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JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS · 2024 · IF 3.1

Simultaneous determination of five constituents of areca nut extract in rat plasma using UPLC-MS/MS and its application in a pharmacokinetic study

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.

CAS / MDL: 540-69-2 64-18-6
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
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Foods · 2024 ·Vol. 13 ·期 7 ·1070 · IF 4.7

Deep Eutectic Solvents for Efficient and Selective Extraction of α-Glucosidase Inhibitors from Waste Seeds of Refined Betel Nuts

Jin Liu,Li Ma,Senwen Deng,Xinzhi Chen,Qi Li,Aiqing Xu,Ting Tong,Shuhua Tan,Mingkang Wang,Jiangtao Cai,Haihua Wang

During the production process of refined betel nuts in China, a large amount of processing by-product, betel nut waste seeds, is generated. Betel nut waste seeds are rich in bioactive elements, but they have not been effectively utilized yet. In this study, an ultrasonic-assisted deep eutectic solvent method (DES) was used to selectively extract α-glucosidase inhibitors from waste seeds. Compared with traditional extraction solvents such as water and ethanol, the extraction efficiency of specific DESs is higher, and the content of alkaloids in the extracts is lower. However, it should be noted that some pure DESs exhibit inhibitory activity towards α-glucosidase. DESs, based on choline chloride/urea, were selected due to the high extraction efficiency of α-glucosidase inhibitors and their low alkaloid content as well as low inhibitory activity. The optimal extraction conditions were determined using single-factor experiments as follows: 30% (v/v) water content, a choline chloride/urea ratio of 5:3, a solid–liquid ratio of 1:10, extraction temperature of 40 °C, and a duration of 30 min. Through recovery experiments, it was found that the DES can be reused four times under these conditions, maintaining an inhibition rate comparable to alcohol extraction methods. The IC50value of the extract was measured at 0.0066 mg/mL, superior to acarbose. In summary, this research has successfully developed an efficient and selective method for extracting α-glucosidase inhibitors from betel nut waste seeds, thereby presenting a promising avenue for future applications.

CAS / MDL: 300-08-3 149-91-7
研究领域: 植物化学 · 药物开发 · 生物技术
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF SEPARATION SCIENCE · 2022 ·Vol. 45 ·期 24 ·4469-4477 · IF 3.614

Quantitative determination of major alkaloids in areca nut products by high-performance liquid chromatography coupled with ion mobility spectrometry

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
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Materials · 2020 ·Vol. 13 ·期 21 ·4896 · IF 3.057

Effect of Silane Coupling Agent on Modification of Areca Fiber/Natural Latex

Yiren Pan,Meng Zhang,Jian Zhang,Xiaoyao Zhu,Huiguang Bian,Chuansheng Wang

In this paper, the areca fiber was extracted by physical and chemical treatment, and then the areca fiber/natural latex composite was prepared by natural latex impregnation technology. In order to combine areca fiber and natural rubber latex better, three silane coupling agents with different action mechanism were selected: Si−69, KH550, and KH570 which were used to treat the areca fiber/natural latex compound. The results show that the silane coupling agent can change the surface of the fiber from hydrophilic surface to organophilic surface, making the bonding of areca fiber to natural latex more closely. At the same time, the mechanical properties, physical and mechanical properties, swelling properties, and dynamic viscoelastic properties of the tightly bonded areca fiber/nature latex composites were improved. After observing the micro-structure through a scanning electron microscope, it was found that the three silane coupling agents could effectively bind areca fiber and natural latex to enhance the performance of the composite material, of which Si−69 performed best, and the tensile strength and tear strength of the composite increased by 21.19% and 12.90% respectively.Keywords:areca fiber;natural latex;silane coupling agent

CAS / MDL: 1314-13-2
研究领域: 材料科学 · 化学工程
✓ 已验证 产品关联 DOI PubMed 高影响因子
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FOOD CHEMISTRY · 2025 · IF 9.8

Analysis of areca alkaloids and their conversions using CE-C4D and identification by CE-MS

