arecoline / Cogent Pharma - LARVOL DELTA

Gene expression analysis of epithelial-mesenchymal transition markers in oral submucous fibrosis fibroblasts treated with arecoline. (PubMed, Bioinformation) - "Arecoline decreased E-cadherin and increased N-cadherin, vimentin, α-SMA, Snail, Twist and migration rate, whereas co-treatment with curcumin or EGCG significantly reversed these effects, with curcumin showing greater efficacy. Thus, we show that curcumin and EGCG inhibit arecoline-induced EMT and may serve as potential therapeutic agents in OSF management."

Journal • Fibrosis • Immunology • CDH1 • CDH2 • VIM

Insecticidal potential of Areca catechu nut extract against multiple life stages of Aedes aegypti and Aedes albopictus. (PubMed, PLoS One) - "Liquid chromatography-mass spectrometry analysis identified arecoline, arecaidine, and N-lauryldiethanolamine as key constituents with known inhibitory effects on neural and detoxification enzymes in insects. This research provides a comprehensive assessment of A. catechu nut extract across multiple mosquito life stages and behavioural endpoints, demonstrating its broad-spectrum efficacy. The results support its potential as a sustainable, plant-derived bioinsecticide for integrated vector control programs targeting Aedes mosquitoes and associated disease transmission."

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Regulation of AKR1Cs' expression of SAS oral cancer cells by areca nut and arecoline (LCC 2026) - "Since AKR1Cs are crucial for cancer development and resistance, regulation of AKR1Cs by ANE and arecoline implied the involvement of AN components in oral carcinogenesis. Future use of AKR1C inhibitors for prevention/treatment of oral cancers awaits investigation."

Addiction (Opioid and Alcohol) • Head and Neck Cancer • Oncology • Oral Cancer • Solid Tumor • Tobacco Addiction • AKR1C1 • AKR1C2 • MMP9

Comprehensive database enables the UHPLC-Q-orbitrap-MS/MS method to discover 16 "overlooked" compounds and supply three new pharmacopoeia quality-markers for charred Semen Arecae (Jiaobinglang). (PubMed, Anal Methods) - "The system can overcome the limitations of the old and risky Q-marker (arecoline). This successful attempt indicates that a comprehensive database can enable UHPLC-Q-orbitrap-MS/MS for the in-depth analysis of Chinese herbal medicines and quality-control update of charred CHMs."

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Metformin alleviates the progression of oral submucous fibrosis through downregulation of metastasis associated lung adenocarcinoma transcript 1 (MALAT1). (PubMed, J Dent Sci) - "Additionally, we showed that administration of metformin prevented the arecoline-induced myofibroblast activation. Most importantly, our results suggest that metformin may exert suppressive effects on myofibroblast activities by inhibiting ROS accumulation through the downregulation of MALAT1. These findings indicate that metformin may serve as a preventive agent against OSF progression."

Journal • Fibrosis • Immunology • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • COL1A1 • MALAT1 • SMAD2

Design, synthesis and preliminary evaluation of mosquitoicidal activity of arecoline derivatives targeting muscarinic acetylcholine receptors. (PubMed, Bioorg Med Chem Lett) - "Notably, compound 13a maintained high insecticidal activity even against pyrethroid-resistant mosquitoes, indicating a mode of action different from conventional neurotoxic insecticides. These results demonstrate that mAChR-targeting derivatives derived from betel alkaloids represent a promising strategy for developing new mosquito control agents and offer a novel approach to combating insecticide resistance."

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Integrated omics analysis identifies mechanical irritation as a driver of OSCC progression via the HIF-1α/ASC/NLRP3 pathway. (PubMed, Biomed J) - "Our MCA model simulating betel nut chewing induces membrane damage, activates the HIF-1α/NLRP3/ASC pathway, and enhances crosstalk between inflammation and HIF-1α signaling. Omics and clinical data reveal that ADAM8, a HIF-1α downstream target, may serve as a poor prognostic marker in OSCC."

