, was assessed. The relationship between arecoline and CAFs was confirmed by cell counting kit-8 assay (CCK-8). CancerSEA was searched to identify the single-cell phenotype.Result: Arecoline-associated fibrosis-related OSCC differentially expressed genes (AFOC-DEGs), namely, PLAU, IL1A, SPP1, CCL11, TERT, and COL1A2, were screened out and selected from the Gene Expression Omnibus (GEO) database and TCGA database. AFOC-DEGs were highly expressed in OSCC, which led to poor survival of patients. Functional enrichment analysis, protein–protein interaction network construction, and Spearman’s correlation analysis all suggested that AFOC-DEGs were closely associated with cuproptosis. Cellular experiments demonstrated that arecoline stimulation could significantly increase the cell viability of CAFs. Single-sample Gene Set Enrichment Analysis (ssGSEA) results showed that GLS and MTF1 were highly expressed when fibroblasts proliferated at high enrichment levels. In addition, analysis of single-cell sequencing results suggested that OSCC cells with high expression of AFOC-DEGs were associated with OSCC metastasis.Conclusion: We found a close association between arecoline, cuproptosis, and CAFs, which might play an important role in the metastasis of OSCC.
研究领域:
肿瘤学
·
分子生物学
·
生物信息学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF SEPARATION SCIENCE
·
2022
·Vol. 45
·期 24
·4469-4477
·
IF 3.614
Ying Lu,Jianna Yu,Wen Liu,Guoxing Jing,Wenshan Li,Wenjie Liu
Areca nut is a popular and addictive food as well as a traditional herbal medicine in many countries. Areca nut contains alkaloids including arecoline, guvacine, and arecaidine, which are the major bioactive compounds in areca products. Areca alkaloids can be carcinogenic, and thus sensitive and specific analytical methods are urgently desired for the identification and quantification of these compounds. High-performance liquid chromatography-based methods are often preferred, but areca alkaloids do not have chromophores, and detection using a traditional UV detector can be difficult. The complexity of areca sample extracts can also lead to the co-elution of peaks leading to poor quantitative performance. We report here high-performance liquid chromatography coupled with an ion mobility spectrometer for sensitive determination of areca alkaloids in various products including areca nut, areca nut products, and herbal oral liquid. An X-Bridge reversed-phase C 18 column was used in the experiment and was combined with high-performance liquid chromatography coupled to an ion mobility spectrometer system. A custom-made adjustable post-column splitter acted as an interface between the high-performance liquid chromatography and the ion mobility spectrometer; it also acted as the electrospray ionization source. The mobile phase was methanol and 0.5% ammonium hydroxide. The results demonstrate that the splitter can afford a wide range of split ratios that match the ion mobility spectrometer ionization source while keeping the separation efficiency of high-performance liquid chromatography. Three major alkaloid compounds were then accurately determined using the resulting method without dativization steps. Many coeluted high-performance liquid chromatography peaks are effectively separated in the ion mobility spectrometer dimension, which in turn improved the quantification accuracy.
研究领域:
分析化学
·
药理学
·
毒理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Toxins
·
2024
·Vol. 16
·期 8
·352
·
IF 3.9
Kaiping Xiang,Bing Wang,Lanying Wang,Yunfei Zhang,Hanzeng Li,Yanping Luo
As the areca nut market is expanding, there is a growing concern regarding areca nut toxicity. Areca nut alkaloids are the major risky components in betel nuts, and their toxic effects are not fully understood. Here, we investigated the parental and transgenerational toxicity of varied doses of areca nut alkaloids inCaenorhabditis elegans. The results showed that the minimal effective concentration of arecoline is 0.2–0.4 mM. First, arecoline exhibited transgenerational toxicity on the worms’ longevity, oviposition, and reproduction. Second, the redox homeostasis ofC. eleganswas markedly altered under exposure to 0.2–0.4 mM arecoline. The mitochondrial membrane potential was thereafter impaired, which was also associated with the induction of apoptosis. Moreover, antioxidant treatments such as lycopene could significantly ameliorate the toxic effects caused by arecoline. In conclusion, arecoline enhances the ROS levels, inducing neurotoxicity, developmental toxicity, and reproductive toxicity inC. elegansthrough dysregulated oxidative stress, cell apoptosis, and DNA damage-related gene expression. Therefore, the drug-induced production of reactive oxygen species (ROS) may be crucial for its toxic effects, which could be mitigated by antioxidants.