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
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Food Analytical Methods · 2024 · IF 2.6

Sensitive Liquid Chromatography-Tandem Mass Spectrometry (LC–MS/MS) Analysis of Alkaloid Nitrogen Oxides at Three Different Processing Stages of Binglang

Pan Xingyu,Chen Jinzi,Guo Tao,Kuang Fengjiao,Kang Zonghua,Luo Jianguang

Betel nut (Areca nut, AN) products are extensively consumed across East and South Asian countries, with Binglang being the predominant chewable AN product in China. Given the increased risk of carcinogenicity associated with alkaloid nitrogen oxides compared to the primary alkaloids in AN, this study aimed to establish a precise and sensitive method for quantitative analysis of the arecoline N-oxide (ACNO) and arecaidine N-oxide (ADNO) at three different processing stages of Binglang using liquid chromatography-tandem mass spectrometry (LC–MS/MS). The developed method underwent comprehensive validation, evaluating key analytical parameters including selectivity, linearity, sensitivity, accuracy, precision, and stability. Notably, the method demonstrated excellent sensitivity, with the limits of detection (LOD) ranging from 0.029 to 0.135 ng/mL, while the limits of quantification (LOQ) ranging from 0.095 to 0.450 ng/mL. Subsequently, the established analytical technique was applied to analyze 15 Binglang samples at three different processing stages, providing the first evidence of the content and variability of alkaloid nitrogen oxides throughout these stages. ACNO and ADNO were detected in all samples, and their total contents ranged from 4.31 to 32.82 μg/g. The changes observed across different processing stages indicated that the roasting process at 80 ℃ resulted in the promotion of alkaloid nitrogen oxides. This analytical approach constitutes a valuable tool for the quality control and risk assessment of Binglang and can be extended to other AN products, thereby assisting in addressing health concerns associated with these products.

CAS / MDL: 64-18-6
研究领域: 药理学 · 分析化学 · 食品安全
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FOOD HYDROCOLLOIDS · 2024 · IF 11

Structural Characteristics of Areca Nut Seed Neutral Polysaccharide and Its Impact on Gut Microbiota from Human Feces

Mengfan Zhang,Haining Zhuang,Xiaowei Zhang,Xiaoyu Wang,Xia Fu,Sheng Chen,Lingyun Yao,Huatian Wang,Min Sun,Chuang Yu,Heng Yue,Tao Feng

ABSTRACT Areca nut ( Areca catechu L .) is considered as the fourth most common psychoactive substance globally. Although areca nut seeds (ACS) are typically discarded as processing waste, some studies indicate that amounts of polysaccharides exist in the seeds. However, research on these polysaccharides remains limited. In this study, polysaccharide (ACSP) from areca catechu seeds was isolated into three fractions, among which neutral fraction had a highest yield up to 31.8%. Subsequently, the structural features of neutral fraction (ACSP-0) were analyzed, along with its impact on short-chain fatty acids and human gut microbiota through in vitro feces fermentation. It was found that the backbone chain of ACSP-0 was composed of →4)α-D-Glc p -(1→, α-D-Glc p -(1→, →3,4)α-D-Glc p -(1→ and →4)β-D-Glc p , and the side chain was consisted of α-D-Glc p -(1→. In vitro digestion experiments demonstrated that ACSP-0 could pass through the upper digestive system without being broken down. Furthermore, in vitro fecal fermentation of ACSP-0 resulted in an increased concentration of short-chain fatty acids and promoted the growth of beneficial bacteria such as norank_f_norank_o_Clostridium UCG-014 , which are known to produce generate antibacterial compounds and mitigate gut barrier damage. Additionally, by reducing the abundance ratio of Firmicutes to Bacteroidota , ACSP-0 may hold potential for obesity management. In conclusion, ACSP-0 shows potential as an innovative ingredient for enhancing gut health in humans. This study suggests a novel utilization strategy for areca nut seeds, which could be beneficial for the areca nut processing industry.