Journal • Oncology • Oral Cancer • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • ADAM8 • HIF1A • IL1B • NLRP3

Synthesis of arecoline benzyl ester derivatives and investigation of insecticidal mechanism against Aedes aegypti. (PubMed, Pest Manag Sci) - "Arecoline benzyl ester 4r is a promising insecticidal lead that perturbs 20E signaling via EcR/USP and Hr3 and dysregulates downstream chitin synthase and chitinase genes, thereby disrupting chitin homeostasis and larval development in Ae. aegypti. These findings provide a scientific basis for further optimization of arecoline-based mosquito control agents targeting the chitin pathway."

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Neuromodulatory Effects of Arecoline on Anxiety-like Behavior in Mice Exposed to Chronic Unpredictable Mild Stress. (PubMed, Int J Mol Sci) - "Collectively, the findings suggest that arecoline exerts multifaceted neuroprotective actions under chronic stress by coordinating neuroendocrine modulation, neurotransmitter homeostasis, antioxidant defenses, and synaptic plasticity. This study provides new mechanistic evidence supporting the potential relevance of arecoline as a functional neuroactive compound for managing stress-induced anxiety disorders."

Journal • Preclinical • CNS Disorders • Mood Disorders • Psychiatry • BDNF • NTRK2

Research progress on Areca catechu (PubMed, Zhongguo Zhong Yao Za Zhi) - "Modern studies have shown that different medicinal parts of this plant are rich in alkaloids, represented by arecoline, and polyphenolic compounds. These components exhibit diverse pharmacological effects, including promoting gastrointestinal motility, antidepressant effects, antioxidant effects, lipid-lowering effects, anthelmintic effects, and antibacterial activities. This article systematically reviews the chemical constituents and pharmacological activities of Arecae Semen, Arecae Pericarpium, and Arecae Flos, and summarizes the toxic side effects and underlying mechanisms of A. catechu products, aiming to provide a scientific basis for the comprehensive development and rational clinical application of A. catechu as a medicinal resource."

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Therapeutic Potential of Methanolic Extract of Areca catechu Nut in Treating Nicotine Use Disorder: evidence from preclinical mouse behavioral models. (PubMed, J Pharmacopuncture) - "Arecoline, the main bioactive compound in Areca catechu nut, interacts with nicotinic acetylcholine receptors (α4β2 and α7), suggesting potential in reducing nicotine cravings and withdrawal symptoms...Antidopaminergic effects and locomotor activity were measured via the haloperidol-induced catalepsy model and actophotometer...MAN (25 and 50 mg/kg, p.o.) showed antidopaminergic activity, reduced nicotine craving, and alleviated withdrawal symptoms (anxiety, depression, anhedonia, memory impairment, hyperalgesia) by enhancing serotonergic neurotransmission. MAN shows potential as a therapeutic candidate for nicotine use disorder."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Depression • Mood Disorders • Nicotine Addiction • Psychiatry

Protective Effects of Arecoline on LPS-Induced Neuroinflammation in BV2 Microglial Cells. (PubMed, Int J Mol Sci) - "Western blot analysis further showed that arecoline suppressed LPS-activated microglial signaling by down-regulating TLR4, inhibiting NF-κB p65 phosphorylation, and limiting PI3K/AKT activation. Collectively, these data reveal that arecoline exerts immunomodulatory and neuroprotective effects through dual signaling regulation in microglia and may serve as a useful pharmacological tool or structural reference for elucidating microglial inflammatory regulation and for guiding the exploration of safer bioactive compounds."

IO biomarker • Journal • Inflammation • Oncology • IL1B • IL6 • TLR4 • TNFA

Salvianolic acid B decreases oxidative stress and alleviates the tumor-promoting effects of arecoline in oral cancer. (PubMed, Curr Res Pharmacol Drug Discov) - "Therefore, SAB, through its ability to reduce oxidative stress, fibrosis, and metabolic dysregulation, is a promising therapeutic candidate for mitigating arecoline-induced tumor progression. Our study offers novel insights into the role of SAB in protecting against the pathophysiology of oral cancer and highlights its potential as a natural compound for the prevention and treatment of this disease."