研究领域:
毒理学
·
分子生物学
·
细胞生物学
·
遗传学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2024
·
IF 3.1
Mingyu Pan,Wenfeng Geng,Yuanxiao Wang,Makoto Tsunoda,Jiatong Liu,Yingxia Zhang,Haimei Yang,Lu-shuang Li,Shiwen Song,Jinqiang Liang,Yanting Song
Areca nuts have been used as a traditional Chinese medicine (TCM) for thousands of years. Recent studies have shown that it exhibits good pharmacological activity and toxicity. In this study, the pharmacokinetics of five major components of areca nut extract in rats were investigated using a highly sensitive ultra-performance liquid chromatography coupled with triple quadrupole mass spectrometry (UPLC-MS/MS) method. Arecoline, arecaidine, guvacoline, guvacine, and catechin were separated and quantified accurately using gradient elution with mobile phases of (A) water containing 0.1 % formic acid-10 mM ammonium formate, and (B) methanol. The constituents were detected under a timing switch between the positive and negative ion modes using multiple reaction monitoring (MRM). Each calibration curve had a high R 2 value of >0.99. The method accuracies ranged −7.09–11.05 % and precision values were less than 14.36 %. The recovery, matrix effect, selectivity, stability, and carry-over of the method were in accordance with the relevant requirements. It was successfully applied for the investigation of the pharmacokinetics of these five constituents after oral administration of areca nut extract. Pharmacokinetic results indirectly indicated a metabolic relationship between the four areca nut alkaloids in rats. For further clarification of its pharmacodynamic basis, this study provided a theoretical reference.
研究领域:
药理学
·
分析化学
·
中药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL TOXICOLOGY
·
2025
·
IF 3.2
Yuejie Wu,Fei Wang,Longxiang Gao,Yunfei Zhang,Lanying Wang,Yanping Luo
Arecoline is a major active alkaloid in Areca catechu L. Currently, its biological toxicity has been extensively explored using multiple models, such as cell lines, animal embryos and representatives of rodent and non-rodent species. However, the intergenerational impacts of this compound on aquatic invertebrate species remain still unclear. Thus, in this study, using Aedes aegypti as the model insect, we evaluated the toxicity of arecoline to the larvae and its subsequent effects on the developmental parameters of the parental ( F 0 ) and offspring ( F 1 ) generations. Arecoline exhibited a high toxicity to A. aegypti larvae with the LC 50 value of 72.68 μg/mL via acute exposure for 48 h. As a result, the cumulative pupation rate of F 0 decreased significantly by ranging from 12.96% to 38.50% with the increase of arecoline concentration from 51.63 to 63.27 μg/mL as compared with that of the blank control. Similarly, the F 0 cumulative emergence rate and the average egg number per female exhibited reductions of 15.30%–43.88% and 26.32%–45.10%, respectively. Meanwhile, leg deformities of F 0 adults were observed as the main visible morphological defects with a maximum rate value of 11.89% at 63.27 μg/mL of arecoline. In contrast, the lifecycle parameters for F 0 mentioned above were not significantly affected in the F 1 generation. In addition, Gene Ontology (GO) analysis of the transcriptome data demonstrated that arecoline-induced leg deformities were associated with extracellular chitin-related biological processes. Furthermore, five chitin synthesis pathway genes ( G6PI , GFAT , GNPNA , UAP and CHS ) of F 0 adults were significantly down-regulated with ranging from 1.62 to 7.80 folds of the control adults. Correspondingly, the activity of chitin synthetase was significantly inhibited by 72.88% after arecoline exposure. As expected, the chitin contents of leg-deformed adults and their legs were also evidently reduced by 61.13% and 65.44%, respectively. These results imply that acute exposure of arecoline is of high toxicity to A. aegypti larvae and affected the subsequent intergenerational growth and development of F 0 rather than F 1 , and that a decrease in chitin synthesis was involved in arecoline-induced leg deformities of A. aegypti .