研究领域: 食品科学 · 微生物学 · 营养学
✓ 已验证 DOI 高影响因子
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Frontiers in Oncology · 2022 · IF 5.738

Arecoline Is Associated With Inhibition of Cuproptosis and Proliferation of Cancer-Associated Fibroblasts in Oral Squamous Cell Carcinoma: A Potential Mechanism for Tumor Metastasis

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
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Toxins · 2021 ·Vol. 13 ·期 4 ·259 · IF 4.546

Pharmaceutical Assessment Suggests Locomotion Hyperactivity in Zebrafish Triggered by Arecoline Might Be Associated with Multiple Muscarinic Acetylcholine Receptors Activation

Petrus Siregar,Gilbert Audira,Ling-Yi Feng,Jia-Hau Lee,Fiorency Santoso,Wen-Hao Yu,Yu-Heng Lai,Jih-Heng Li,Ying-Ting Lin,Jung-Ren Chen,Chung-Der Hsiao

Arecoline is one of the nicotinic acid-based alkaloids, which is found in the betel nut. In addition to its function as a muscarinic agonist, arecoline exhibits several adverse effects, such as inducing growth retardation and causing developmental defects in animal embryos, including zebrafish, chicken, and mice. In this study, we aimed to study the potential adverse effects of waterborne arecoline exposure on zebrafish larvae locomotor activity and investigate the possible mechanism of the arecoline effects in zebrafish behavior. The zebrafish behavior analysis, together with molecular docking and the antagonist co-exposure experiment using muscarinic acetylcholine receptor antagonists were conducted. Zebrafish larvae aged 96 h post-fertilization (hpf) were exposed to different concentrations (0.001, 0.01, 0.1, and 1 ppm) of arecoline for 30 min and 24 h, respectively, to find out the effect of arecoline in different time exposures. Locomotor activities were measured and quantified at 120 hpf. The results showed that arecoline caused zebrafish larvae locomotor hyperactivities, even at a very low concentration. For the mechanistic study, we conducted a structure-based molecular docking simulation and antagonist co-exposure experiment to explore the potential interactions between arecoline and eight subtypes, namely, M1a, M2a, M2b, M3a, M3b, M4a, M5a, and M5b, of zebrafish endogenous muscarinic acetylcholine receptors (mAChRs). Arecoline was predicted to show a strong binding affinity to most of the subtypes. We also discovered that the locomotion hyperactivity phenotypes triggered by arecoline could be rescued by co-incubating it with M1 to M4 mAChR antagonists. Taken together, by a pharmacological approach, we demonstrated that arecoline functions as a highly potent hyperactivity-stimulating compound in zebrafish that is mediated by multiple muscarinic acetylcholine receptors.Keywords:arecoline;locomotion;zebrafish;betel nut;muscarinic acetylcholine receptor;molecular docking;antagonistKey Contribution:We provides in vivo and in silico evidences to support arecoline affected larvae zebrafish locomotor activity is associated with multiple muscarinic acetylcholine receptor interactions. Co-exposure with muscarinic acetylcholine antagonist receptors can restore locomotor hyperactivity trigger by arecoline exposure strengthen this hypothesis.

CAS / MDL: 65-29-2
研究领域: 药理学 · 神经科学 · 毒理学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Frontiers in Microbiology · 2025 · IF 4.5

Development of a colloidal gold-based immunochromatographic strip for rapid detection of Areca palm velarivirus 1