Journal • Fibrosis • Head and Neck Cancer • Immunology • Metabolic Disorders • Oncology • Oral Cancer • Solid Tumor • Tongue Carcinoma • EGFR • TGFB1

Computer prediction and genetic analysis identifies retinoic acid modulation as a driver of conserved longevity pathways in genetically diverse Caenorhabditis nematodes. (PubMed, Elife) - "While 11 compounds (aldosterone, arecoline, bortezomib, dasatinib, decitabine, dexamethasone, erlotinib, everolimus, gefitinib, temsirolimus, and thalidomide) either had no effect on median lifespan or were toxic, 5 compounds (all-trans retinoic acid, berberine, fisetin, propranolol, and ritonavir) extended lifespan in Caenorhabditis elegans. While the canonical Akt-target FOXO/DAF-16 was largely dispensable, other conserved Akt-targets (Nrf2/SKN-1 and HSF1/HSF-1), as well as the conserved catalytic subunit of AMPK AAK-2, were all necessary for longevity extension by atRA. Our results highlight the potential of combining computational prediction of longevity interventions with the power of nematode functional genetics and underscore that the manipulation of a conserved metabolic regulatory circuit by co-opting endogenous signaling molecules is a powerful approach for discovering aging interventions."

Journal • AKT1 • AKT2 • AMPK • HSF1

Evaluation of the Intergenerational Effects of Arecoline on Aedes aegypti via Acute Exposure and Its Role in Inducing the Leg Deformities Involved in Chitin Synthesis Inhibition. (PubMed, Environ Toxicol) - "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 F0 rather than F1, and that a decrease in chitin synthesis was involved in arecoline-induced leg deformities of A. aegypti."

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Synthesis, Bioactivity, and Mechanistic Insights of Novel Arecoline-Fused Quinazoline Derivatives as Potential Agents for Controlling Tea Tree Fungal Diseases. (PubMed, J Agric Food Chem) - "Mechanistically, it disrupted fungal membranes; induced hyphal abnormalities; upregulated tea plant defense enzymes (CAT, POD, and SOD); and modulated jasmonic/salicylic acid pathways, metabolism, and oxidative responses (omics analyses). This study not only expands the application scope of the natural product quinazolin but also provides promising lead compounds for the development of eco-friendly fungicides in tea plant protection."

Journal • Infectious Disease

Mechanistic link between eIF4E phosphorylation and viral pathogenesis: Therapeutic insights from a porcine model. (PubMed, Vet Microbiol) - "Furthermore, hypophosphorylation of eIF4E effectively restored antioxidant defenses by regulating the levels of superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) induced by arecoline treatment. These findings suggest that inhibitors targeting the MNK1/2-eIF4E axis confer tissue homeostasis and protection through coordinated anti-inflammatory and antioxidant effects. This work not only elucidates a druggable host factor in virus pathogenesis but also provides preclinical evidence for repurposing eFT508-class compounds in antiviral therapy and livestock resilience enhancement."

Journal • Preclinical • Infectious Disease • CAT • EIF4E • IL6 • NLRP3 • TNFA • TNFAIP3

Exploring the relationship between gut microbiota-metabolite axis and Jiawei Danxuan Koukang's therapeutic effects in male rats with oral submucous fibrosis: A multi-omics analysis. (PubMed, Arch Oral Biol) - "JDK alleviates OSF by normalizing inflammation and fibrosis-related metabolic pathways, linking gut microbiota remodeling to metabolic homeostasis."

Journal • Preclinical • Fibrosis • Immunology • Inflammation • COL1A1 • IL10 • IL1B • IL6 • TGFB1

Arecoline upregulates CD155 expression to facilitate immune evasion in oral squamous cell carcinoma. (PubMed, J Immunother Cancer) - "This study unveils a novel mechanism by which arecoline promotes immune evasion in OSCC and highlights promising immune therapeutic targets and strategies for the treatment of areca nut-associated OSCC."