研究领域:
毒理学
·
昆虫学
·
分子生物学
·
环境科学
·
昆虫生理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Pharmaceutics
·
2026
·Vol. 18
·期 3
·324
·
IF 6.9
Ting-Syuan Lin,Jingting Wan,Jingjin He,Shidong Cui,Yun Huang,Bojian Zhang,Hsi-Yuan Huang,Kexin Zhu,Jihang Chen,Tao Zhang,Shangfu Li,Liao Hu,Yongfei Wang,Hsien-Da Huang,Ping Tang,Yang-Chi-Dung Lin
Background/Objectives: ATPase family AAA domain-containing protein 2 (ATAD2) is an oncogenic chromatin regulator that amplifies E2F/MYC transcriptional programs, yet direct modulators remain scarce. Arecoline (ARE), the primary alkaloid of the areca nut, is a known carcinogen but paradoxically exhibits context-dependent anti-proliferative activities. In this study, we resolve this paradox by defining ARE’s anti-cancer mechanism.Methods: Breast cancer cell proliferation and colony formation assays were performed to evaluate the anti-proliferative effects of ARE. Cell-cycle distribution was analyzed to determine phase-specific effects. Transcriptomic profiling was conducted to identify affected gene networks. An unbiased Cellular Thermal Shift Assay–Mass Spectrometry (CETSA-MS) screening was used to identify direct protein targets, followed by CETSA–Western blotting for validation. Finally, in silico structure-based design was applied to generate novel derivatives with improved predicted properties.Results: ARE suppressed breast cancer cell proliferation and colony formation by inducing G1/S phase arrest. Transcriptomic analysis revealed that this phenotype was driven by profound suppression of the E2F/Cell Cycle gene network. CETSA-MS identified ATAD2 through multi-omics convergence, as the 67 direct targets were collectively most significantly enriched in the E2F pathway. CETSA–Western blotting confirmed that ARE binds and thermally stabilizes ATAD2. Mechanistically, ARE engagement of ATAD2 led to downregulation of key downstream proteins, including MYC and Cyclin D1, directly linking target modulation to G1/S arrest. Structure-based design further yielded novel derivatives with predicted enhanced ATAD2 binding and substantially reduced toxicity.Conclusions: Together, these findings uncover ATAD2 as a druggable target of ARE, establish proof-of-concept for repurposing this scaffold, and provide a rational framework for developing safer ATAD2-targeted therapies.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Scientific Reports
·
2025
·Vol. 15
·期 1
·1-12
·
IF 3.9
Sun Honglan,Yang Chao,Yin Xiaoyunqing,Chen Shizhao,Huang Yuqi,Kuang Huifang,Luo Wen
The chronic illness known as oral submucous fibrosis (OSF) results in tissue fibrosis, precancerous lesions, and scarring. It usually manifests itself in the buccal mucosa. It frequently occurs in the buccal mucosa. Von Hippel-Lindau (VHL) is an essential component of E3 ubiquitin ligase complex. The loss of VHL led to reduced fibrotic responses, accompanied by ameliorated fiber deposition. However, the precise impact of VHL on OSF is yet unclear. OSF tissues and normal mucosal tissues were applied to analyze the distinct expression of VHL and histone deacetylase 6 (HDAC6). Oral fibroblasts were treated to arecoline to simulate OSF in vitro, and molecular biological experiments were conducted to identify the role of VHL in buccal mucosa fibroblasts (BMFs). VHL was downregulated and HDAC6 was upregulated in OSF tissues and BMFs. Overexpression of VHL inhibited fibrosis in arecoline-treated BMFs. VHL inhibits the level of HDAC6 by inducing the ubiquitination of HDAC6. Knockdown of HDAC6 reduces the fibrogenic ability of BMFs. Furthermore, overexpression of HDAC6 contributes to the activation of NF-κB signaling in BMFs. HDAC6 selective inhibitor ACY-1215 inhibited the NF-κB signaling pathway. VHL attenuated arecoline-induced OSF by inhibiting the ubiquitination of HDAC6 and blocking NF-κB pathway. As a result, our study offers new perspectives into the discovery of novel tactics that can be employed against OSF.
研究领域:
医学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CELL BIOCHEMISTRY AND BIOPHYSICS
·
2024
·
IF 1.8
Yin Lifen,Wang Xiao
Oral submucous fibrosis (OSF) is a precancerous lesion of the oral cavity. Areca nut consumption can cause OSF through sustained activation of buccal mucosal fibroblasts (BMFs). This study explored the effect of curcumin on arecoline-induced BMF activation and its mechanism of action. BMFs were isolated and identified by immunofluorescence detection of fibroblast surface markers vimentin and S100A4. After transfection with FOSL1- or MAPK8-related vectors, BMFs were activated by arecoline and treated with curcumin. Scratch and transwell assays were performed to detect cell migration. ChIP and luciferase reporter assays were conducted to detect the binding of FOSL1 to the MAPK8 promoter. RT-qPCR was used to detect FOSL1 and MAPK8 mRNA expression. Western blotting was used to detect FOSL1, MAPK8, COL1A1, α-SMA, Smad2, and p-Smad2 proteins. Curcumin treatment inhibited arecoline-induced fibroblast migration, reduced the expression of myofibroblast markers COL1A1, α-SMA, and p-Smad2, and downregulated the expression of FOSL1 and MAPK8. FOSL1 or MAPK8 overexpression enhanced migration and increased COL1A1, α-SMA, and p-Smad2 expression in curcumin-treated cells. FOSL1 bound to the MAPK8 promoter and promoted MAPK8 expression. Simultaneous FOSL1 overexpression and MAPK8 knockdown, compared to FOSL1 overexpression, reduced cell migration and inhibited COL1A1, α-SMA, and p-Smad2 expression. In conclusion, curcumin targets FOSL1 to reduce MAPK8 expression, thereby suppressing arecoline-induced fibroblast activation.
研究领域:
药理学
·
分子生物学
·
肿瘤学
·
牙医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）