Jie Lu,Weifan He,Yuxing Liu,Shiqi Li,Xi Huang,Hongxing Wang,Xianmei Cao

Background: Areca palm velarivirus 1 (APV1), the causal agent of betel palm yellow leaf disease (YLD), has caused significant yield losses and decreased product quality of betel nuts, posing a serious economic threat to local farmers. There is an urgent need for a convenient and reliable method for the rapid detection and surveillance of APV1.Methods: The Capsid protein (CP) of APV1 was expressed in Escherichia coli and purified as antigen to immunize BALB/c mice. Two specific monoclonal antibodies (MAbs), APV1CP-1 and APV1CP-10, were generated through the hybridoma technique. APV1CP-1 was conjugated with colloidal gold served as detection reagent, while APV1CP-10 was coated onto a porous nitrocellulose membrane to act as the detection line. Goat anti-mouse IgG was used as the control line. These components were then assembled into a colloidal gold immunochromatographic strip (CGICS) for effective detection of APV1.Results: The MAbs APV1CP-1 and APV1CP-10 were successfully obtained with titers exceeding 1:102,400. Colloidal gold particles used in the assay had an approximate diameter of 30–40 nm, and exhibited a surface plasmon resonance peak around 530 nm. The CGICS allowed for the detection of APV1 by applying infected sap to the test strip, with results visible within 5–10 min. The test showed no cross-reactivity with other viruses tested, and the visual detection limit for APV1 was established at a 100-fold dilutions of APV1-infected leaf samples.Conclusion: The monoclonal antibody-based colloidal gold immunochromatographic strip developed in this study demonstrates significant convenience, rapidity, and reliability for APV1 detection. These advancements are anticipated to facilitate rapid diagnosis and surveillance of APV1 in field settings.

CAS / MDL: 7647-01-0
研究领域: 植物病理学 · 分子生物学 · 病毒学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Foods · 2025 ·Vol. 14 ·期 17 ·2954 · IF 5.1

In Vitro Digestion and Fecal Fermentation of Arecanut Polysaccharides: Effects on Gut Microbiota and Metabolites

Xiaolong Ji,Ke Jiang,Yuqing Liu,Chenyu Zhao,Jun Du,Liang Chen,Zhigang Zhu,Xiaoqiong Li

Recent studies have increasingly emphasized the regulatory potential of plant-derived polysaccharides on gut microbial composition and metabolic function. Despite this growing interest, investigations focusing specifically on the simulated digestion and fermentation properties of arecanut polysaccharide (PAP1b) remain limited. In this work, we employed the standardized INFOGEST 2.0 protocol to mimic the oral, gastric, and intestinal digestion of PAP1b, followed by 48 h anaerobic fermentation using pooled human fecal samples from healthy adult donors. PAP1b treatment led to a progressive decrease in pH and a substantial elevation in SCFAs levels, notably acetic, propionic, and butyric acids. Simultaneously, PAP1b significantly promoted the growth of SCFA-producing microbial taxa, particularly members of theFirmicutesphylum such asLachnospiraceae,Lachnoclostridium,Bilophila, andPhascolarctobacterium, while markedly suppressingBacteroidotapopulations. Metabolomic analysis further indicated that PAP1b intake enhanced bile acid metabolism, suggesting its potential as a prebiotic candidate for improving intestinal health.

研究领域: 食品科学 · 微生物学 · 营养学 · 胃肠病学 · 代谢组学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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INTERNATIONAL JOURNAL OF FOOD SCIENCES AND NUTRITION · 2012 · IF 1.151

The inhibiting activity of areca inflorescence extracts on human low density lipoprotein oxidation induced by cupric ion

Weijun Chen,Chunmei Zhang,Yulin Huang,Fangfang Cheng,Yan Shen,Rencai Wang,Minmin Tang,Yajun Zheng,Songlin Zhao

The oxidative modification of human low density lipoprotein (LDL) plays a significant role in atherosclerosis. In this study, the inhibiting activity of areca inflorescence extracts (AIEs) on LDL oxidation was investigated by an in vitro study with Trolox as the standard antioxidant. The kinetics of LDL oxidation, thiobarbituric acid reactive substances assay, ferric-reducing antioxidant power assay and copper chelation assay were also evaluated to assess the antioxidant activities of AIEs, and the results revealed that AIEs could delay the lag time and inhibit the formation of malondialdehyde in the process of LDL peroxidation induced by Cu2+. The boiled water extract displayed the highest antioxidant activity compared with the ambient water extract and ethanol extract. The total phenolic contents and phenolic components of AIEs were also measured by high performance liquid chromatography method. Epicatechin, gallic acid and coumalic acid were the primary phenolic acids in AIEs.

研究领域: 医学 · 生物化学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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