IO biomarker • Journal • Head and Neck Cancer • Oncology • Oral Cancer • Solid Tumor • Squamous Cell Carcinoma • CD8 • PVR • RHOA • TIGIT

TGF-β1 Directs TFAM-Mediated Mitochondrial Reprogramming in Oral Submucous Fibrosis. (PubMed, J Dent Res) - "TGF-β1 appears to modulate mitochondrial responses in arecoline-induced cytotoxicity, resulting in fibroblast survival, leading to a profibrotic phenotype. These observations suggest that selective targeting of the mitochondria driving these surviving myofibroblasts may serve as a novel therapeutic target for clinical translation."

Journal • Fibrosis • Immunology • TFAM • TGFB1 • VIM

Oxidative stress markers as a diagnostic tool in oral cancer and premalignant lesions: A systematic review. (PubMed, J Dent Res Dent Clin Dent Prospects) - "Standardized methodologies and therapeutic approaches targeting oxidative stress could enhance early detection and treatment, especially in resource-limited settings. However, the findings must be interpreted with caution due to methodological limitations, geographic bias, and the lack of inclusion of grey literature."

Journal • Review • Fibrosis • Head and Neck Cancer • Immunology • Oncology • Oral Cancer • Solid Tumor • Squamous Cell Carcinoma

High-fat diet exacerbates risk of prostate cancer in arecoline-induced prostatic hyperplasia via modulation of periprostatic adipose tissues in rats. (PubMed, Food Chem Toxicol) - "Our findings underscore that perilous synergy between arecoline and HFD drives an immune-metabolic remodelling in the prostate-adipose microenvironment. On a therapeutic standpoint, the study underscores lipid metabolism to be a potential target for prostate health intervention, reinforcing the necessity of lifestyle modifications to counteract diet- and habit-induced metabolic disruptions."

Journal • Preclinical • Genito-urinary Cancer • Metabolic Disorders • Oncology • Prostate Cancer • Solid Tumor • TGFB1

Stem Cell Secretome Reverse Areca Nut Extract Induced Fibrosis in Human Fibroblast and Patient-Derived Biopsies. (PubMed, J Oral Pathol Med) - "Secretome exhibited promising cytoprotective and anti-fibrotic properties, reduction in cell death, senescence, collagen expression, and oxidative stress. These findings support the potential of secretome as a novel therapeutic candidate for oral submucous fibrosis, meriting further investigation in preclinical and clinical trials."

Journal • Fibrosis • Immunology • TGFB1 • TGFB2

Neuroprotective Effects and Mechanisms of Arecoline Against H2O2-Induced Damage in SH-SY5Y Cells. (PubMed, Int J Mol Sci) - "Collectively, the findings suggest that arecoline safeguards neurons against oxidative stress by simultaneously activating antioxidant defenses and restraining apoptosis. This study adds novel molecular evidence supporting the potential neuroprotective relevance of arecoline in oxidative stress-related neuropathology."

IO biomarker • Journal • B Cell Lymphoma • CNS Disorders • Lymphoma • Neuroblastoma • Oncology • Solid Tumor • BAX • CASP3 • HMOX1 • KEAP1

Tropomyosin-1 positively regulates TGF-β/Smad3 signaling through STUB1 in arecoline-induced oral submucosal fibrosis. (PubMed, Odontology) - "In conclusion, activation of the TGF-β/Smad3 pathway upregulates TPM1, which in turn blocks STUB1-mediated ubiquitination of the same cascade, establishing a positive-feedback loop that exacerbates arecoline-induced OSF. These findings improve our understanding of OSF's molecular pathogenesis and offer a potential target for its prevention and treatment."

Journal • Fibrosis • Immunology • Oncology • Targeted Protein Degradation • SMAD3 • SMAD4 • TGFB1